Aging & Longevity

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Aging research has made remarkable progress in describing aging through the genetic architecture of longevity, epigenetic clocks, proteomic signatures, and systems-level analyses. Yet a critical dimension remains underrepresented: the role of genome integrity, germline and somatic mutation accumulation in individual-specific vulnerability, frailty, and multimorbidity across the life course. The need for individual-level thinking has deep roots, from Darwin's emphasis on individual variation in...

CONCLUSIONS: Older Chinese adults in the UK exhibit diverse PA patterns and face a range of barriers, underscoring the need to consider their varied needs and experiences when designing interventions. Factors influencing PA engagement align with the COM-B framework, highlighting the importance of addressing capability, opportunity, and motivation. These findings provide a practical evidence base to inform behaviour change interventions, supporting the development of culturally tailored...

CONCLUSION: Long-term PA shows a clear dose-response relationship with sarcopenia risk in later life. While sustained activity across adulthood confers the greatest benefit, initiating PA even later in life remains associated with lower odds of sarcopenia.

Arterial stiffness is a hallmark of vascular aging and a major risk factor for cardiovascular disease. While immune aging-typically characterized by reduced T cell receptor (TCR) diversity and CD8^(+) memory expansion-contributes to this process, growing evidence suggests that peripheral immune dysregulation may impair vascular function through mechanisms distinct from classical immunosenescence. To investigate this, we profiled peripheral TCRβ repertoires from 563 adults without clinically...

The adsorption of charged nanoparticles at water-oil interfaces constitutes a fundamental phenomenon, underlying pivotal technologies spanning from emulsion stabilization to the sophisticated fabrication of foams. However, the diffusional behavior of these nanoparticles remains poorly understood. Here, we use single-molecule tracking experiments to show that the diffusion of like-charged nanoparticles at the water-oil interface not only becomes anomalous but also displays a diffusional aging...

Gait stability arises from interactions between physiological, cognitive, and psychological systems, yet these domains are often assessed in isolation. This study examined multisystem predictors of anteroposterior margin of stability during walking (MoS(AP)) in community-dwelling older adults. Of 340 participants, 143 were retained after data quality screening (105 females; age: 70.8 ± 7.8 years). Participants completed the Physiological Profile Assessment (PPA), cognitive testing using Montreal...

Fractional anisotropy (FA) from diffusion MRI is a widely used marker of white matter (WM) integrity, but conventional FA-based genetic studies typically rely on tract- or atlas-defined averages that may obscure spatially distributed WM variation and limit genetic discovery. Here, we propose a deep learning framework, termed unsupervised deep representation of WM (UDR-WM), which uses voxel-wise FA maps to derive brain-wide unsupervised deep imaging phenotypes (UDIP-FA) without prior anatomical...

The protein arginine methyl transferase 5 (PRMT5) emerges as a therapeutic target in S-methyl-5'-thioadenosine phosphorylase (MTAP)-deleted cancers, where 5'-methylthioadenosine (MTA) accumulation partially inhibits its activity. However, it remains unclear whether other genetic alterations can dictate PRMT5 activity in cancer. Here, we identify liver kinase B1 (LKB1) as an alternative predictor of PRMT5 inhibition in lung cancer independent of MTAP. Mechanistically, LKB1 loss activates...

Individuals with post-traumatic stress disorder (PTSD) are at higher risk for age-related physical comorbidities, such as cardiovascular disorders, and exhibit accelerated epigenetic and brain aging. The present study examined PTSD as a moderator of the association between DNA methylation (DNAm)-based systemic aging (GrimAge, PhenoAge) and brain aging, indexed by MRI-based and DNAm-derived BrainAge estimates, in 174 lifetime PTSD cases and 138 trauma-exposed controls from four cohorts....

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CONCLUSIONS: While the + AGIL Barcelona program had a limited quantitative impact on polypharmacy, it significantly reduced PIMs' use, particularly in nervous system-acting medications, which are involved in increased risk of falling and cognitive impairment in older adults. The study highlights the importance of medication review in multidimensional frailty management, although future research with larger samples and standardized medication review protocols is needed.

CONCLUSIONS: This observational study highlights that the relationship between DSI and cognitive impairment varied by personal responsibility for health. It is crucial to focus on the cognitive function of older adults with DSI and low personal health responsibility in rural China.

CONCLUSIONS: These findings underscore the need to review the type and range of activities offered in institutional settings, reducing time devoted to highly structured leisure activities and promoting more enriching experiences. To do so, experience-based co-design approaches involving institutionalised older adults and professionals in these settings are essential to develop person-centred programmes to enhance engagement in meaningful activities and occupational balance. Future research...

Heart failure (HF) is characterized by a severe disruption of myocardial energy metabolism, with mitochondrial dysfunction standing as a central pathological feature. However, the upstream regulatory mechanisms that drive metabolic remodeling, particularly across distinct HF phenotypes, remain inadequately defined. Mounting evidence reveals that, beyond their metabolic role, mitochondria act as central signaling hubs. This review proposes that dysfunctional mitochondrial-organelle crosstalk is a...

Peripheral immunosenescence has been increasingly implicated in dementia pathogenesis. However, the contributions of specific lymphocyte subsets to cognitive outcomes remain poorly defined, and evidence from large-scale longitudinal studies is scarce. We leveraged data from the US Health and Retirement Study (n = 7444; mean age: 67.7 ± 9.7 years). Our primary analysis calculated three ratio metrics to quantify T-cell immunosenescence: the CD4:CD8 ratio, CD4 + EMRA: Naïve and CD8 + EMRA: Naïve...

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Biguanides, including metformin, the world's most prescribed oral hypoglycemic, extend health span and lifespan in vertebrates and invertebrates. Given the widespread use and apparent safety of metformin, it is assumed that its effects are not associated with toxicity, except when in marked excess. Here, we determine that accumulation of damaging reducing equivalents is an unanticipated toxicity associated with biguanides, defense against which requires post-transcriptional protection of de novo...

Posttraumatic stress disorder (PTSD) exhibits high rates of comorbidity with Substance Use Disorders (SUDs) and Traumatic Brain Injury (TBI), especially in older adults who are subject to the effects of psychological trauma due to combat exposure, health-related and psychosocial outcomes, and aging. This narrative review explores the associations between PTSD and comorbidities of psychoactive substance abuse and traumatic brain injuries on the incidence of Alzheimer's disease (AD) in veterans...

CONCLUSIONS: Physical activity levels were non-linearly associated with the risk of intrinsic capacity impairment, with moderate levels being associated with a lower risk. This study further identified marked heterogeneity in the associations between physical activity and different intrinsic capacity domains, suggesting that the benefits are not uniform across functional domains. These findings highlight the importance of maintaining an appropriate level of physical activity and support the...