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Aging is identified as a significant risk factor for severe coronavirus disease-2019 (COVID-19), often resulting in profound lung damage and mortality. Yet, the biological relationship between aging, aging-related comorbidities, and COVID-19 remains incompletely understood. This study aimed to elucidate the age-related COVID19 pathogenesis using an Hutchinson-Gilford progeria syndrome (HGPS) mouse model, a premature aging disease model, with humanized ACE2 receptors. Pathological features were compared between young, aged, and HGPS hACE2 mice following SARS-CoV-2 challenge. We demonstrated that young mice display robust interferon response and antiviral activity, whereas this response is attenuated in aged mice. Viral infection in aged mice results in severe respiratory tract hemorrhage, likely contributing a higher mortality rate. In contrast, HGPS hACE2 mice exhibit milder disease manifestations characterized by minor immune cell infiltration and dysregulation of multiple metabolic processes. Comprehensive transcriptome analysis revealed both shared and unique gene expression dynamics among different mouse groups. Collectively, our studies evaluated the impact of SARS-CoV-2 infection on progeroid syndromes using a HGPS hACE2 mouse model, which holds promise as a useful tool for investigating COVID-19 pathogenesis in individuals with premature aging. [ABSTRACT FROM AUTHOR]

Fanconi anemia, a rare disorder with an incidence of 1 in 300,000, is caused by mutations in FANC genes, which affect the repair of DNA interstrand crosslinks. The disease is characterized by congenital malformations, bone marrow failure within the first decade of life, and recurrent squamous cell carcinomas of the oral cavity, esophagus, and anogenital regions starting around age 20. In this review, we propose that Fanconi anemia should be considered a premature-aging syndrome. Interestingly, the onset and severity of the life-limiting clinical features of Fanconi anemia can be influenced by lifestyle choices, such as a healthy diet and physical activity. These factors shape the epigenetic status of at-risk cell types and enhance the competence of the immune system through nutritional signaling. Fanconi anemia may serve as a model for understanding the aging process in the general population, addressing research gaps in its clinical presentation and suggesting prevention strategies. Additionally, we will discuss how the balance of genetic and environmental risk factors—affecting both cancer onset and the speed of aging—is interlinked with signal transduction by dietary molecules. The underlying nutrigenomic principles will offer guidance for healthy aging in individuals with Fanconi anemia as well as for the general population. [ABSTRACT FROM AUTHOR]

As the limits of fetal viability have increased over the past 30 years, there has been a growing body of evidence supporting the idea that chronic disease should be taken into greater consideration in addition to survival after preterm birth. Accumulating evidence also suggests there is early onset of biologic aging after preterm birth. Similarly, chronic kidney disease (CKD) is also associated with a phenotype of advanced biologic age which exceeds chronologic age. Yet, significant knowledge gaps remain regarding the link between premature biologic age after preterm birth and kidney disease. This review summarizes the four broad pillars of aging, the evidence of premature aging following preterm birth, and in the setting of CKD. The aim is to provide additional plausible biologic mechanisms to explore the link between preterm birth and CKD. There is a need for more research to further elucidate the biologic mechanisms of the premature aging paradigm and kidney disease after preterm birth. Given the emerging research on therapies for premature aging, this paradigm could create pathways for prevention of advanced CKD. [ABSTRACT FROM AUTHOR]

Abstract Aging is identified as a significant risk factor for severe coronavirus disease-2019 (COVID-19), often resulting in profound lung damage and mortality. Yet, the biological relationship between aging, aging-related comorbidities, and COVID-19 remains incompletely understood. This study aimed to elucidate the age-related COVID19 pathogenesis using an Hutchinson-Gilford progeria syndrome (HGPS) mouse model, a premature aging disease model, with humanized ACE2 receptors. Pathological features were compared between young, aged, and HGPS hACE2 mice following SARS-CoV-2 challenge. We demonstrated that young mice display robust interferon response and antiviral activity, whereas this response is attenuated in aged mice. Viral infection in aged mice results in severe respiratory tract hemorrhage, likely contributing a higher mortality rate. In contrast, HGPS hACE2 mice exhibit milder disease manifestations characterized by minor immune cell infiltration and dysregulation of multiple metabolic processes. Comprehensive transcriptome analysis revealed both shared and unique gene expression dynamics among different mouse groups. Collectively, our studies evaluated the impact of SARS-CoV-2 infection on progeroid syndromes using a HGPS hACE2 mouse model, which holds promise as a useful tool for investigating COVID-19 pathogenesis in individuals with premature aging.

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The extracellular matrix (ECM), the main component of the extracellular space, mediates signal transmission between cells and controls their key functions: proliferation, differentiation, and migration. The relevance of studying ECM research is stipulated to the wide range of its biological properties, which can be used in regenerative medicine and bioengineering. Particular interest is presented the study of the regulatory activity on various cellular functions of cell-derived decellularized ECM (dECM). In this work, we tested the hypothesis about the modulating effect of dECM deposited by young MSC from Wharton's jelly on the aging phenotype of endometrial human multipotent mesenchymal stromal cells (eMSCs), which the cells acquired in response to oxidative stress. This aspect of ECM functioning in the context of eMSCs has not yet been considered. A comparative study of H2O2-induced senescence of eMSCs cultured on dECM and on plastic for a long time showed a significant change in the hallmarks of aging in the cell population maintained on dECM. Taken together, the results obtained suggest that the dECM is able to partially reverse (retard) premature senescence of eMSCs in response to oxidative stress, as well as expanding the understanding of the ECM as a regulator of the functional activity of cells. [ABSTRACT FROM AUTHOR]

BACKGROUND: Difficulty performing basic daily activities such as bathing and dressing (functional impairment) affects more than 15% of middle-aged people, and this proportion is increasing. Little is known about the experiences and needs of individuals who develop functional impairment in middle age. OBJECTIVE: To examine the experiences and needs of adults who developed functional impairment in middle age. DESIGN: Qualitative study using semi-structured interviews. PARTICIPANTS: Forty patients aged 50-64 years who developed functional impairment in middle age, recruited from four primary care clinics in San Francisco. APPROACH: Interviews included open-ended questions about participants daily life, ability to perform activities of daily living (ADLs), and needs related to functional impairment. We analyzed interviews using qualitative thematic analysis. KEY RESULTS: Interviews revealed several themes related to the psychosocial and physical impacts of developing functional impairment in middle age. Participants noted that losses associated with functional impairment, such as loss of independence, control, and social roles, caused conflict in their sense of identity. To cope with these losses, participants used strategies including acceptance, social comparison, adjusting standards, and engaging in valued life activities. Participants reflected on the intersection of their functional impairment with the aging process, noting that their impairments seemed premature compared to the more natural aging process in older adults. In terms of physical impacts, participants described how a lack of accommodations in the built environment exacerbated their impairments. While participants used behavioral strategies to overcome these challenges, unmet needs remained, resulting in downstream physical and psychological impacts including safety risks, falls, frustration, and fear. CONCLUSIONS: Unmet psychosocial and physical needs were common among middle-aged adults with functional impairment and led to negative downstream effects. Eliciting and addressing unmet needs may help mitigate downstream health consequences for this growing population, optimizing function and quality of life.

According to current views the major hallmarks of physiological aging may be subdivided into three categories, primary causes of cellular damage (genomic instability, telomere attrition, loss of proteostasis, epigenetic alterations and compromised macroautophagy), antagonistic hallmarks that represent response to damage (deregulated nutrient sensing, cellular senescence, mitochondrial dysfunction) and integrative hallmarks that represent culprits of the phenotype (stem cell exhaustion, altered intercellular communication, chronic inflammation, dysbiosis). In contrast to physiological aging, premature aging diseases are driven by one or two distinct primary causes of aging, such as genomic instability in the case of Werner syndrome (WS), each displaying other hallmarks of aging to a variable extent. In this review we will focus on primary causes of well-investigated premature aging diseases Hutchinson-Gilford progeria syndrome (HGPS), WS, and Cockayne syndrome (CS) and for each provide an overview of reported aging hallmarks to elucidate resemblance to physiological aging on the mechanistic level and in the context of characteristic age-related diseases. Ubiquitous and tissue specific animal models of premature aging diseases will be discussed as useful tools to decipher fundamental aging- related mechanisms and develop intervention strategies to combat premature aging and age-related diseases. [ABSTRACT FROM AUTHOR]

Background: Individuals with Down syndrome (DS) experience premature aging. Whether accelerated aging involves changes in body composition parameters and is associated with early development of sarcopenia is unclear. Aims: To compare parameters of body composition and the prevalence of sarcopenia between adults with DS and the general population. Methods: Body composition was assessed by whole-body dual-energy X-ray absorptiometry (DXA). Fat mass (FMI) and skeletal mass indices (SMI) were calculated as the ratio between total body fat mass and appendicular lean mass and the square of height, respectively. Fat mass distribution was assessed by the android/gynoid fat ratio (A/G). Sarcopenia was defined according to the criteria and cut-points recommended by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Data on age- and sex-matched non-DS controls were retrieved from the 2001–2002 National Health and Nutrition Examination Survey (NHANES) population. Results: Sixty-four DS adults (mean age 37.2 ± 12.0 years, 20.3% women) were enrolled and compared with age- and sex-matched NHANES participants (n = 256), in a 1:4 ratio. FMI (7.96 ± 3.18 kg/m2 vs. 8.92 ± 4.83 kg/m2, p = 0.135), SMI (7.38 ± 1.01 kg/m2 vs. 7.46 ± 2.77 kg/m2, p = 0.825) and A/G (0.98 ± 0.17 vs. 1.01 ± 0.22, p = 0.115) were not significantly different between DS and control participants. When the sample was stratified by sex, women with DS had a higher FMI compared with their NHANES controls (10.16 ± 4.35 kg/m2 vs. 8.11 ± 4.29 kg/m2, p < 0.001), while men with DS had lower A/G ratio (1.04 ± 0.16 vs. 1.11 ± 0.22, p = 0.002). Sarcopenia was more frequent in individuals with DS than in controls (35.6% vs. 19.9%, p = 0.007). This association was stronger in men 40 years and older. Conclusions: Adults with DS have a higher prevalence of sarcopenia compared with the general population. This finding suggests that DS is associated with early muscle aging and calls for the design of interventions targeting the skeletal muscle to prevent or treat sarcopenia. [ABSTRACT FROM AUTHOR]

The animal models used in biomedical research cover virtually every human disease. RatDEGdb, a knowledge base of the differentially expressed genes (DEGs) of the rat as a model object in biomedical research is a collection of published data on gene expression in rat strains simulating arterial hypertension, age-related diseases, psychopathological conditions and other human afflictions. The current release contains information on 25,101 DEGs representing 14,320 unique rat genes that change transcription levels in 21 tissues of 10 genetic rat strains used as models of 11 human diseases based on 45 original scientific papers. RatDEGdb is novel in that, unlike any other biomedical database, it offers the manually curated annotations of DEGs in model rats with the use of independent clinical data on equal changes in the expression of homologous genes revealed in people with pathologies. The rat DEGs put in RatDEGdb were annotated with equal changes in the expression of their human homologs in affected people. In its current release, RatDEGdb contains 94,873 such annotations for 321 human genes in 836 diseases based on 959 original scientific papers found in the current PubMed. RatDEGdb may be interesting first of all to human geneticists, molecular biologists, clinical physicians, genetic advisors as well as experts in biopharmaceutics, bioinformatics and personalized genomics. RatDEGdb is publicly available at https://www.sysbio.ru/RatDEGdb.

Fanconi anemia, a rare disorder with an incidence of 1 in 300,000, is caused by mutations in FANC genes, which affect the repair of DNA interstrand crosslinks. The disease is characterized by congenital malformations, bone marrow failure within the first decade of life, and recurrent squamous cell carcinomas of the oral cavity, esophagus, and anogenital regions starting around age 20. In this review, we propose that Fanconi anemia should be considered a premature-aging syndrome. Interestingly, the onset and severity of the life-limiting clinical features of Fanconi anemia can be influenced by lifestyle choices, such as a healthy diet and physical activity. These factors shape the epigenetic status of at-risk cell types and enhance the competence of the immune system through nutritional signaling. Fanconi anemia may serve as a model for understanding the aging process in the general population, addressing research gaps in its clinical presentation and suggesting prevention strategies. Additionally, we will discuss how the balance of genetic and environmental risk factors—affecting both cancer onset and the speed of aging—is interlinked with signal transduction by dietary molecules. The underlying nutrigenomic principles will offer guidance for healthy aging in individuals with Fanconi anemia as well as for the general population.

Background and objectivesAfrican American women experience faster telomere shortening (i.e., cellular aging) compared with other racial-gender groups. Prior research demonstrates that race and gender interact to influence culturally specific norms for responding to socially-relevant stress and other stress-coping processes, which may affect healthy aging.Research design and methodsData are from African American Women's Heart & Health Study participants who consented to DNA extraction (n = 140). Superwoman Schema (SWS) was measured using 5 validated subscales: presenting strength, emotion suppression, resisting vulnerability, motivation to succeed, and obligation to help others. Racial identity was measured using 3 subscales from the Multidimensional Inventory of Black Identity: racial centrality, private regard, and public regard. Relative telomere length (rTL) was measured using DNA extracted from blood samples. Path analysis tested associations and interactions between SWS and racial identity dimensions with rTL.ResultsFor SWS, higher resistance to being vulnerable predicted longer telomeres. For racial identity, high private regard predicted longer telomeres while high public regard predicted shorter telomeres. Interactions were found between public regard and 2 SWS dimensions: among women with high public regard, emotion suppression (β = 0.20, p < .05) and motivation to succeed (β = 0.18, p < .05) were associated with longer rTL. The interaction between high centrality and emotion suppression predicted shorter rTL (β = -0.17, p < .05).Discussion and implicationsCulturally specific responses to gendered racism and racial identity, developed early in life and shaped over the life course, are important psychosocial determinants of cellular aging among African American women.

In mammals, the most remarkable T cell variations with aging are the shrinking of the naïve T cell pool and the enlargement of the memory T cell pool, which are partially caused by thymic involution. However, the mechanism underlying the relationship between T‐cell changes and aging remains unclear. In this study, we find that T‐cell‐specific Rip1 KO mice show similar age‐related T cell changes and exhibit signs of accelerated aging‐like phenotypes, including inflammation, multiple age‐related diseases, and a shorter lifespan. Mechanistically, Rip1‐deficient T cells undergo excessive apoptosis and promote chronic inflammation. Consistent with this, blocking apoptosis by co‐deletion of Fadd in Rip1‐deficient T cells significantly rescues lymphopenia, the imbalance between naïve and memory T cells, and aging‐like phenotypes, and prolongs life span in T‐cell‐specific Rip1 KO mice. These results suggest that the reduction and hyperactivation of T cells can have a significant impact on organismal health and lifespan, underscoring the importance of maintaining T cell homeostasis for healthy aging and prevention or treatment of age‐related diseases. Synopsis: T‐cell specific Rip1 KO mice show signs of accelerated aging‐like phenotypes, along with premature death. Blocking apoptosis by co‐deleting Fadd in Rip1tKO mice significantly rescues aging‐like phenotypes and prolongs shortened lifespan.Rip1tKO mice show similar age‐related T cell changes and exhibit signs of accelerated aging and a shorter lifespan.Rip1‐deficient T cells undergo excessive apoptosis, promoting chronic inflammation.Blocking necroptosis has little effect on the multimorbidity and premature aging seen in Rip1tKO mice.Blocking T cell apoptosis by co‐deleting Fadd rescues premature aging and multimorbidity in Rip1tKO mice. [ABSTRACT FROM AUTHOR]

Background: Cockayne syndrome (CS, OMIM #133540, #216400) is a rare autosomal recessive disease involving multiple systems, typically characterized by microcephaly, premature aging, growth retardation, neurosensory abnormalities, and photosensitivity. The age of onset is related to the severity of the clinical phenotype, which may lead to fatal outcomes. Methods: We report a 3‐year‐old girl who presented with photosensitivity, gait abnormalities, stunting, and microcephaly and showed atypical clinical classification due to mild clinical manifestations at an early onset age. Results: Next‐generation sequencing reveals the frameshift mutation (c.394_398del, p.Leu132Asnfs*6) and a novel microdeletion of ERCC8 (exon4del, p.Arg92fs). Conclusion: Therefore, it is still necessary to carry out next‐generation sequencing for CS patients with atypical clinical manifestations, which is essential for diagnosis and accurate genetic counseling. [ABSTRACT FROM AUTHOR]

Objective: The field of targeting cellular senescence with drug candidates to address age-related comorbidities has witnessed a notable surge of interest and research and development. This study aimed to gather valuable insights from pharmaceutical experts and healthcare practitioners regarding the potential and challenges of translating senolytic drugs for treatment of vascular aging-related disorders. Methods: This study employed a qualitative approach by conducting in-depth interviews with healthcare practitioners and pharmaceutical experts. Participants were selected through purposeful sampling. Thematic analysis was used to identify themes from the interview transcripts. Results: A total of six individuals were interviewed, with three being pharmaceutical experts and the remaining three healthcare practitioners. The significant global burden of cardiovascular diseases presents a potentially large market size that offer an opportunity for the development and marketability of novel senolytic drugs. The pharmaceutical sector demonstrates a positive inclination towards the commercialization of new senolytic drugs targeting vascular aging-related disorders. However potential important concerns have been raised, and these include increasing specificity toward senescent cells to prevent off-site targeting, thus ensuring the safety and efficacy of these drugs. In addition, novel senolytic therapy for vascular aging-related disorders may encounter competition from existing drugs that treat or manage risk factors of cardiovascular diseases. Healthcare practitioners are also in favor of recommending the novel senolytic drugs for vascular aging-related disorders but cautioned that its high cost may hinder its acceptance among patients. Besides sharing the same outcome-related concerns as with the pharmaceutical experts, healthcare practitioners anticipated a lack of awareness among the general public regarding the concept of targeting cellular senescence to delay vascular agingrelated disorders, and this knowledge gap extends to healthcare practitioner themselves as well. Conclusion: Senolytic therapy for vascular aging-related disorders holds great promise, provided that crucial concerns surrounding its outcomes and commercial hurdles are effectively addressed. [ABSTRACT FROM AUTHOR]

Introduction: Eotaxin-1/CCL11 is a pivotal chemokine crucial for eosinophil homing to the lungs of asthmatic patients. Recent studies also suggest that CCL11 is involved in the aging process, as it is upregulated in elderly, and correlated with shorter telomere length in leukocytes from asthmatic children. Despite its potential pro-aging effects, the precise contribution of CCL11 and the underlying mechanisms involved in the promotion of cellular senescence remains unclear. Therefore, the primary goal of this study was to explore the role of CCL11 on senescence development and the signaling pathways activated by this chemokine in lung fibroblasts. Methods: To investigate the targets potentially modulated by CCL11, we performed an in silico analysis using PseudoCell. We validated in vitro the activation of these targets in the human lung fibroblast cell line MRC-5 following rhCCL11 exposure. Finally, we performed differential gene expression analysis in human airway epithelial cells of asthmatic patients to assess CCL11 signaling and activation of additional senescent markers. Results: Our study revealed that eotaxin-1/CCL11 promote reactive oxygen secretion (ROS) production in lung fibroblasts, accompanied by increased activation of the DNA damage response (DDR) and p-TP53 and gH2AX. These modifications were accompanied by cellular senescence promotion and increased secretion of senescence-associated secretory phenotype inflammatory cytokines IL-6 and IL-8. Furthermore, our data show that airway epithelial lung cells from atopic asthmatic patients overexpress CCL11 along with aging markers such as CDKN2A (p16INK4a) and SERPINE1. Discussion: These findings provide new insights into the mechanisms underlying the pro-aging effects of CCL11 in the lungs of asthmatic patients. Understanding the role of CCL11 on senescence development may have important implications for the treatment of age-related lung diseases, such as asthma. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases, atherosclerosis, and strokes are the most common causes of death in patients with Hutchinson-Gilford progeria syndrome (HGPS). The LMNA variant c.1824C > T accounts for ~ 90% of HGPS cases. The detailed molecular mechanisms of Lamin A in the heart remain elusive due to the lack of appropriate in vitro models. We hypothesize that HGPS patient's induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMCs) will provide a model platform to study the cardio-pathologic mechanisms associated with HGPS. To elucidate the effects of progerin in cardiomyocytes, we first obtained skin fibroblasts (SFs) from a de-identified HGPS patient (hPGP1, proband) and both parents from the Progeria Research Foundation. Through Sanger sequencing and restriction fragment length polymorphism, with the enzyme EciI, targeting Lamin A, we characterized hPGP1-SFs as heterozygous mutants for the LMNA variant c.1824 C > T. Additionally, we performed LMNA exon 11 bisulfite sequencing to analyze the methylation status of the progeria cells. Furthermore, we reprogrammed the three SFs into iPSCs and differentiated them into iCMCs, which gained a beating on day 7. Through particle image velocimetry analysis, we found that hPGP1-iCMCs had an irregular contractile function and decreased cardiac-specific gene and protein expressions by qRT-PCR and Western blot. Our progeria-patient-derived iCMCs were found to be functionally and structurally defective when compared to normal iCMCs. This in vitro model will help in elucidating the role of Lamin A in cardiac diseases and the cardio-pathologic mechanisms associated with progeria. It provides a new platform for researchers to study novel treatment approaches for progeria-associated cardiac diseases. [ABSTRACT FROM AUTHOR]

According to current views the major hallmarks of physiological aging may be subdivided into three categories, primary causes of cellular damage (genomic instability, telomere attrition, loss of proteostasis, epigenetic alterations and compromised macroautophagy), antagonistic hallmarks that represent response to damage (deregulated nutrient sensing, cellular senescence, mitochondrial dysfunction) and integrative hallmarks that represent culprits of the phenotype (stem cell exhaustion, altered intercellular communication, chronic inflammation, dysbiosis). In contrast to physiological aging, premature aging diseases are driven by one or two distinct primary causes of aging, such as genomic instability in the case of Werner syndrome (WS), each displaying other hallmarks of aging to a variable extent. In this review we will focus on primary causes of well-investigated premature aging diseases Hutchinson-Gilford progeria syndrome (HGPS), WS, and Cockayne syndrome (CS) and for each provide an overview of reported aging hallmarks to elucidate resemblance to physiological aging on the mechanistic level and in the context of characteristic age-related diseases. Ubiquitous and tissue specific animal models of premature aging diseases will be discussed as useful tools to decipher fundamental aging-related mechanisms and develop intervention strategies to combat premature aging and age-related diseases.

Background: Women's market traders are jobs that are often exposed to free radicals, including air pollution, cigarette smoke, sun exposure and have a high workload that causes stress. Antioxidants can protect the skin from free radicals and can inhibit the process of premature aging of facial skin which are found in vegetables and fruits such as vitamins A, C, E. Objective: To determine the relationship between intake of vitamins A, C, and E with premature aging of market traders in the form of wrinkles around the face. Methods: Observational research with cross sectional method. The sampling technique is multi-stage cluster sampling. This research was conducted at Beringharjo Market with a total sample of 172 respondents with inclusion criteria namely female traders, aged 26–45 years, workers in the market area. The exclusion criteria are tourists/market visitors, women who are pregnant and breastfeeding. The research variables for intake of vitamins A, C, and E used the SQ-FFQ (Semi-Quantitative Food Frequency Questionnaire) questionnaire with the interview method. In measuring the number of wrinkles on facial skin using photoaging through facial shooting using a Sony A7R3 camera with a 24-70 lens that is analyzed by a dermatologist (skin expert). Data analysis technique using multiple logistic regression analysis. This analysis uses SPSS software version 22.0. Results: In the multiple logistic regression test, p = 0.037 (p 0.05), meaning that there is no relationship between vitamin C intake and premature aging of facial skin. And on vitamin E intake, p = 0.171 (p> 0.05) there is no relationship between vitamin E intake and premature aging of facial skin. Conclusion: Intake of vitamin A has a significant relationship with the occurrence of premature aging of the face, but vitamins C and E do not have a significant relationship with the occurrence of premature aging of the facial skin

Abstract Background Cockayne syndrome (CS, OMIM #133540, #216400) is a rare autosomal recessive disease involving multiple systems, typically characterized by microcephaly, premature aging, growth retardation, neurosensory abnormalities, and photosensitivity. The age of onset is related to the severity of the clinical phenotype, which may lead to fatal outcomes. Methods We report a 3‐year‐old girl who presented with photosensitivity, gait abnormalities, stunting, and microcephaly and showed atypical clinical classification due to mild clinical manifestations at an early onset age. Results Next‐generation sequencing reveals the frameshift mutation (c.394_398del, p.Leu132Asnfs*6) and a novel microdeletion of ERCC8 (exon4del, p.Arg92fs). Conclusion Therefore, it is still necessary to carry out next‐generation sequencing for CS patients with atypical clinical manifestations, which is essential for diagnosis and accurate genetic counseling.

Aging of the central nervous system (CNS) leads to motoric and cognitive decline and increases the probability for neurodegenerative disease development. Astrocytes fulfill central homeostatic functions in the CNS including regulation of immune responses and metabolic support of neurons and oligodendrocytes. In this study, we investigated the effect of redox imbalance in astrocytes by using a conditional astrocyte‐specific SOD2‐deficient mouse model (SOD2ako) and analyzed these animals at different stages of their life. SOD2ako mice did not exhibit any overt phenotype within the first postnatal weeks. However, already as young adults, they displayed progressive motoric impairments. Moreover, as these mice grew older, they exhibited signs of a progeroid phenotype and early death. Histological analysis in moribund SOD2ako mice revealed the presence of age‐related brain alterations, neuroinflammation, neuronal damage and myelin impairment in brain and spinal cord. Additionally, transcriptome analysis of primary astrocytes revealed that SOD2 deletion triggered a hypometabolic state and promoted polarization toward A1‐neurotoxic status, possibly underlying the neuronal and myelin deficits. Conclusively, our study identifies maintenance of ROS homeostasis in astrocytes as a critical prerequisite for physiological CNS aging. [ABSTRACT FROM AUTHOR]

Atypical progeroid syndromes (APS) are premature aging syndromes caused by pathogenic LMNA missense variants, associated with unaltered expression levels of lamins A and C, without accumulation of wild‐type or deleted prelamin A isoforms, as observed in Hutchinson‐Gilford progeria syndrome (HGPS) or HGPS‐like syndromes. A specific LMNA missense variant, (p.Thr528Met), was previously identified in a compound heterozygous state in patients affected by APS and severe familial partial lipodystrophy, whereas heterozygosity was recently identified in patients affected by Type 2 familial partial lipodystrophy. Here, we report four unrelated boys harboring homozygosity for the p.Thr528Met, variant who presented with strikingly homogeneous APS clinical features, including osteolysis of mandibles, distal clavicles and phalanges, congenital muscular dystrophy with elevated creatine kinase levels, and major skeletal deformities. Immunofluorescence analyses of patient‐derived primary fibroblasts showed a high percentage of dysmorphic nuclei with nuclear blebs and typical honeycomb patterns devoid of lamin B1. Interestingly, in some protrusions emerin or LAP2α formed aberrant aggregates, suggesting pathophysiology‐associated clues. These four cases further confirm that a specific LMNA variant can lead to the development of strikingly homogeneous clinical phenotypes, in these particular cases a premature aging phenotype with major musculoskeletal involvement linked to the homozygous p.Thr528Met variant. [ABSTRACT FROM AUTHOR]

IntroductionEotaxin-1/CCL11 is a pivotal chemokine crucial for eosinophil homing to the lungs of asthmatic patients. Recent studies also suggest that CCL11 is involved in the aging process, as it is upregulated in elderly, and correlated with shorter telomere length in leukocytes from asthmatic children. Despite its potential pro-aging effects, the precise contribution of CCL11 and the underlying mechanisms involved in the promotion of cellular senescence remains unclear. Therefore, the primary goal of this study was to explore the role of CCL11 on senescence development and the signaling pathways activated by this chemokine in lung fibroblasts.MethodsTo investigate the targets potentially modulated by CCL11, we performed an in silico analysis using PseudoCell. We validated in vitro the activation of these targets in the human lung fibroblast cell line MRC-5 following rhCCL11 exposure. Finally, we performed differential gene expression analysis in human airway epithelial cells of asthmatic patients to assess CCL11 signaling and activation of additional senescent markers.ResultsOur study revealed that eotaxin-1/CCL11 promote reactive oxygen secretion (ROS) production in lung fibroblasts, accompanied by increased activation of the DNA damage response (DDR) and p-TP53 and γH2AX. These modifications were accompanied by cellular senescence promotion and increased secretion of senescence-associated secretory phenotype inflammatory cytokines IL-6 and IL-8. Furthermore, our data show that airway epithelial lung cells from atopic asthmatic patients overexpress CCL11 along with aging markers such as CDKN2A (p16INK4a) and SERPINE1.DiscussionThese findings provide new insights into the mechanisms underlying the pro-aging effects of CCL11 in the lungs of asthmatic patients. Understanding the role of CCL11 on senescence development may have important implications for the treatment of age-related lung diseases, such as asthma.

The long-term insurance branch that covers the income losses incurred by employees in the event of old age, which they inevitably face as a social risk, is old age insurance. In general, the conditions for entitlement to a pension in case of old age arise in different ways due to the personal situation of the insured or due to the work in which he works. "Retirement in case of premature aging" provides the insured with the opportunity to retire more easily in the presence of certain special circumstances. In general, the requirement to be eligible for early aging, which is less well-known and less common in practice than the conditions for earning an old-age pension, is regulated by the 28th article of the Law number 5510 as follows: "Insured persons who have reached the age of 55 and have been found to have aged prematurely will benefit from the old-age pension if they meet other conditions other than age".Although the age requirement required to qualify for a pension has not been filled in terms of time, people who biologically age like a person who has reached the age required to qualify for an oldage pension and whose working capacity has decreased to this level are considered prematurely aged individuals.In our study, it is aimed to evaluate this special type of pension, which is generally not well known except for those who are entitled to a normal old-age pension. By examining the legal regulations and conditions of entitlement to early retirement, it will be emphasized why this special retirement condition, which is usually not found much in judicial decisions, is less common in practice and its necessity in legislation. [ABSTRACT FROM AUTHOR]

Based on a thematic review of research by foreign and domestic authors, the analysis of current trends in the aging of the population and labor force as a global demographic problem is carried out. The stages of formation of ideas about healthy aging in the world and Russia are presented. The risks of the development of premature aging and the prospects of prolonging the longevity of workers in modern conditions are considered.

Neural stem cell aging is a fundamental question in neurogenesis. Premature nuclear Pros is considered as an indicator of early neural stem cell aging in Drosophila. The underlying mechanism of how neural stem cells prevent premature nuclear Pros remains largely unknown. Here we identified that two pipsqueak family genes, distal antenna (dan) and distal antenna-related (danr), promote the proliferation of neural stem cells (also called neuroblasts, NBs) in third instar larval brains. In the absence of Dan and Danr (dan/danr), the NBs produce fewer daughter cells with smaller lineage sizes. The larval brain NBs in dan/danr clones show premature accumulation of nuclear Prospero (Pros), which usually appears in the terminating NBs at early pupal stage. The premature nuclear Pros leads to NBs cell cycle defects and NB identities loss. Removal of Pros from dan/danr MARCM clones prevents lineage size shrinkage and rescues the loss of NB markers. We propose that the timing of nuclear Pros is after the downregulation of dan/danr in the wt terminating NBs. dan/danr and nuclear Pros are mutually exclusive in NBs. In addition, dan/danr are also required for the late temporal regulator, Grainyhead (Grh), in third instar larval brains. Our study uncovers the novel function of dan/danr in NBs cell fate maintenance. dan/danr antagonize nuclear Pros to prevent NBs aging in Drosophila larval brains. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) have gained much attention due to their superb properties, which make them promising options for the reinforcing composite materials with desirable mechanical properties. However, little is known about the linkage between lung exposure to nanomaterials and kidney disease. In this study, we compared the effects on the kidneys and aging for two different types of multiwall carbon nanotubes (MWCNTs): pristine MWCNTs (PMWCNTs) and acid-treated MWCNTs (TMWCNTs), with TMWCNTs being the preferred form for use as a composite material due to its superior dispersion properties. We used tracheal instillation and maximum tolerated dose (MTD) for both types of CNTs. MTD was determined as a 10% weight loss dose in a 3-month subchronic study, and the appropriate dosage for 1-year exposure was 0.1 mg/mouse. Serum and kidney samples were analyzed using ELISA, Western blot, and immunohistochemistry after 6 months and 1 year of treatment. PMWCNT-administered mice showed the activation of pathways for inflammation, apoptosis, and insufficient autophagy, as well as decreased serum Klotho levels and increased serum levels of DKK-1, FGF-23, and sclerostin, while TMWCNTs did not. Our study suggests that lung exposure to PMWCNTs can induce premature kidney aging and highlights a possible toxic effect of using MWCNTs on the kidneys in the industrial field, further highlighting that dispersibility can affect the toxicity of the nanotubes. [ABSTRACT FROM AUTHOR]

As life expectancy increases in many countries, the prevalence of age-related diseases also rises. Among these conditions, chronic kidney disease is predicted to become the second cause of death in some countries before the end of the century. An important problem with kidney diseases is the lack of biomarkers to detect early damage or to predict the progression to renal failure. In addition, current treatments only retard kidney disease progression, and better tools are needed. Preclinical research has shown the involvement of the activation of cellular senescence-related mechanisms in natural aging and kidney injury. Intensive research is searching for novel treatments for kidney diseases as well as for anti-aging therapies. In this sense, many experimental shreds of evidence support that treatment with vitamin D or its analogs can exert pleiotropic protective effects in kidney injury. Moreover, vitamin D deficiency has been described in patients with kidney diseases. Here, we review recent evidence about the relationship between vitamin D and kidney diseases, explaining the underlying mechanisms of the effect of vitamin D actions, with particular attention to the modulation of cellular senescence mechanisms. [ABSTRACT FROM AUTHOR]

Barrier-to-autointegration factor (BAF/BANF) is a nuclear lamina protein essential for nuclear integrity, chromatin structure, and genome stability. Whereas complete loss of BAF causes lethality in multiple organisms, the A12T missense mutation of the BANF1 gene in humans causes a premature aging syndrome, called Néstor-Guillermo Progeria Syndrome (NGPS). Here, we report the first in vivo animal investigation of progeroid BAF, using CRISPR editing to introduce the NGPS mutation into the endogenous Drosophila baf gene. Progeroid BAF adults are born at expected frequencies, demonstrating that this BAF variant retains some function. However, tissue homeostasis is affected, supported by studies of the ovary, a tissue that depends upon BAF for stem cell survival and continuous oocyte production. We find that progeroid BAF causes defects in germline stem cell mitosis that delay anaphase progression and compromise chromosome segregation. We link these defects to decreased recruitment of centromeric proteins of the kinetochore, indicating dysfunction of cenBAF, a localized pool of dephosphorylated BAF produced by Protein Phosphatase PP4. We show that DNA damage increases in progenitor germ cells, which causes germ cell death due to activation of the DNA damage transducer kinase Chk2. Mitotic defects appear widespread, as aberrant chromosome segregation and increased apoptosis occur in another tissue. Together, these data highlight the importance of BAF in establishing centromeric structures critical for mitosis. Further, these studies link defects in cenBAF function to activation of a checkpoint that depletes progenitor reserves critical for tissue homeostasis, aligning with phenotypes of NGPS patients. [ABSTRACT FROM AUTHOR]

The nuclear matrix protein lamin A is a multifunctional protein with roles in DNA replication and repair, gene activation, transcriptional regulation, and maintenance of higher-order chromatin structure. Phosphorylation is the main determinant of lamin A mobility in the nucleus and nuclear membrane dissolution during mitosis. However, little is known about the regulation of lamin A phosphorylation during interphase. Interestingly, C-terminal lamin A mutations trigger cellular senescence. Recently, we showed that the C-terminal region of lamin A interacts with casein kinase II (CK2). In the present study, we have expanded on our previous research to further investigate lamin A phosphorylation and elucidate the mechanisms underlying the effect of C-terminal mutations on cellular senescence. Our results indicate that glycogen synthase kinase 3β (GSK3β) and CK2 jointly mediate the phosphorylation of lamin A at C-terminal Ser628 and Ser636 residues. Furthermore, a loss of phosphorylation at either of these two sites affects the nuclear distribution of lamin A, leading to an impaired DNA damage response as well as cellular senescence. Thus, phosphorylation at C-terminal sites in lamin A appears to be important for maintaining genomic stability and preventing cellular senescence. These findings provide insight into how loss of the C-terminal region of lamin A may induce premature aging. Furthermore, enhancement of GSK3β and CK2 activity may represent a possible therapeutic approach for the treatment of aging-related diseases. [ABSTRACT FROM AUTHOR]

Aging‐associated microbial dysbiosis exacerbates various disorders and dysfunctions, and is a major contributor to morbidity and mortality in the elderly, but the underlying cause of this aging‐related syndrome is confusing. SIRT6 knockout (SIRT6 KO) mice undergo premature aging and succumb to death by 4 weeks, and are therefore useful as a premature aging research model. Here, fecal microbiota transplantation from SIRT6 KO mice into wild‐type (WT) mice phenocopies the gut dysbiosis and premature aging observed in SIRT6 KO mice. Conversely, an expanded lifespan was observed in SIRT6 KO mice when transplanted with microbiota from WT mice. Antibiotic cocktail treatment attenuated inflammation and cell senescence in KO mice, directly suggesting that gut dysbiosis contributes to the premature aging of SIRT6 KO mice. Increased Enterobacteriaceae translocation, driven by the overgrowth of Escherichia coli, is the likely mechanism for the premature aging effects of microbiome dysregulation, which could be reversed by a high‐fat diet. Our results provide a mechanism for the causal link between gut dysbiosis and aging, and support a beneficial effect of a high‐fat diet for correcting gut dysbiosis and alleviating premature aging. This study provides a rationale for the integration of microbiome‐based high‐fat diets into therapeutic interventions against aging‐associated diseases. [ABSTRACT FROM AUTHOR]

The phenomenon of human aging is the result of a complex interaction among several factors in which the immune system plays a key role. Cortisol is a glucocorticoid secreted by the adrenal gland and has a specific secretion pattern. The current study aimed at identifying the cause and pathogenesis of premature aging using biological markers. This study was performed based on the results of clinical and instrumental examinations on 91 middle-aged men aged 45-59 years. VaseraVS-1500 sphygmomanometer based on standard methods was used to measure biological age. The relationship between biological age and circadian rhythms of cortisol secretion was calculated to elucidate the pathophysiological mechanisms of aging development. The recorded data showed that the violation of the circadian rhythms of cortisol secretion characterized by a consistently high level of the hormone throughout the day was typical among individuals with accelerated types of aging. Based on the obtained data, a formula for determining the biological age of the studied groups of patients was prepared by considering the circadian rhythm of cortisol secretion, which can be an additional tool for early detection of aging in men.

In societies where resources are unequally distributed, structural inequities can be physically embodied over lifetimes. Lived experiences including racism, sexism, classism, and poverty can lead to chronic stress that prematurely ages body systems. This study tests the hypothesis that members of structurally vulnerable groups will exhibit premature aging in the form of antemortem tooth loss (AMTL). Analyzing Black, Indigenous, and People of Color (BIPOC) and white skeletal donors from the University of Tennessee, we predict that individuals from structurally vulnerable groups will exhibit more AMTL than individuals with more social privilege. We find some evidence for increased AMTL in BIPOC individuals, but significantly more AMTL in low-socioeconomic-status white individuals than either BIPOC or high-SES white individuals. We maintain that high rates of AMTL provide evidence of embodied consequences of social policies and utilize the violence continuum to theorize the ways in which poverty and inequity are normalized in U.S. society.

Down syndrome (DS) induces a variable phenotype including intellectual disabilities and early development of Alzheimer's disease (AD). Moreover, individuals with DS display accelerated aging that affects diverse organs, among them the brain. The Ts65Dn mouse is the most widely used model to study DS. Progressive loss of cholinergic neurons is one of the hallmarks of AD present in DS and in the Ts65Dn model. In this study, we quantify the number of cholinergic neurons in control and Ts65Dn mice, observing a general reduction in their number with age but in particular, a greater loss in old Ts65Dn mice. Increased expression of the m1 muscarinic receptor in the hippocampus counteracts this loss. Cholinergic neurons in the Ts65Dn mice display overexpression of the early expression gene c-fos and an increase in the expression of β-galactosidase, a marker of senescence. A possible mechanism for senescence induction could be phosphorylation of the transcription factor FOXO1 and its retention in the cytoplasm, which we are able to confirm in the Ts65Dn model. In our study, using Ts65Dn mice, we observe increased cholinergic activity, which induces a process of early senescence that culminates in the loss of these neurons. [ABSTRACT FROM AUTHOR]

Aging is natural process & it is continuously increased when time passes. It is very important phenomenon of human body to get change from one form to another. child when get older it transforms into teenager and teenager get older it transforms into adult. It is lifelong process. Every stage of life it doing crucial role in development, physiological change, psychological change, emotional change. but when premature aging occurs it shows their sign & symptoms like Skin changes like wrinkles, age spots, dryness, loss of skin tone, hyperpigmentation around your chest and sagging. That is really unwanted condition so, we recover ourself from that condition by using Ashwagandha like herbal drug. ashwagandha mainly contains high number of Antioxidants. It acts on free radicals and neutralize cell from free radicals. that mainly help to slowing the aging process that help a human life to live more years. [ABSTRACT FROM AUTHOR]

A rare and autosomal recessive premature aging disorder, Werner syndrome (WS) is characterized by the early onset of aging-associated diseases, including shortening stature, alopecia, bilateral cataracts, skin ulcers, diabetes, osteoporosis, arteriosclerosis, and chromosomal instability, as well as cancer predisposition. WRN, the gene responsible for WS, encodes DNA helicase with a 3′ to 5′ exonuclease activity, and numerous studies have revealed that WRN helicase is involved in the maintenance of chromosome stability through actions in DNA, e.g., DNA replication, repair, recombination, and epigenetic regulation via interaction with DNA repair factors, telomere-binding proteins, histone modification enzymes, and other DNA metabolic factors. However, although these efforts have elucidated the cellular functions of the helicase in cell lines, they have not been linked to the treatment of the disease. Life expectancy has improved for WS patients over the past three decades, and it is hoped that a fundamental treatment for the disease will be developed. Disease-specific induced pluripotent stem (iPS) cells have been established, and these are expected to be used in drug discovery and regenerative medicine for WS patients. In this article, we review trends in research to date and present some perspectives on WS research with regard to the application of pluripotent stem cells. Furthermore, the elucidation of disease mechanisms and drug discovery utilizing the vast amount of scientific data accumulated to date will be discussed. [ABSTRACT FROM AUTHOR]

This paper describes changes in ionic homeostasis associated with premature senescence in human endometrial mesenchymal stem cells (eMSCs). Changes in the intracellular potassium and sodium content and potassium fluxes through the plasma membrane have been examined/ with flame photometry, It was found that, during oxidative stress-induced cell-cycle arrest and the development of premature aging, eMSCs retained the high ionic heterogeneity that is common for functionally active animal cells. Premature cell aging is accompanied by increased intracellular sodium content and transmembrane potassium fluxes associated with the functioning of the Na/K pump, but does not affect the passive transport of potassium across the plasma membrane. One distinctive feature of stress-induced arrested eMSCs is reduced specific intracellular potassium content (500–600 μmol per 1 g of protein) compared to proliferating eMSCs (800–900 μmol per 1 g of protein). It is suggested that decreased intracellular potassium content associated with the development of premature aging shows the participation of potassium ions in the regulation of cell volume and may indicate a decreased hydration of aging eMSCs. [ABSTRACT FROM AUTHOR]

It is unclear whether traditional Chinese patent medicines can resist premature aging. This prospective study investigated the effects of Bazi Bushen Capsule (BZBS) which is a traditional Chinese patent medicine for tonifying the kidney essence on premature senility symptoms and quality of life, telomerase activity and telomere length. It was a parallel, multicenter, double-blind, randomized, and placebo-controlled trial. Subjects (n = 530) aged 30–78 years were randomized to receive BZBS or placebo capsules 12 weeks. The primary outcome was the clinical feature of change in kidney deficiency for aging evaluation scale (CFCKD-AES) and tilburg frailty indicator (TFI). The secondary outcomes were SF-36, serum sex hormone level, five times sit-to-stand time (FTSST), 6MWT, motor function test—grip strength, balance test, walking speed, muscle mass measurement, telomerase and telomere length. After 12 weeks of treatment, the CFCKD-AES and TFI scores in the BZBS group decreased by 13.79 and 1.50 respectively (6.42 and 0.58 in the placebo group, respectively); The SF-36 in the BZBS group increased by 98.38 (23.79 in the placebo group). The FTSST, motor function test grip strength, balance test, walking speed, and muscle mass in the elderly subgroup were all improved in the BZBS group. The telomerase content in the BZBS group increased by 150.04 ng/ml compared to the placebo group. The fever led one patient in the placebo group to discontinue the trial. One patient in the placebo group withdrew from the trial due to pregnancy. None of the serious AEs led to treatment discontinuation, and 3 AEs (1.14%) were assessed as related to BZBS by the primary investigator. BZBS can improve premature aging symptoms, frailty scores, and quality of life, as well as improve FTSST, motor function: grip strength, balance test, walking speed, and muscle mass in elderly subgroups of patients, and enhance telomerase activity, but it is not significantly associated with increasing telomere length which is important for healthy aging. https://www.chictr.org.cn/showproj.html?proj=166181 [ABSTRACT FROM AUTHOR]

The expression of a mutant Lamin A, progerin, in Hutchinson-Gilford Progeria Syndrome leads to alterations in genome architecture, nuclear morphology, epigenetic states, and altered phenotypes in all cells of the mesenchymal lineage. Here, we report a comprehensive analysis of the transcriptional status of patient derived HGPS fibroblasts, including nine cell lines not previously reported, in comparison with age-matched controls, adults, and old adults. We find that Progeria fibroblasts carry abnormal transcriptional signatures, centering around several functional hubs: DNA maintenance and epigenetics, bone development and homeostasis, blood vessel maturation and development, fat deposition and lipid management, and processes related to muscle growth. Stratification of patients by age revealed misregulated expression of genes related to endochondral ossification and chondrogenic commitment in children aged 4–7 years old, where this differentiation program starts in earnest. Hi-C measurements on patient fibroblasts show weakening of genome compartmentalization strength but increases in TAD strength. While the majority of gene misregulation occurs in regions which do not change spatial chromosome organization, some expression changes in key mesenchymal lineage genes coincide with lamin associated domain misregulation and shifts in genome compartmentalization.

Association of lonafarnib treatment vs no treatment with mortality rate in patients with Hutchinson-Gilford progeria syndrome. Keywords: Editorials; premature aging; progeria; progerin EN Editorials premature aging progeria progerin 1745 1747 3 06/02/23 20230606 NES 230606 Even for the rarest of the rare diseases, clinically relevant biological markers of disease are needed to evaluate clinical trials outcome and to analyze disease progression. [Extracted from the article]

Type 2 diabetes (T2D) constitutes a major public health problem, and despite prevention efforts, this pandemic disease is one of the deadliest diseases in the world. In 2022, 6.7 million patients with T2D died prematurely from vascular complications. Indeed, diabetes increases the risk of myocardial infarction or stroke eightfold. The identification of the molecular factors involved in the occurrence of cardiovascular complications and their prevention are therefore major axes. Our hypothesis is that factors brought into play during physiological aging appear prematurely with diabetes progression. Our study focused on the aging of the extracellular matrix (ECM), a major element in the maintenance of vascular homeostasis. We characterized the morphological and functional aspects of aorta, with a focus on the collagen and elastic fibers of diabetic mice aged from 6 mo to nondiabetic mice aged 6 mo and 20 mo. The comparison with the two nondiabetic models (young and old) highlighted an exacerbated activity of proteases, which could explain a disturbance in the collagen accumulation and an excessive degradation of elastic fibers. Moreover, the generation of circulating elastin-derived peptides reflects premature aging of the ECM. These extracellular elements contribute to the appearance of vascular rigidity, often the origin of pathologies such as hypertension and atherosclerosis. In conclusion, we show that diabetic mice aged 6 mo present the same characteristics of ECM wear as those observed in mice aged 20 mo. This accelerated aortic wall remodeling could then explain the early onset of cardiovascular diseases and, therefore, the premature death of patients with T2D. NEW & NOTEWORTHY Aortic elastic fibers of young (6-mo old) individuals with diabetes degrade prematurely and exhibit an appearance like that found in aged (20-mo old) nondiabetic mice. Exacerbated elastolysis and elastin-derived peptide production are characteristic elements, contributing to early aortic wall rigidity and hypertension development. Therefore, limiting this early aging could be a judicious therapeutic approach to reduce cardiovascular complications and premature death in patients with diabetes.