Aging & Longevity

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.

CpG dinucleotides are mutational hotspots due to spontaneous deamination of 5-methylcytosine (5mC), resulting in T:G mismatches that can lead to CpG>TpG transitions. These mutations are a hallmark of aging and cancer and play a central role in the evolution of vertebrate genomes. We have previously uncovered MBD4 as the primary base excision repair (BER) glycosylase responsible for 5mC deamination repair. Here, we employ an APOBEC1 deaminase fused to a catalytically dead Cas9 to induce targeted...

Reductive stress has remained underappreciated as a significant disrupter of redox homeostasis. Recent studies have begun to link the accumulation of NADH and NADPH to the development and progression of metabolic diseases such as cancer, cardiac disease, and diabetes. In this study we use the nematode Caenorhabditis elegans to examine the phenomenon of catastrophic reductive-death caused by combined biguanide treatment and fasn-1 deficiency. This process of synergistic biguanide-induced...

BackgroundAmenable mortality, deaths preventable through timely and effective healthcare, is a widely used indicator of health system performance, yet evidence is lacking on its individual-level determinants in Brazil.MethodsWe used data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), a representative cohort of adults aged 50 and older. Deaths were classified as amenable using both the Brazilian and the Pan American Health Organization's definitions. Semi-parametric competing risks...

Neurons accumulate somatic mutations with age, but how mutation processes vary among neuronal types remains unclear. Characterizing this variability may elucidate the role of genome integrity in brain function and disease and reveal determinants of mutation rates and patterns. Using high-fidelity duplex DNA sequencing, we profiled somatic mutations across the lifespan in human cerebellar Purkinje and granule neurons, which differ markedly in size and physiology. Surprisingly, they exhibited...

Dioscin, a naturally occurring steroidal saponin isolated from various kinds of herbs with pleiotropic pharmacological properties, remains mechanistically undefined regarding its mammalian aging modulation. This study discovered that dioscin extended the lifespan of Caenorhabditis elegans. Concurrently, dioscin improved the motor function of C. elegans and reduced age pigment accumulation, while having no effect on the reproductive performance of the C. elegans. By pathway screening, we...

Cardiac aging is a central biological process underlying most cardiovascular diseases. Lysosomes, once regarded as terminal degradative compartments, are now recognized as dynamic metabolic and signaling hubs whose dysfunction has profound consequences for the aging heart. Human lysosomal storage disorders provide compelling evidence that isolated lysosomal defects are sufficient to cause early cardiomyopathy, underscoring the myocardium's exceptional dependence on sustained lysosomal...

Parkinson's disease (PD) is an age-associated neurodegenerative disorder in which affective non-motor symptoms substantially contribute to disease burden, yet their neurobiological basis remains incompletely understood. We investigated region-specific alterations of corticotropin-releasing hormone (CRH) family neuropeptides in a rotenone-induced rat model of PD and evaluated the effects of combined dopaminergic (benserazide/L-DOPA) and antidepressant (fluoxetine) treatment. Motor performance,...

Frailty syndrome, characterized by diminished physiological reserves and heightened vulnerability to adverse health outcomes, is a major concern in aging populations. Physical activity (PA) is a proven intervention for frailty syndrome prevention and treatment, but evidence on how different intensities, durations, and doses of PA affect frailty and survival in China populations remains limited. We analyzed data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally...

Identifying biological and clinical signals that consistently predict physical resilience, defined as one's ability to maintain or regain function following a health stressor, is essential for advancing precision approaches to aging and recovery. High-dimensional datasets hold tremendous promise but pose analytic challenges due to correlation, distributed signals, instability, and sensitivity to analytic choices. The complexity of these data requires strategies that prioritize transparency and...

CONCLUSIONS: IC impairments, severity, and patterns independently predicted fall-related ED visits. Integrating ICOPE screening into primary care may enhance fall prevention strategies.

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Knee osteoarthritis (KOA) is a leading cause of late-life pain, mobility loss, and disability, and is increasingly recognized as a phenotype-dependent manifestation of joint aging rather than a purely mechanical disorder. Cellular senescence, inflammaging, mitochondrial dysfunction, synovial inflammation, vascular remodeling, and impaired repair capacity converge to shape KOA symptoms and progression. This narrative review synthesizes evidence on conservative and minimally invasive KOA therapies...

Successful repair after brain injury requires a chain of events, including the generation, migration, and successful integration of adult-born neurons into preexisting circuits. In mammals, the capacity for neuronal regeneration is extremely limited and further declines with age, constraining recovery. Regeneration-competent vertebrates offer a unique opportunity to uncover mechanistic principles of seamless brain repair. We here introduce the African turquoise killifish, a naturally short-lived...