6,691 results on '"Aging drug effects"'
Search Results
2. Effects of sacubitril-valsartan on aging-related cardiac dysfunction.
- Author
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Telesca M, De Angelis A, Donniacuo M, Bellocchio G, Riemma MA, Mele E, Canonico F, Cianflone E, Torella D, D'Amario D, Patti G, Liantonio A, Imbrici P, De Luca A, Castaldo G, Rossi F, Cappetta D, Urbanek K, and Berrino L
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- Animals, Female, Rats, Renin-Angiotensin System drug effects, Fibrosis, Oxidative Stress drug effects, Angiotensin Receptor Antagonists pharmacology, Angiotensin Receptor Antagonists therapeutic use, Stroke Volume drug effects, Disease Models, Animal, Neprilysin antagonists & inhibitors, Neprilysin metabolism, Myocytes, Cardiac drug effects, Myocytes, Cardiac pathology, Aminobutyrates pharmacology, Aminobutyrates therapeutic use, Biphenyl Compounds pharmacology, Valsartan pharmacology, Valsartan therapeutic use, Drug Combinations, Aging drug effects, Aging pathology, Tetrazoles pharmacology, Tetrazoles therapeutic use, Rats, Inbred F344, Heart Failure drug therapy, Heart Failure physiopathology
- Abstract
Heart failure (HF) remains a huge medical burden worldwide, with aging representing a major risk factor. Here, we report the effects of sacubitril/valsartan, an approved drug for HF with reduced EF, in an experimental model of aging-related HF with preserved ejection fraction (HFpEF). Eighteen-month-old female Fisher 344 rats were treated for 12 weeks with sacubitril/valsartan (60 mg/kg/day) or with valsartan (30 mg/kg/day). Three-month-old rats were used as control. No differential action of sacubitril/valsartan versus valsartan alone, either positive or negative, was observed. The positive effects of both sacubitril/valsartan and valsartan on cardiac hypertrophy was evidenced by a significant reduction of wall thickness and myocyte cross-sectional area. Contrarily, myocardial fibrosis in aging heart was not reduced by any treatment. Doppler echocardiography and left ventricular catheterization evidenced diastolic dysfunction in untreated and treated old rats. In aging rats, both classical and non-classical renin-angiotensin-aldosterone system (RAAS) were modulated. In particular, with respect to untreated animals, both sacubitril/valsartan and valsartan showed a partial restoration of cardioprotective non-classical RAAS. In conclusion, this study evidenced the favorable effects, by both treatments, on age-related cardiac hypertrophy. The attenuation of cardiomyocyte size and hypertrophic response may be linked to a shift towards cardioprotective RAAS signaling. However, diastolic dysfunction and cardiac fibrosis persisted despite of treatment and were accompanied by myocardial inflammation, endothelial activation, and oxidative stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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3. A review on polyamines as promising next-generation neuroprotective and anti-aging therapy.
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Arthur R, Jamwal S, and Kumar P
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- Humans, Animals, Neuroprotective Agents therapeutic use, Neuroprotective Agents pharmacology, Polyamines metabolism, Polyamines pharmacology, Aging drug effects, Aging metabolism, Neurodegenerative Diseases metabolism, Neurodegenerative Diseases drug therapy
- Abstract
Neurodegenerative disorders are diseases characterized by progressive degeneration of neurons and associated structures and are a major global issue growing more widespread as the global population's average age increases. Despite several investigations on their etiology, the specific cause of these disorders remains unknown. However, there are few symptomatic therapies to treat these disorders. Polyamines (PAs) (putrescine, spermidine, and spermine) are being studied for their role in neuroprotection, aging and cognitive impairment. They are ubiquitous polycations which have relatively higher concentrations in the brain and possess pleiotropic biochemical activities, including regulation of gene expression, ion channels, mitochondria Ca
2+ transport, autophagy induction, programmed cell death, and many more. Their cellular content is tightly regulated, and substantial evidence indicates that their altered levels and metabolism are strongly implicated in aging, stress, cognitive dysfunction, and neurodegenerative disorders. In addition, dietary polyamine supplementation has been reported to induce anti-aging effects, anti-oxidant effects, and improve locomotor abnormalities, and cognitive dysfunction. Thus, restoring the polyamine level is considered a promising pharmacological strategy to counteract neurodegeneration. This review highlights PAs' physiological role and the molecular mechanism underpinning their proposed neuroprotective effect in aging and neurodegenerative disorders., Competing Interests: Declaration of competing interest Authors declare no known conflict of interest whatsoever., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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4. Propofol ameliorates cognitive deficits following splenectomy in aged rats by inhibiting ferroptosis via the SIRT1/Nrf2/GPX4 pathway.
- Author
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Wen Y, Zhang W, Wang D, and Lu M
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- Animals, Rats, Male, Postoperative Cognitive Complications metabolism, Postoperative Cognitive Complications prevention & control, Signal Transduction drug effects, Hippocampus drug effects, Hippocampus metabolism, Aging drug effects, Aging metabolism, Propofol pharmacology, Sirtuin 1 metabolism, Splenectomy, NF-E2-Related Factor 2 metabolism, Cognitive Dysfunction metabolism, Cognitive Dysfunction drug therapy, Cognitive Dysfunction etiology, Ferroptosis drug effects, Ferroptosis physiology, Rats, Sprague-Dawley, Phospholipid Hydroperoxide Glutathione Peroxidase metabolism
- Abstract
The aim of this study was to investigate the mechanism by which propofol reduces postoperative cognitive dysfunction after splenectomy in aged rats. The rats in the model group and propofol group were subjected to splenectomy, and anesthetized with isoflurane and propofol, respectively. Utilizing the western blotting to assess the expression of sirtuin-1 (SIRT1) in the hippocampus. Molecular docking technology was used to predict the binding ability of propofol and SIRT1. Behavioral tests were performed using the Morris water maze, and the hippocampus was isolated for mechanistic investigations. Molecular docking showed that propofol and SIRT1 had a strong binding affinity. The expression of SIRT1 and its related proteins Nrf2, HO-1, NQO1, and GPX4 in the model rats was decreased compared with the sham group. Moreover, the model group exhibited cognitive decline, such as extended escape latency and decreased number of platform crossings. Pathological analysis showed that the number of apoptotic neurons, the levels of oxidative stress and neuroinflammation, the iron deposition, and the expressions of ACSL4 and TFR1 were increased, while the expressions of SLC7A11 and FTH1 were decreased in the hippocampal CA1 region within the model group. These pathological changes in the propofol group were, however, less than those in the model group. Nevertheless, the SIRT1 inhibitor increased these pathological changes compared with the propofol group. Compared with isoflurane, propofol inhibits ferroptosis in the hippocampus of splenectomized rats by causing less downregulation of the SIRT1/Nrf2/GPX4 pathway, thereby reducing the negative impact on cognitive function., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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5. Tetramethylpyrazine nitrone delays the aging process of C. elegans by improving mitochondrial function through the AMPK/mTORC1 signaling pathway.
- Author
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Zhang T, Jing M, Fei L, Zhang Z, Yi P, Sun Y, and Wang Y
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- Animals, Caenorhabditis elegans Proteins metabolism, Caenorhabditis elegans Proteins genetics, Nitrogen Oxides metabolism, Caenorhabditis elegans metabolism, Caenorhabditis elegans drug effects, Mechanistic Target of Rapamycin Complex 1 metabolism, Pyrazines pharmacology, Mitochondria metabolism, Mitochondria drug effects, Signal Transduction drug effects, AMP-Activated Protein Kinases metabolism, Aging metabolism, Aging drug effects
- Abstract
Aging is characterized as the process of functional decline in an organism from adulthood, often marked by a progressive loss of cellular function and systemic deterioration of multiple tissues. Among the numerous molecular, cellular, and systemic hallmarks associated with aging, mitochondrial dysfunction is considered one of the pivotal factors that initiates the aging process. During aging, mitochondria undergo varying degrees of damage, resulting in impaired energy production and disruption of the homeostatic regulation of mitochondrial quality control systems, which in turn affects cellular energy metabolism and results in cellular dysfunction, accelerating the aging process. AMP-activated protein kinase (AMPK) and the mechanistic target of rapamycin complex 1 (mTORC1) are two central kinase complexes responsible for sensing intracellular nutrient levels, regulating metabolic homeostasis, modulating aging and play a crucial role in maintaining the homeostatic balance of mitochondria. Our previous studies found that the novel compound tetramethylpyrazine nitrone (TBN) can protect mitochondria via the AMPK/mTOR pathway in many animal models, extending healthy lifespan through the Nrf2 signaling pathway in nematodes. Building upon this foundation, we have posited a reasonable hypothesis, TBN can improve mitochondrial function to delay aging by regulating the AMPK/mTORC1 signaling pathway. This study focuses on the C. elegans, exploring the impact and underlying mechanisms of TBN on aging and mitochondrial function (especially the mitochondrial quality control system) during the aging process. The present studies demonstrated that TBN extends lifespan of wild-type nematodes and is associated with the AMPK/mTORC1 signaling pathway. TBN elevated ATP and NAD
+ levels in aging nematodes while orchestrating mitochondrial biogenesis and mitophagy. Moreover, TBN was observed to significantly enhance normal activities during aging in C. elegans, such as mobility and pharyngeal pumping, concurrently impeding lipofuscin accumulation that were closely associated with AMPK and mTORC1. This study not only highlights the delayed effects of TBN on aging but also underscores its potential application in strategies aimed at improving mitochondrial function via the AMPK/mTOR pathway in C. elegans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)- Published
- 2024
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6. Revitalizing elixir with orange peel amplification of alginate fish oil beads for enhanced anti-aging efficacy.
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Dhasmana A, Preetam S, Malik S, Jadon VS, Joshi N, Bhandari G, Gupta S, Mishra R, Rustagi S, and Samal SK
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- Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents chemistry, Humans, Aging drug effects, Animals, Plant Extracts chemistry, Plant Extracts pharmacology, Microspheres, Mice, Alginates chemistry, Fish Oils chemistry, Hydrogels chemistry, Antioxidants pharmacology, Antioxidants chemistry
- Abstract
The research introduces a novel method for creating drug-loaded hydrogel beads that target anti-aging, anti-oxidative, and anti-inflammatory effects, addressing the interconnected processes underlying various pathological conditions. The study focuses on the development of hydrogel beads containing anti-aging compounds, antioxidants, and anti-inflammatory drugs to effectively mitigate various processes. The synthesis, characterization and in vitro evaluations, and potential applications of these multifunctional hydrogel beads are discussed. A polymeric alginate-orange peel extract (1:1) hydrogel was synthesized for encapsulating fish oil. Beads prepared with variable fish oil concentrations (0.1, 0.3, and 0.5 ml) were characterized, showing no significant decrease in size i.e., 0.5 mm and a reduction in pore size from 23 to 12 µm. Encapsulation efficiency reached up to 98% within 2 min, with controlled release achieved upto 45 to 120 min with increasing oil concentration, indicating potential for sustained delivery. Fourier-transform infrared spectroscopy confirmed successful encapsulation by revealing peak shifting, interaction between constituents. In vitro degradation studies showed the hydrogel's biodegradability improved from 30 to 120 min, alongside anti-inflammatory, anti-oxidative, anti-collagenase and anti-elastase activities, cell proliferation rate enhanced after entrapping fish oil. In conclusion, the synthesized hydrogel beads are a promising drug delivery vehicle because they provide stable and effective oil encapsulation with controlled release for notable anti-aging and regenerative potential. Targeted delivery for inflammatory and oxidative stress-related illnesses is one set of potential uses. Further research may optimize this system for broader applications in drug delivery and tissue engineering., (© 2024. The Author(s).)
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- 2024
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7. Transformation of mulberry polyphenols by Lactobacillus plantarum SC-5: Increasing phenolic acids and enhancement of anti-aging effect.
- Author
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Li M, Xu X, Jia Y, Yuan Y, Na G, Zhu L, Xiao X, Zhang Y, and Ye H
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- Animals, Mice, Male, Fruit and Vegetable Juices, Aging drug effects, Brain-Derived Neurotrophic Factor metabolism, Gastrointestinal Microbiome drug effects, Anthocyanins pharmacology, Oxidative Stress drug effects, Fatty Acids, Volatile metabolism, Sirtuin 1, Morus chemistry, Polyphenols pharmacology, Lactobacillus plantarum metabolism, Hydroxybenzoates pharmacology, Fermentation
- Abstract
Fermentation can transform bioactive compounds in food and improve their biological activity. This study aims to explore the transformation of polyphenols in mulberry juice and the improvement of its anti-aging effect. The results demonstrated that Lactobacillus plantarum SC-5 transformed anthocyanin in mulberry juice into more phenolic acids, especially improved 2-hydroxy-3-(4-hydroxyphenyl) propanoic acid from 4.16 ± 0.06 to 10.07 ± 0.03. In the D-gal-induced mouse model, fermented mulberry juice significantly raised the abundance of Bifidobacteriaceae (303.7 %) and Lactobacillaceae (237.2 %) and Short-chain fatty acids (SCFAs) in intestine, further reducing the level of oxidative stress (12.3 %). Meanwhile, the expression of Sirtuin 1 (SIRT1) and Brain-derived neurotrophic factor (BDNF) increased, which protected the integrity of hippocampal tissue. Morris water maze results approved that fermented mulberry juice improved cognitive ability in aging mice (30.3 %). This study provides theoretical support for the view that fermentation is an effective means of developing functional foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2024
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8. Anti-IL-11 antibody shows anti-ageing properties.
- Author
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Eccleston A
- Subjects
- Humans, Animals, Mice, Antibodies, Monoclonal pharmacology, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal immunology, Aging immunology, Aging drug effects, Interleukin-11 immunology
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- 2024
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9. Effects of ashwagandha (Withania somnifera) root extract on aging-related changes in healthy geriatric dogs: A randomized, double-blinded placebo-controlled study.
- Author
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Bharani KK, Devarasetti AK, Carey L, Khurana A, Kollipaka R, Hanuman DDV, Chetla VS, and Banothu AK
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- Animals, Dogs, Double-Blind Method, Male, Female, Random Allocation, Plant Extracts pharmacology, Plant Extracts administration & dosage, Withania chemistry, Aging drug effects, Plant Roots chemistry
- Abstract
Background and Aim: This study aimed to explore the clinical potential of Withania somnifera/ashwagandha root extract (ARE) to mitigate age-related changes in healthy geriatric dogs. We hypothesized that ARE can reduce the effects of advancing age, including physiological changes, immune response decline and susceptibility to diseases, by its immunomodulatory effects., Methods: A randomized, double-blind, placebo-controlled trial was conducted in Telangana, India, from July 2022 to September 2022. Twenty apparently healthy dogs, aged 8 years or older, were enrolled. The dogs were divided into two groups to receive ARE (15 mg/kg, once daily, orally) or a placebo control. Various parameters, including serum cortisol levels, haematological profiles, biochemical markers, antioxidant indicators and anti-inflammatory responses, were assessed at the initiation of study, day 30, and day 60., Results: The erythrocyte count and haemoglobin levels were significantly increased with ARE (p < 0.001), whereas leukocyte count decreased (p < 0.05). Moreover, significant decreases in important markers of liver function (alanine aminotransferase, aspartate aminotransferase, albumin and globulin; p < 0.001 at day 60), as well as kidney function markers (creatinine and blood urea nitrogen; p < 0.001 at days 30 and 60), were observed in ARE-treated dogs compared to the placebo control group. In addition, the levels of markers of oxidative stress (superoxide dismutase, catalase, glutathione and malondialdehyde) were significantly modulated by ARE intervention, indicating strong antioxidant effects. Interestingly, serum cortisol levels reduced significantly with ARE (p < 0.001). Compared to baseline, ARE significantly decreased key inflammatory markers, including interferon-γ, tumour necrosis factor-α, nuclear factor kappa light chain enhancer of activated B cells and interleukin-10 (p < 0.001) levels at day 60., Conclusion: In conclusion, the findings of this study suggest that ARE has adaptogenic properties in healthy geriatric dogs by improving haematological and biochemical profiles, enhancing antioxidant defence, reducing stress and modulating inflammatory responses., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)
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- 2024
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10. Aging and cognitive resilience: Molecular mechanisms as new potential therapeutic targets.
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Cordeiro A, Gomes C, Bicker J, and Fortuna A
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- Humans, Animals, Cognition drug effects, Cognitive Dysfunction drug therapy, Drug Repositioning, Aging drug effects
- Abstract
As the global population ages, the need to prolong lifespan and healthspan becomes increasingly imperative. Understanding the molecular determinants underlying cognitive resilience, together with changes during aging and the (epi)genetic factors that predispose an individual to decreased cognitive resilience, open avenues for researching novel therapies. This review provides a critical and timely appraisal of the molecular mechanisms underlying cognitive resilience, framed within a critical analysis of emerging therapeutic strategies to mitigate age-related cognitive decline. Significant insights from both animals and human subjects are discussed herein, directed either toward active pharmaceutical ingredients (drug repositioning or macromolecules), or, alternatively, advanced cellular therapies., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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11. Relaxin suppresses atrial fibrillation, reverses fibrosis and reduces inflammation in aged hearts.
- Author
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Romero G, Martin B, Gabris B, and Salama G
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- Animals, Male, Rats, Inflammation metabolism, Inflammation drug therapy, Rats, Inbred F344, Relaxin pharmacology, Fibrosis, Atrial Fibrillation metabolism, Atrial Fibrillation drug therapy, Atrial Fibrillation prevention & control, Aging drug effects
- Abstract
Healthy aging results in cardiac structural and electrical remodeling that increase susceptibility to cardiovascular diseases. Relaxin has shown broad cardioprotective effects including anti-fibrotic, anti-arrhythmic and anti-inflammatory outcomes in multiple models. This paper focuses on the cardioprotective effects of Relaxin in a rat model of aging. Sustained atrial or ventricular fibrillation are readily induced in the hearts of aged but not young control animals. Treatment with Relaxin suppressed this arrhythmogenic response by increasing conduction velocity, decreasing fibrosis and promoting substantial cardiac remodeling. Relaxin treatment resulted in a significant increase in the levels of: Nav1.5, Cx43, βcatenin and Wnt1 in rat hearts. In isolated cardiomyocytes, Relaxin increased Nav1.5 expression. These effects were mimicked by CHIR 99021, a pharmacological activator of canonical Wnt signaling, but blocked by the canonical Wnt inhibitor Dickkopf1. Relaxin prevented TGF-β-dependent differentiation of cardiac fibroblasts into myofibroblasts while increasing the expression of Wnt1; the effects of Relaxin on cardiac fibroblast differentiation were blocked by Dickkopf1. RNASeq studies demonstrated reduced expression of pro-inflammatory cytokines and an increase in the expression of α- and β-globin in Relaxin-treated aged males. Relaxin reduces arrhythmogenicity in the hearts of aged rats by reduction of fibrosis and increased conduction velocity. These changes are accompanied by substantial remodeling of the cardiac tissue and appear to be mediated by increased canonical Wnt signaling. Relaxin also exerts significant anti-inflammatory and anti-oxidant effects in the hearts of aged rodents. The mechanisms by which Relaxin increases the expression of Wnt ligands, promotes Wnt signaling and reprograms gene expression remain to be determined., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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12. The Citrus flavanone naringenin prolongs the lifespan in C. elegans and slows signs of brain aging in mice.
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Piragine E, De Felice M, Germelli L, Brinkmann V, Flori L, Martini C, Calderone V, Ventura N, Da Pozzo E, and Testai L
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- Animals, Mice, Antioxidants pharmacology, Male, Mice, Inbred C57BL, Flavanones pharmacology, Brain drug effects, Brain metabolism, Aging drug effects, Longevity drug effects, Caenorhabditis elegans drug effects, Sirtuin 1 metabolism, Citrus chemistry
- Abstract
Aging is one of the main risk factors for neurodegenerative disorders, which represent a global burden on healthcare systems. Therefore, identifying new strategies to slow the progression of brain aging is a compelling challenge. In this article, we first assessed the potential anti-aging effects of the Citrus flavanone naringenin (NAR), an activator of the enzyme sirtuin-1 (SIRT1), in a 3R-compliant and short-lived aging model (i.e., the nematode C. elegans). Then, we investigated the preventive effects of a 6-month treatment with NAR (100 mg/kg, orally) against brain aging and studied its mechanism of action in middle-aged mice. We demonstrated that NAR (100 μM) extends lifespan and improves healthspan in C. elegans. In the brain of middle-aged mice, NAR promotes the activity of metabolic enzymes (citrate synthase, cytochrome C oxidase) and increases the expression of the SIRT1 enzyme. Consistently, NAR up-regulates the expression of downstream antioxidant (Foxo3, Nrf2, Ho-1), anti-senescence (p16), and anti-inflammatory (Il-6, Il-18) markers. Our findings support NAR supplementation to slow the signs of brain aging., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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13. Resveratrol impinges on retrograde communication without inducing mitochondrial biogenesis in aged rat soleus muscle.
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Di Lorenzo R, Chimienti G, Picca A, Trisolini L, Latronico T, Liuzzi GM, Pesce V, Leeuwenburgh C, and Lezza AMS
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- Animals, Male, Rats, Stilbenes pharmacology, Antioxidants pharmacology, Peroxiredoxins metabolism, DNA, Mitochondrial metabolism, Oxidative Stress drug effects, Dynamins metabolism, Mitochondrial Dynamics drug effects, Resveratrol pharmacology, Muscle, Skeletal drug effects, Muscle, Skeletal metabolism, Organelle Biogenesis, Aging drug effects, Aging metabolism, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism, Sirtuin 1 metabolism, Rats, Wistar, Mitochondria, Muscle drug effects, Mitochondria, Muscle metabolism
- Abstract
The natural polyphenol resveratrol (RSV) might counteract the skeletal muscle age-related loss of muscle mass and strength/function partly acting on mitochondria. This work analysed the effects of a six-week administration of RSV (50 mg/kg/day) in the oxidative Soleus (Sol) skeletal muscle of old rats (27 months old). RSV effects on key mitochondrial biogenesis proteins led to un unchanged amount of SIRT1 protein and a marked decrease (60 %) in PGC-1α protein. In addition, Peroxyredoxin 3 (PRXIII) protein decreased by 50 %, which on overall suggested the absence of induction of mitochondrial biogenesis by RSV in old Sol. A novel direct correlation between PGC-1α and PRXIII proteins was demonstrated by correlation analysis in RSV and ad-libitum (AL) rats, supporting the reciprocally coordinated expression of the proteins. RSV supplementation led to an unexpected 50 % increase in the frequency of the oxidized base OH8dG in mtDNA. Furthermore, RSV supplementation induced a 50 % increase in the DRP1 protein of mitochondrial dynamics. In both rat groups an inverse correlation between PGC-1α and the frequency of OH8dG as well as an inverse correlation between PRXIII and the frequency of OH8dG were also found, suggestive of a relationship between oxidative damage to mtDNA and mitochondrial biogenesis activity. Such results may indicate that the antioxidant activity of RSV in aged Sol impinged on the oxidative fiber-specific, ROS-mediated, retrograde communication, thereby affecting the expression of SIRT1, PGC-1α and PRXIII, reducing the compensatory responses to the age-related mitochondrial oxidative stress and decline., Competing Interests: Declaration of competing interest The authors declare that there is no potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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14. Glioprotective Effects of Sulforaphane in Hypothalamus: Focus on Aging Brain.
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Santos CL, Weber FB, Belló-Klein A, Bobermin LD, and Quincozes-Santos A
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- Animals, Rats, Male, Cells, Cultured, Antioxidants pharmacology, Sulfoxides, Isothiocyanates pharmacology, Rats, Wistar, Aging drug effects, Aging metabolism, Neuroprotective Agents pharmacology, Astrocytes drug effects, Astrocytes metabolism, Hypothalamus drug effects, Hypothalamus metabolism
- Abstract
Sulforaphane is a natural compound with neuroprotective activity, but its effects on hypothalamus remain unknown. In line with this, astrocytes are critical cells to maintain brain homeostasis, and hypothalamic astrocytes are fundamental for sensing and responding to environmental changes involved in a variety of homeostatic functions. Changes in brain functionality, particularly associated with hypothalamic astrocytes, can contribute to age-related neurochemical alterations and, consequently, neurodegenerative diseases. Thus, here, we investigated the glioprotective effects of sulforaphane on hypothalamic astrocyte cultures and hypothalamic cell suspension obtained from aged Wistar rats (24 months old). Sulforaphane showed anti-inflammatory and antioxidant properties, as well as modulated the mRNA expression of astroglial markers, such as aldehyde dehydrogenase 1 family member L1, aquaporin 4, and vascular endothelial growth factor. In addition, it increased the expression and extracellular levels of trophic factors, such as glia-derived neurotrophic factor and nerve growth factor, as well as the release of brain-derived neurotrophic factor and the mRNA of TrkA, which is a receptor associated with trophic factors. Sulforaphane also modulated the expression of classical pathways associated with glioprotection, including nuclear factor erythroid-derived 2-like 2, heme oxygenase-1, nuclear factor kappa B p65 subunit, and AMP-activated protein kinase. Finally, a cell suspension with neurons and glial cells was used to confirm the predominant effect of sulforaphane in glial cells. In summary, this study indicated the anti-aging and glioprotective activities of sulforaphane in aged astrocytes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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15. Psychedelics and Older Adults: What Do They Do Compared to Younger People?
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Harvey PD
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- Humans, Aged, Age Factors, Aging drug effects, Aging psychology, Hallucinogens pharmacology
- Abstract
Competing Interests: Disclosure Last 24 months: Dr. Harvey has received consulting fees or travel reimbursements from Alkermes, Boehringer Ingelheim, Karuna Therapeutics, Merck Pharma, Minerva Neurosciences, and Sunovion (DSP) Pharma in the past year. He receives royalties from the Brief Assessment of Cognition in Schizophrenia (Owned by WCG Endpoint Solutions, Inc. and contained in the MCCB). He is chief scientific officer of i-Function, Inc and Scientific Consultant to EMA Wellness, Inc.
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- 2024
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16. Dexmedetomidine enhances Mitophagy via PINK1 to alleviate hippocampal neuronal Pyroptosis and improve postoperative cognitive dysfunction in elderly rat.
- Author
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Chen Y, Wei G, Feng X, Lei E, and Zhang L
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- Animals, Rats, Male, Aging drug effects, Dexmedetomidine pharmacology, Dexmedetomidine therapeutic use, Postoperative Cognitive Complications drug therapy, Postoperative Cognitive Complications metabolism, Postoperative Cognitive Complications prevention & control, Hippocampus drug effects, Hippocampus metabolism, Pyroptosis drug effects, Mitophagy drug effects, Protein Kinases metabolism, Protein Kinases genetics, Neurons drug effects, Neurons metabolism, Rats, Sprague-Dawley
- Abstract
Postoperative cognitive dysfunction (POCD) is a common complication in elderly surgical patients, significantly affecting their quality of life. Dexmedetomidine (Dex), an anesthetic, has shown promise in alleviating POCD, but its underlying mechanism remains unclear. This study aims to explore how Dex improves POCD in aged rats by targeting the PINK1-mediated mitochondrial autophagy pathway, reducing caspase-1/11-GSDMD-induced hippocampal neuronal pyroptosis. Transcriptome sequencing identified 300 differentially expressed genes enriched in the mitochondrial autophagy pathway in Dex-treated POCD rat hippocampal tissue, with Pink1 as a key candidate. In a POCD rat model, Dex treatment upregulated hippocampal PINK1 expression. In vitro experiments using H19-7 rat hippocampal neurons revealed that Dex enhanced mitochondrial autophagy and suppressed neuronal pyroptosis by upregulating PINK1. Further mechanistic validation demonstrated that Dex activated PINK1-mediated mitochondrial autophagy, inhibiting caspase-1/11-GSDMD-induced neuronal pyroptosis. In vivo experiments confirmed Dex's ability to reduce caspase-1/11-GSDMD-dependent hippocampal neuronal pyroptosis and improve postoperative cognitive function in aged rats. Dexmedetomidine improves postoperative cognitive dysfunction in elderly rats by enhancing mitochondrial autophagy via PINK1 upregulation, mitigating caspase-1/11-GSDMD-induced neuronal pyroptosis., Competing Interests: Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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17. GLP-2 ameliorates D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a signaling pathway in C2C12 cells and mice.
- Author
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Ye YL, Kuai Z, Qian DD, He YT, Shen JP, Wu KF, Ren WY, and Hu Y
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- Animals, Mice, Aging drug effects, Apoptosis drug effects, Male, Muscle Fibers, Skeletal drug effects, Muscle Fibers, Skeletal metabolism, Muscle Fibers, Skeletal pathology, Galactose, Forkhead Box Protein O3 metabolism, Signal Transduction drug effects, Insulin-Like Growth Factor I metabolism, Insulin-Like Growth Factor I pharmacology, Mice, Inbred C57BL, Proto-Oncogene Proteins c-akt metabolism, Glucagon-Like Peptide 2 pharmacology, Muscle, Skeletal drug effects, Muscle, Skeletal metabolism, Phosphatidylinositol 3-Kinases metabolism
- Abstract
Background: The study aimed to investigate the effect of Glucagon-like peptide-2 (GLP-2) on muscle aging in vivo and in vitro., Methods: Six-week-old C57BL/6J mice were administered with D-galactose (200 mg/kg/day, intraperitoneally) for 8weeks, followed by daily subcutaneous injections of GLP-2 (300 or 600 μg/kg/day) for 4weeks. Skeletal muscle function and mass were evaluated using relative grip strength and muscle weight. The sizes and types of muscle fibers and apoptosis were assessed through histological analysis, immunofluorescence staining, and TUNEL staining, respectively. C2C12 myotubes were treated with D-galactose (40 mg/mL) and GLP-2. Protein expression of differentiation-related myogenic differentiation factor D (MyoD), myogenin (MyoG), and myosin heavy chain (Myhc), degradation-related Muscle RING finger 1 (MuRF-1), and muscle atrophy F-box (MAFbx)/Atrogin-1, and apoptosis-related B-cell leukemia/lymphoma 2 (Bcl-2) and Bax, were assessed using western blots. The Pi3k inhibitor LY294002 was applied to investigate whether GLP-2 regulated myogenesis and myotube aging via IGF-1/Pi3k/Akt/FoxO3a signaling pathway., Results: The results demonstrated that GLP-2 significantly reversed the decline in muscles weight, relative grip strength, diameter, and cross-sectional area of muscle fibers induced by D-galactose in mice. Apart from suppressing the expressions of MuRF-1 and Atrogin-1 in the muscles and C2C12 myotubes, GLP-2 significantly increased the expressions of MyoD, MyoG, and Myhc compared to the D-galactose. GLP-2 significantly suppressed cell apoptosis. Western blot analysis indicated that the regulation of GLP-2 may be attributed to the activation of theIGF-1/Pi3k/Akt/FoxO3a phosphorylation pathway., Conclusions: This study suggested that GLP-2 ameliorated D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a pathway., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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18. Investigation of oxidative, inflammatory and apoptotic effects of favipiravir use alone and combined with vitamin C on brain tissue of elderly rats.
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Kaya K, Şahin Y, Demirel HH, and Çiftçi O
- Subjects
- Animals, Rats, Male, Rats, Wistar, Antioxidants pharmacology, Antioxidants administration & dosage, Dose-Response Relationship, Drug, COVID-19 Drug Treatment, Aging drug effects, Pyrazines pharmacology, Pyrazines administration & dosage, Amides pharmacology, Ascorbic Acid pharmacology, Ascorbic Acid administration & dosage, Apoptosis drug effects, Brain drug effects, Brain metabolism, Brain pathology, Antiviral Agents pharmacology, Antiviral Agents toxicity, Antiviral Agents administration & dosage, Oxidative Stress drug effects
- Abstract
Favipiravir is a nucleoside analogue antiviral drug and inhibits the replication of many RNA viruses, especially influenza viruses. Favipiravir has also been used to treat patients with mild to moderate COVID-19 disease. However, various side effects, including neurological side effects, have been reported related to the use of favipiravir. Therefore, in this study, we aimed to investigate the possible effects of favipiravir alone or in combination with vitamin C on aged rats' brain tissue and the possible mechanisms of these effects. A total of 30 rats used in the study were randomly divided into 5 equal groups and the first group was kept as the control group. High-dose (100 mg/kg) or low-dose (20 mg/kg) favipiravir was administered alone or in combination with vitamin C (150 mg/kg) to other groups. Administration of both high and low doses of favipiravir significantly increased TBARS levels in brain tissue of aged rats. Similarly, both high and low doses of favipiravir led to significant increases in Bcl-2 and caspase-3 relative mRNA expression. However, only low dose favipiravir caused a significant increase in iNOS and IL-1β relative mRNA expression levels. Similar results were also observed in histopathological examinations. However, co-administration of vitamin C with favipiravir attenuated some of the adverse effects of favipiravir. In conclusion, in this study, it was shown that the use of favipiravir caused some adverse effects through oxidative, inflammatory and apoptotic processes in the brain tissue of aged rats, and the potential of vitamin C to alleviate these effects.
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- 2024
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19. Histological investigation in aging male and female gerbil prostates after prenatal exposure to pequi ( Caryocar brasiliense Cambess ) oil and 17α-ethinylestradiol.
- Author
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Carvalho E Silva PM, Zuffo JA, de Souza Mendes MEH, Silva LT, de Souza JVO, Marques Martins TM, and da Silva Perez AP
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- Animals, Male, Female, Pregnancy, Plant Oils, Aging drug effects, Endocrine Disruptors toxicity, Ericales, Gerbillinae, Prostate drug effects, Prostate pathology, Prenatal Exposure Delayed Effects chemically induced, Ethinyl Estradiol toxicity
- Abstract
The female prostate, also known as Skene's gland, is present in both humans and rodents. Prenatal exposure to ethinylestradiol (EE2), a synthetic estrogen found in oral contraceptives, induces pormotes neoplasic prostate lesions in gerbils ( Meriones unguiculatus ). Conversely, pequi oil (Pe), extracted from the Brazilian Cerrado fruit, has antioxidant, anti-inflammatory, and anticancer properties, mitigates risks associated with chronic diseases related to lifestyle and aging. This study evaluates the impact of prenatal exposure to Pe (300 mg/kg) on senile gerbil offspring's male and female prostates under normal conditions and EE2 exposure (15 μg/kg/day). Histological and morphometric analyses revealed that Pe reduced male body weight and prostate epithelial height, along with a thinner muscle layer. In females, EE2 exposure reduced prostatic weight, while Pe exposure lowered epithelial height and the relative stromal compartment volume, increasing the muscle layer. Pequi oil holds potential in mitigating alterations induced by exposure to the endocrine disruptor EE2.
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- 2024
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20. COP-22 Alleviates D-Galactose-Induced Brain Aging by Attenuating Oxidative Stress, Inflammation, and Apoptosis in Mice.
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Ma Y, Wang X, Li X, Chen X, Teng Z, Wang X, Yang J, and Liu G
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- Animals, Male, Mice, Antioxidants pharmacology, Antioxidants metabolism, Aging drug effects, Aging pathology, Aging metabolism, Apoptosis drug effects, Brain drug effects, Brain metabolism, Brain pathology, Galactose adverse effects, Inflammation pathology, Inflammation metabolism, Oxidative Stress drug effects, Curcumin analogs & derivatives
- Abstract
Aging is a natural and inevitable process of organisms. With the intensification of population aging, research on aging has become a hot topic of global attention. The most obvious manifestation of human aging is the aging of brain function, which has been linked to the development of neurodegenerative diseases. In this study, COP-22, a mono-carbonyl curcumin derivative, was evaluated for its anti-aging ability, especially its ability to resist brain aging induced by D-galactose (D-gal) in mice. For brain protection, COP-22 could resist D-gal-induced oxidative stress by increasing the activity of antioxidative defense enzymes and enhancing antioxidant capacity in the brain tissue; COP-22 could improve the dysfunction of the cholinergic system by decreasing the increased activity of acetylcholinesterase and increasing the reduced content of acetylcholine induced by D-gal; and COP-22 could protect nerve cells of the brain. Further, western blot was used to determine related proteins of the brain. We found that COP-22 could effectively protect against brain injury (SIRT1, p53, p21, and p16) by inhibiting oxidative stress (Nrf2 and HO-1), inflammation (IL-6 and TNF-α), and apoptosis (Bax and caspase-3) in D-gal-induced aging mice. Additionally, COP-22 demonstrated the ability to reduce oxidative stress in serum and liver caused by D-gal, as well as relieve the damages in the liver and kidney induced by D-gal. These results indicated that COP-22 had potential anti-aging activity and could be used in the therapy of aging and aging-associated diseases like Alzheimer disease., (© 2024. The Author(s).)
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- 2024
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21. Anti-aging effect of peptides on Caenorhabditis elegans: a meta-analysis.
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Huang C, Zhu L, Zhang H, Liu T, Wang L, and Wu G
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- Animals, Longevity drug effects, Aging drug effects, Caenorhabditis elegans drug effects, Peptides pharmacology, Peptides chemistry
- Abstract
Background: Recently, peptides have been studied in Caenorhabditis elegans for anti-aging research. Due to the lack of sufficient evidence, we conducted this meta-analysis focusing on the anti-aging effect of peptides in C. elegans to provide more convincing evidence., Results: A literature search in PubMed, SCOUPUS, and Web of Science databases yielded 2879 articles. After removing duplicates and based on inclusion criteria and STAIR checklist quality assessment, nine articles were selected. Data extraction and analysis showed that, compared to the control group without peptide intervention, peptide supplementation significantly reduced nematode mortality risk [hazard ratio = 0.54, 95% confidence interval (CI) = 0.47, 0.62; P < 0.05], significantly increased the pharyngeal pumping rate [standardized mean difference (SMD) = 1.64, 95% CI = 0.87, 2.41; P < 0.05], bending frequency (SMD = 1.67, 95% CI = 1.16, 2.18; P < 0.05), and significantly decreased the accumulation of lipofuscin levels within nematodes (SMD = -4.48, 95% CI = -6.85, -2.12; P < 0.05). Additionally, subgroup analysis showed that doses ranging from 0.1 to 1 mg/mL (HR = 0.50, 95% CI = 0.38, 0.65; P < 0.05) displayed better anti-aging effects compared to other dose ranges., Conclusion: The findings suggest that peptides can significantly extend the lifespan of C. elegans under normal circumstances and improve three indicators of healthy life. More importantly, subgroup analysis revealed that a dosage of 0.1-1 mg/mL demonstrated superior anti-aging effects. This meta-analysis provides more convincing evidence that peptides can play an anti-aging role in C. elegans. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)
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- 2024
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22. Light-responsive functional nanomaterials as pioneering therapeutics: a paradigm shift to combat age-related disorders.
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Singh SK, Parihar S, Jain S, Ho JA, and Vankayala R
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- Humans, Aging drug effects, Animals, Light, Nanostructures chemistry
- Abstract
Aging, marked by dysregulated cellular systems, gives rise to a spectrum of age-related disorders, including neurodegeneration, atherosclerosis, immunosenescence, and musculoskeletal issues. These conditions contribute significantly to the global disease burden, posing challenges to health span and economic resources. Current therapeutic approaches, although diverse in mechanism, often fall short in targeting the underlying cellular pathologies. They fail to address the issues compounded by altered pharmacokinetics in the elderly. Nanotechnology emerges as a transformative solution, offering tissue-specific targeted therapies through nanoparticles. Functional nanomaterials (FNMs) respond to internal or external stimuli, with light-responsive nanomaterials gaining prominence. Harnessing the benefits of deep tissue penetration and ease of manipulation particularly in the near-infrared spectrum, light-responsive FNMs present innovative strategies for age-related comorbidities. This review comprehensively summarizes the potential of light-responsive FNM-based approaches for targeting cellular environments in age-related disorders, and also emphasizes the advantages over traditional treatment modalities. Specifically, it focuses on the development of various classes of light-responsive functional nanomaterials including plasmonic nanomaterials, nanomaterials as carriers, upconversion nanomaterials, 2D nanomaterials, transition metal oxide and dichalcogenide nanomaterials and carbon-based nanomaterials against age related diseases. We foresee that such advanced developments in the field of nanotechnology could provide a new hope for clinical diagnosis and treatment of age-related disorders.
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- 2024
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23. Advances in Nanotherapy for Targeting Senescent Cells.
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Shi Y, Zhang Y, Zhang Y, Yao J, Guo J, Xu X, and Wang L
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- Humans, Animals, Drug Delivery Systems methods, Aging drug effects, Aging physiology, Nanoparticles chemistry, Cellular Senescence drug effects, Nanomedicine
- Abstract
Aging is an inevitable process in the human body, and cellular senescence refers to irreversible cell cycle arrest caused by external aging-promoting mechanisms. Moreover, as age increases, the accumulation of senescent cells limits both the health of the body and lifespan and even accelerates the occurrence and progression of age-related diseases. Therefore, it is crucial to delay the periodic irreversible arrest and continuous accumulation of senescent cells to address the issue of aging. The fundamental solution is targeted therapy focused on eliminating senescent cells or reducing the senescence-associated secretory phenotype. Over the past few decades, the remarkable development of nanomaterials has revolutionized clinical drug delivery pathways. Their unique optical, magnetic, and electrical properties effectively compensate for the shortcomings of traditional drugs, such as low stability and short half-life, thereby maximizing the bioavailability and minimizing the toxicity of drug delivery. This article provides an overview of how nanomedicine systems control drug release and achieve effective diagnosis. By presenting and analyzing recent advances in nanotherapy for targeting senescent cells, the underlying mechanisms of nanomedicine for senolytic and senomorphic therapy are clarified, providing great potential for targeting senescent cells., Competing Interests: The authors declare no competing interests in this work., (© 2024 Shi et al.)
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- 2024
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24. Citrus Flavanone Effects on the Nrf2-Keap1/GSK3/NF-κB/NLRP3 Regulation and Corticotroph-Stress Hormone Loop in the Old Pituitary.
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Miler M, Živanović J, Kovačević S, Vidović N, Djordjevic A, Filipović B, and Ajdžanović V
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- Animals, Rats, Male, Oxidative Stress drug effects, Adrenocorticotropic Hormone metabolism, Adrenocorticotropic Hormone blood, Aging metabolism, Aging drug effects, Signal Transduction drug effects, Antioxidants pharmacology, Antioxidants metabolism, Rats, Wistar, Hesperidin pharmacology, NF-E2-Related Factor 2 metabolism, Kelch-Like ECH-Associated Protein 1 metabolism, Flavanones pharmacology, Pituitary Gland metabolism, Pituitary Gland drug effects, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Citrus chemistry, NF-kappa B metabolism
- Abstract
Oxidative stress and inflammation are significant causes of aging. At the same time, citrus flavanones, naringenin (NAR), and hesperetin (HES) are bioactives with proven antioxidant and anti-inflammatory properties. Nevertheless, there are still no data about flavanone's influence and its potential effects on the healthy aging process and improving pituitary functioning. Thus, using qPCR, immunoblot, histological techniques, and biochemical assays, our study aimed to elucidate how citrus flavanones (15 mg/kg b.m. per os ) affect antioxidant defense, inflammation, and stress hormone output in the old rat model. Our results showed that HES restores the redox environment in the pituitary by down-regulating the nuclear factor erythroid 2-related factor 2 (Nrf2) protein while increasing kelch-like ECH-associated protein 1 (Keap1), thioredoxin reductase (TrxR1), and superoxide dismutase 2 (SOD2) protein expression. Immunofluorescent analysis confirmed Nrf2 and Keap1 down- and up-regulation, respectively. Supplementation with NAR increased Keap1 , Trxr1 , glutathione peroxidase ( Gpx ), and glutathione reductase ( Gr ) mRNA expression. Decreased oxidative stress aligned with NLRP3 decrement after both flavanones and glycogen synthase kinase-3 (GSK3) only after HES. The signal intensity of adrenocorticotropic hormone (ACTH) cells did not change, while corticosterone levels in serum decreased after both flavanones. HES showed higher potential than NAR in affecting a redox environment without increasing the inflammatory response, while a decrease in corticosterone level has a solid link to longevity. Our findings suggest that HES could improve and facilitate redox and inflammatory dysregulation in the rat's old pituitary.
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- 2024
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25. Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence.
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Nunes YC, Mendes NM, Pereira de Lima E, Chehadi AC, Lamas CB, Haber JFS, Dos Santos Bueno M, Araújo AC, Catharin VCS, Detregiachi CRP, Laurindo LF, Tanaka M, Barbalho SM, and Marin MJS
- Subjects
- Humans, Oxidative Stress drug effects, Dietary Supplements, Aged, Quality of Life, Aging drug effects, Cognition drug effects, Anti-Inflammatory Agents pharmacology, Curcumin pharmacology, Curcumin therapeutic use, Healthy Aging, Antioxidants pharmacology
- Abstract
Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, and mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties, has emerged as a promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms of curcumin's effects and the optimal dosages for different conditions necessitate further investigation. This systematic review synthesizes current evidence on curcumin's potential in addressing age-related disorders, emphasizing its impact on cognitive function, neurodegeneration, and muscle health in older adults. By evaluating the safety, efficacy, and mechanisms of action of curcumin supplementation, this review aims to provide insights into its therapeutic potential for promoting healthy aging. A systematic search across three databases using specific keywords yielded 2256 documents, leading to the selection of 15 clinical trials for synthesis. Here, we highlight the promising potential of curcumin as a multifaceted therapeutic agent in combating age-related disorders. The findings of this review suggest that curcumin could offer a natural and effective approach to enhancing the quality of life of aging individuals. Further research and well-designed clinical trials are essential to validate these findings and optimize the use of curcumin in personalized medicine approaches for age-related conditions.
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- 2024
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26. ML365 ameliorates postoperative cognitive impairment in aged mice by inhibiting NLRP3 inflammasome activation in the hippocampus.
- Author
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Wang Z, Li B, Yang J, Gao Y, Gao L, Jia Q, Yu L, and Ling Y
- Subjects
- Animals, Mice, Male, Cognitive Dysfunction metabolism, Cognitive Dysfunction drug therapy, Interleukin-1beta metabolism, Disease Models, Animal, Aging metabolism, Aging drug effects, Caspase 1 metabolism, Furans, Indenes, Sulfonamides, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Hippocampus metabolism, Hippocampus drug effects, Inflammasomes metabolism, Inflammasomes drug effects, Postoperative Cognitive Complications metabolism, Mice, Inbred C57BL
- Abstract
The aim of this study was to examine the effects of ML365, a two-pore potassium channel (K2P) inhibitor, on postoperative cognitive impairment (POCD). A mouse model of POCD was constructed by subjecting aged C57BL/6 mice to exploratory laparotomy. Changes in cognitive function were assessed using the Morris water maze test. Western blotting and qPCR were used to detect hippocampal NLRP3, Caspase-1 and IL-1β expression levels on days 3 and 7 post-surgery. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) expression level was also assessed by western blotting. Pathological changes and nerve damage in the hippocampal CA1 and CA3 regions were detected by H&E staining, while the concentration of malondialdehyde (MDA) in the plasma was measured. We found that pretreatment with ML365 (administered intraperitoneally at a dose of 10 mg/kg) 30 min prior to exploratory laparotomy effectively ameliorated POCD in mice. ML365 pretreatment also reduced NLRP3, Caspase-1, ASC and IL-1β expression levels in the hippocampus, improved POCD-induced pathological changes in the hippocampal CA1 and CA3 areas of aged mice, and decreased levels of plasma MDA and oxidative stress. Together, our findings indicate that ML365 can alleviate POCD in mice by inhibiting NLRP3 inflammasome activation in the hippocampus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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27. Experimental Models in Unraveling the Biological Mechanisms of Mushroom-Derived Bioactives against Aging- and Lifestyle-Related Diseases: A Review.
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Sharika R, Mongkolpobsin K, Rangsinth P, Prasanth MI, Nilkhet S, Pradniwat P, Tencomnao T, and Chuchawankul S
- Subjects
- Humans, Animals, Antioxidants pharmacology, Neoplasms prevention & control, Gastrointestinal Microbiome drug effects, Functional Food, Agaricales chemistry, Aging drug effects, Life Style
- Abstract
Mushrooms have garnered considerable interest among researchers due to their immense nutritional and therapeutic properties. The presence of biologically active primary and secondary metabolites, which includes several micronutrients, including vitamins, essential minerals, and other dietary fibers, makes them an excellent functional food. Moreover, the dietary inclusion of mushrooms has been reported to reduce the incidence of aging- and lifestyle-related diseases, such as cancer, obesity, and stroke, as well as to provide overall health benefits by promoting immunomodulation, antioxidant activity, and enhancement of gut microbial flora. The multifunctional activities of several mushroom extracts have been evaluated by both in vitro and in vivo studies using cell lines along with invertebrate and vertebrate model systems to address human diseases and disorders at functional and molecular levels. Although each model has its own strengths as well as lacunas, various studies have generated a plethora of data regarding the regulating players that are modulated in order to provide various protective activities; hence, this review intends to compile and provide an overview of the plausible mechanism of action of mushroom-derived bioactives, which will be helpful in future medicinal explorations.
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- 2024
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28. mTOR and SGLT-2 Inhibitors: Their Synergistic Effect on Age-Related Processes.
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Troise D, Mercuri S, Infante B, Losappio V, Cirolla L, Netti GS, Ranieri E, and Stallone G
- Subjects
- Humans, Animals, MTOR Inhibitors pharmacology, MTOR Inhibitors therapeutic use, Cellular Senescence drug effects, Sodium-Glucose Transporter 2 Inhibitors pharmacology, TOR Serine-Threonine Kinases metabolism, TOR Serine-Threonine Kinases antagonists & inhibitors, Aging drug effects, Aging metabolism, Drug Synergism
- Abstract
The aging process contributes significantly to the onset of chronic diseases, which are the primary causes of global mortality, morbidity, and healthcare costs. Numerous studies have shown that the removal of senescent cells from tissues extends lifespan and reduces the occurrence of age-related diseases. Consequently, there is growing momentum in the development of drugs targeting these cells. Among them, mTOR and SGLT-2 inhibitors have garnered attention due to their diverse effects: mTOR inhibitors regulate cellular growth, metabolism, and immune responses, while SGLT-2 inhibitors regulate glucose reabsorption in the kidneys, resulting in various beneficial metabolic effects. Importantly, these drugs may act synergistically by influencing senescence processes and pathways. Although direct studies on the combined effects of mTOR inhibition and SGLT-2 inhibition on age-related processes are limited, this review aims to highlight the potential synergistic benefits of these drugs in targeting senescence.
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- 2024
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29. Applying Spatial Metabolomics To Investigate Age- and Drug-Induced Neurochemical Changes.
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Vallianatou T, Angerer TB, Kaya I, Nilsson A, Shariatgorji R, Svenningsson P, and Andrén PE
- Subjects
- Animals, Mice, Tacrine pharmacology, Brain metabolism, Brain drug effects, Male, Mice, Inbred C57BL, Cholinesterase Inhibitors pharmacology, Lysophospholipids metabolism, Sulfoglycosphingolipids metabolism, Mass Spectrometry methods, Metabolomics methods, Aging metabolism, Aging drug effects
- Abstract
In an era when population aging is increasing the burden of neurodegenerative conditions, deciphering the mechanisms underlying brain senescence is more important than ever. Here, we present a spatial metabolomics analysis of age-induced neurochemical alterations in the mouse brain using negative ionization mode mass spectrometry imaging. The age-dependent effects of the acetylcholinesterase inhibitor tacrine were simultaneously examined. For ultrahigh mass resolution analysis, we utilized a Fourier-transform ion cyclotron resonance spectrometer. To complement this, a trapped ion mobility spectrometry time-of-flight analyzer provided high speed and lateral resolution. The chosen approach facilitated the detection and identification of a wide range of metabolites, from amino acids to sphingolipids. We reported significant, age-dependent alterations in brain lipids which were most evident for sulfatides and lysophosphatidic acids. Sulfatide species, which are mainly localized to white matter, either increased or decreased with age, depending on the carbon chain length and hydroxylation stage. Lysophosphatidic acids were found to decrease with age in the detailed cortical and hippocampal subregions. An age-dependent increase in the glutamine/glutamate ratio, an indicator of glia-neuron interconnection and neurotoxicity, was detected after tacrine administration. The presented metabolic mapping approach was able to provide visualizations of the lipid signaling and neurotransmission alterations induced by early aging and can thus be beneficial to further elucidating age-related neurochemical pathways.
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- 2024
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30. Identification of adrenergic presynaptic and postsynaptic protein locations at neuromuscular junctions, their decrease during aging, and recovery by nicotinamide mononucleotide administration.
- Author
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Takeno K, Watanabe N, Morifuji M, Hotta H, and Nishimune H
- Subjects
- Animals, Mice, Male, Presynaptic Terminals metabolism, Presynaptic Terminals drug effects, Mice, Inbred C57BL, Vesicular Monoamine Transport Proteins metabolism, Sympathetic Nervous System drug effects, Sympathetic Nervous System metabolism, Receptors, Adrenergic, beta-2 metabolism, Neuromuscular Junction drug effects, Neuromuscular Junction metabolism, Aging metabolism, Aging drug effects, Nicotinamide Mononucleotide pharmacology, Nicotinamide Mononucleotide administration & dosage
- Abstract
Neuromuscular junctions are innervated by motor and sympathetic nerves. The sympathetic modulation of motor innervation shows functional decline during aging, but the cellular and molecular mechanism of this change is not fully known. This study aimed to evaluate the effect of aging on sympathetic nerves and synaptic proteins at mouse neuromuscular junctions. Sympathetic nerves, presynaptic, and postsynaptic proteins of sympathetic nerves at neuromuscular junctions were visualized using immunohistochemistry, and aging-related changes were compared between adult-, aged-, and nicotinamide mononucleotide (NMN) administered aged mice. Sympathetic nerves were detected by anti-tyrosine hydroxylase antibody, and presynaptic protein vesicular monoamine transporter 2 colocalized with the sympathetic nerves. These two signals surrounded motor nerve terminals and acetylcholine receptor clusters. Postsynaptic neurotransmitter receptor β2-adrenergic receptors colocalized with motor nerve terminals and resided in reduced density at extrasynaptic sarcolemma. The signal intensity of the sympathetic nerve marker did not show a significant difference at neuromuscular junctions between 8.5-month-old adult mice and 25-month-old aged mice. However, the signal intensity of vesicular monoamine transporter 2 and β2-adrenergic receptors showed age-related decline at neuromuscular junctions. Interestingly, both age-related declines reverted to the adult level after 1 month of oral administration of NMN by drinking water. In contrast, NMN administration did not alter the expression level of sympathetic marker tyrosine hydroxylase at neuromuscular junctions. The results suggest a functional decline of sympathetic nerves at aged neuromuscular junctions due to decreases in presynaptic and postsynaptic proteins, which can be reverted to the adult level by NMN administration., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
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31. Apigenin and baicalein ameliorate thoracic aortic structural deterioration and cognitive deficit via inhibiting AGEs/RAGE/NF-κB pathway in D-galactose-induced aging rats.
- Author
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Ma Y, Ma Z, Zhang Y, Luo C, Huang P, Tong J, Ding H, and Liu H
- Subjects
- Animals, Male, Rats, Hippocampus drug effects, Hippocampus metabolism, Hippocampus pathology, Cognitive Dysfunction drug therapy, Cognitive Dysfunction metabolism, Cognitive Dysfunction chemically induced, Antioxidants pharmacology, Receptor for Advanced Glycation End Products metabolism, Glycation End Products, Advanced metabolism, Flavanones pharmacology, Flavanones therapeutic use, Galactose, Apigenin pharmacology, Apigenin therapeutic use, Aging drug effects, Aging metabolism, NF-kappa B metabolism, Signal Transduction drug effects, Oxidative Stress drug effects, Aorta, Thoracic drug effects, Aorta, Thoracic metabolism, Aorta, Thoracic pathology, Rats, Sprague-Dawley
- Abstract
Apigenin and baicalein are structurally related flavonoids that have been reported to have multiple pharmacological activities. The aim of this study was to investigate the protective effects and potential mechanisms of apigenin and baicalein in D-galactose-induced aging rats. First, apigenin and baicalein showed remarkable antioxidant activity and anti-glycation activity in vitro. Secondly, the protective effects of apigenin and baicalein on aging rats were investigated. We found that apigenin and baicalein supplementation significantly ameliorated aging-related changes such as declines in the spatial learning and memory and histopathological damage of the hippocampus and thoracic aorta. In addition, our data showed that apigenin and baicalein alleviated oxidative stress as illustrated by decreasing MDA level, increasing SOD activity and GSH level. Further data showed that they significantly reduced the accumulation of advanced glycation end products (AGEs), inhibited the expression of RAGE, down-regulated phosphorylated nuclear factor (p-NF-κB (p65)). Our results suggested that the protective effects of apigenin and baicalein on aging rats were at least partially related to the inhibition of AGEs/RAGE/NF-κB pathway and the improvement of oxidative damage. Overall, apigenin and baicalein showed almost equal anti-aging efficacy. Our results provided an experimental basis for the application of apigenin and baicalein to delay the aging process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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32. Effects of Ginger ( Zingiber officinale ) on the Hallmarks of Aging.
- Author
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Matin M, Joshi T, Wang D, Tzvetkov NT, Matin FB, Wierzbicka A, Jóźwik A, Horbańczuk JO, and Atanasov AG
- Subjects
- Humans, Animals, Plant Extracts pharmacology, Plant Extracts chemistry, Longevity drug effects, Inflammation drug therapy, Mitochondria drug effects, Mitochondria metabolism, Dysbiosis, Zingiber officinale chemistry, Aging drug effects
- Abstract
Ginger ( Zingiber officinale Roscoe) is broadly used as a traditional remedy and food ingredient, and numerous preclinical and clinical studies have demonstrated health benefits in a range of age-related disorders. Moreover, longevity-promoting effects have been demonstrated in several (preclinical) research models. With this work, we aimed to comprehensively review the reported effects of ginger and its bioactive constituents on the twelve established hallmarks of aging, with the ultimate goal of gaining a deeper understanding of the potential for future interventions in the area of longevity-extension and counteracting of aging-related diseases. The reviewed literature supports the favorable effects of ginger and some of its constituents on all twelve hallmarks of aging, with a particularly high number of animal research studies indicating counteraction of nutrient-sensing dysregulations, mitochondrial dysfunction, chronic inflammation, and dysbiosis. On this background, validation in human clinical trials is still insufficient or is entirely missing, with the exception of some studies indicating positive effects on deregulated nutrient-sensing, chronic inflammation, and dysbiosis. Thus, the existing body of literature clearly supports the potential of ginger to be further studied in clinical trials as a supplement for the promotion of both lifespan and health span.
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- 2024
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33. Blocking IL-11 improves healthspan and lifespan in mice.
- Author
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Walters H
- Subjects
- Animals, Mice, Aging drug effects, Longevity drug effects, Interleukin-11 metabolism
- Published
- 2024
- Full Text
- View/download PDF
34. Blocking an inflammatory protein slows the pace of ageing.
- Author
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Miller RA
- Subjects
- Animals, Humans, Mice, Time Factors, Longevity immunology, Healthy Aging immunology, Aging drug effects, Inflammation immunology, Inflammation metabolism, Inflammation prevention & control, Interleukin-11 antagonists & inhibitors
- Published
- 2024
- Full Text
- View/download PDF
35. Inhibition of IL-11 signalling extends mammalian healthspan and lifespan.
- Author
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Widjaja AA, Lim WW, Viswanathan S, Chothani S, Corden B, Dasan CM, Goh JWT, Lim R, Singh BK, Tan J, Pua CJ, Lim SY, Adami E, Schafer S, George BL, Sweeney M, Xie C, Tripathi M, Sims NA, Hübner N, Petretto E, Withers DJ, Ho L, Gil J, Carling D, and Cook SA
- Subjects
- Animals, Female, Male, Mice, AMP-Activated Protein Kinases metabolism, Frailty genetics, Frailty metabolism, Frailty prevention & control, Inflammation metabolism, Inflammation drug therapy, Interleukin-11 Receptor alpha Subunit metabolism, Interleukin-11 Receptor alpha Subunit deficiency, Mechanistic Target of Rapamycin Complex 1 metabolism, Mechanistic Target of Rapamycin Complex 1 antagonists & inhibitors, Mice, Inbred C57BL, Humans, Extracellular Signal-Regulated MAP Kinases metabolism, Muscle, Skeletal drug effects, Muscle, Skeletal physiology, Aging drug effects, Aging genetics, Aging metabolism, Aging pathology, Interleukin-11 antagonists & inhibitors, Interleukin-11 deficiency, Interleukin-11 genetics, Interleukin-11 metabolism, Longevity drug effects, Longevity genetics, Signal Transduction drug effects
- Abstract
For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark
1-7 . Here we examined whether IL-11, a pro-inflammatory cytokine of the IL-6 family, has a negative effect on age-associated disease and lifespan. As mice age, IL-11 is upregulated across cell types and tissues to regulate an ERK-AMPK-mTORC1 axis to modulate cellular, tissue- and organismal-level ageing pathologies. Deletion of Il11 or Il11ra1 protects against metabolic decline, multi-morbidity and frailty in old age. Administration of anti-IL-11 to 75-week-old mice for 25 weeks improves metabolism and muscle function, and reduces ageing biomarkers and frailty across sexes. In lifespan studies, genetic deletion of Il11 extended the lives of mice of both sexes, by 24.9% on average. Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%. Together, these results demonstrate a role for the pro-inflammatory factor IL-11 in mammalian healthspan and lifespan. We suggest that anti-IL-11 therapy, which is currently in early-stage clinical trials for fibrotic lung disease, may provide a translational opportunity to determine the effects of IL-11 inhibition on ageing pathologies in older people., (© 2024. The Author(s).)- Published
- 2024
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36. Pre-clinical Models for Geriatric Pharmacotherapy.
- Author
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Hilmer SN, Johnell K, and Mach J
- Subjects
- Humans, Aged, Animals, Polypharmacy, Drug Evaluation, Preclinical, Aging drug effects, Drug Therapy methods, Geriatrics methods
- Abstract
With ageing of the population worldwide and discovery of new medications for prevention and management of age-related conditions, there is increasing use of medications by older adults. There are international efforts to increase the representativeness of participants in clinical trials to match the intended real-world users of the medications across a range of characteristics including age, multimorbidity, polypharmacy and frailty. Currently, much of the data on medication-related harm in older adults are from pharmacovigilance studies. New methods in pre-clinical models have allowed for measurement of exposures (such as chronic exposure, polypharmacy and deprescribing) and outcomes (such as health span functional measures and frailty) that are highly relevant to geriatric pharmacotherapy. Here we describe opportunities for design and implementation of pre-clinical models that can better predict drug effects in geriatric patients. This could improve the translation of new drugs from bench to bedside and improve outcomes of pharmacotherapy in older adults., (© 2024. The Author(s).)
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- 2024
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37. Is exposure to pesticides associated with biological aging? A systematic review and meta-analysis.
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Zuo S, Sasitharan V, Di Tanna GL, Vonk JM, De Vries M, Sherif M, Ádám B, Rivillas JC, and Gallo V
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- Humans, Biomarkers, Epigenesis, Genetic drug effects, Telomere drug effects, Telomere Homeostasis drug effects, Aging drug effects, Environmental Exposure adverse effects, Pesticides toxicity
- Abstract
Objective: Exposure to pesticides is a risk factor for various diseases, yet its association with biological aging remains unclear. We aimed to systematically investigate the relationship between pesticide exposure and biological aging., Methods: PubMed, Embase and Web of Science were searched from inception to August 2023. Observational studies investigating the association between pesticide exposure and biomarkers of biological aging were included. Three-level random-effect meta-analysis was used to synthesize the data. Risk of bias was assessed by the Newcastle-Ottawa Scale., Results: Twenty studies evaluating the associations between pesticide exposure and biomarkers of biological aging in 10,368 individuals were included. Sixteen reported telomere length and four reported epigenetic clocks. Meta-analysis showed no statistically significant associations between pesticide exposure and the Hannum clock (pooled β = 0.27; 95 %CI: -0.25, 0.79), or telomere length (pooled Hedges'g = -0.46; 95 %CI: -1.10, 0.19). However, the opposite direction of effects for the two outcomes showed an indication of possible accelerated biological aging. After removal of influential effect sizes or low-quality studies, shorter telomere length was found in higher-exposed populations., Conclusion: The existing evidence for associations between pesticide exposure and biological aging is limited due to the scarcity of studies on epigenetic clocks and the substantial heterogeneity across studies on telomere length. High-quality studies incorporating more biomarkers of biological aging, focusing more on active chemical ingredients of pesticides and accounting for potential confounders are needed to enhance our understanding of the impact of pesticides on biological aging., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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38. Esketamine Prevents Postoperative Emotional and Cognitive Dysfunction by Suppressing Microglial M1 Polarization and Regulating the BDNF-TrkB Pathway in Ageing Rats with Preoperative Sleep Disturbance.
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Wen Y, Xu J, Shen J, Tang Z, Li S, Zhang Q, Li J, and Sun J
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- Animals, Male, Rats, Cell Polarity drug effects, Emotions drug effects, Hippocampus metabolism, Hippocampus drug effects, Neuronal Plasticity drug effects, Rats, Sprague-Dawley, Signal Transduction drug effects, Aging drug effects, Brain-Derived Neurotrophic Factor metabolism, Cognitive Dysfunction metabolism, Cognitive Dysfunction prevention & control, Cognitive Dysfunction drug therapy, Cognitive Dysfunction etiology, Ketamine pharmacology, Ketamine therapeutic use, Microglia metabolism, Microglia drug effects, Receptor, trkB metabolism, Sleep Wake Disorders metabolism, Sleep Wake Disorders drug therapy
- Abstract
Postoperative depression (POD) and postoperative cognitive dysfunction (POCD) have placed heavy burden on patients' physical and mental health in recent years. Sleep disturbance before surgery is a common phenomenon that has been increasingly believed to affect patients' recovery, especially in aged patients, while little attention has been paid to sleep disruption before surgery and the potential mechanism remains ambiguous. Ketamine has been reported to attenuate POCD after cardiac surgery and elicit rapid-acting and sustained antidepressant actions. The present study aimed to clarify the effect of esketamine's (the S-enantiomer of ketamine) protective effects and possible mechanisms of action in POCD and POD. Our results showed that sleep disturbance before surgery exacerbated microglial M1 polarization and microglial BDNF-TrkB signalling dysfunction induced by surgery, resulting in postoperative emotional changes and cognitive impairments. Notably, treatment with esketamine reversed the behavioural abnormalities through inhibiting the M1 polarization of microglia and the inflammatory response thus improving BDNF-TrkB signalling in vivo and vitro. In addition, esketamine administration also reversed the impaired hippocampal synaptic plasticity which has been perturbed by sleep disturbance and surgery. These findings warrant further investigations into the interplay of esketamine and may provide novel ideas for the implication of preoperative preparations and the prevention of postoperative brain-related complications., (© 2023. The Author(s).)
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- 2024
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39. Chemical reversion of age-related oocyte dysfunction fails to enhance embryo development in a bovine model of postovulatory aging.
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Ferreira AF, Machado-Simões J, Moniz I, Soares M, Carvalho A, Diniz P, Ramalho-Santos J, Sousa AP, Lopes-da-Costa L, and Almeida-Santos T
- Subjects
- Animals, Cattle, Female, Ovulation drug effects, Blastocyst drug effects, Blastocyst metabolism, Mitochondria drug effects, Mitochondria metabolism, Aging drug effects, Reactive Oxygen Species metabolism, Resveratrol pharmacology, Oocytes drug effects, Oocytes growth & development, Embryonic Development drug effects, In Vitro Oocyte Maturation Techniques methods, Oxidative Stress drug effects, Antioxidants pharmacology, Fertilization in Vitro methods
- Abstract
Purpose: There are no clinical treatments to prevent/revert age-related alterations associated with oocyte competence decline in the context of advanced maternal age. Those alterations have been attributed to oxidative stress and mitochondrial dysfunction. Our study aimed to test the hypothesis that in vitro maturation (IVM) medium supplementation with antioxidants (resveratrol or phloretin) may revert age-related oocyte competence decline., Methods: Bovine immature oocytes were matured in vitro for 23 h (young) and 30 h (aged). Postovulatory aged oocytes (control group) and embryos obtained after fertilization were examined and compared with oocytes supplemented with either 2 μM of resveratrol or 6 μM phloretin (treatment groups) during IVM., Results: Aged oocytes had a significantly lower mitochondrial mass and proportion of mitochondrial clustered pattern, lower ooplasmic volume, higher ROS, lower sirtuin-1 protein level, and a lower blastocyst rate in comparison to young oocytes, indicating that postovulatory oocytes have a lower quality and developmental competence, thus validating our experimental model. Supplementation of IVM medium with antioxidants prevented the generation of ROS and restored the active mitochondrial mass and pattern characteristic of younger oocytes. Moreover, sirtuin-1 protein levels were also restored but only following incubation with resveratrol. Despite these findings, the blastocyst rate of treatment groups was not significantly different from the control group, indicating that resveratrol and phloretin could not restore the oocyte competence of postovulatory aged oocytes., Conclusion: Resveratrol and phloretin can both revert the age-related oxidative stress and mitochondrial dysfunction during postovulatory aging but were insufficient to enhance embryo developmental rates under our experimental conditions., (© 2024. The Author(s).)
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- 2024
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40. RNA-sequencing exploration on SIR2 and SOD genes in Polyalthia longifolia leaf methanolic extracts (PLME) mediated anti-aging effects in Saccharomyces cerevisiae BY611 yeast cells.
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Hemagirri M, Chen Y, Gopinath SCB, Adnan M, Patel M, and Sasidharan S
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- Aging drug effects, Aging genetics, Gene Expression Regulation, Fungal drug effects, Methanol chemistry, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, Sequence Analysis, RNA methods, Silent Information Regulator Proteins, Saccharomyces cerevisiae genetics, Silent Information Regulator Proteins, Saccharomyces cerevisiae metabolism, Superoxide Dismutase metabolism, Superoxide Dismutase genetics, Superoxide Dismutase-1 genetics, Superoxide Dismutase-1 metabolism, Plant Extracts pharmacology, Plant Leaves chemistry, Polyalthia chemistry, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae drug effects, Sirtuin 2 genetics, Sirtuin 2 metabolism
- Abstract
Polyalthia longifolia is well-known for its abundance of polyphenol content and traditional medicinal uses. Previous research has demonstrated that the methanolic extract of P. longifolia leaves (PLME, 1 mg/mL) possesses anti-aging properties in Saccharomyces cerevisiae BY611 yeast cells. Building on these findings, this study delves deeper into the potential antiaging mechanism of PLME, by analyzing the transcriptional responses of BY611 cells treated with PLME using RNA-sequencing (RNA-seq) technology. The RNA-seq analysis results identified 1691 significantly (padj < 0.05) differentially expressed genes, with 947 upregulated and 744 downregulated genes. Notably, the expression of three important aging-related genes, SIR2, SOD1, and SOD2, showed a significant difference following PLME treatment. The subsequent integration of these targeted genes with GO and KEGG pathway analysis revealed the multifaceted nature of PLME's anti-aging effects in BY611 yeast cells. Enriched GO and KEGG analysis showed that PLME treatment promotes the upregulation of SIR2, SOD1, and SOD2 genes, leading to a boosted cellular antioxidant defense system, reduced oxidative stress, regulated cell metabolism, and maintain genome stability. These collectively increased longevities in PLME-treated BY611 yeast cells and indicate the potential anti-aging action of PLME through the modulation of SIR2 and SOD genes. The present study provided novel insights into the roles of SIR2, SOD1, and SOD2 genes in the anti-aging effects of PLME treatment, offering promising interventions for promoting healthy aging., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
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- 2024
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41. Piperine improves the health span of Drosophila melanogaster with age- and sex-specific effect.
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Lee HY, Lee JH, Baek J, Cho KA, and Min KJ
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- Animals, Male, Female, Fertility drug effects, Sex Factors, Piperidines pharmacology, Polyunsaturated Alkamides pharmacology, Drosophila melanogaster drug effects, Drosophila melanogaster physiology, Alkaloids pharmacology, Benzodioxoles pharmacology, Longevity drug effects, Aging physiology, Aging drug effects
- Abstract
Piperine, a dietary phytochemical isolated from the Piper species, has been used as a natural medicine for pain, flu, and fever in ancient China and India. Although the health benefits of piperine have been widely studied, research on its effect on aging is limited. This study aimed to determine whether piperine has the potential to mitigate aging-related changes in the fruit fly (Drosophila melanogaster), which is an excellent model organism for studies on aging. The experiments were conducted using the newly eclosed or 30-day-old D. melanogaster wild-type strain Cantonized-white. Piperine was dissolved in 99% ethanol and added to the sucrose-yeast medium at a final concentration of 10, 35, 70, or 100 μM. The study examined the effects of piperine supplementation on the lifespan of D. melanogaster and other physiological functions, such as fecundity, feeding, lipid content, and resistance to environmental stress. Log-rank tests, Shapiro-Wilk test, F-test, t-test, or Wilcoxon rank sum test were used to analyze the data. Piperine failed to change the lifespan and body weight, but increased the fecundity and decreased the feeding rate in one-week-old flies. However, when piperine was fed to 30-day-old flies, it increased the lifespan of male flies and the fecundity and feeding rate of female flies. These results indicate that piperine can improve the health of aged flies. The findings suggest that piperine has age-dependent and sex-specific anti-aging effects in fruit flies., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
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- 2024
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42. Nrf2 activation by pyrroloquinoline quinone inhibits natural aging-related intervertebral disk degeneration in mice.
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Xue Q, Li J, Qin R, Li M, Li Y, Zhang J, Wang R, Goltzman D, Miao D, and Yang R
- Subjects
- Animals, Mice, Humans, Male, Mice, Inbred C57BL, Cellular Senescence drug effects, Oxidative Stress drug effects, Intervertebral Disc Degeneration metabolism, Intervertebral Disc Degeneration drug therapy, Intervertebral Disc Degeneration pathology, NF-E2-Related Factor 2 metabolism, Aging drug effects, Aging metabolism, PQQ Cofactor pharmacology
- Abstract
Age-related intervertebral disk degeneration (IVDD) involves increased oxidative damage, cellular senescence, and matrix degradation. Pyrroloquinoline quinone (PQQ) is a water-soluble vitamin-like compound with strong anti-oxidant capacity. The goal of this study was to determine whether PQQ can prevent aging-related IVDD, and the underlying mechanism. Here, we found that dietary PQQ supplementation for 12 months alleviated IVDD phenotypes in aged mice, including increased disk height index and reduced histological scores and cell loss, without toxicity. Mechanistically, PQQ inhibited oxidative stress, cellular senescence, and senescence-associated secretory phenotype (SASP) in the nucleus pulposus and annulus fibrosus of aged mice. Similarly, PQQ protected against interleukin-1β-induced matrix degradation, reactive oxygen species accumulation, and senescence in human nucleus pulposus cells (NPCs) in vitro. Molecular docking predicted and biochemical assays validated that PQQ interacts with specific residues to dissociate the Keap1-Nrf2 complex, thereby increasing nuclear Nrf2 translocation and activation of Nrf2-ARE signaling. RNA sequencing and luciferase assays revealed Nrf2 can transcriptionally upregulate Wnt5a by binding to its promoter, while Wnt5a knockdown prevented PQQ inhibition of matrix metalloproteinase-13 in NPCs. Notably, PQQ supplementation failed to alleviate aging-associated IVDD phenotypes and oxidative stress in aged Nrf2 knockout mice, indicating Nrf2 is indispensable for PQQ bioactivities. Collectively, this study demonstrates Nrf2 activation by PQQ inhibits aging-induced IVDD by attenuating cellular senescence and matrix degradation. This study clarifies Keap1-Nrf2-Wnt5a axis as the novel signaling underlying the protective effects of PQQ against aging-related IVDD, and provides evidence for PQQ as a potential agent for clinical prevention and treatment of natural aging-induced IVDD., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
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- 2024
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43. The effects of ghrelin and LEAP-2 in energy homeostasis are modulated by thermoneutrality, high-fat diet and aging.
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Casado S, Varela-Miguéns M, de Oliveira Diz T, Quintela-Vilariño C, Nogueiras R, Diéguez C, and Tovar S
- Subjects
- Animals, Mice, Male, Antimicrobial Cationic Peptides metabolism, Mice, Inbred C57BL, Thermogenesis drug effects, Adiposity drug effects, Adiposity physiology, Body Weight drug effects, Eating physiology, Eating drug effects, Blood Proteins, Ghrelin pharmacology, Ghrelin metabolism, Diet, High-Fat adverse effects, Energy Metabolism drug effects, Energy Metabolism physiology, Homeostasis drug effects, Homeostasis physiology, Aging physiology, Aging drug effects, Aging metabolism
- Abstract
Purpose: Liver-expressed antimicrobial peptide 2 (LEAP-2) has been recently identified as the endogenous non-competitive allosteric antagonist of the growth hormone secretagogue receptor 1a (GHSR1a). In rodents, LEAP-2 blunts ghrelin-induced feeding and its plasma levels are modulated in response to nutritional status, being decreased upon fasting and increased in high-fat diet (HFD) fed mice. Clinical data support the regulation of circulating LEAP-2 by nutrient availability in humans. In this work, our primary objective was to examine the chronic effects of ghrelin and LEAP-2 administration on food intake, adiposity, and energy expenditure in young mice subjected to standard and HFD at both room temperature and at thermoneutrality. Furthermore, we aimed to assess the impact of these two hormones on aging mice., Results: Our results indicate that LEAP-2 produces a significant decrease of body weight and adiposity, an increase in energy expenditure, and activation of the thermogenic program in white and brown adipose tissue depots. However, this effect is not maintained under HFD or under thermoneutral conditions and is only partially observed in aging mice., Conclusion: In summary our studies describe the central effects of LEAP-2 within distinct experimental contexts, and contribute to the comprehension of LEAP-2's role in energy metabolism., (© 2024. The Author(s).)
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- 2024
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44. Guanosine increases global SUMO1-ylation in the hippocampus of young and aged mice and improves the short-term memory of young mice.
- Author
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Zanella CA, Marques N, Junqueira S, Prediger RD, Tasca CI, and Cimarosti HI
- Subjects
- Animals, Mice, Male, Maze Learning drug effects, Guanosine pharmacology, Hippocampus drug effects, Hippocampus metabolism, Mice, Inbred C57BL, Aging metabolism, Aging drug effects, Memory, Short-Term drug effects, Sumoylation drug effects, SUMO-1 Protein metabolism
- Abstract
The nucleoside guanosine is an endogenous neuromodulator associated with neuroprotection. The roles of guanosine during aging are still not fully elucidated. Guanosine modulates SUMOylation in neurons and astrocytes in vitro, but it is not known whether guanosine can modulate SUMOylation in vivo and improve cognitive functions during aging. SUMOylation is a post-translational protein modification with potential neuroprotective roles. In this follow-up study, we investigated whether guanosine could modulate SUMOylation in vivo and behavior in young and aged mice. Young (3-month-old) and aged (24-month-old) C57BL/6 mice were treated with guanosine (8 mg/kg intraperitoneal) daily for 14 days. Starting on day 8 of treatment, the following behavioral tests were performed: open field, novel object location, Y-maze, sucrose splash test, and tail suspension test. Treatment with guanosine did not change the locomotor activity of young or aged mice in the open-field test. Treatment with guanosine improved short-term memory only for young mice but did not change the working memory of either young or aged mice, as evaluated using object recognition and the Y-maze tests, respectively. Depressive-like behaviors, such as impaired grooming evaluated through the splash test, did not change in either young or aged mice. However, young mice treated with guanosine increased their immobility time in the tail suspension test, suggesting an effect on behavioral coping strategies. Global SUMO1-ylation was significantly increased in the hippocampus of young and aged mice after 14 days of treatment with guanosine, whereas no changes were detected in the cerebral cortex of either young or aged mice. Our findings demonstrate that guanosine also targets hippocampal SUMOylation in vivo, thereby contributing to a deeper understanding of its mechanisms of action. This highlights the involvement of SUMOylation in guanosine's modulatory and neuroprotective effects., (© 2023 International Society for Neurochemistry.)
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- 2024
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45. A novel mechanism of major ginsenosides from Panax ginseng against multiple organ aging in middle-aged mice: Phosphatidylcholine-myo-inositol metabolism based on metabolomic analysis.
- Author
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E M, Zhang Z, Ji P, Liu Q, Qi H, Hou T, Su H, Wang Z, and Li X
- Subjects
- Animals, Mice, Male, Liver metabolism, Liver drug effects, Mice, Inbred C57BL, Panax chemistry, Ginsenosides pharmacology, Aging drug effects, Aging metabolism, Phosphatidylcholines metabolism, Metabolomics, Inositol pharmacology
- Abstract
Aging is a complex, degenerative process associated with various metabolic abnormalities. Ginsenosides (GS) is the main active components of Panax ginseng, which has anti-aging effects and improves metabolism. However, the anti-aging effect and the mechanism of GS in middle-aged mice has not been elucidated. In this study, GS after 3-month treatment significantly improved the grip strength, fatigue resistance, cognitive indices, and cardiac function of 15-month-old mice. Meanwhile, GS treatment reduced the fat content and obviously inhibited histone H2AX phosphorylation at Ser 139 (γ-H2AX), a marker of DNA damage in major organs, especially in the heart and liver. Further, the correlation analysis of serum metabolomics combined with aging phenotype suggested that myo-inositol (MI) upregulated by GS was positively correlated with left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), the main indicators of cardiac function. More importantly, liver tissue metabolomic analysis showed that GS increased MI content by promoting the synthesis pathway from phosphatidylcholine (PC) to MI for the inhibition of liver aging. Finally, we proved that MI reduced the percentage of senescence-associated β-galactosidase staining, γ-H2AX immunofluorescence staining, p21 expression, and the production of reactive oxygen species in H
2 O2 -induced cardiomyocytes. These results suggest that GS can enhance multiple organ functions, especially cardiac function for promoting the healthspan of aging mice, which is mediated by the conversion of PC to MI in the liver and the increase of MI level in the serum. Our study might provide new insights into the potential mechanisms of ginsenosides for prolonging the healthspan of natural aging mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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46. Nanoligomers targeting NF-κB and NLRP3 reduce neuroinflammation and improve cognitive function with aging and tauopathy.
- Author
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Wahl D, Risen SJ, Osburn SC, Emge T, Sharma S, Gilberto VS, Chatterjee A, Nagpal P, Moreno JA, and LaRocca TJ
- Subjects
- Animals, Mice, Cognition drug effects, Cognition physiology, Mice, Inbred C57BL, Male, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, NLR Family, Pyrin Domain-Containing 3 Protein antagonists & inhibitors, NF-kappa B metabolism, Aging drug effects, Tauopathies drug therapy, Tauopathies metabolism, Tauopathies pathology, Neuroinflammatory Diseases drug therapy, Neuroinflammatory Diseases metabolism, Mice, Transgenic
- Abstract
Neuroinflammation contributes to impaired cognitive function in brain aging and neurodegenerative disorders like Alzheimer's disease, which is characterized by the aggregation of pathological tau. One major driver of both age- and tau-associated neuroinflammation is the NF-κB and NLRP3 signaling axis. However, current treatments targeting NF-κB or NLRP3 may have adverse/systemic effects, and most have not been clinically translatable. In this study, we tested the efficacy of a novel, nucleic acid therapeutic (Nanoligomer) cocktail specifically targeting both NF-κB and NLRP3 in the brain for reducing neuroinflammation and improving cognitive function in old (aged 19 months) wildtype mice, and in rTg4510 tau pathology mice (aged 2 months). We found that 4 weeks of NF-κB/NLRP3-targeting Nanoligomer treatment strongly reduced neuro-inflammatory cytokine profiles in the brain and improved cognitive-behavioral function in both old and rTg4510 mice. These effects of NF-κB/NLRP3-targeting Nanoligomers were also associated with reduced glial cell activation and pathology, favorable changes in transcriptome signatures of glia-associated inflammation (reduced) and neuronal health (increased), and positive systemic effects. Collectively, our results provide a basis for future translational studies targeting both NF-κB and NLRP3 in the brain, perhaps using Nanoligomers, to inhibit neuroinflammation and improve cognitive function with aging and neurodegeneration., (© 2024. The Author(s).)
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- 2024
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47. Polygonatum polysaccharide ameliorates D-galactose-induced cognitive dysfunction in aging rats by inhibiting ferroptosis through activation of Nrf2.
- Author
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Xiao L, Wen H, Peng S, Chen B, Tang B, and Liu B
- Subjects
- Animals, Rats, Male, Hippocampus drug effects, Hippocampus metabolism, Hippocampus pathology, Maze Learning drug effects, Galactose, NF-E2-Related Factor 2 metabolism, Cognitive Dysfunction drug therapy, Cognitive Dysfunction metabolism, Cognitive Dysfunction chemically induced, Polysaccharides pharmacology, Polysaccharides therapeutic use, Polygonatum chemistry, Aging drug effects, Aging metabolism, Ferroptosis drug effects, Rats, Sprague-Dawley
- Abstract
Context: Aging is a major risk factor for various neurodegenerative diseases, and ferroptosis has been identified as an important mode of cell death during accelerated aging. As the main component of the edible plant YuZhu in China, Polygonatum polysaccharide (POP) is an important natural compound with anti-aging properties., Objective: To evaluate the anti-aging effects of POP and the underlying molecular mechanisms involved and to evaluate the overall anti-aging effects of POP on cognitive impairment due to accelerated aging., Materials and Methods: A D-galactose (D-gal)-induced accelerated aging rat model was established to evaluate the anti-aging effects of POP and the underlying molecular mechanisms involved. In turn, Morris water maze and open field experiments were used to evaluate the anti-aging effects of POP on cognitive impairment due to accelerated aging., Results: The mechanism by which POP affects nuclear factor E2-related factor 2 (Nrf2), an essential transcription factor, was confirmed. POP significantly improved d-gal-induced cognitive dysfunction in treated model rats, which exhibited reduced pathological changes in the hippocampus, reduced latency of the water maze platform, and increased exploration time in the central area in the open field experiment compared to those of untreated model rats. Furthermore, POP intervention downregulated ferroptosis-related proteins and upregulated Nrf2 expression, and selective inhibition of Nrf2 eliminated the ability of POP to reduce ferroptosis., Conclusions: POP is a natural ingredient with therapeutic potential due to its ability to alleviate aging by activating Nrf2, inhibiting ferroptosis, and alleviating cognitive dysfunction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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48. Curcumin improves atrial fibrillation susceptibility by regulating tsRNA expression in aging mouse atrium.
- Author
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Luo X, Liu P, Ye X, He J, Lai Y, Lv Y, Wu X, Liu Y, Zhang Q, Yang H, Wei W, Deng C, Kuang S, Wu S, Xue Y, and Rao F
- Subjects
- Animals, Mice, RNA, Transfer genetics, RNA, Transfer metabolism, Male, RNA, Small Untranslated genetics, RNA, Small Untranslated metabolism, Reactive Oxygen Species metabolism, Fibrosis, Disease Models, Animal, Mice, Inbred C57BL, Curcumin pharmacology, Atrial Fibrillation genetics, Atrial Fibrillation metabolism, Atrial Fibrillation drug therapy, Aging drug effects, Aging genetics, Heart Atria drug effects, Heart Atria metabolism, Heart Atria pathology, Oxidative Stress drug effects
- Abstract
Age is an independent risk factor for atrial fibrillation (AF), and curcumin can delay aging related disease through reducing oxidative stress and inflammation. However, its target in aging-related AF remains unclear. Transfer RNA-derived small RNA (tsRNA) is a novel short non-coding RNA (sncRNA), and exerts a potential regulatory function in aging. This study was to explore the therapeutic targets of curcumin in atrium of aged mice by PANDORA-seq. Aged mice (18 month) were treated with curcumin (100 mg/kg). Rapid transjugular atrial pacing was performed to observe AF inducibility. SA-β-gal staining, reactive oxygen species (ROS) detection and qRT-PCR were used to assess the degree of aging and oxidative stress/inflammation levels. PANDORA-seq was performed to reveal the differentially expressed sncRNAs in the atrium of mice. The results showed that curcumin reduced the susceptibility AF of aged mice by improving aging-related atrial fibrosis. Compared to young mice (5 month) group, aged mice yielded 473 significantly altered tsRNA sequences, while 947 tsRNA sequences were significantly altered after treated with curcumin. Enrichment analysis revealed that the target genes were mainly related to DNA damage and protein modification. Compared with the 5 month group, the expression levels of mature-mt_tRNA-Val-TAC_CCA_end, mature-mt_tRNA-Glu-TTC_CCA_end, and mature-tRNA-Asp-GTC_CCA_end were up-regulated in the 18 month group, while the expression of mature-mt_tRNA-Thr-TGT_5_end was down-regulated. This trend was reversed in the 18 month + curcumin group. Increased cellular ROS levels, inflammation expression and senescence in aged mice atrium were improved by the down-regulation of mature-mt_tRNA-Val-TAC_CCA_end. In conclusion, our findings identified mature-mt_tRNA-Val-TAC_CCA_end participated in the mechanism of aging-related atrial fibrosis, providing new intervention target of aging-related AF., Competing Interests: The authors declare that they have no competing interests., (© 2024 Luo et al.)
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- 2024
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49. Lithium Ions as Modulators of Complex Biological Processes: The Conundrum of Multiple Targets, Responsiveness and Non-Responsiveness, and the Potential to Prevent or Correct Dysregulation of Systems during Aging and in Disease.
- Author
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Hart DA
- Subjects
- Humans, Animals, Aging drug effects, Aging metabolism, Lithium pharmacology
- Abstract
Lithium is one of the lightest elements on Earth and it has been in the environment since the formation of the galaxy. While a common element, it has not been found to be an essential element in biological processes, ranging from single cell organisms to Homo sapiens . Instead, at an early stage of evolution, organisms committed to a range of elements such as sodium, potassium, calcium, magnesium, zinc, and iron to serve essential functions. Such ions serve critical functions in ion channels, as co-factors in enzymes, as a cofactor in oxygen transport, in DNA replication, as a storage molecule in bone and liver, and in a variety of other roles in biological processes. While seemingly excluded from a major essential role in such processes, lithium ions appear to be able to modulate a variety of biological processes and "correct" deviation from normal activity, as a deficiency of lithium can have biological consequences. Lithium salts are found in low levels in many foods and water supplies, but the effectiveness of Li salts to affect biological systems came to recent prominence with the work of Cade, who reported that administrating Li salts calmed guinea pigs and was subsequently effective at relatively high doses to "normalize" a subset of patients with bipolar disorders. Because of its ability to modulate many biological pathways and processes (e.g., cyclic AMP, GSK-3beta, inositol metabolism, NaK ATPases, neuro processes and centers, immune-related events, respectively) both in vitro and in vivo and during development and adult life, Li salts have become both a useful tool to better understand the molecular regulation of such processes and to also provide insights into altered biological processes in vivo during aging and in disease states. While the range of targets for lithium action supports its possible role as a modulator of biological dysregulation, it presents a conundrum for researchers attempting to elucidate its specific primary target in different tissues in vivo. This review will discuss aspects of the state of knowledge regarding some of the systems that can be influenced, focusing on those involving neural and autoimmunity as examples, some of the mechanisms involved, examples of how Li salts can be used to study model systems, as well as suggesting areas where the use of Li salts could lead to additional insights into both disease mechanisms and natural processes at the molecular and cell levels. In addition, caveats regarding lithium doses used, the strengths and weaknesses of rodent models, the background genetics of the strain of mice or rats employed, and the sex of the animals or the cells used, are discussed. Low-dose lithium may have excellent potential, alone or in combination with other interventions to prevent or alleviate aging-associated conditions and disease progression.
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- 2024
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50. Trilobatin suppresses aging-induced cognitive impairment by targeting SIRT2: Involvement of remodeling gut microbiota to mediate the brain-gut axis.
- Author
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Xie DY, Lin M, Luo YM, Dong L, Wei Y, Gao JM, Zhu YZ, and Gong QH
- Subjects
- Animals, Mice, Male, Blood-Brain Barrier drug effects, Blood-Brain Barrier metabolism, Molecular Docking Simulation, Hippocampus drug effects, Hippocampus metabolism, Disease Models, Animal, Gastrointestinal Microbiome drug effects, Cognitive Dysfunction drug therapy, Aging drug effects, Sirtuin 2 metabolism, Brain-Gut Axis drug effects
- Abstract
Background: Aging is associated with learning and memory disorder, affecting multiple brain areas, especially the hippocampus. Previous studies have demonstrated trilobatin (TLB), as a natural food additive, can extend the life of Caenorhabditis elegans and exhibit neuroprotection in Alzheimer's disease mice. However, the possible significance of TLB in anti-aging remains elusive., Purpose: This study aimed to delve into the physiological mechanism by which TLB ameliorated aging-induced cognitive impairment in senescence-accelerated mouse prone 8 (SAMP8) mice., Methods: 6-month-old SAMP8 mice were administrated with TLB (5, 10, 20 mg/kg/day, i.g.) for 3 months. The therapeutic effect of TLB on aging-induced cognitive impairment was assessed in mice using behavioral tests and aging score. The gut microbiota composition in fecal samples was analyzed by metagenomic analysis. The protective effects of TLB on blood-brain barrier (BBB) and intestinal barrier were detected by transmission electron microscope, H&E staining and western blot (WB) assay. The inhibitive effects of TLB on inflammation in brain and intestine were assessed using immunofluorescence, WB and ELISA assay. Molecular docking and surface plasma resonance (SPR) assay were utilized to investigate interaction between TLB and sirtuin 2 (SIRT2)., Results: Herein, the findings exhibited TLB mitigated aging-induced cognitive impairment, neuron injury and neuroinflammation in hippocampus of aged SAMP8 mice. Moreover, TLB treatment repaired imbalance of gut microbiota in aged SAMP8 mice. Furthermore, TLB alleviated the damage to BBB and intestinal barrier, concomitant with reducing the expression of SIRT2, phosphorylated levels of c-Jun NH2 terminal kinases (JNK) and c-Jun, and expression of MMP9 protein in aged SAMP8 mice. Molecular docking and SPR unveiled TLB combined with SIRT2 and down-regulated SIRT2 protein expression. Mechanistically, the potential mechanism of SIRT2 in TLB that exerted anti-aging effect was validated in vitro. As expected, SIRT2 deficiency attenuated phosphorylated level of JNK in HT22 cells treated with d-galactose., Conclusion: These findings reveal, for the first time, SIRT2-mediated brain-gut barriers contribute to aging and aging-related diseases, and TLB can rescue aging-induced cognitive impairment by targeting SIRT2 and restoring gut microbiota disturbance to mediate the brain-gut axis. Overall, this work extends the potential application of TLB as a natural food additive in aging-related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)
- Published
- 2024
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