Aging & Longevity

Frailty, a clinical syndrome of multisystem decline and homeostatic vulnerability, is a critical public health priority. While the gut microbiome regulates immune and metabolic signaling, current evidence remains fragmented. We performed a metagenomic meta-analysis of 955 individuals from 28 independent cohorts across 24 countries to identify universal microbial signatures and develop a generalizable discriminative model. Frailty was determined using a Proxy Frailty Index based on the deficit...

CONCLUSION: High-intensity aerobic exercise increased serum zonulin more than low-intensity exercise in older adults, suggesting differential effects on intestinal barrier-related responses. Although inflammatory markers tended to improve more with high-intensity exercise, these findings should be interpreted cautiously. Individualized exercise prescription may be needed when considering effects on intestinal barrier function in older adults.

CONCLUSION: Our integrative study demonstrates that aging-induced SPARCL1 deficiency in brain endothelial cells causally contributes to VaD pathogenesis. These findings highlight SPARCL1 as a mechanistically grounded and therapeutically promising target for VaD.

Telomere-driven replicative crisis transforms the architecture of the evolving cancer genome, yet the mechanisms and consequences remain incompletely resolved, with potential biomarkers undiscovered. To address this, we have employed novel tools and methodologies to explore a human fibroblast model of crisis using high resolution multi-omics analyses. We have developed a unique chromatin conformation capture procedure for identifying distant genomic loci that interact with eroding telomeres,...

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ONC201 is a first-in-class, FDA-approved small molecule activator of the mitochondrial ATP-dependent caseinolytic peptidase P (ClpP). This and other related small molecules referred to as ClpP agonists, exert antiproliferative effects in several cancer cell types. We report that ONC201 and highly potent second generation ClpP agonists (TR-57, TR-107), promote induction of senescence in triple-negative breast cancer (TNBC) cell lines. Senescence was determined by increased β-galactosidase (β-gal)...

Over the past decades, numerous studies aimed to discover the fundamental cause of the aging process. Rather than a single root cause, multiple factors were identified, suggesting that aging manifests itself through a progressive degradation of different molecules, cells and in the end, entire systems, directly affecting an individual's health. To address this rapidly growing challenge, various anti-aging strategies have been proposed, among which partial reprogramming has emerged as a promising...

Aging is associated with neuromuscular decline, but how sex modulates motor unit adaptations across adulthood remains unclear. This study examined age- and sex-related differences in motor unit firing behavior in young (YG), middle-aged (MA), and older (OLD) adults by integrating high-density surface EMG decomposition with assessments of muscle morphology and daily physical activity. Linear mixed-effects models revealed significant effects of age and sex on mean firing rate: females showed...

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The long-term impact of common cardiovascular medications on sarcopenia in older people is unclear. The objective was to investigate whether long-term intake of statins and renin-angiotensin system inhibitors (RASi), i.e., angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), is associated with muscle mass, strength, and physical performance in community-dwelling older adults. This exploratory observational cohort study included 1083 participants of the Berlin...

Biomarkers of aging, particularly DNA methylation-based clocks, have shown promise as tools to assess whether interventions may impact the rate of biological aging. Among possible interventions physical exercise has shown protective effects against many age-associated diseases, while time-restricted feeding (TRF) has shown metabolic benefits in preclinical models. The combined effect of exercise and TRF on aging biomarkers remains largely unexplored. In this 52-week four-armed, randomized,...

Age-related strength loss may reflect morphological and neural adaptations that differ between muscles. However, it is unclear how ageing affects motor unit (MU) discharge rate modulation and estimates of persistent inward currents (PICs) across contraction levels. Thirty young (24 ± 4 years) and thirty older adults (73 ± 4 years) underwent magnetic resonance imaging and performed unilateral isometric dorsiflexion and knee extension contractions. Individual MU spike trains were identified from...

CONCLUSION: Barriers and facilitators should be addressed in policies to promote greater involvement of geriatricians in research and research consortia.

Assessment of biological aging using proteomic clocks may enhance risk prediction and elucidate the molecular links between aging and chronic diseases. Here, among 17,473 participants of the European Prospective Investigation into Cancer and Nutrition, we examined associations of plasma SomaScan-based proteomic clocks, including organ-specific clocks, with risk factors, 24 incident chronic diseases and all-cause mortality, over up to 28 years of follow-up. Replication was conducted in the...

Mitochondria play central roles in cellular metabolism and in key processes such as inflammation, stress response, cell death and signalling. Mitochondrial quality control (MQC) mechanisms continuously monitor organelle integrity and function, and repair or eliminate damaged mitochondria to replace them with newly formed, healthy organelles. MQC is particularly important under metabolic or environmental stress conditions. Failure of MQC paves the way to chronic diseases, such as diabetes,...

CONCLUSION: This study offers an empirically grounded, contextually situated understanding of well-being among older adults in an urban Indonesian setting, extending existing frameworks by foregrounding lived experience and relational interdependence.

CONCLUSIONS: Respondents demonstrated positive attitudes towards their own ageing in the domains of physical change and psychological growth, whereas more negative attitudes were observed in the psychosocial loss domain. Loneliness and depressive symptoms were significantly associated with a more negative self-perception of ageing among older adults. A more negative self-perception of ageing was also more frequently observed among respondents with a poorly developed social network, poorer...

CONCLUSION: Adults aged 65 and above in this study demonstrated a moderate level of resilience and lower well-being scores. Higher resilience scores were significantly correlated with increased subjective well-being. These results suggest that resilience acts as a vital internal resource that relates to mental health outcomes in the aging population, highlighting the potential for interventions focused on enhancing psychological strengths.