Aging & Longevity

Frailty, defined by multisystem physiological decline and heightened vulnerability to stressors, is typically associated with aging and chronic disease. However, its relevance in apparently healthy individuals remains poorly understood. Identifying frailty in this population could inform primary prevention, as these individuals often remain outside healthcare systems. We investigated the association between frailty and incident chronic conditions and mortality in middle-aged adults free of...

Despite the substantial variability in physical function among older adults, the molecular mechanisms remain poorly characterized, particularly within skeletal muscle. This study aimed to determine the patterns of DNA methylation in skeletal muscle associated with physical function in healthy older adults. We analyzed DNA methylation (EPIC v2 array; 875,554 CpG sites) in skeletal muscle from 92 healthy older adults (median age 74; 62% female). Associations were examined across five phenotypes:...

Rapamycin supplementation has been reported to extend life spans in numerous species, including Drosophila melanogaster, but a recent study in this laboratory revealed a marked life-shortening effect in y w male flies. The experiments reported here were performed to characterize conditions under which rapamycin could extend or shorten life spans in five fly strains. On a cornmeal/torula yeast-based medium, rapamycin extended life in one experiment, had no effect in six and was harmful in 19. On...

CONCLUSIONS: Grab bar installations provided by community paramedics to community-dwelling older adults with a prior fall resulted in a significant reduction in fall-related EMS activations. This prevention approach demonstrates high potential for community paramedicine to offer an evidence-based intervention targeting at-risk older adults.

Young patients with traumatic brain injury (TBI) have a better prognosis than the aged, but the underlying mechanisms are not clear. Here, we identified a population of IL-19^(+) monocytes derived from cranial bone marrow appearing in the brain after TBI. IL-19^(+) monocytes inhibit the glial hyper-response and promote neurological recovery after TBI through the IL-19/IL-20R axis, which is defective in aged patients. Further studies have proven that CX3CR1 on the IL-19^(+) monocytes is attracted...

Population aging represents one of the most significant social transformations of our time, with profound implications for health systems, social protection, and intergenerational solidarity. By 2050, 1 in 6 people globally will be aged 60 years or older, with the fastest growth occurring in low- and middle-income countries least prepared to respond. Alongside demographic shifts, sociocultural transitions-urbanization, changing family structures, and increased women's labor participation-are...

Central nervous system (CNS) disorders are fundamentally linked to metabolic dysregulation within immune and glial cells. This review provides a systematic synthesis of immunometabolic reprogramming-encompassing glucose, lipid, and amino acid metabolism, and oxidative phosphorylation-in CNS-resident microglia, immunomodulatory astrocytes, and peripherally infiltrating immune cells (T cells, B cells, and neutrophils) across Alzheimer's disease, Parkinson's disease, multiple sclerosis, and...

Aging reshapes neurotransmitter systems through nonlinear and region-specific shifts that alter excitatory-inhibitory balance, weaken metabolic coupling, and destabilize large-scale neural networks. PET, MRS, molecular MRI, and optical imaging quantify elements of these trajectories, but modality-specific artifacts, cross-site variability, and limited spatial or temporal resolution fragment mechanistic interpretation. Artificial intelligence now enables the integration of these heterogeneous...

Impaired oligodendrocyte precursor cell (OPC) differentiation limits myelin renewal in aging and contributes to multiple sclerosis (MS) progression. How aging drives OPC deficits remains incompletely understood. We find dysregulation of genes associated with the circadian clock, including Bmal1, and metabolism in aged compared with young OPCs. Targeted loss of Bmal1 in OPCs drives metabolic dysfunction, leading to cellular senescence and impaired dynamics. OPC proliferation and differentiation...

CONCLUSION: AI-based CT volumetry identifies low skeletal muscle volume as an independent predictor of long-term mortality after TAVI. Muscle quantity, rather than muscle quality, appears to be the dominant prognostic determinant. AI-driven body composition analysis may serve as an imaging biomarker of biological aging and reduced physiological reserve in older adults undergoing TAVI.

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De novo mutations (DNMs) are an important source of congenital diseases. With delayed parenthood and assisted reproductive technology (ART) use increasing, it is essential to elucidate how these reproductive factors influence DNMs and whether resulting mutations influence offspring health. Here we performed whole-genome sequencing of 24,030 individuals from 7,851 parent-offspring families, identifying 390,924 de novo single-nucleotide variants (dnSNVs). Paternal and maternal aging exhibited...

Dementia arises from multifactorial neurodegenerative processes, with growing evidence implicating blood-brain barrier dysfunction, neuroinflammation, and vascular injury as contributors to progressive brain tissue damage. Because decline in white matter microstructural integrity is a prominent feature of brain aging, biomarkers that capture this process may improve dementia risk stratification beyond conventional clinical factors. Fractional anisotropy (FA), derived from diffusion tensor...

White matter integrity is a sensitive marker of cerebrovascular health and aging. Physical activity may promote white matter health, but previous studies were limited by self-reported activity and small sample sizes. We examined the association between accelerometer-based physical activity and novel indices of white matter integrity while identifying potential mediators. We analyzed cross-sectional baseline data from 4188 participants (58% women, mean age: 55.4 years) of the Rhineland Study, a...

CONCLUSION: GTC in older trauma patients helps identify delirium and potentially reduces the need for antipsychotics and improves mortality. A randomized controlled trial is needed to verify these findings.

Recent studies debate whether caldera-forming silicic magma is primarily stored in a crystal-poor, eruptible state for >100,000 years (kyr) ("warm storage") or exists as a crystal-rich "mush" with defrosting events causing brief periods (<1 kyr) of eruptibility ("cold storage"). To address this, we examined Aira Caldera (Japan), where the 400-cubic kilometer Aira-Tanzawa (AT) eruption (30,000 years ago) was preceded by three smaller eruptions over 3.5 kyr. All eruptions consist of roughly...

To date, the identity and maintenance of postnatal thymic epithelial progenitor cells (TEPCs) remain unclear, as does the persistence of bipotent TEPCs after birth or whether lineage-restricted progenitors independently maintain separate TEC compartments. Using an inducible lineage-tracing system based on expression of the thymoproteasomal protein β5t, which is expressed in embryonic and a subset of postnatal TEPCs, we explored the early dynamics of the relationships between thymic epithelial...

Chronic oxidative stress has long been implicated in renal pathologies, but whether sustained oxidative damage primarily promotes chronic kidney disease (CKD) or tumorigenesis remains unclear. To address this question, we investigated the long-term effects of oxidative stress on human embryonic kidney (HEK293T) cells chronically exposed to a low dose of hydrogen peroxide (H(2)O(2), 50 μM H(2)O(2)) for 9 months, generating two adapted lines, 50R30 and 50R45. These cells exhibited enhanced...

Aging is a multifactorial process affects different tissues and organs and is modulated by genetic and environmental factors. In aging, the frequency of DNA repair errors and genomic instability are augmented. Depletion of endogenous antioxidant capacity during aging promotes the development of oxidative stress which triggers oxidative stress-induced DNA injury. Brain aging is manifested by cognitive impairment and memory disorders. Development of neuronal senescence is the major pathway in the...

Cognitive aging is shaped by genetic variation, environmental factors, and health-related conditions. Until now, it is largely unclear why some individuals maintain their cognitive function, and others show progressive cognitive decline. This study uncovered determinants of distinct cognitive aging trajectories in the older population. To approach the inter-individual variability in cognitive aging, we clustered n = 696 dementia-free individuals from the prospective TREND study based on their...