Aging & Longevity

Microbiota-derived metabolites have emerged as key regulators of longevity. The metabolic activity of the gut microbiota, influenced by dietary components and ingested chemical compounds, profoundly impacts host fitness. While the benefits of dietary prebiotics are well-known, chemically targeting the gut microbiota to enhance host fitness remains largely unexplored. Here, we report a novel chemical approach to induce a pro-longevity bacterial metabolite in the host gut. We discovered that...

Mice overexpressing Sirt6 or fed a caloric restriction (CR) diet live longer with improved health. CR increases Sirt6 levels, and its beneficial effects are mediated by the gasotransmitter H(2)S, a one-carbon pathway product. Yet, the role of this pathway in Sirt6-regulated longevity remains elusive. Here, we show that Sirt6 controls hepatic one-carbon metabolism, preventing the aging-dependent H(2)S reduction, and the elevation of the methyl donor, S-adenosylmethionine (SAM). Sirt6...

CONCLUSION: Our findings suggest that subjective well-being is a nonlinear modifiable determinant of low muscle mass in older adults. These results indicate that interventions aimed at enhancing subjective well-being may complement conventional strategies for regulating muscle homeostasis.

CONCLUSION: This study highlights a substantial prevalence of physical inactivity among older persons in Malaysia. Key factors significantly associated with physical inactivity include the presence of chronic conditions such as diabetes mellitus, functional limitations, self-care difficulties, overall disability, and sedentary behavior of more than 4 h. These findings underscore the need for targeted interventions and policies that address health conditions and functional impairments to promote...

CONCLUSIONS: This study demonstrates the feasibility of organising geriatric screening in an infectious diseases unit. The proportion of changes that were implemented highlights the relevance of using these screening tests. It is, however, important to improve some of the screening tests used and raise awareness amongst people living with HIV and their doctors.

CONCLUSIONS: Psychological resilience mediated the association between LTAs and all-cause mortality. Frequent participation in leisure activities may play a beneficial role in preventing premature death by improving resilience levels in community-dwelling older people.

CONCLUSION: The Roy Adaptation Model-based educational programs seem to be a successful strategy for raising the standard of living and fostering general health among senior citizens living in assisted living facilities.

Dietary restriction (DR) improves insulin sensitivity, however, it has not been tested in long-term interventions and with diet type as variable. Therefore, we exposed mice to either a low-fat (LF) or high-fat-sucrose (HFS) diet, either fed ad libitum (AL) or in a DR regimen from weaning till 2 years of age. Using an oral glucose tolerance test with [6,6-²H(2)]-labelled glucose, we found that DR markedly reduced plasma insulin concentrations and strongly elevated hepatic and peripheral insulin...

Recently, we have identified rs1333046 as one of the candidate functional single nucleotide polymorphisms (fSNPs) on the atherosclerosis-associated CDKN2A/B locus. However, how rs1333046 influences the pathogenesis of and susceptibility to atherosclerosis is unknown. In this work, we demonstrate that rs1333046 is part of a cis-regulatory element (cis-RE) that regulates p16^(INK4a) and p16^(INK4a)-dependent cellular senescence in human endothelial cells (ECs). This is achieved by recruiting...

Social drivers of health (SDOH) impact health outcomes across the lifespan, with distinct effects on the health and well-being of older adults. SDOH contribute to outcomes of particular importance to older adults, including physical and cognitive functioning and aging in place, highlighting the critical importance of addressing SDOH as part of comprehensive, patient-centered geriatrics care. Yet, there is limited guidance on best practices for the integration of SDOH into healthcare,...

The mechanisms underlying skeletal muscle ageing, whilst poorly understood, are thought to involve dysregulated micro (mi)RNA expression. Using young and aged rat skeletal muscle tissue, we applied high-throughput RNA sequencing to comprehensively study alterations in miRNA expression occurring with age, as well as the impact of caloric restriction (CR) on these changes. Furthermore, the function of the proteins targeted by these age- and CR-associated miRNAs was ascertained. Numerous known and...

Epigenetic clocks are increasingly proposed as surrogate endpoints in aging trials, yet their short-term behavior in healthy older adults is not well characterized. We analyzed DNA methylation at baseline, year 1, and year 2 in 899 COSMOS-Blood participants (mean age 70.0; 50% women), deriving Horvath, Hannum, PhenoAge, and GrimAge clocks (original and principal component [PC] versions) and DunedinPACE. Epigenetic age acceleration was computed by regressing each clock on chronological age....

Alzheimer's disease (AD), a prevalent neurodegenerative disorder, is primarily characterized by β-amyloid (Aβ) deposition. Current therapies alleviate symptoms but lack agents capable of modifying disease progression. Meanwhile, cross-regional studies indicate that AD patients exhibit disrupted gut microbiota composition, which is closely associated with cerebral molecular dysregulation. Building on this gut-brain connection, this study aimed to attenuate AD progression by targeting gut...

Skeletal muscles, which constitute 40-50% of body mass, regulate whole-body energy expenditure and glucose and lipid metabolism. Peroxisomes are dynamic organelles that play a crucial role in lipid metabolism and clearance of reactive oxygen species, however their role in skeletal muscle remains poorly understood. To clarify this issue, we generated a muscle-specific transgenic mouse line with peroxisome import deficiency through the deletion of peroxisomal biogenesis factor 5 (Pex5). Here, we...

Transcription factors DAF-16/FOXO and HLH-30/TFEB have been linked to aging regulation, but how they synergize to promote longevity is not fully understood. Here, we reveal a functional interaction between these two transcription factors that supports healthier aging in Caenorhabditis elegans. Namely, DAF-16 and HLH-30 cooperate to trigger robust lysosomal tubulation under various contexts, which contributes to systemic health benefits in late age. Remarkably, lysosome tubulation can be...

Optimizing the activity and longevity of oxygen evolution reaction (OER) electrocatalysts requires an atomic-scale understanding of multiple reconstruction and transformation processes occurring in the surface and sub-surface regions of the electrocatalyst. Herein, a multimodal method combining X-ray absorption fine structure and photoemission spectroscopy, in situ Raman spectroscopy, transmission electron microscopy and atom probe tomography with electrochemical measurements is employed to...

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Aging trajectories are influenced by modifiable risk factors, and prior evidence has hinted that multilingualism may have protective potential. However, reliance on suboptimal health markers, small samples, inadequate confounder control and a focus on clinical cohorts led to mixed findings and limited applicability to healthy populations. Here, we developed biobehavioral age gaps, quantifying delayed or accelerated aging in 86,149 participants across 27 European countries. National surveys...

Gut microbes play a crucial role in modulating host lifespan. However, the microbial factors that influence host longevity and their mechanisms of action remain poorly understood. Using the expression of Caenorhabditis elegans FAT-7, a stearoyl-CoA 9-desaturase, as a proxy for lifespan modulation, we conduct a genome-wide bacterial mutant screen and identify 26 Escherichia coli mutants that enhance host lifespan. Transcriptomic and biochemical analyses reveal that these mutant diets induce...

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