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Studies of longevity rely on baseline life expectancy of reference genotypes measured in standardized conditions. Variation among labs, protocols, and genotypes makes longevity intervention studies difficult to compare. Furthermore, extending lifespan under suboptimal conditions or that of a short-lived genotype may be of a lesser theoretical and translational value than extending the maximal possible lifespan. Daphnia is becoming a model organism of choice for longevity research complementing data obtained on traditional models. In this study, we report longevity of several genotypes of a long-lived species D. magna under a variety of protocols, aiming to document the highest lifespan, factors reducing it, and parameters that change with age and correlate with longevity. Combining longevity data from 25 experiments across two labs, we report a strong intraspecific variation, moderate effects of group size and medium composition, and strong genotype-by-environment interactions with respect to food level. Specifically, short-lived genotypes show no caloric restriction (CR) effect, while long-lived ones expand their lifespan even further under CR. We find that the CR non-responsive clones show little correlation between longevity and two measures of lipid peroxidation. In contrast, the long-lived, CR-responsive clones show a positive correlation between longevity and lipid hydroperoxide abundance, and a negative correlation with MDA concentration. This indicates differences among genotypes in age-related accumulation and detoxification of LPO products and their effects on longevity. Our observations support the hypothesis that a long lifespan can be affected by CR and levels of oxidative damage, while genetically determined short lifespan remains short regardless. [ABSTRACT FROM AUTHOR]

The aging process significantly impacts lung physiology and is a major risk factor for chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and non-IPF interstitial lung fibrosis. This narrative clinical review explores the molecular and biochemical hallmarks of aging, such as oxidative stress, telomere attrition, genomic instability, epigenetic modifications, proteostasis loss, and impaired macroautophagy, and their roles in lung senescence. Central to this process are senescent cells, which, through the senescence-associated secretory phenotype (SASP), contribute to chronic inflammation and tissue dysfunction. The review highlights parallels between lung aging and pathophysiological changes in respiratory diseases, emphasizing the role of cellular senescence in disease onset and progression. Despite promising research into modulating aging pathways with interventions like caloric restriction, mTOR inhibitors, and SIRT1 activators, clinical evidence for efficacy in reversing or preventing age-related lung diseases remains limited. Understanding the interplay between aging-related mechanisms and environmental factors, such as smoking and pollution, is critical for developing targeted therapies. This review underscores the need for future studies focusing on therapeutic strategies to mitigate aging's detrimental effects on lung health and improve outcomes for patients with chronic respiratory conditions. [ABSTRACT FROM AUTHOR]

In recent years, there has been a surge in the popularity of fasting as a method to enhance one's health and overall well-being. Fasting is a customary practice characterized by voluntary refraining from consuming food and beverages for a specified duration, ranging from a few hours to several days. The potential advantages of fasting, including enhanced insulin sensitivity, decreased inflammation, and better cellular repair mechanisms, have been well documented. However, the effects of fasting on cancer therapy have been the focus of recent scholarly investigations. Doxorubicin (Dox) is one of the most widely used chemotherapy medications for cancer treatment. Unfortunately, cardiotoxicity, which may lead to heart failure and other cardiovascular issues, has been linked to Dox usage. This study aims to comprehensively examine the possible advantages and disadvantages of fasting concerning Dox-induced cardiotoxicity. Researchers have investigated the potential benefits of fasting in lowering the risk of Dox-induced cardiac damage to solve this problem. Nevertheless, new studies indicate that prolonged alternate-day fasting may adversely affect the heart's capacity to manage the cardiotoxic properties of Dox. Though fasting may benefit overall health, it is essential to proceed cautiously and consider the potential risks in certain circumstances. [ABSTRACT FROM AUTHOR]

Weight regain (WR) after bariatric surgery, particularly sleeve gastrectomy, is a significant challenge, often driven by a combination of metabolic, behavioral, and lifestyle factors. Non-surgical interventions to manage WR are critical, given the increased risks and reduced efficacy of revisional surgeries. In this context, very low-calorie ketogenic diets (VLCKDs) have gained attention for their potential to promote weight loss and improve body composition in individuals struggling with WR. This study assessed the safety and efficacy of a VLCKD in 11 patients who experienced WR following sleeve gastrectomy. Over an 8-week period, patients demonstrated a significant average weight loss of 6.3% (p = 0.005), along with improvements in body composition, including reductions in body fat percentage (p = 0.003) and waist circumference (p = 0.003). Metabolic markers, such as insulin resistance (HOMA-IR), also improved significantly (p = 0.041). Although a decrease in the glomerular filtration rate was observed (p = 0.007), this finding is unlikely to be clinically relevant over the short term. Importantly, no major adverse events were reported, with only mild constipation observed. These results suggest that VLCKDs may be a promising non-surgical approach for managing WR post-bariatric surgery, though further studies are needed to assess long-term effects, especially on renal function. [ABSTRACT FROM AUTHOR]

Background: Time-restricted eating (TRE) is a dietary regimen that limits food intake for at least 12 h daily. Unlike other fasting protocols, TRE does not dictate what or how much to eat but rather focuses on the timing of meals. This approach has been previously demonstrated to improve body composition in individuals with obesity or metabolic impairments. However, its impact on body composition and cardiometabolic factors in healthy individuals remains unclear. Furthermore, the optimal fasting duration is still debated. Thus, we aimed to compare the effects of 8 weeks of different fasting durations on body composition and biochemical parameters in metabolically healthy, non-trained individuals using a parallel randomized controlled trial. Methods: Forty-one volunteers were randomly assigned to one of the four experimental groups: TRE 16:8 (16 h of fasting,8 h of eating), TRE 14:10 (14 h of fasting,10 h of eating), TRE 12:12 (12 h of fasting,12 h of eating) or a normal diet group (ND; no dietary restriction). Participants underwent body composition measurements and blood tests for lipid profiles (i.e., total cholesterol, LDL, HDL, and triglycerides), fasting glucose, leptin, and anabolic hormones (i.e., insulin and testosterone) levels. Data were analyzed using both intention-to-treat (ITT) and per-protocol (PP) analysis to account for compliance. A two-way ANOVA for repeated measures was employed to assess interactions between time and group. Results: In the ITT analysis, TRE 16:8 reduced body mass (-2.46%, p = 0.003) and absolute fat mass (-8.65%, p = 0.001) with no changes in lean soft tissue and in calorie intake. These results were consistent with the PP analysis which included 8 participants in TRE 16:8, 5 in TRE 14:10, 9 in TRE 12:12, and the entire ND group. Participants in the TRE 16:8 group spontaneously reduced their total caloric intake, although this reduction was not statistically significant. None of the other measurements significantly changed after 8 weeks. Conclusions: Our results suggest that a 16-hour fasting window, even without caloric restriction, may be a viable strategy for improving body composition in healthy and non-trained individuals, whereas a shorter fasting period may be insufficient to produce significant changes in a healthy population. Trial registration: NCT, NCT04503005. Registered 4 August 2020, https://clinicaltrials.gov/study/NCT04503005. [ABSTRACT FROM AUTHOR]

Environmental factors and individual attributes, and their interactions, impact survival, growth and reproduction of an individual throughout its life. In the clonal rotifer Brachionus, low food conditions delay reproduction and extend lifespan. This species also exhibits maternal effect senescence; the offspring of older mothers have lower survival and reproductive output. In this paper, we explored the population consequences of the individual‐level interaction of maternal age and low food availability. We built matrix population models for both ad libitum and low food treatments, in which individuals are classified both by their age and maternal age. Low food conditions reduced population growth rate (Δλ=−0.0574$$ \Delta \lambda =-0.0574 $$) and shifted the population structure to older maternal ages, but did not detectably impact individual lifetime reproductive output. We analysed hypothetical scenarios in which reduced fertility or survival led to approximately stationary populations that maintained the shape of the difference in demographic rates between the ad libitum and low food treatments. When fertility was reduced, the populations were more evenly distributed across ages and maternal ages, while the lower‐survival models showed an increased concentration of individuals in the youngest ages and maternal ages. Using life table response experiment analyses, we compared populations grown under ad libitum and low food conditions in scenarios representing laboratory conditions, reduced fertility and reduced survival. In the laboratory scenario, the reduction in population growth rate under low food conditions is primarily due to decreased fertility in early life. In the lower‐fertility scenario, contributions from differences in fertility and survival are more similar, and show trade‐offs across both ages and maternal ages. In the lower‐survival scenario, the contributions from decreased fertility in early life again dominate the difference in λ$$ \lambda $$. These results demonstrate that processes that potentially benefit individuals (e.g. lifespan extension) may actually reduce fitness and population growth because of links with other demographic changes (e.g. delayed reproduction). Because the interactions of maternal age and low food availability depend on the population structure, the fitness consequences of an environmental change can only be fully understood through analysis that takes into account the entire life cycle. [ABSTRACT FROM AUTHOR]

Although it is established that caloric restriction offers metabolic and clinical benefits, the molecular mechanisms underlying these effects remain unclear. Thus, this study aimed to investigate whether caloric restriction can modulate mitochondrial function and remodeling and stimulate autophagic flux in the PBMCs of patients with obesity. This was an interventional study of 38 obese subjects (BMI >35 kg/m2) who underwent 6 months of dietary therapy, including a 6-week very-low-calorie diet (VLCD) followed by an 18-week low-calorie diet (LCD). We determined clinical variables, mitochondrial function parameters (by fluorescence imaging of mitochondrial ROS and membrane potential), and protein expression of markers of mitochondrial dynamics (MNF1, MFN2, OPA, DRP1 and FIS1) and autophagy (LC3, Beclin, BCL2 and NBR1) by Western blot. Caloric restriction induced an improvement in metabolic outcomes that was accompanied by an increase in AMPK expression, a decrease of mitochondrial ROS and mitochondrial membrane potential, which was associated with increased markers of mitochondrial dynamics (MFN2, DRP1 and FIS1) and activation of autophagy as evidenced by augmented LC3 II/I, Beclin1 and NBR1, and a decrease in BCL2. These findings shed light on the specific molecular mechanisms by which caloric restriction facilitates metabolic improvements, highlighting the relevance of pathways involving energy homeostasis and cell recovery, including mitochondrial function and dynamics and autophagy. [Display omitted] • 38 patients with obesity underwent a 6-month hipocaloric diet. • Caloric restriction improved metabolism by modulating mitochondria and reducing ROS. • Enhanced mitochondrial dynamics and autophagy are key in caloric restriction benefits. • AMPK expression aids mitochondrial remodeling and energy homeostasis in restriction. • Insights could lead to new obesity therapies, including pharmacological targets. [ABSTRACT FROM AUTHOR]

One key goal of basic aging research is the development of reliable assays of both current and future health. These assays could dramatically accelerate progress toward developing health-extending interventions by obviating the need for full lifespan studies, especially if they were informative relatively early in life. One potential approach is the assessment of physiological resilience, defined as the ability to recover from an adverse event. Here, using CB6F1 mice, we evaluated four potential resilience assays, each quantifying recovery from a physiological challenge with clear relevance to humans. The challenges were: (1) anesthesia recovery, (2) restoration of hemoglobin levels after a blood draw, (3) speed of wound healing, and (4) survival after pathogen exposure. We evaluated how each changed with age and with interventions known to extend health in males only (17α-estradiol) or both sexes (calorie restriction). We found that three of the four (recovery from anesthesia, blood draw, and pathogen exposure) showed significant and expected age effects, but wound healing did not. None of the three age-sensitive assays responded to the health-extending interventions in the way we expected, and for some assays, including anesthesia response, interventions actually worsened outcomes. Possible explanations are: (1) our interventions were too brief, (2) the ages we evaluated were too young, (3) our assays did not capture important features of organismal resilience, or (4) organismal resilience is not as clearly related to current or future health as hypothesized. Future studies are needed to determine which of these interpretations is valid and to determine whether other resilience metrics may be more informative about current and future health. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Method Results Discussion Renourishment and weight restoration are critical first steps in anorexia nervosa (AN) treatment. The ability of the gastrointestinal tract to harvest and utilize energy from food is essential for successful weight restoration, but the functional capacity of the intestine after prolonged caloric restriction remains unknown. In an exploratory study, we quantified the stool energy content of individuals with AN before and after renourishment.We used archived stool samples from a multisite cohort (NCT03119272) of 103 individuals with AN at admission and discharge from inpatient renourishment and 122 sex‐matched non‐eating disorder controls (non‐ED). To determine whether bomb calorimetry may have utility in AN, we measured stool calorie loss as the number of kilocalories per gram of stool. Analyses included ANOVA, paired/unpaired t‐tests, and Spearman rank correlations for associations between stool energy and clinical variables.Following 25.10 ± 19.73 days of renourishment, patients gained an average of 5.67 ± 4.27 kg. Raw stool energy at discharge (AN‐DIS: 5.72 ± 0.86 kcal/g) was significantly higher than admission (AN‐AD: 5.41 ± 0.86 kcal/g; p < 0.01). Weight and BMI at admission and discharge were negatively correlated with raw stool energy at discharge.Energy content in stool increases after inpatient refeeding, likely due to increased calorie consumption. Findings should be interpreted cautiously due to methodological limitations in this post hoc study design. Future studies should use a priori, gold‐standard protocols to investigate stool calorie loss in AN, as prolonged restriction in AN may disrupt the gut and impede energy harvest.Trial Registration: clinicaltrials.gov: NCT03119272 [ABSTRACT FROM AUTHOR]

In light of research indicating that normal TSH levels do not necessarily reflect clinical euthyroidism in hypothyroid patients, and given the patient dissatisfaction with levothyroxine (LT4) monotherapy, we evaluate the response to weight loss treatment in patients with obesity and primary hypothyroidism who are euthyroid under LT4 therapy, with a focus on weight and metabolic parameters. The retrospective study included 138 subjects with obesity (BMI ≥ 30 kg/m2), 69 women with hypothyroidism on levothyroxine, and 69 age- and BMI-matched women without thyroid disease. Secondary causes of obesity, medications that may affect thyroid functions and metabolic parameters, chronic and oncological disease, pregnancy, TSH outside the reference range, follow-up periods of less than one year, and bariatric surgery were the exclusion criteria. Patients' characteristics and metabolic responses to weight reduction treatment consisting of calorie restriction, moderate exercise, and metformin if needed were evaluated. TSH and fT4 levels were higher, and fT3 and T3/T4 ratios were lower all within the reference ranges in hypothyroid women. They were less insulin resistant. Both patient' groups experienced a significant decrease in body weight, BMI, and atherogenic index of plasma (AIP) during the follow-up (p = 0.001). Insulin resistance was not changed. The groups' body weight, BMI, HOMA-IR, and AIP changes were similar at the end of the study (p = 0.876, p = 0.850, p = 0.555, p = 0.293). The results suggest that achieving euthyroid status via levothyroxine monotherapy in hypothyroid women leads to weight loss responses comparable to those in women with normal thyroid. This supports the effectiveness of current hypothyroidism treatment strategies, emphasizing TSH level normalization, in achieving clinical euthyroidism concerning weight loss outcomes. [ABSTRACT FROM AUTHOR]

Pancreatic neoplasm, a highly aggressive and often fatal cancer, poses challenges due to late detection and nonspecific symptoms. Therefore, both early diagnosis and appropriate therapeutic approaches are necessary to augment the condition of these patients. Cancer cells undergo metabolic deregulation, which enables their proliferation, survival, and invasion. As a result, it is crucial to focus on the metabolic pathways in prevalent cancers and explore treatment strategies that target these pathways to control tumor growth effectively. This is particularly relevant in cancers like pancreatic cancer, which undergo numerous metabolic alterations. The ketogenic regimen, characterized by low carbohydrate and protein contents and high-fat sources, does not involve caloric restriction. This allows for the induction of ketogenesis and an increase in ketone bodies, while insulin and glucose levels remain low even after meals. This unique metabolic state may influence the tumor microenvironment. Given the lack of unanimous agreement on the precise role and mechanism of the ketogenic diet, this review aims to clarify the diagnostic value and accuracy of ketone bodies in various types of pancreatic tumors and explore the potential anti-cancer effects of the ketogenic diet when used alone or in conjunction with chemotherapy, also to determine the potential of the ketogenic diet to be used as adjuvant therapy. The outcomes of this study are instrumental in enhancing our understanding of the benefits and drawbacks associated with employing this diet for the management and diagnosis of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Aging is associated with a global decline in stem cell function. To date, several strategies have been proposed to rejuvenate aged stem cells: most of these result in functional improvement of the tissue where the stem cells reside, but the impact on the lifespan of the whole organism has been less clearly established. Here, we review some of the most recent work dealing with interventions that improve the regenerative capacity of aged somatic stem cells in mammals and that might have important translational possibilities. Overall, we underscore that somatic stem cell rejuvenation represents a strategy to improve tissue homeostasis upon aging and present some recent approaches with the potential to affect health span and lifespan of the whole organism. [ABSTRACT FROM AUTHOR]

Vascular calcification is a complication that is frequently encountered in patients affected by atherosclerosis, diabetes, and chronic kidney disease (CKD), and that is characterized by the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). At present, there remains a pressing lack of any effective therapies that can treat this condition. The sodium-glucose transporter 2 (SGLT2) inhibitor dapagliflozin (DAPA) has shown beneficial effects in cardiovascular disease. The role of this inhibitor in the context of vascular calcification, however, remains largely uncharacterized. Our findings revealed that DAPA treatment was sufficient to alleviate in vitro and in vivo osteogenic transdifferentiation and vascular calcification. Interestingly, our study demonstrated that DAPA exerts its anti-calcification effects on VSMCs by directly targeting SGLT2, with the overexpression of SGLT2 being sufficient to attenuate these beneficial effects. DAPA was also able to limit the glucose levels and NAD+/NADH ratio in calcified VSMCs, upregulating sirtuin 1 (SIRT1) in a caloric restriction (CR)-dependent manner. The SIRT1-specific siRNA and the SIRT1 inhibitor EX527 attenuated the anti-calcification effects of DAPA treatment. DAPA was also to drive SIRT1-mediated deacetylation and consequent degradation of hypoxia-inducible factor-1α (HIF-1α). The use of cobalt chloride and proteasome inhibitor MG132 to preserve HIF-1α stability mitigated the anti-calcification activity of DAPA. These analyses revealed that the DAPA/SGLT2/SIRT1 axis may therefore represent a viable novel approach to treating vascular calcification, offering new insights into how SGLT2 inhibitors may help prevent and treat vascular calcification. [ABSTRACT FROM AUTHOR]

Caloric restriction (CR) has been proposed as a nutritional strategy to combat chronic diseases, including neurodegenerative diseases, as well as to delay aging. However, despite the benefits of CR, questions remain about its underlying mechanisms and cellular and molecular targets. Objective: As inflammatory processes are the basis or accompany chronic diseases and aging, we investigated the protective role of CR in the event of an acute inflammatory stimulus. Methods: Peripheral inflammatory and metabolic parameters were evaluated in Wistar rats following CR and/or acute lipopolysaccharide (LPS) administration, as well as glial changes (microglia and astrocytes), in two regions of the brain (hippocampus and hypothalamus) involved in the inflammatory response. We used a protocol of 30% CR, for 4 or 8 weeks. Serum and brain parameters were analyzed by biochemical or immunological assays. Results: Benefits of CR were observed during the inflammatory challenge, where the partial reduction of serum interleukin-6, mediated by CR, attenuated the systemic response. In the central nervous system (CNS), specifically in the hippocampus, CR attenuated the response to the LPS, as evaluated by tumor necrosis factor alpha (TNFα) levels. Furthermore, in the hippocampus, CR increased the glutathione (GSH) levels, resulting in a better antioxidant response. Discussion: This study contributes to the understanding of the effects of CR, particularly in the CNS, and expands knowledge about glial cells, emphasizing their importance in neuroprotection strategies. [ABSTRACT FROM AUTHOR]

The biological rhythms generated by the endogenous circadian clocks across the tree of life regulate numerous behavioral, metabolic, and physiological processes. Although evidence from various studies in Drosophila melanogaster indicates the importance of the core circadian clock genes in the intricate interplay between the circadian clock and metabolism, little is known about the contribution of the circadian photoreceptor/s in this process. The deep brain circadian photoreceptor CRYPTOCHROME (CRY) is essential for resetting the clock in response to light and is also highly expressed in metabolically active tissues in Drosophila. In this study, we sought to explore the possible roles played by CRY in triglyceride (TG) metabolism. We observed that the cry mutant (cry01) flies exhibited increased starvation resistance and TG levels under both 12-hour (h) light:12-h dark cycle (LD) and under constant light compared with the control w1118 flies. We also observed that cry01 flies had significantly increased food intake, glycogen concentrations, and lifespan under LD. In addition, cryptochrome seemed to affect TG levels in adult flies in response to calorie-restricted and high-fat diets. These results suggest a role for the circadian photoreceptor CRY in TG metabolism in Drosophila. [ABSTRACT FROM AUTHOR]

Caloric restriction (CR) alongside its ability to increase longevity, exerts inhibitory effects against various tumors. The purpose of this current research was to investigate the conceivable implications of CR, either independently or in conjunction with a cyclooxygenase 2 inhibitor (Celecoxib), on the pathophysiology of induced hepatocellular carcinoma (HCC). Forty adult male Wistar rats were allocated into four groups: Control, HCC; induced by injecting diethylnitrosamine intraperitoneally, then subsequently given a weekly subcutaneous injection of carbon tetrachloride (CCl4) once a week for 6 consecutive weeks, CR group, and CR-Celecoxib group. The results revealed enhanced serum insulin growth factor-I (IGF-I) and- II (IGF-II) levels, along with a significant increase in COX-2 and IL-6 gene expression as well as acceleration of pathological changes, glycogen depletion, enhanced fibrosis, and decreased caspase 3 expression in the liver. However, both IGF-I, II, and alpha-fetoprotein (AFP) were significantly decreased in the CR group co-treated with Celecoxib which was positively reflected on the liver architecture. We concluded that combined CR and COX-2 inhibition interferes with the pathogenesis of HCC. [ABSTRACT FROM AUTHOR]

Calcineurin is a highly conserved calcium/calmodulin-dependent serine/threonine protein phosphatase with diverse functions. Inhibition of calcineurin is known to enhance the lifespan of Caenorhabditis elegans through multiple signaling pathways. Aiming to study the role of calcineurin in regulating innate immunity, we discover that calcineurin is required for the rhythmic defecation motor program (DMP) in C. elegans. Calcineurin inhibition leads to defects in the DMP, resulting in intestinal bloating, rapid colonization of the gut by bacteria, and increased susceptibility to bacterial infection. We demonstrate that intestinal bloating caused by calcineurin inhibition mimics the effects of calorie restriction, resulting in enhanced lifespan. The TFEB ortholog, HLH-30, is required for lifespan extension mediated by calcineurin inhibition. Finally, we show that the nuclear hormone receptor, NHR-8, is upregulated by calcineurin inhibition and is necessary for the increased lifespan. Our studies uncover a role for calcineurin in the C. elegans DMP and provide a new mechanism for calcineurin inhibition-mediated longevity extension. [ABSTRACT FROM AUTHOR]

Cancer is the second leading cause of death in the United States and among the most prevalent diseases globally, with an incidence expected to grow because of smoking, pollution, poor dietary habits, obesity, and the rise in the older population. Given their ability to reduce risk factors, albeit with varying efficacy, nutrition and fasting could help prevent cancer and other age-related disorders. Calorie restriction (CR), various forms of intermittent fasting (IF) or periodic fasting (PF), and fasting-mimicking diets (FMDs) have been shown to improve health span, increase lifespan, and prevent or postpone cancer in rodents. The effects of specific diets and fasting regimens on aging and cancer appear to be mediated in part by the reduction in the activity of the growth hormone (GH)/insulin-like-growth-factor-I (IGF-1) axis. Nevertheless, recent data indicate that the alternation of low and normal levels of these hormones and factors may be ideal for optimizing longevity and function. Here, we review the role of nutrition, CR, and fasting/FMD on cancer, focusing on the hypothesis that the modulation of GH, IGF-1, and insulin signaling partly mediates the effect of these dietary interventions on cancer prevention. [ABSTRACT FROM AUTHOR]

Sarcopenia, a leading cause for global disability and mortality, is an age‐related muscular disorder, characterized by accelerated muscle mass loss and functional decline. It is known that caloric restriction (CR), ketogenic diet or endurance exercise lessen sarcopenia and elevate circulating β‐hydroxybutyrate (β‐HB) levels. Whether the elevated β‐HB is essential to the reversal of sarcopenia, however, remains unclear. Here we show in both Caenorhabditis elegans and mouse models that an increase of β‐HB reverse myofiber atrophy and improves motor functions at advanced ages. β‐HB‐induced histone lysine β‐hydroxybutyrylation (Kbhb) is indispensable for the reversal of sarcopenia. Histone Kbhb enhances transcription of genes associated with mitochondrial pathways, including oxidative phosphorylation, ATP metabolic process and aerobic respiration. This ultimately leads to improve mitochondrial integrity and enhance mitochondrial respiration. The histone Kbhb are validated in mouse model with CR. Thus, we demonstrate that β‐HB induces histone Kbhb, increases mitochondrial function, and reverses sarcopenia. [ABSTRACT FROM AUTHOR]

Peripheral neuropathy (PN) is a prevalent and debilitating complication of obesity, prediabetes, and type 2 diabetes, which remains poorly understood and lacks disease-modifying therapies. Fortunately, diet and/or exercise have emerged as effective treatment strategies for PN. Here, we examined the impact of caloric restriction (CR) and high-intensity interval training (HIIT) interventions, alone or combined (HIIT-CR), on metabolic and PN outcomes in high-fat diet (HFD) mice. HFD feeding alone resulted in obesity, impaired glucose tolerance, and PN. Peripheral nerves isolated from these mice also developed insulin resistance (IR). CR and HIIT-CR, but not HIIT alone, improved HFD-induced metabolic dysfunction. However, all interventions improved PN to similar extents. When examining the underlying neuroprotective mechanisms in whole nerves, we found that CR and HIIT-CR activate the fuel-sensing enzyme AMPK. We then performed complimentary in vitro work in Schwann cells, the glia of peripheral nerves. Treating primary Schwann cells with the saturated fatty acid palmitate to mimic prediabetic conditions caused IR, which was reversed by the AMPK activator, AICAR. Together, these results enhance our understanding of PN pathogenesis, the differential mechanisms by which diet and exercise may improve PN, and Schwann cell-specific contributions to nerve insulin signaling and PN progression. Article Highlights: Diet and exercise are recommended for treating peripheral neuropathy in prediabetes. To identify the optimal regimen and the underlying neuroprotective mechanisms, we compared the effects of caloric restriction (CR), high-intensity interval training (HIIT), and their combination (HIIT-CR), on metabolic and neuropathy outcomes following high-fat diet feeding. While all interventions improved neuropathy, CR and HIIT-CR, but not HIIT alone, improved metabolic profiles and promoted insulin sensitivity in peripheral nerves of high-fat diet–fed mice. In vitro, palmitate-treated Schwann cells developed insulin resistance, which was reversed by AMPK activation. CR, alone or combined with HIIT, ameliorates neuropathy by restoring nerve insulin sensitivity. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION The black goji berry (Lycium ruthenicum Murr.) is known for its abundance of high‐quality natural antioxidants, particularly anthocyanins. Black goji berry anthocyanins (BGA) are receiving increasing attention because of their high safety and beneficial biological activities. Studies have shown that oxidative stress is a key factor affecting aging, whereas antioxidants are critical preventive and delaying strategies.In the present study, we investigated the potential anti‐aging effects and mechanism of BGA using the Caenorhabditis elegans model. We found that BGA prolonged the mean lifespan of nematodes and improve their healthspan, including locomotion, pharyngeal pumping rate and stress resistance. Subsequently, we observed a significant decrease in reactive oxygen species and malondialdehyde levels in nematodes after administering BGA. Moreover, BGA enhanced the activities of the antioxidant enzymes superoxide dismutase and catalase, and elevated the glutathione disulfide/glutathione ratio. We confirmed that BGA exerted excellent antioxidative stress activity in nematodes, which may contribute substantially to its anti‐aging effects. The health benefits of BGA in C. elegans might be closely related to petunidin‐3‐O‐glucoside, the most abundant anthocyanin in BGA. Further mechanistic investigation revealed that the JNK‐1 and DAF‐16/FOXO pathways, rather than the calorie restriction pathway, were responsible for the antioxidant stress and life‐prolonging effects of BGA in nematodes.Our research provides a theoretical foundation for studying the anti‐aging effect of BGA and a basis for developing black goji berry and its anthocyanins as functional foods with anti‐aging and antioxidative stress benefits. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The maintenance of germ cells is critical for the prosperity of offspring. The amount of food consumption is known to be closely related to reproduction, i.e. the number of eggs decreases under calorie-restricted conditions in various organisms. Previous studies in Caenorhabditis elegans have reported that calorie restriction reduces the number of eggs and the reduction can be rescued by methionine. However, the effect of methionine on the reproductive process has not been fully understood. In this study, to assess the gonadal function of methionine metabolism, we firstly demonstrated that a depletion in dietary methionine resulted in reduced levels of S -adenosyl- l -methionine (SAM) and S -adenosyl homocysteine in wild-type N2, but not in glp-1 mutants, which possess only a few germ cells. Second, we found no recovery in egg numbers upon methionine administration in SAM synthase (sams) -1 mutants. Furthermore, a reduced number of proliferative zone nuclei exhibited in the sams-1 mutants was not rescued via methionine. Thus, our results have shown that dietary methionine is required for the normal establishment of both the germline progenitor pool and fecundity, mediated by sams-1. [ABSTRACT FROM AUTHOR]

Bone fragility is a well-documented long-term side effect of radiotherapy, which currently has no preventative treatments. In this study, we applied a caloric restriction (CR) diet to attenuate both local and systemic bone loss after irradiation (RTx) in an established female Balb/c mouse model (4 consecutive daily doses of 5 Gy to the right hindlimb only). CR mice were tapered down to a 30% reduced calorie diet (RTx/CR) one week before irradiation, while regular diet (RD) mice received food ad libitum (RTx/RD). Unirradiated (sham) mice received either a 30% CR diet (SH/CR) or received food ad libitum (SH/RD). Irradiated, contralateral, and unirradiated hindlimbs were evaluated at 2, 4, and 8 weeks postirradiation using micro-computed tomography (μCT) to assess bone morphology and 3-point bending to quantify femur strength. Histological analysis of irradiated and unirradiated tibiae was performed to examine general bone tissue cytology and serum biomarker analysis was performed using terminal blood draw samples. After treatment, femur strength and metaphyseal bone quantity was decreased in irradiated and contralateral femora of RTx/RD mice compared to SH/RD femurs; this finding is consistent with previous studies. RTx/CR mice had positive effects when compared to RTx/RD mice, including increased strength relative to body mass in both the irradiated and contralateral limb, increased trabecular bone mass, and decreased marrow adiposity. However, a number of adverse effects were also observed, including a significant decrease in body mass and decreased cortical bone. Overall, CR shows promise as a preventative treatment for postirradiated bone fragility, yet questions remain to be addressed in future studies. Ideal diet duration, impact to normal tissue, and mechanism of action must be explored to better understand the clinical implication of a CR diet. [ABSTRACT FROM AUTHOR]

Obesity is associated with important changes in cardiac energetics and function, and an increased risk of adverse cardiovascular outcomes. Multi‐nuclear MRS and MRI techniques have the potential to provide a comprehensive non‐invasive assessment of cardiac metabolic perturbation in obesity. A rat model of obesity was created by high‐fat diet feeding. This model was characterized using in vivo hyperpolarized [1‐13C]pyruvate and [2‐13C]pyruvate MRS, echocardiography and perfused heart 31P MRS. Two groups of obese rats were subsequently treated with either caloric restriction or the glucagon‐like peptide‐1 analogue/agonist liraglutide, prior to reassessment. The model recapitulated cardiovascular consequences of human obesity, including mild left ventricular hypertrophy, and diastolic, but not systolic, dysfunction. Hyperpolarized 13C and 31P MRS demonstrated that obesity was associated with reduced myocardial pyruvate dehydrogenase flux, altered cardiac tricarboxylic acid (TCA) cycle metabolism, and impaired myocardial energetic status (lower phosphocreatine to adenosine triphosphate ratio and impaired cardiac ΔG~ATP). Both caloric restriction and liraglutide treatment were associated with normalization of metabolic changes, alongside improvement in cardiac diastolic function. In this model of obesity, hyperpolarized 13C and 31P MRS demonstrated abnormalities in cardiac metabolism at multiple levels, including myocardial substrate selection, TCA cycle, and high‐energy phosphorus metabolism. Metabolic changes were linked with impairment of diastolic function and were reversed in concert following either caloric restriction or liraglutide treatment. With hyperpolarized 13C and 31P techniques now available for human use, the findings support a role for multi‐nuclear MRS in the development of new therapies for obesity. [ABSTRACT FROM AUTHOR]

Background: Leptin, an adipokine essential for regulating energy balance, exerts important effects on brain function, notably within the hippocampus, a region integral to learning and memory. Leptin resistance, characterized by diminished responsiveness to elevated leptin levels, disrupts hippocampal function and exacerbates both obesity and cognitive impairments. Scope: This review critically examines how leptin resistance impairs hippocampal synaptic plasticity processes, specifically affecting long-term potentiation (LTP) and long-term depression (LTD), which are crucial for cognitive performance. Findings: Recent research highlights that leptin resistance disrupts N-methyl-D-aspartate (NMDA) receptor dynamics and hippocampal structure, leading to deficits in spatial learning and memory. Additionally, high-fat diets (HFDs), which contribute to leptin resistance, further deteriorate hippocampal function. Potential therapeutic strategies, including leptin sensitizers, show promise in mitigating brain disorders associated with leptin resistance. Complementary interventions such as caloric restriction and physical exercise also enhance leptin sensitivity and offer potential benefits to alleviating cognitive impairments. Aims of the review: This review synthesizes recent findings on the molecular pathways underlying leptin resistance and its impact on synaptic transmission and plasticity in the hippocampus. By identifying potential therapeutic targets, this work aims to provide an integrated approach for addressing cognitive deficits in obesity, ultimately improving the quality of life for affected individuals. [ABSTRACT FROM AUTHOR]

Background and Purpose: Obesity is a complex metabolic disorder characterized by an imbalance in energy hemostasis and abnormal increases of adipose tissue. Obesity is directly related to cardiovascular risk factors, including dyslipidemia, type 2 diabetes, and hypertension. Body weight loss can significantly reduce the risk of developing obesity-related complications. However, long-term maintanance of weight loss is difficult. This study aimed at comparing the effect of diet along with liraglutide drug injection and exercise training on weight loss, body composition, weight loss and maintenance in obese women. Material and Methods: For this purepose, 234 women with BMI>30 kg/m² and average age of 34±9 years old were divided into four groups: diet (n=75), exercise+diet (n=48), liraglutide+diet (n=56), and liraglutide+exercise+diet (n=55). Body composition and anthropometric variables were measured before and after 12 weeks intervention. All groups had a low-calorie diet (caloric deficit of 500-600 kcal daily). Two groups of exercise training with and without liraglutide performed combined exercises (180-220 minutes of aerobic training plus two days of resistance training per week). In two liraglutide groups, the medicine was administered by subcutaneous injection. The initial dose was 0.6 mg daily and increased to 1.2 mg in the second week, and 1.8 mg in the third week until the twelfth week. Body composition variables were measured before, and after 12 weeks period. The subjects' weight was measured one year after the start of the intervention. Data were analyzed using variance analysis with repeated measurements at a significant level (P < 0.05) with SPSS26 statistical software. Results: Within-group comparisons showed that there is a significant difference between the pre- and post-test measurements for all variables (p<0.01). Moreover, between-group comparisons revealed significant differences among the study groups for weight, BMI, waist circumference and WHtR (p<0.05). The follow-up test showed more weight loss in the groups of liraglutide (-6.7 kg), liraglutide and exercise training (8.7 kg) and exercise training (-6.5 kg) compared to diet (-3.8 kg). Weight measurement after one year showed that the trend of weight loss continued in the exercise training (-4.13 kg), liraglutide +exercise training (-2.22 kg) and diet (-2.73 kg) groups, whereas, in the liraglutide group there was a weight maintenance with no significant changes. Waist circumference decreased by 8 and 7 cm in the exercise training+liraglutide, and exercise training groups, respectively, and by 5 cm in the diet+liraglutide groups. Conclusion: Physical activity, diet and liraglutide injection led to weight loss and reductions in body mass index. The combination of modified lifestyle and drug injection enhanced long-term maintanance ofweight loss. [ABSTRACT FROM AUTHOR]

Caloric restriction mimetics mimic the beneficial effects of dietary restriction approaches, such as caloric restriction approaches, without limiting the dietary intake. Chlorogenic acid (CGA) acts as a caloric restriction mimetic; however, its neuroprotective mechanisms remain ambiguous. Therefore, in this study, we aimed to elucidate the neuroprotective effects of CGA on SH‐SY5Y cells treated with amyloid‐beta (Aβ)1‐42. Aβ1‐42 (1.25 μM) induced oxidative stress by significantly increasing the pro‐oxidant levels and decreasing the antioxidant levels in the cells. Additionally, it decreased the Na+/K+‐ATPase and Ca2+‐ATPase ion transporter activities and enhanced the acetylcholinesterase activity. However, CGA (100 μM) reversed these Aβ1‐42‐induced changes in SH‐SY5Y cells. Overall, CGA exerted neuroprotective effects against Aβ1‐42‐induced oxidative stress and impaired ion transporter and acetylcholinesterase activities, serving as a promising therapeutic candidate for neurodegenerative diseases, such as Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Maternal undernutrition is the most common cause of fetal growth restriction (FGR) worldwide. FGR increases morbidity and mortality during infancy, as well as contributes to adult-onset diseases including obesity and type 2 diabetes. The role of the maternal or offspring microbiome in growth outcomes following FGR is not well understood. Methods: FGR was induced by 30% maternal calorie restriction (CR) during the second half of gestation in C57BL/6 mice. Pup weights were obtained on day of life 0, 1, and 7 and ages 3, 4 and 16 weeks. Fecal pellets were collected from pregnant dams at gestational day 18.5 and from offspring at ages 3 and 4 weeks of age. Bacterial genomic DNA was used for amplification of the V4 variable region of the 16S rRNA gene. Multivariable associations between maternal CR and taxonomic abundance were assessed using the MaAsLin2 package. Associations between microbial taxa and offspring outcomes were performed using distance-based redundancy analysis and Pearson correlations. Results: FGR pups weighed about 20% less than controls. Beta but not alpha diversity differed between control and CR dam microbiomes. CR dams had lower relative abundance of Turicibacter, Flexispira, and Rikenella, and increased relative abundance of Parabacteroides and Prevotella. Control and FGR offspring microbiota differed by beta diversity at ages 3 and 4 weeks. At 3 weeks, FGR offspring had decreased relative abundance of Akkermansia and Sutterella and increased relative abundance of Anaerostipes and Paraprevotella. At 4 weeks, FGR animals had decreased relative abundance of Allobaculum, Sutterella, Bifidobacterium, and Lactobacillus, among others, and increased relative abundance of Turcibacter, Dorea, and Roseburia. Maternal Helicobacter abundance was positively associated with offspring weight. Akkermansia abundance at age 3 and 4 weeks was negatively associated with adult weight. Conclusions: We demonstrate gut microbial dysbiosis in pregnant dams and offspring at two timepoints following maternal calorie restriction. Additional research is needed to test for functional roles of the microbiome in offspring growth outcomes. [ABSTRACT FROM AUTHOR]

Background: The use of pre-operative very low-calorie diets (VLCD) is established within bariatric and gallbladder surgery. However, their use in patients with high BMI and hepatic steatosis (HS) requiring upper abdominal procedures is unclear. This review aims to assess the safety, adherence, and outcomes of a pre-operative VLCD prior to non-bariatric elective surgery. Methods: A systematic search on PubMed MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL and AMED was performed to identify the included studies. Studies were included, if they administered a VLCD to patients undergoing non-bariatric elective surgery and reported on outcomes. Results: Eight studies were included in this review and all administered a VLCD through either dietician led diet plans or meal replacement shakes. The adherence to the VLCD was heterogeneously measured but was excellent overall with a good safety profile. The VLCD was able to significantly reduce HS and resulted in a less technically difficult operation with reduced intra-operative blood loss. There was no significant impact on intraoperative or early post-operative outcomes. Conclusion: This review highlights that a VLCD can be administered safely during the pre-operative period and overall adherence is excellent, however heterogeneously measured. There was an overall positive impact on reducing hepatic steatosis, operative difficulty and intraoperative blood loss, however no significant impact on overall morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Considering differences in body composition and inflammatory status between sexes, as well as recent recommendations advocating for personalized dietary approaches, this study aimed to explore how sex influences weight loss, changes in body composition, and inflammatory status in subjects with grade I and II obesity undergoing a 45-day of the Very Low-Energy Ketogenic Therapy (VLEKT). Methods: Participants (21 premenopausal females and 21 males), included in the study adhered to the 45-day of the VLEKT and underwent assessments of anthropometric parameters (weight, height, body mass index—BMI –, and waist circumference), body composition via bioelectrical impedance analysis, and inflammatory status measured by high sensitivity C-reactive protein (hs-CRP) levels at baseline and post-intervention. Results: At baseline, premenopausal females and males did not differ in BMI (p = 0.100) and hs-CRP levels (p = 0.948). Males demonstrated overall larger benefits than premenopausal females from the VLEKT in terms of weight loss (Δ% = − 11.63 ± 1.76 vs − 8.95 ± 1.65 kg, p < 0.001), fat mass (Δ% = − 30.84 ± 12.00 vs -21.36 ± 4.65 kg, p = 0.002), and hs-CRP levels (Δ% = − 41.42 ± 21.35 vs − 22.38 ± 17.30 mg/L, p = 0.003). Of interest, in males phase angle values are statistically improved compared to female (Δ% = 17.11 ± 9.00 vs 7.05 ± 3.30°, p < 0.001). Conclusion: These findings underscore the importance of considering sex-specific responses in personalized obesity treatment strategies, particularly dietary interventions like VLEKTs. [ABSTRACT FROM AUTHOR]

Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes. Caloric restriction (CR) can extend the organism life- and health-span. Here, the authors show that mild caloric restriction enhances insulin sensititivy to promote beta cell health and longevity, through an optimization of energy metabolism and homeostasis pathways. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammation, demyelination, and neurodegeneration within the central nervous system. Brain plasticity, the brain's ability to adapt its structure and function, plays a crucial role in mitigating MS's impact. This paper explores the potential benefits of lifestyle changes and nutraceuticals on brain plasticity in the MS population. Lifestyle modifications, including physical activity and dietary adjustments, can enhance brain plasticity by upregulating neurotrophic factors, promoting synaptogenesis, and reducing oxidative stress. Nutraceuticals, such as vitamin D, omega-3 fatty acids, and antioxidants like alpha lipoic acid, have shown promise in supporting brain health through anti-inflammatory and neuroprotective mechanisms. Regular physical activity has been linked to increased levels of brain-derived neurotrophic factor and improved cognitive function. Dietary interventions, including caloric restriction and the intake of polyphenols, can also positively influence brain plasticity. Integrating these lifestyle changes and nutraceuticals into the management of MS can provide a complementary approach to traditional therapies, potentially improving neurological outcomes and enhancing the quality of life for the MS population. [ABSTRACT FROM AUTHOR]

Aging, an inevitable physiological process leading to a progressive decline in bodily functions, has been an abundantly researched domain with studies attempting to slow it down and reduce its debilitating effects. Investigations into the cellular and molecular pathways associated with aging have allowed the formulation of therapeutic strategies. Of these, caloric restriction (CR) has been implicated for its role in promoting healthy aging by modulating key molecular targets like Insulin/IGF-1, mTOR, and sirtuins. However, CR requires dedication and commitment to a strict regimen which poses a difficulty in maintaining consistency. To maneuver around cumbersome diets, Caloric Restriction Mimetics (CRMs) have emerged as promising alternatives by mimicking the beneficial effects of CR. This review elucidates the molecular foundations enabling CRMs like rapamycin, metformin, resveratrol, spermidine, and many more to function as suitable anti-aging molecules. Moreover, it explores clinical trials (retrieved from the clinicaltrials.gov database) aimed at demonstrating the efficacy of CRMs as effective candidates against age-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. [ABSTRACT FROM AUTHOR]

AbstractContext:Objective:Results:Conclusions: Energy homeostasis is a primary factor for the survival of mammals. Many tissues and organs, among which is the liver, keep this homeostasis in varied circumstances, including caloric restriction (CR) and physical activity.This study investigated glucose metabolism using the following groups of eight-week-old male Swiss mice: CS, sedentary and fed freely; RS, sedentary and RT, trained, both under 30% CR (n = 20–23 per group).Organs and fat depots of groups RS and RT were similar to CS, although body weight was lower. CR did not impair training performance nor affected systemic or hepatic glucose metabolism. Training combined with CR (group RT) improved in vivo glucose tolerance and did not affect liver gluconeogenesis.The mice tolerated the prolonged moderate CR without impairment of their well-being, glucose homeostasis, and resistance training performance. But the higher liver gluconeogenic efficiency previously demonstrated using this training protocol in mice was not evidenced under CR. [ABSTRACT FROM AUTHOR]

Calorie restriction increases lifespan. Among the tissue-specific protective effects of calorie restriction, the impact on the gastrointestinal tract remains unclear. We report increased numbers of chromogranin A-positive (+), including orexigenic ghrelin+ cells, in the stomach of calorie-restricted mice. This effect was accompanied by increased Notch target Hes1 and Notch ligand Jag1 and was reversed by blocking Notch with DAPT, a gamma-secretase inhibitor. Primary cultures and genetically modified reporter mice show that increased endocrine cell abundance is due to altered Lgr5+ stem and Neurog3+ endocrine progenitor cell proliferation. Different from the intestine, calorie restriction decreased gastric Lgr5+ stem cells, while increasing a FOXO1/Neurog3+ subpopulation of endocrine progenitors in a Notch-dependent manner. Further, activation of FOXO1 was sufficient to promote endocrine cell differentiation independent of Notch. The Notch inhibitor PF- 03084014 or ghrelin receptor antagonist GHRP-6 reversed the phenotypic effects of calorie restriction in mice. Tirzepatide additionally expanded ghrelin+ cells in mice. In summary, calorie restriction promotes Notch-dependent, FOXO1-regulated gastric endocrine cell differentiation. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to evaluate the effectiveness of the combined use of empagliflozin (EMPA) and topiramate (TPM) versus a placebo in overweight/obese individuals without diabetes on a calorie-restricted diet. Methods: In this study, 44 non-diabetic and overweight/obese subjects who were on a calorie restricted diet were randomly assigned into 2 groups: (1) Participants received a 10 mg EMPA tablet daily plus TPM tablet (at the 1st week 25 mg once a day and from the second week 25 mg twice a day); (2) Participants received an empagliflozin placebo (daily) plus a topiramate placebo (as mentioned for topiramate tablet in group 1), for 12 weeks. At baseline and weeks 4, 8, 12, weight, height, body mass index (BMI), waist circumference (WC), and body composition were evaluated. Before and after the intervention, blood pressure, C reactive protein, and glucose and lipid profile parameters were measured. Results: The EMPA/TPM group, compared to placebo, had a greater percent change of weight at week 12 (− 8.92 ± 1.80 vs. − 4.93 ± 1.17). The intervention group had a greater percent change of fat mass and fat percent at week 12 (P < 0.05). However, there was no difference in the percent of change in fat-free percent between the two groups at week 12 (P = 0.577). Within-group analysis found a significant reduction in SBP, DBP, FBS, insulin, HOMA-IR, TC, LDL, HDL, TG, and CRP in both groups (P < 0.05). At week 12, no statistically significant difference was observed between the two groups in any of mentioned variables (P > 0.05). Conclusion: In non-diabetic overweight/obese individuals, the combination of EMPA/TPM and calorie restriction led to a notable decrease in body weight and was generally well-tolerated. Further research is required to evaluate the potential advantages of utilizing this combination for sustained weight management in the long run. Level I : Randomized clinical trial. [ABSTRACT FROM AUTHOR]

There is a pressing need to develop new strategies for enhancing health in the elderly and preventing the rise in age-related diseases. Calorie restriction without malnutrition (CR) stands among the different antiaging interventions. Lifelong CR leads to increased expression and activity of plasma membrane CYB5R3, and male mice overexpressing CYB5R3 exhibit some beneficial adaptations that are also seen with CR. However, the mechanisms involved in both interventions could be independent since key aspects of energy metabolism and tissue lipid profile do not coincide, and many of the changes induced by CR in mitochondrial abundance and dynamics in the liver and skeletal muscle could be counteracted by CYB5R3 overexpression. In this study, we sought to elucidate the impact of CR on key markers of metabolic status, mitochondrial function, and pro-oxidant/antioxidant balance in transgenic (TG) female mice overexpressing CYB5R3 compared to their WT littermates. In females fed ad libitum , CYB5R3 overexpression decreased fat mass, led to a preferred utilization of fatty acids as an energy source, upregulated key antioxidant enzymes, and boosted respiration both in skeletal muscle and liver mitochondria, supporting that CYB5R3 overexpression is phenotypic closer to CR in females than in males. Whereas some markers of mitochondrial biogenesis and dynamics were found decreased in TG females on CR, as also found for the levels of Estrogen Receptor α, mitochondrial abundance and activity were maintained both in skeletal muscle and in liver. Our results reveal overlapping metabolic adaptations resulting from the overexpression of CYB5R3 and CR in females, but a specific crosstalk occurs when both interventions are combined, differing from the adaptations observed in TG males. [Display omitted] • CYB5R3 overexpression reduces fat mass, enhances mitochondrial respiration, and boosts antioxidant protection in female mice. • There is a preferred utilization of fatty acids as an energy source in females overexpressing CYB5R3. • CYB5R3 overexpression is phenotypic closer to calorie restriction in females than in males. • CYB5R3 overexpression plus CR maintain mitochondrial abundance and activity in skeletal muscle and liver of female mice. • Calorie restriction and CYB5R3 overexpression crosstalk exhibits sexual dimorphism. [ABSTRACT FROM AUTHOR]

Several recent studies have attempted to understand how fasting has benefits for body health, especially the nervous system. To evaluate the impact of intermittent fasting on body weight, brain neurotransmitters, brain oxidative stress, and brain-derived neurotrophic factor (BDNF) in several areas of the brain, this study was conducted in rats. Thirty male Wistar rats were randomly divided into two groups. Group 1 (15 rats) served as the control and group 2 (15 rats) underwent intermittent fasting (IF; 24 h) for 1, 7, or 15 days. The findings demonstrated that intermittent fasting significantly reduced body weight. In this sense, brain monoamines and amino acids, namely dopamine, glutamate, aspartate, and oxidative stress markers (malondialdehyde and nitric oxide), decreased significantly after 1 day of IF. However, norepinephrine, serotonin, gamma-amino butyric acid, and glycine increased significantly. Additionally, glutathione levels were markedly elevated in IF. Surprisingly, the neuromodulatory effect of intermittent fasting fluctuates depending on the IF period. To support this fluctuation, BDNF levels increased after 1 day in the hippocampus and decreased after 15 days of intermittent fasting in all areas of the brain tested. In conclusion, our results show that intermittent fasting has beneficial influences on the brain; however, prolonged intermittent fasting can also induce some unfavorable physiological outcomes that prevent optimal neurological function. [ABSTRACT FROM AUTHOR]

This study investigates failure mechanisms in a typical thermal barrier coating (TBC) system comprising an EB-PVD columnar top coat, an aluminide bond coat, and a Ni-based single crystal superalloy substrate, simulating gas turbine operating conditions using a burner rig. TBC degradation, initiated by interfacial defects from the LASAT method, was studied during thermal gradient cycling under fast and slow cooling. In-situ optical and infrared imaging, along with ex-situ SEM cross-sectional analysis, monitored failure mechanisms. The Laser Shock for Damage Monitoring (LASDAM) technique provided insights into gradient and cooling rate impacts on columnar TBC damage. Results showed significant effects of cooling rate on delamination and localized failure at blister sites, with LASDAM revealing significant overheating at damage sites. Analysis included full-field temperature and damage assessment, emphasizing blister-driven delamination under severe thermal gradients. Discussion focused on elastic stored energy effects, noting that fast cooling induced transient conditions where reversed temperature gradients increased damage, limiting TBC lifespan. • LASDAM demonstrates simplicity and effectiveness for burner rig conditions. • Multiple points within a given specimen are analyzed under different conditions. • Blister formation induces overheating in gradients configuration. • The damage rate is directly influenced by both cooling rate and thermal gradient. • The local maximum temperature is also considered in our study. [ABSTRACT FROM AUTHOR]

Irisin, a novel adipomyokine, has been proposed to be a therapeutic agent against obesity‐related metabolic disease. Royal Jelly (RJ) and tocotrienol‐rich fraction (TRF) are suggested to promote obesity and its related problems through potential mutual mechanistic pathways. This investigation intended to evaluate the glycemic and inflammation‐promoting effects of RJ, TRF, and their combinations to evaluate their synergic effects through irisin action in obese rats induced by a high‐fat diet (HFD) that underwent a calorie restriction diet (CRD). Fifty HFD‐fed obese rats received the following interventions: RJ, TRF, or RJ + TRF in combination with a CRD for eight consecutive weeks. After the investigation, body weight, fasting blood sugar (FBS), irisin, insulin, C‐reactive protein (CRP), interleukin‐6 (IL‐6), interleukin‐1 beta (IL‐1β), leptin, adiponectin, and insulin resistance (IR) were assessed. After 8 weeks of treatment, significant weight reduction was noticed in rats that received RJ and RJ + TRF related to the CRD rats (p <.001), although this reduction was not considerable in TRF‐treated rats. RJ and RJ + TRF supplementation markedly elevated irisin concentrations in CRD rats (p <.05), but TRF did not. Glycemic indices, inflammatory indices including IL‐1β and CRP levels, and leptin concentrations were significantly decreased after RJ, TRF, and their combinations were added to CRD (p <.05). According to the mediational analysis results, irisin mediated the promoting effects of RJ on glycemic hemostasis. Based on the results of this investigation, RJ and TRF are novel nutrients that have the potential to improve obesity‐related disorders. This research suggests that RJ exerts its beneficial glycemic regulatory effects through irisin. [ABSTRACT FROM AUTHOR]

Background: The main objective of the work was the analysis and description of data on body composition and resting energy expenditure (REE) values of selected groups of patients with obesity whose REE measurement results using indirect calorimetry reached a level below 95% of the predicted REE calculated using the Harris–Benedict (H–B) equation. The sub-goals were to describe the dependence of body composition on the size of the REE and to find out if the deviations between the number of the total measured REE and the REE calculated using H–B in the adapted group (patients with altered REE values, lower than expected caused by long caloric restriction) are significant. Methods: For the research, 71 (39 women and 32 men) patients treated in obesitology were selected. Patients underwent the measurement of resting metabolism using indirect calorimetry (IC) and body composition measurement on the bioimpedance device and, at the same time, the value of resting metabolism was calculated for everyone using the H–B equation. The whole group was divided into five groups according to the deviation of the measurement using IC and the calculation of the H–B equation. Results: In the total set of examined individuals, there were 32.4% with a reduced REE value compared to the REE calculation according to the H–B equation, which corresponds to 23 individuals. In the adapted group, the average measured REE was 2242 ± 616 kcal compared to the H–B calculation of 2638 ± 713 kcal. Statistically, these results were not significant, but a high case-to-case variation was found. The highest deviation from the H–B predictive calculation was −42% and +43% in the whole research group. The amount of muscle tissue in the adapted group averaged 44.3 ± 11.9 kg and the amount of fat-free mass (FFM) 77.9 ± 20.1 kg. When statistically testing the dependence of REE on FFM and muscle tissue in the adapted group, a strong correlation was found. Conclusions: The H–B equation alone is not suitable for setting a suitable diet therapy for an individual with obesity. In order to select and characterize a group of adapted individuals, it will be necessary to use other methods or a larger research sample, and preferably examine and divide patients with specific comorbidities or include their health status. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain aging in mammals is characterized by morphological and functional changes in neural cells. This process, although physiological, leads to progressive cerebral tissue volume loss and functional decline, including memory loss motor neuron deficits and behavioral disorders. It is generally accepted that aging is associated with a shift in the proportion between the functional cell (neuron) and support cells (astrocytes) in favor of the latter, which also appear different from those of healthy and young brain tissue. Also, dysfunctional autophagy contributes to altering brain homeostasis. This review summarizes and updates the most recent knowledge about brain aging through a comparative approach, where similarities and differences in some mammalian species are considered. Brain aging in mammals is characterized by morphological and functional changes in neural cells. Macroscopically, this process, leading to progressive cerebral volume loss and functional decline, includes memory and motor neuron deficits, as well as behavioral disorders. Morphologically, brain aging is associated with aged neurons and astrocytes, appearing enlarged and flattened, and expressing enhanced pH-dependent β-galactosidase activity. Multiple mechanisms are considered hallmarks of cellular senescence in vitro, including cell cycle arrest, increased lysosomal activity, telomere shortening, oxidative stress, and DNA damage. The most common markers for senescence identification were identified in (i) proteins implicated in cell cycle arrest, such as p16, p21, and p53, (ii) increased lysosomal mass, and (iii) increased reactive oxygen species (ROS) and senescence-associated secretory phenotype (SASP) expression. Finally, dysfunctional autophagy, a process occurring during aging, contributes to altering brain homeostasis. The brains of mammals can be studied at cellular and subcellular levels to elucidate the mechanisms on the basis of age-related and degenerative disorders. The aim of this review is to summarize and update the most recent knowledge about brain aging through a comparative approach, where similarities and differences in some mammalian species are considered. [ABSTRACT FROM AUTHOR]

The gut microbiome may be related to the prevalence of overweight and obesity, but high interindividual variability of the human microbiome complicates our understanding. Obesity often occurs concomitantly with micronutrient deficiencies that impair energy metabolism. Microbiota composition is affected by diet. Host–microbiota interactions are bidirectional. We propose three pathways whereby these interactions may modulate the gut microbiome and obesity: (1) ingested compounds or derivatives affecting small intestinal transit, endogenous secretions, digestion, absorption, microbiome balance, and gut barrier function directly affect host metabolism; (2) substrate availability affecting colonic microbial composition and contact with the gut barrier; and (3) microbial end products affecting host metabolism. The quantity/concentration, duration, and/or frequency (circadian rhythm) of changes in these pathways can alter the gut microbiome, disrupt the gut barrier, alter host immunity, and increase the risk of and progression to overweight and obesity. Host‐specific characteristics (e.g., genetic variations) may further affect individual sensitivity and/or resilience to diet‐ and microbiome‐associated perturbations in the colonic environment. In this narrative review, the effects of selected interventions, including fecal microbiota transplantation, dietary calorie restriction, dietary fibers and prebiotics, probiotics and synbiotics, vitamins, minerals, and fatty acids, on the gut microbiome, body weight, and/or adiposity are summarized to help identify mechanisms of action and research opportunities. [ABSTRACT FROM AUTHOR]

Introduction: Although behavioural interventions have been found to help control type 2 diabetes (T2D), it is important to understand how the delivery context can influence implementation and outcomes. The NHS committed to testing a low‐calorie diet (LCD) programme designed to support people living with excess weight and T2D to lose weight and improve diabetes outcomes. Understanding what influenced implementation during the programme pilot is important in optimising rollout. This study explored the transferability of the NHS LCD Programme prior to wider adoption. Methods: Twenty‐five interviews were undertaken with stakeholders involved in implementing the LCD programme in pilot sites (health service leads, referring health professionals and programme deliverers). Interviews with programme participants (people living with T2D) were undertaken within a larger programme of work, exploring what worked, for whom and why, which is reported separately. The conceptual Population–Intervention–Environment–Transfer Model of Transferability (PIET‐T) guided study design and data collection. Constructs of the model were also used as a deductive coding frame during data analysis. Key themes were identified which informed recommendations to optimise programme transfer. Results: Population: Referral strategies in some areas lacked consideration of population characteristics. Many believed that offering a choice of delivery model would promote acceptability and accessibility of the eligible population. Intervention: Overall, stakeholders had confidence in the LCD programme due to the robust evidence base along with anecdotal evidence, but some felt the complex referral process hindered engagement from GP practices. Environment: Stakeholders described barriers to accessing the programme, including language and learning difficulties. Transferability: Multidisciplinary working and effective communication supported successful implementation. Conclusion: Referral strategies to reach underrepresented groups should be considered during programme transfer, along with timely data from service providers on access and programme benefits. A choice of delivery models may optimise uptake. Knowledge sharing between sites on good working practices is encouraged, including increasing engagement with key stakeholders. [ABSTRACT FROM AUTHOR]

In recent times, dietary restriction (DR) has received considerable attention for its promising effects on metabolism and longevity. Previous studies on DR have mainly focused on the health benefits produced by different restriction patterns, whereas comprehensive reviews of the role of gut microbiota during DR are limited. In this review, we discuss the effects of caloric restriction, fasting, protein restriction, and amino acid restriction from a microbiome perspective. Furthermore, the underlying mechanisms by which DR affects metabolic health by regulating intestinal homeostasis are summarized. Specifically, we reviewed the impacts of different DRs on specific gut microbiota. Additionally, we put forward the limitations of the current research and suggest the development of personalized microbes-directed DR for different populations and corresponding next-generation sequencing technologies for accurate microbiological analysis. DR effectively modulates the composition of the gut microbiota and microbial metabolites. In particular, DR markedly affects the rhythmic oscillation of microbes which may be related to the circadian clock system. Moreover, increasing evidence supports that DR profoundly improves metabolic syndrome, inflammatory bowel disease, and cognitive impairment. To summarize, DR may be an effective and executable dietary manipulation strategy for maintaining metabolic health, however, further investigation is needed to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of concentrated topinambur extract (CTE) on low-density lipoprotein cholesterol (LDLC) and high-density lipoprotein cholesterol (HDLC) levels in individuals suffering from atherogenic dyslipidemia. The control group adhered to a standard low-calorie diet throughout the treatment period. Meanwhile, the main group followed a modified version of the same diet, incorporating 100 mL of CTE. Our research into the use of CTE in treating dyslipidemia yielded valuable data. The findings indicate that this treatment option is well-tolerated and comparable to standard diet therapy in terms of weight loss. Moreover, we observed a positive impact on blood lipid profile. There was a statistically significant reduction in LDLC levels, while HDLC remained unchanged. This suggests a targeted effect on cholesterol levels without compromising overall cardiovascular health. Furthermore, there were no changes in liver function markers such as aspartate transaminase (AST), alanine aminotransferase (ALT), creatinine, or uric acid among patients receiving CTE. [ABSTRACT FROM AUTHOR]

Aim: To assess the impact of intermittent fasting, with or without probiotic supplementation, versus a calorie‐restricted diet on anthropometric measures, metabolic status and gonadal variables in women with polycystic ovary syndrome (PCOS). Methods: This is a randomized, placebo‐controlled, parallel‐arm clinical trial. The effects of the 14:10 early time‐restricted eating (eTRE) strategy alone or combined with probiotics, on obese women with PCOS, were investigated. Participants were divided into three groups: eTRE plus probiotics (n = 30), eTRE plus placebo (n = 30) and a control group following a standard three‐meal‐per‐day diet with daily calorie restriction (DCR) (n = 30). Over 8 weeks, various anthropometric, metabolic, menstrual and gonadal variables were assessed. Results: A total of 90 individuals were included in the study, with a mean body weight of 81.4 kg, and a mean age of 30 years. Mean (standard deviation) weight loss was not different between the groups at week 8 (TRE + probiotic: −2.2 [1.6] kg vs. TRE + placebo: −2.9 [2.7] kg vs. DCR: −2.5 [1.7] kg). Results revealed that, while all three regimes led to reductions in body weight, body mass index, vascular risk indicators, hirsutism and acne scores, there were no statistically significant differences between the eTRE groups and the control group in terms of weight loss, or improvements in metabolic, menstrual and gonadal variables (P >.05). Additionally, combining probiotics with eTRE did not benefit hormonal and cardiometabolic factors (P >.05). Conclusions: The eTRE alone or eTRE plus probiotics did not result in significantly greater weight loss or improvements in metabolic, menstrual and gonadal variables compared with the standard three‐meal DCR diet. [ABSTRACT FROM AUTHOR]

Long-term fasting (LTF) and caloric restriction (CR) have garnered increasing interest as interventions that may confer numerous health benefits, including improved metabolic health, enhanced cardiovascular function, neuroprotection, and extended longevity. The potential to influence physiological processes such as insulin sensitivity, lipid metabolism, inflammation, oxidative stress, and cellular repair mechanisms makes these interventions promising avenues for both disease prevention and health optimization. This systematic review examines the body of research surrounding LTF and CR, their physiological impacts, the molecular mechanisms driving these changes, and the challenges and risks associated with their long-term application. We also explore future research directions and possible therapeutic applications in the context of aging and age-related diseases. [ABSTRACT FROM AUTHOR]

The article discusses the establishment of the National Institute on Aging (NIA) in 1974 and its significant contributions to aging research over the past 50 years. It highlights the advocacy efforts that led to the founding of NIA, emphasizing the importance of interdisciplinary research in understanding aging across the life course. The NIA's work includes funding genetic, biological, clinical, behavioral, social, and economic research on aging, as well as supporting the development of research scientists and disseminating research findings to various audiences. The collaboration between the Gerontological Society of America (GSA) and NIA has been instrumental in advancing research on aging and improving health outcomes for older adults. [Extracted from the article]