Aging & Longevity

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Despite the thousands of genes implicated in age-related phenotypes, effective interventions for aging remain elusive, due to the multifactorial nature of longevity and the interconnectedness of molecular components involved. Here we introduce a network medicine framework to map 2,358 longevity-associated genes onto the human interactome to identify drug-repurposing candidates capable of modulating specific hallmarks of aging. We find that genes associated with each hallmark form a connected...

Epigenetic changes, in particular DNA methylation, accumulate with age across different tissues, but whether these changes follow consistent patterns across different organs remains poorly understood. Here we show, through a meta-analysis of more than 15,000 human methylation profiles spanning 17 tissues, that aging produces both conserved and tissue-specific epigenetic signatures. We identify systemic shifts in methylation levels, increases in methylation variability, and growing molecular...

CONCLUSION: Plasma p-tau217 and Aβ42/40 were associated with neurostructural and cognitive impairment in PD and older adults, supporting the potential utility of AD-related plasma biomarkers-particularly p-tau217-for the clinical-biological characterization of cognitive decline in PD.

Genomic instability drivers of senescence and carcinogenesis. The ribosomal RNA gene (rDNA) locus in budding yeast provides an excellent model to study these processes. Because of its highly repetitive structure and the gene amplification system that maintains its copy number, rDNA represents one of the most unstable regions in the genome. Here, we demonstrate that the integrity of rDNA transcription is essential for maintaining genomic stability and lifespan. Loss of Paf1, an elongation factor...

CONCLUSION: Primary same-day TJA can be safely and effectively performed in selected octogenarian patients when guided by comprehensive preoperative assessment and multidisciplinary perioperative care. This case series reinforces growing evidence that age alone should not preclude surgical intervention. Our findings contribute to an evolving understanding of evidence-based, age-inclusive arthroplasty practices.

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Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, with ageing constituting a major underlying risk factor. Ubiquitination, a highly conserved and reversible posttranslational modification, has emerged as a pivotal regulator of CVDs through the modulation of target proteins through various mechanisms, including protein stability, activity, subcellular localization, and molecular interactions. This process is orchestrated by ubiquitin-activating (E1),...

Neurodegenerative diseases are frequently associated with proteotoxic stress linked to disease specific proteins. The autophagy-lysosome system provides essential control of proteotoxic stress and its failure can lead to initiation of apoptosis. However, in aging and neurodegenerative diseases apoptosis is insufficient to account for all neuronal death, and several different cell death types have been reported in these contexts. Here we show that karyoptosis, a distinct form of cell death, can...

Somatic mutations accumulate with age and can cause cell death, but their quantitative contribution to limiting human lifespan remains unclear. We developed an incremental modeling framework that progressively incorporates factors contributing to aging into a model of population survival dynamics, which we used to estimate lifespan limits if all aging hallmarks were eliminated except somatic mutations. Our analysis reveals fundamental asymmetry across organs: post-mitotic cells such as neurons...

Leukocyte telomere length (LTL) is a widely studied biomarker of biological aging, reflecting cumulative cellular damage beyond chronological age. However, its prognostic relevance in clinically complex populations such as hospitalized older adults remains uncertain. In this prospective observational study, 872 patients aged ≥ 65 years admitted to acute care wards of IRCCS INRCA within the Report-AGE cohort were included. LTL was measured by quantitative real-time PCR and expressed as...

BACKGROUND: Amid the accelerating aging trend, addressing mild cognitive impairment (MCI) is critical for dementia prevention. Current evidence suggests that standalone interventions have limited efficacy, whereas combined physical‑cognitive training may yield greater benefits. However, the neurophysiological mechanisms of sequential combinations, particularly their effects on regional brain activation and functional connectivity, remain unclear. Functional near‑infrared spectroscopy (fNIRS)...

CONCLUSIONS: The article contributes to the methodological literature on involving older people in the development of technology for ageing in place by challenging the assumption that medical conditions are prime drivers of older people's needs. It illustrates how this assumption may point technology developers in the wrong direction unless it is supplemented by a strong focus on the everyday experience of ageing.

CONCLUSIONS: Lean mass showed the strongest independent association with whole-body BMD in community-dwelling older Chilean adults, with modest differences between women and men. These findings support the relevance of lean mass as an important correlate of bone health during aging and provide evidence from a Latin American population.

CONCLUSION: Our study suggests the clinical relevance of combining anthropometric markers of obesity in community-dwelling older adults. We provide initial evidence that the coexistence of low BMI and high WC, although rare, is suggestive of potential clinical implications due to its association with higher odds of functional impairment. Additionally, both underweight and obesity may offer added clinical value beyond single measures.

In the low Reynolds number regime, active biological systems utilize nonreciprocal cyclic activities to achieve motility, as seen in the spinning of bacterial flagella and the beating of cilia. Coupling among these active mechanical components leads to synchronization and emergence of metachronal waves. Here, we report that biofilms of Pseudomonas nitroreducens form active carpet-like surfaces textured with diverse topological defects, generating Mexican-wave-like collective behavior in which...

Long-living individuals (LLIs) possess remarkable genetic resilience, characterized by protective variants that confer immune robustness and resistance to age-related diseases. The longevity-associated variant of BPIFB4 (LAV-BPIFB4), enriched in centenarians, demonstrated pleiotropic benefits including reduced inflammation, cardiovascular protection, and immune system rejuvenation. However, the molecular mechanisms underlying these protective effects remain incompletely understood. Here, we...

Renal aging shortens healthspan and propagates organ dysfunction beyond the kidney, yet its molecular drivers remain incompletely defined. Here we identify microsomal prostaglandin E synthase-2 (mPGES-2) as a critical regulator of renal aging and its skeletal consequence. Genetic ablation of Ptges2 improved health indices in aged mice, prolonged median survival, and markedly alleviated glomerulosclerosis, podocyte injury, and renal senescence. Single-cell transcriptomic analysis, together with...

Intrinsic capacity (IC), introduced by the World Health Organization, provides a multidimensional framework for evaluating functional aging across locomotion, cognition, sensory, psychological, and vitality domains. However, gut microbial features associated with IC among community-dwelling older adults remain incompletely understood. In this exploratory cross-sectional study, we enrolled 52 community-dwelling older adults and assessed gut microbiota using full-length 16S rRNA sequencing....