Aging & Longevity

Three-dimensional ultrasound shape analysis reveals distinct structural patterns in muscle aging and sarcopenia

1 day 1 hour ago
CONCLUSION: Aging and sarcopenia induce distinct and measurable muscle shape alterations. Advanced shape modeling, particularly using INR, showed higher sensitivity. Rectus Femoris emerged as a promising candidate for a shape-based biomarker. Although the metrics presented here should not be interpreted as classification metrics, this study provides a reproducible, open-source framework for muscle shape analysis relevant to aging research.
Jeremie Huet

Beyond the Barrier: Physiological Determinants of Nanoformulation Availability in the Aging Brain

1 day 1 hour ago
Nanomedicine has revolutionized brain-targeted therapeutics; however, most design paradigms remain centered on overcoming the blood-brain barrier while overlooking the dynamic physiological milieu that governs nanoparticle fate after entry. Emerging evidence reveals that barrier penetration alone is insufficient to ensure efficacy, particularly in the aging brain, where vascular stiffness, impaired interstitial flow, reduced glymphatic clearance, and chronic immune activation reshape...
Ruei-Dun Teng

Protein thiol alterations drive pathologic liquid-liquid phase separation in the aging brain

1 day 1 hour ago
Cellular homeostasis relies on regulation of processes, including protein post-translational modifications (PTMs) and biomolecular condensation. Aging disrupts the equilibrium of these processes, increasing susceptibility to disease and mortality. Here we used chemoproteomic techniques to generate an atlas of cysteine PTMs in the mouse brain and showed that age-related increases in thiol oxidation promoted the formation of biomolecular condensates. By contrast, protein persulfidation, regulated...
Thibaut Vignane

The chemotherapy-induced senescence-associated secretome promotes cell detachment and metastatic dissemination through metabolic reprogramming

1 day 1 hour ago
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...
Aidan R Cole

Mistakes matter, age doesn't: task outcome modulates implicit motor adaptation similarly in young and older adults

1 day 1 hour ago
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...
Matheus Maia Pacheco

Insufficiency of cohesin regulatory protein PDS5B triggers meiotic failure and aneuploidy in oocytes during advanced maternal aging

1 day 1 hour ago
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...
Yu Zhang

Guanylate kinase 1 is an enzyme responsible for inosine accumulation in RNA of mammalian cells deficient in inosine triphosphatase

1 day 1 hour ago
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...
Daisuke Tsuchimoto

Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders

1 day 1 hour ago
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,...
Anna M Puszynska

Algorithmic Inequity in Aging: How AI-Driven Healthcare Decision Tools Amplify Socioeconomic Disparities in Health Outcomes Among Older Adults

1 day 1 hour ago
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...
Isaac Eshun

Oral LNAD+ rapidly elevates whole blood intracellular NAD and metabolic flux without elevating plasma NAD: evidence from a randomized controlled trial

1 day 1 hour ago
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)...
Sergey A Kornilov

Dual decline in gait and cognition as a high-risk clinical phenotype: differential associations with cerebral amyloid-<em>β</em> deposition and the apolipoprotein E ε4 allele and implications for integrated assessment

1 day 1 hour ago
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.
Chenxi Ren

Methodological innovations in studying marginalized populations in research on neurodegeneration and ageing

1 day 1 hour ago
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,...
Anja K Leist

Inactivation of V-ATPase induces autophagy and ectopic Notch activation to promote intestinal stem cell differentiation in adult <em>drosophila</em> midgut

1 day 1 hour ago
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,...
Zhengran Li

Targeting chaperone-mediated autophagy by nutritional interventions mitigates age-related cardiac fibrosis and diastolic dysfunction

1 day 1 hour ago
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...
Ziwen Wang

CRISPR screens identify targets to rescue age-related T cell dysfunction in cancer

2 days 1 hour ago
Immune aging impairs T cell-mediated tumor control as well as cancer immunotherapy outcomes. The most important drivers of T cell dysfunction in aged tumors remain unknown. We performed single-cell CRISPR screens to identify Dusp5 and Zfp219 as key regulators of CD8^(+) T cell persistence and effector differentiation within aged tumors. Loss of Dusp5 increased extracellular signal-regulated kinase (ERK) phosphorylation and globally enhanced T cell proliferation. Conversely, Zfp219 deletion...
Alex C Y Chen

Restoring testosterone homeostasis: The therapeutic potential of stem Leydig cells for late-onset hypogonadism

2 days 1 hour ago
Late-Onset Hypogonadism (LOH), also known as male menopause syndrome, is a common health problem plaguing middle-aged and elderly men. Its core pathophysiological change lies in the progressive decline of testosterone levels in men with age. This leads to a series of symptoms involving sexual function, physical, and psychological aspects, seriously affecting the quality of life and overall health of patients. The core pathophysiological link of LOH lies in the progressive decline of testosterone...
Shenghan Xu
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