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Cellular senescence is a consequence of many chemotherapeutics that plays context-dependent roles in cancer. Senescent cells secrete an array of factors collectively known as the senescence-associated secretory phenotype (SASP). Here we show that the cisplatin-induced SASP enhances the detachment of high-grade serous ovarian cancer (HGSOC) cells in vitro and dissemination in vivo. We identify fructose as a metabolic component of the SASP that facilitates cell detachment and show that a...

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Despite several age-related processes impacting motor performance, older adults often retain the ability to implicitly adapt to sensory prediction errors. Here, we leverage the fact that implicit adaptation is not attenuated by aging to study the impact of aging on responses to motor errors. In other domains, such as reinforcement learning, aging has been shown to influence how task outcomes or rewards are processed and used to guide subsequent actions, with some studies emphasizing that older...

Understanding sex-dependent differences in disease risk, manifestation, and treatment response is essential for precision medicine. While funding agencies now mandate consideration of Sex as a Biological Variable (SABV), existing bioinformatics tools lack systematic approaches to characterize sex-related molecular mechanisms. Current practices frequently treat sex as a confounding variable, which may obscure important biological differences such as sex-specific alterations, sex-dimorphic changes...

Oocytes rely on a cohort of proteins whose sustained expression ensures normal meiotic progression and reproductive competence throughout an animal's reproductive life. Age-related declines in these proteins are a major cause of reduced oocyte quality and female fertility during reproductive aging. Here, we report that the cohesin regulatory protein PDS5B, a dynamically maintained factor in oocytes, declines with age and plays a noncanonical role in the spindle pole formation independent of its...

Inosine triphosphate (ITP) is a noncanonical nucleotide. Human cells possess inosine triphosphate pyrophosphatase (ITPA), and ITPA deficiency causes ITP accumulation within cells, leading to the onset of "Developmental and Epileptic Encephalopathy 35." Two potential pathways for ITP biosynthesis have been proposed: i) oxidative deamination of the adenine base in adenosine triphosphate or ii) a two-step phosphorylation reaction of inosine monophosphate (IMP), an intermediate in the de novo...

Lysosomal dysfunction is a well-recognized feature of aging. Here, we used a suite of tools for rapid lysosomal isolation to construct a multitissue atlas of the metabolite changes lysosomes undergo during aging. Aged lysosomes in brain, heart, muscle, and white adipose tissue accumulated glycerophosphodiesters and cystine, metabolites that are causally linked to juvenile lysosomal storage disorders, Batten disease, and cystinosis. Levels of these metabolites increased linearly with age,...

Changes in lysosomal metabolites are associated with both aging organs and lysosomal storage diseases.

Background and ObjectivesArtificial intelligence (AI) is increasingly used in healthcare decision-making to improve clinical efficiency and patient risk assessment. However, emerging evidence suggests these tools may disadvantage older adults from lower socioeconomic backgrounds, potentially worsening health disparities. This scoping review examines how AI-driven healthcare decision tools affect health outcomes among socioeconomically disadvantaged older adults.MethodsFollowing the Arksey and...

Declines in nicotinamide adenine dinucleotide (NAD+) are linked to metabolic stress accompanying aging and disease. While precursor-based approaches elevate systemic NAD, their clinical translation can be constrained by biosynthetic bottlenecks and first-pass metabolism. RENEWAL-NAD+ (ClinicalTrials.gov NCT07336836; retrospectively registered 01/04/2026) was a double-blind, randomized, placebo-controlled Phase 0/1b trial in healthy adults aged 45-75 years (60 randomized; primary analysis n = 50)...

CONCLUSION: The co-occurrence of slow gait and mild cognitive impairment (MCI-SG) represents a distinct high-risk clinical phenotype strongly linked to AD pathology. Aβ and APOE ε4 show differential associations across the gait-cognitive spectrum. Integrated assessment of gait and cognition improves risk stratification in older adults and may guide early intervention strategies.

Underrepresented populations, often characterized by minority ethnicity, sex/gender or low socioeconomic status, have a higher risk burden and more adverse lifetime experiences of conditions negatively impacting cognitive health than better represented populations. There are several methodological challenges of research in and with marginalized populations that hinder research on improvements to their cognitive health. This review aims at presenting challenges of recruitment, data collection,...

The self-renewal and differentiation of stem cells are tightly controlled to maintain tissue homeostasis. Failure in stem cell maintenance results in stem cell depletion and precocious aging. However, how stem cells are maintained still remains not fully understood. Here, through a large-scale RNAi screen for maintenance and proliferation of adult Drosophila intestinal stem cells (ISCs), we identify several subunits of V-ATPase including Vha68-2/ATP6V1A, required for ISC proliferation,...

Cardiac fibrosis, a major pathological hallmark of aging that leads to heart failure, is characterized by excessive collagen deposition. Our knowledge of what sustains collagen synthesis in the aging heart is still very preliminary. Here, we uncover a central role for chaperone-mediated autophagy (CMA), a selective lysosomal degradation pathway, in this process. We demonstrate that CMA is suppressed in the aging heart, which promotes collagen overproduction in fibroblasts, whereas enhancing CMA...