Aging & Longevity

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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Metabolic rewiring helps to construct efficient microbial cell factories; however, these cells suffer from metabolic stress during long-term fed-batch fermentation. Thus, the construction of robust cells is vital for industrial application of microbial cell factories at the laboratory scale. Here, we systematically characterized longevity factors and pathways for biosynthesis of the diterpenoid sclareol and found that weakening nutrient-sensing pathways and enhancing mitophagy synergistically...

People tend to form impressions of others' trustworthiness based on their facial appearance and make trust-related decisions accordingly. In such face-based trustworthiness judgments (FBTJs), older adults are generally more likely than younger adults to attribute higher trustworthiness. This pattern is sometimes referred to as positivity bias and has been proposed as a potential risk factor for fraud victimization in later life. However, previous studies lack objective ground-truth measures of...

CONCLUSIONS: Relative muscle power showed superior predictive performance for self-reported walking difficulty, as an indicator of mobility limitation, compared to other normalization methods. Future longitudinal studies are needed to confirm these findings and explore their relevance for other clinically meaningful outcomes.

This letter provides a critical reflection on the article "Sex- and age-related declines in muscle mass, strength, physical performance, and muscle quality among community-dwelling older adults: A cross-sectional study" (Asano et al., 2025). The study significantly advances our understanding of age-related muscle deterioration by examining multiple domains, including muscle mass, strength, physical performance, and quality, in a large cohort of Japanese older adults. Key findings highlight that...

The endurance capacity of the spinal extensor muscles plays a key role in maintaining spinal function. This systematic review and meta-analysis aims to synthesise current evidence on how ageing influences fatigue of the spinal extensor muscles, addressing the inconsistent findings reported across existing studies. Medline, EMBASE, PubMed, Web of Science and CINAHL Plus databases were searched from their inception to 28 June 2025. Cross-sectional studies assessing fatigue of the spinal extensor...

Intrinsic capacity (IC) is a composite that includes five different domains related to a person's capacities: sensory, locomotion, vitality, psychological and cognitive. IC represents part of a global effort to promote healthy ageing, one aspect of which is healthy cognitive functioning. This study aimed to elucidate the association of IC and cognitive decline in older adults. Using data from the English Longitudinal Study of Ageing (ELSA, wave 6), IC composite was derived through z-score and...

The field of ageing science has gone through remarkable progress in recent decades, yet many fundamental questions remain unanswered or unexplored. Here we present a curated list of 100 open problems in ageing and longevity science. These questions were collected through community engagement and further analysed using Natural Language Processing to assess their prevalence in the literature and to identify both well-established and emerging research gaps. The final list is categorised into...