Aging & Longevity

Advanced age is a major determinant of adverse outcomes during acute infections, yet the immunological mechanisms by which aging alters immune regulation and shapes disease trajectories remain poorly understood. Using SARS-CoV-2 infection as a model of acute viral challenge, we investigated how aging alters myeloid responses in the lungs. Across infected mouse models and human cohorts, disease severity was associated with a pronounced shift in myeloid balance, characterized by an increased...

Frailty is a dynamic and potentially reversible condition, yet limited evidence has examined whether oral functional limitation is associated not only with frailty onset but also with long-term frailty transitions. We analyzed 6-year prospective data (2016-2023) from 2731 community-dwelling adults aged 70-84 years in the Korean Frailty and Aging Cohort Study. Oral functional limitation was defined as self-reported difficulty in chewing or pronunciation. Frailty was assessed using Fried's...

CONCLUSIONS: Abnormal health indicators among rural older adults exhibit a metabolism-centered and systemically interconnected co-occurrence pattern. Fatty liver, diabetes, and hypertension are structurally central nodes in the network, highlighting their prominence rather than implying causality. Females show stronger indicator interconnections, and advanced age is associated with more complex co-occurrence patterns. These findings provide network-based, hypothesis-generating evidence to...

CONCLUSIONS: Social frailty was independently associated with all-cause mortality among older adults in this Colombian regional cohort. These findings suggest that incorporating social vulnerability measures into geriatric assessment may improve risk stratification and help identify individuals who could benefit from supportive interventions.

CONCLUSION: Digital technologies provide a limited but meaningful contribution to sustaining social cohesion among older adults in rural, conflict-affected Myanmar by supporting communication, emotional connection, and access to information. However, their contribution remains uneven, as structural inequalities, political constraints, and infrastructural limitations continue to restrict equitable access. Addressing these challenges requires context-sensitive, age-appropriate digital inclusion...

Autophagy constitutes a major adaptive response that preserves cellular and organismal homeostasis during stress. However, stress responses also engage systemic communication pathways that may either maintain resilience or propagate pathology. We previously identified acyl-CoA-binding protein, also known as diazepam-binding inhibitor (DBI/ACBP), as a phylogenetically conserved extracellular factor secreted by stressed cells through an unconventional autophagy-dependent pathway. Once released,...

Adult stem cells are essential for maintaining tissue homeostasis and facilitating tissue repair. The ability of aged stem cells to generate functional progeny declines, which is closely associated with the onset and progression of age-related diseases. The aging of adult stem cells in various tissues is regulated jointly by local microenvironments (stem cell niches) and systemic factors. Caloric restriction (CR), a widely studied anti-aging strategy, has been demonstrated to rejuvenate aged...

Cellular senescence plays a critical role in diabetic nephropathy (DN). Understanding the mechanisms underlying the senescence response is therefore essential for developing effective therapies for DN. In this study, we provide evidence that NAT10 expression was markedly elevated in the kidney tissues of patient with DN and was associated with adverse clinical outcomes. NAT10 directly bound to PAPP-A, induced ac4C acetylation modification of the PAPP-A transcript, and enhanced its stability,...

Advances in proteomics are transforming our understanding of mammalian oocyte maturation and preimplantation embryo development. These resources and their findings provide unprecedented insights into the molecular underpinnings of developmental competence. Here we summarize the ongoing development of proteomic methodologies and highlight the stage-specific reprogramming events of the proteome in both humans and mice, underscoring the unique utility of proteomics in deciphering oocyte maturation...

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Cellular senescence comprises diverse cell states emerging across human tissues during aging and disease. Integrating single-cell and spatial multi-omics with AI-driven analyses enables systematic mapping of senescent cell heterogeneity ("senotypes"), revealing tissue-specific programs and microenvironmental interactions. These advances provide frameworks for biomarker discovery and development of targeted senotherapeutic strategies.

Microglia are brain-resident immune cells with complex physiological functions. Exploring their proteomic heterogeneity at the single-cell level has remained technically challenging. Here, we optimized a label-free single-cell proteomics (SCP) workflow using Orbitrap Astral mass spectrometry (MS) and applied it to fluorescence-activated cell sorting (FACS)-sorted microglia from the hippocampus and prefrontal cortex of young, middle-aged, and aged mice. This yielded one of the largest SCP...

Cellular senescence is implicated in age-related pathologies, and identifying circulating biomarkers of senescence holds great diagnostic potential. Circulating senescence signatures are predictive of age-related traits and diseases, though cell type senescence signatures have not been comprehensively explored. In this study, senescence signatures from the Senescence Catalog (SenCat), including 14 human cell types are examined in circulation for clinical relevance in two longitudinal...

There is an urgent need to comprehensively catalog senescence markers across cell types in an organism in order to characterize senescent-cell heterogeneity. Here, we profiled the transcriptomes and proteomes in 14 different primary human cell types undergoing over 30 senescence paradigms to create a senescence catalog we termed "SenCat." We found that while senescent cells from all primary cell types did not share a single unique marker, they did activate shared specific metabolic and...

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White matter hyperintensities (WMHs) are increasingly recognized as neuroimaging biomarkers of cerebrovascular pathology in Alzheimer's disease (AD), yet their temporal relationship with amyloid and tau accumulation remains unclear. While previous studies suggest bidirectional associations between WMHs and AD pathology, regional associations between WMHs and AD pathology have yet to be examined. This study investigated the temporal and regional associations between PET measures of amyloid (Aβ)...

Similarities and differences in the self-assembly of actin filaments from different species inform our understanding of its evolution. However, this basic knowledge is largely incomplete. Here, we systematically characterize assembly kinetics for actin from two yeast species that are five hundred million years apart in evolution, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and compare them to the well-studied rabbit muscle actin from which they diverged a billion years ago. We find...

CONCLUSION: Awareness of age-related losses may be adaptive when it reflects realistic recognition of age-related challenges, like hearing difficulties. Promoting positive, gain-focused views of aging could support earlier informal help-seeking among older adults by encouraging open conversations about hearing concerns within their close social networks.

Cancer and cell-aging studies may have relied on antibodies to incorrect molecule.

Labor is mediated proximately by prostaglandin signaling within gestational tissues and must be tightly regulated for birth to occur after appropriate fetal development. Metabolic changes accompanying gestational aging have been postulated as a determinant of birth timing, but specific nutrients, sensors, and messengers remain obscure. We report that placental nicotinamide adenine dinucleotide (NAD^(+)) dynamically tunes gestational length. Depletion of placental NAD^(+) in mice provoked labor...