Aging & Longevity

CONCLUSION: Operational definitions of multimorbidity substantially influence prevalence estimates, while associations with mortality appear more robust across count-based approaches. Clustering analyses provide complementary insights into heterogeneity within multimorbid populations. Future translational studies are warranted to determine how multimorbidity definitions can be optimized to ultimately improve clinical management and health outcomes in practice.

Metaplasticity is homeostatic regulation of brain excitability through which neurons change their threshold for response based on synaptic history. Transcranial direct current stimulation (tDCS) induced metaplastic shifts in cortical excitability have been shown to improve motor learning in older adults. However, this has not been explored in the context of a fatiguing contraction. We aimed to explore modulation of fatiguing exercise performance, corticospinal excitability and gamma-aminobutyric...

As a cutaneous appendage, the hair follicle is tightly associated with the skin during growth, pigmentation, and aging. These two interconnected tissues share evolutionarily conserved regulatory mechanisms-including stem cell niche signaling, inflammatory cascades, and oxidative stress-and collectively function as hallmarks of systemic organismal aging. Hair abnormalities are well-established concomitant manifestations of aged skin. The crosstalk between skin aging and hair aging is particularly...

Declining tissue function and regenerative capacity underlie many chronic diseases. Experimentally establishing the mechanistic basis for such tissue aging presents substantial challenges, given decades-long timescales and multifactorial origins. Epigenetic alterations have been proposed to have a key etiological role, but whether they are correlative or causal remains a key unanswered question, as does their contribution to specific age-related pathologies. Here we describe an epigenetically...

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WNT proteins have been recognized as key regulators of skeletal health. However, developing WNT-associated bone anabolic agents is clinically challenging and expensive. Here we identify the reconstructed thumb and index domains of WNT7B (WNT7B^(RTID)) as a WNT-derived bone anabolic peptide via Alphafold-empowered sequence prediction and in silico docking screening. In aged mice and pigs models of osteoporosis, WNT7B^(RTID) peptides demonstrate therapeutic potential by improving the osteogenic...

Adipose tissue has emerged as a dynamic endocrine organ that coordinates systemic energy balance and cardiometabolic health. This Review highlights the dual humoral and neuronal pathways through which adipose tissue regulates systemic metabolism. Humoral signals include peptide hormones, lipid mediators, metabolites, chemokines and exosomal microRNAs secreted by adipose depots. Neuronal circuits control adipose function rapidly and precisely: sympathetic efferents trigger lipolysis in white...

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White matter hyperintensities are ubiquitous in magnetic resonance imaging scans of older adults and reflect multiple pathological causes, particularly cardiovascular and metabolic disease risk factors. Elevated white matter hyperintensity burden is a predictor of dementia, but the relationship between white matter hyperintensity progression and cognitive change in typical aging remains unclear, arguably due to the scarcity of longitudinal evidence. Here, we estimated white matter hyperintensity...

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.