Aging & Longevity

Investigating age-associated changes in intestine and understanding immune-related intestinal dysfunctions is essential for promoting healthy ageing. Mucosal surfaces represent a distinct immune compartment enriched with specialised lymphocytes that interact dynamically with the epithelial layer. In this study, we present novel spatially resolved insights into the cellular and molecular alterations in the ageing murine gut mucosa. Our findings reveal a complex network of interdependent...

T cell output from the thymus falls throughout life and is associated with profound remodeling of the thymic stroma. To what extent the decline in T cell output is caused by aging of the hematopoietic stem and progenitor cells (HSPCs) has been difficult to define because of HSPC heterogeneity, the multi-stage process of HSPC migration, and the cross-talk between hematopoietic and stromal elements of the thymus. To address the contribution of HSPC aging on T cell development, we interrogated T...

CONCLUSION: These findings identify oxidative stress and disrupted autophagy as key mediators of saturated-fat-induced neuronal decline and highlight a sex-specific vulnerability to dietary fat composition. This work establishes Drosophila as a powerful model for dissecting nutritional drivers of neural aging and suggests that metabolic stress pathways represent critical early targets in diet-associated neurodegeneration.

CONCLUSIONS: Personal EHR engagement among the vulnerable aging population is influenced by a complex interplay of patient, HCP, and technology-related factors, which must be addressed holistically to ensure inclusive usage and adherence to digital health tools.

Age-related declines in motor learning are commonly attributed to changes in sensorimotor neurophysiology. However, direct links between neurochemistry, electrophysiology, and behavior are scarce. Here, we investigated whether age-related differences in GABAergic inhibition and cortical reactivity mediate age-related simple and complex motor learning declines. To do so, we employed magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation-electroencephalography (TMS-EEG) in...

CONCLUSIONS: Low DOBS and accelerated PhenoAge were jointly associated with a higher likelihood of CMM among U.S. older adults, highlighting the potential relevance of dietary oxidative balance and biological aging in cardiometabolic multimorbidity.

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...