Aging & Longevity

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...

Microglia, the resident macrophages of the central nervous system (CNS), are key players in maintaining brain and spinal cord homeostasis and protecting the CNS from damage and disease. During aging, the brain undergoes profound changes-including chronic low-grade inflammation, synaptic dysfunction, and increased vulnerability to neurodegenerative diseases-all of which are closely related to alterations in microglial function. One emerging theme is that microglial metabolism is a crucial...

Telomere length (TL) is a well-established biomarker of biological ageing, sensitive to cumulative physiological and psychosocial stress. This review synthesises current evidence on how pregnancy, postpartum stressors, and reproductive history shape maternal biological ageing, integrating findings from telomere biology and emerging epigenetic ageing measures. Pregnancy represents a period of substantial metabolic, hormonal, and immunological demand and is increasingly conceptualised as a...

Chronic subdural hematoma (CSDH) is among the commonest cranial neurosurgical conditions of older adults and is projected, on the basis of incidence modeling, to become the most common cranial neurosurgical condition in adults by 2030. Despite this clinical centrality, CSDH has not been formally examined through the conceptual lens of geroscience. This minireview reframes CSDH as a geroscience disease by mapping its pathogenesis onto the twelve hallmarks of aging articulated by López-Otín and...

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by the early development of pathological features associated with aging, ultimately leading to premature death. HGPS primarily affects tissues of mesenchymal origin, as evidenced by the clinical manifestations characteristic of this premature aging disorder, including, but not limited to, osteoporosis, muscle wasting, lipodystrophy, and cardiovascular disease. In this study, we used preclinical mouse models and...

The incidence of breast cancer shows its largest peak around the age of 65 but also a peak around 45 indicating a bimodal distribution. While some potential explanations, such as age-related enrichment in specific breast cancer sub-types and BRCA1/2 mutations were proposed, they do not explain why the peaks are at 45 and 65, raising the possibility that the way the breast ages may play a role. Here using two mouse models, we show two distinct aging patterns of the mammary gland; one being...