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Aging is associated with progressive deterioration of vascular function and cardiovascular risk. Cardiorespiratory fitness (CRF) is closely associated with cardiovascular health, yet longitudinal data in healthy older adults remain limited. This study examined 3-year changes in vascular and echocardiographic parameters in older adults and their associations with CRF and muscle strength. Forty-nine participants (mean age 63.8 ± 3.8 years) underwent vascular assessments (brachial/central blood...

Aging is a complex process influenced by various factors, including gut microbiota and food likings. Focusing on gut and dietary health is a crucial strategy for promoting long-term health and active aging. This study investigates the reciprocal causal relationships between gut microbiota, food likings and aging using Mendelian Randomization (MR) approaches. We leveraged the summary statistics of gut microbiota (n = 5,959), food likings (n = 161,625), and three aging phenotypes including...

The ubiquitin-proteasome system is essential for neuronal proteostasis, yet its function declines with age. How aging affects deubiquitylating enzymes (DUBs) in the vertebrate brain remains unclear. Here we used activity-based proteomics to profile cysteine protease DUBs in aging mouse and killifish brains. We identified a subset of DUBs that progressively lose catalytic activity with age despite stable protein abundance. Mechanistically, oxidative stress impaired DUB function through thiol...

Alternative lengthening of telomeres (ALT) is a recombination-based pathway enabling cancer cells to maintain telomeres. ALT establishment remains poorly understood due to difficulties identifying its molecular steps. Here, using Oxford Nanopore sequencing and computational modeling, we track the evolution of individual chromosome end structures during ALT establishment in yeast and delineate three molecular milestones. First, homologous recombination via break-induced replication (BIR) at...

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The naked mole-rat (NMR), Heterocephalus glaber, is an unusual mammal that lives underground in eusocial colonies. NMRs show remarkable longevity and are resistant to cancer, neurodegeneration, and cardiovascular disease. The gut microbiome is known to modulate human health and disease; here, we investigate the microbiome of NMRs, comparing fecal samples from individuals over different social ranks and over a span of more than three decades. In contrast to a cohort of C57BL6/J mice, which showed...

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The liver is a major metabolic organ, responsible for synthesizing and breaking down diverse metabolites. Recently, the liver's immunological functions have gradually been unveiled: combating pathogens and maintaining tissue homeostasis. Age-related functional alterations in these immune cells emerge as potential drivers of hepatic dysfunction and age-associated pathologies. However, systematic investigations into spatiotemporal immune cell dynamics during liver aging remain limited. To address...

As the global population ages, cellular senescence contributes increasingly to the burden of age-related diseases. Hallmarks of this process include telomere shortening and loss of proteostasis, frequently linked to DNA damage-associated transcriptional stress. Although telomere dysfunction-induced foci (TIF) have been well documented in lungs from patients with idiopathic pulmonary fibrosis (IPF), their occurrence and role during physiological lung aging remain unclear. Analysis of senescence...

Skeletal muscle mass and force decline with age, and the loss of muscle force precedes muscle atrophy. However, the underlying mechanisms remain unclear. Here, we investigated the role of the myosin co-chaperone, uncoordinated mutant number-45 myosin chaperone B (UNC45B), in regulating muscle mass and force. UNC45B expression decreased in mouse gastrocnemius muscle with age, particularly at 24 months old, and adeno-associated virus vector-mediated knockdown of Unc45b in 3-month-old mouse triceps...