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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,...

The Endless Frontier traces the lives of three scientists as they train students and deal with funding pressures