Aging & Longevity

Human GWAS have shown that obesogenic FTO polymorphisms correlate with lean mass, but the mechanisms have remained unclear. It is counterintuitive because lean mass is inversely correlated with obesity and metabolic diseases. Here, we use CRISPR to knock-in FTO^(rs9939609-A) into hESC-derived tissue models, to elucidate potentially hidden roles of FTO during development. We find that among human tissues, FTO^(rs9939609-A) most robustly affect human muscle progenitors' proliferation,...

The capacity to regenerate myelin in the central nervous system diminishes with age. This decline is particularly evident in multiple sclerosis (MS), a chronic demyelinating disease. Whether cellular senescence, a hallmark of aging, contributes to remyelination impairment remains unknown. Here, we show that senescent cells accumulate within demyelinated lesions after injury, and treatments with senolytics enhances remyelination in young and middle-aged mice but not aged mice. In young mice, we...

Torpor and hibernation are extreme physiological adaptations of homeotherms associated with pro-longevity effects. Yet the underlying mechanisms of how torpor affects aging, and whether hypothermic and hypometabolic states can be induced to slow aging and increase healthspan, remain unknown. Here we demonstrate that the activity of a spatially defined neuronal population in the preoptic area, which has previously been identified as a torpor-regulating brain region, is sufficient to induce a...

CONCLUSIONS: The CCE for PD is high, and individuals and families are the main bearers of health expenditures. It is recommended to optimize medical insurance policies, increase outpatient insurance coverage, and gradually increase the level of insurance benefits. Furthermore, it is necessary to explore multi-party collaboration to establish a diversified and multi-level medical security system for PD.

Metabolic dysregulation and altered metabolite concentrations are widely recognized as key characteristics of aging. Comprehensive exploration of endogenous metabolites that drive aging remains insufficient. Here, we conducted an untargeted metabolomics analysis of aging mice, revealing citrulline as a consistently down-regulated metabolite associated with aging. Systematic investigations demonstrated that citrulline exhibited antiaging effects by reducing cellular senescence, protecting against...

CONCLUSIONS: Healthy lifestyle changes were inversely related to comprehensive and organ-specific biological aging in Southwest China, with diet and smoking contributing most to comprehensive and metabolic BA separately. Our findings highlight the potential of lifestyle interventions to decelerate aging and identify intervention targets to limit organ-specific aging in less-developed regions.

CONCLUSION: From the perspective of public health and aging, this study constructed an interpretable sarcopenia risk prediction model on the basis of routine clinical data. This model can be used for early screening and risk assessment of symptomatic KOA patients, assisting health departments and clinicians in the early detection and follow-up of relevant populations, thereby improving the quality of life and health outcomes of elderly individuals.

CD25KO mice are a model of Sjögren disease. CD25KO mice have severe inflammation and infiltrating lymphocytes to the lacrimal glands (LG). Whether the pathogenicity of CD25KO CD4^(+) T cells can be controlled in vivo by Tregs is unknown. Eight-week-old B6 and CD25KO mice LGs were submitted for RNA bulk sequencing. A total of 3481 genes were differentially expressed in CD25KO LG compared to B6. Tear washing analysis identified CD25KO mice had elevated protein levels of TNF, IFN-γ, and CCL5 and...

CONCLUSIONS: This study initially elucidates that PCBP2 as an intrinsic aging factor regulates the replicative senescence of hBMSCs through the ROS-FGF2 signaling axis.

Aging disrupts immune regulation, affecting tissue function and increasing vulnerability to various diseases. However, the effects of aging on immune cells within human testes are not well understood. In this study, we utilized single-cell RNA sequencing to profile immune cells from 33 human testis samples from individuals aged 21 to 69. Our analysis revealed key immune cell types, including CD8^(+) T cells, monocytes, cDC2 cells, and various macrophage subtypes within the testes. We observed an...

Although the phenomena underlying cognitive decline and dementia are complex, there is growing evidence suggesting that degraded sensory inputs caused by age-related hearing loss may play a central role in accelerating cognitive decline in older individuals. Further supporting this notion is evidence that hearing augmentation with hearing aids can mitigate hearing loss-related cognitive impairments. Despite this evidence, few studies have attempted to investigate hearing aid efficacy with a...

CONCLUSION: Apigenin upregulates EIF6 expression and mitigates H2O2-induced chondrocyte senescence, highlighting its potential as a therapeutic agent for KOA. These findings provide insights into the nutritional health benefits of Apigenin and its implications for KOA treatment.

The aging of hematopoietic stem cells (HSCs) substantially alters their characteristics. Mitochondria, essential for cellular metabolism, play a crucial role, and their dysfunction is a hallmark of aging-induced changes. The impact of mitochondrial mass on aged HSCs remains incompletely understood. Here we demonstrate that HSCs with high mitochondrial mass during aging are not merely cells that have accumulated damaged mitochondria and become exhausted. In addition, these HSCs retain a high...

Epigenetic aging clocks represent contemporary aging biomarkers that predict age using methylomic data. These models can be categorized as first-generation clocks that estimate chronological age or next-generation clocks that are designed to associate with health, lifestyle, and/or outcomes. Recently, we created a next-generation buccal clock called CheekAge that associates with all-cause mortality risk in older adults. To better understand our model, we collated 25 Infinium MethylationEPIC...

Biological age is an important measure of aging that reflects an individual's physical health and is linked to various diseases. Current prediction models are still limited in precision, and the risk factors for accelerated aging remain underexplored. Therefore, we aimed to develop a precise biological age and assess the impact of socio-demographic and behavioral patterns on the aging process.We utilized Deep Neural Networks (DNN) to construct biological age from participants with physical...

Ageing is associated with a range of chronic diseases and has diverse hallmarks. Mitochondrial dysfunction is implicated in ageing, and mouse-models with artificially enhanced mitochondrial DNA mutation rates show accelerated ageing. A scarcely studied aspect of ageing, because it is invisible in aggregate analyses, is the accumulation of somatic mitochondrial DNA mutations which are unique to single cells (cryptic mutations). We find evidence of cryptic mitochondrial DNA mutations from diverse...

CONCLUSION: This study provided real-world empirical cost estimates of AD burden in Malaysia. Informal care is a significant contributor to the societal cost of AD. Optimal healthcare resource allocation is essential in the decision making of healthcare stakeholders to address rising demands.

Nicotinamide adenine dinucleotide kinase (NADK) is essential to the generation of nicotinamide adenine dinucleotide phosphate (NADP(H)), an important metabolic coupling factor involved in glucose-stimulated insulin secretion. In the present study, we showed that the expression of Nadk and Nadk2 transcripts and NADP(H) content were lower in islets of 80-week-old (aged) mice than those of 8-week-old (young) mice. This was associated with diminished oral glucose tolerance of old mice and the...

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This study investigates the relationship between white matter hyperintensities (WMHs) and longitudinal cognitive decline in older adults. Using data from The Irish Longitudinal Study on Ageing (TILDA), we examined WMH characteristics, including volume, location, and microstructural integrity, in a community-dwelling population of 497 individuals over a six-year period. WMHs were categorised into phenotypes based on their size, fractional anisotropy (FA), and mean diffusivity (MD), with subtypes...