Aging & Longevity

Age-related macular degeneration (AMD), characterized by pathologic choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. Vascular endothelial growth factor A (VEGFa) antagonists can prevent acute vision loss, but high treatment burden and loss of efficacy with chronic therapy highlight the need to explore alternative mechanisms. Recently, microRNA-34a (miR-34a) has emerged as a key regulator in aging and age-related diseases, but its role in neovascular AMD is...

Although the causal association between aging and osteoarthritis (OA) has been documented, our understanding of the underlying mechanism remains incomplete. To define the regulatory molecules governing chondrocyte aging, we performed transcriptomic analysis of young and old human chondrocytes from healthy donors. The data predicted that GATA-binding protein 4 (GATA4) may play a key role in mediating the difference between young and old chondrocytes. Results from immunostaining and western blot...

Aqueous zinc-ion batteries have advanced rapidly, but practical deployment is limited by excessive negative-to-positive (N/P) ratios (>50), decreasing the energy density. Zinc powder anodes can lower N/P, yet their high specific surface area accelerates parasitic reactions and shortens lifespan. Here we report a high-loading and highly reversible dry-processed zinc powder anode with a non-electrochemically driven solid-electrolyte interphase (SEI). The dry process retains a homogeneous...

Mild mitochondrial stress could extend lifespan across species, yet the underlying mechanism remains unclear. Here, we show that inhibition of mitochondrial respiration induces a sustained transcriptional program that enhances lysosomal proteolysis during aging in Caenorhabditis elegans. Mechanistically, this response is primarily regulated by the intestinal GATA transcription factor ELT-2, which retains high expression and directly binds to GATA motifs in the promoters of lysosomal protease...

Resting-state electroencephalography (EEG) provides a sensitive measure of large-scale neural dynamics and has been widely used to characterize age-related changes in brain function. However, many prior studies have relied on relatively small samples or single-condition recordings, limiting the generalizability of findings. In this study, we investigated normative age-related trajectories of EEG spectral features across eyes-closed (EC) and eyes-open (EO) conditions in a large cohort of healthy...

CONCLUSION: This study delineates two IC profiles among Chinese older adults. The XGBoost-based model was explored for rapid IC profile classification. These findings highlight heterogeneity in IC and support the feasibility of a simplified digital approach, with external validation warranted.

CONCLUSION: This study shows that the presence of MASLD is significantly associated with an increased risk of a worse depression trajectory. In subgroup analysis, this relationship was particularly pronounced amongst females and among individuals with key cardiometabolic morbidities such as dyslipidaemia.

Epidemiological links between cognition and body physiology in aging are well established, but their strength and drivers remain unclear. Which physiological systems - from body composition to cardiovascular, pulmonary, renal, hepatic, immune, metabolic, and musculoskeletal - best predict cognition, and to what extent are cognition-body associations linked to brain variation across aging? We examined 19 physiological phenotypes alongside three neuroimaging modalities in over 30,000 UK Biobank...

Myeloid cells, including microglia and perivascular macrophages, are central to Alzheimer's disease (AD) neurobiology, yet their role remains incompletely understood. We profiled 832,505 human myeloid cells from the prefrontal cortex of 1,607 donors spanning the lifespan and showing varying degrees of AD neuropathology. We delineated six subclasses comprising 13 transcriptionally distinct subtypes and identified adaptive changes associated with aging and AD progression. Here we show that a...

Senescence, which is defined as a state of stable cell cycle arrest, can occur in all tissues of the body. The surveillance and clearance of senescent cells by the immune system is necessary for tissue homeostasis; when this immune surveillance does not occur efficiently, for example, during tumorigenesis and ageing, it has pathological consequences. For example, if the immune clearance of senescent cells is evaded, such as through recruitment of immunosuppressive cells, expression of immune...

CONCLUSION: Isoorientin alleviates age-related bone loss by suppressing TLR4-mediated inflammation, reducing osteoclast activation, and restoring impaired osteogenesis. These findings identify isoorientin as a promising therapeutic candidate for age-associated osteoporosis.

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Aging is characterized by a decline in function of intestinal stem cells (ISCs), but the extent to which this is shaped by systemic factors is unclear. Here we show that the ISC aging phenotype can be propagated from old to young mice utilizing heterochronic parabiosis, and implicate a role for inflammation in these effects, as anti-inflammatory drugs, including TNF antibodies, restored function. Parabiotic rescue experiments demonstrate that TNFR1 knockout protected young ISCs from the old...

Aging is the major risk factor for neurodegenerative disease, yet the mechanisms linking physiological aging to brain dysfunction remain unclear. We investigated the brains of telomere-shortened mice and observed lipofuscinosis, hypomyelination, microglial atrophy, and cognitive deficits. Single-nucleus RNA sequencing (snRNA-seq) revealed accelerated glial aging and elevated microglial senescence pathways. In a senescence model of human induced pluripotent stem cell (iPSC)-derived microglia,...

Clonal hematopoiesis of undetermined potential (CHIP), initially discovered as a mere hematological curiosity, now represents a clinically significant factor that is changing our view of ageing, inflammaging and the risk of age-related diseases (ARDs). In line with this, new meta-analyses link the presence of CHIP to higher all-cause mortality from ARDs and to an increase in adverse events in the presence of larger clones. Mechanistically, CHIP induces inflammaging, but a bidirectional...

Aging is a complex, irreversible physiological process characterized by gradual deterioration of tissue structure and function, accompanied by impaired regenerative capacity, dysregulated immune homeostasis, and increased susceptibility to chronic age-related diseases (e.g., neurodegenerative disorders, metabolic syndromes, age-related skin lesions, and inflammatory bowel disease). In recent years, plant-derived extracellular vesicles (PDEVs), the lipid bilayer membrane vesicles released by...

Cellular senescence is a stress-response program characterized by durable proliferative arrest, but senescence entry does not determine a single biological outcome. Confusion between the fate of an individual cell and the behavior of a senescent-cell population has obscured interpretation across development, ageing and disease. This Review develops a fate-resolved framework that distinguishes continued arrest, cell death, physical shedding and, under restricted conditions, sustained...

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Phenotypic traits often covary through shared genetic and environmental influences, shaping the evolution of integrated life-history strategies. In particular, correlations between behavioral and life-history traits form the core of the pace-of-life syndrome (POLS) hypothesis, yet direct experimental tests of its evolutionary and molecular foundations remain limited. Here, we combined experimental evolution and transcriptomic analyses to investigate the phenotypic and molecular architecture of...

Astrocytes, oligodendrocyte lineage cells, and microglia dynamically shape the neural extracellular matrix (ECM) across brain development and aging. Recent findings highlight the potential of glial regulation of the ECM as a framework for understanding circuit formation and identify previously unrecognized targets in neurological diseases.