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Centromeres are essential regions of the genome that ensure chromosome segregation during mitosis but are also hotspots for chromosome breaks and rearrangements in cancer. The mechanisms underlying this fragility are not fully elucidated. Here, we show that oxidative DNA damage destabilizes centromeres and promotes chromosome instability. Using a chemoptogenetic system to generate singlet oxygen locally at centromeres, we uncouple centromeric oxidative damage from global oxidative stress....

Aging is characterized by a progressive decline in cellular homeostasis accompanied by chronic, low-grade sterile inflammation, termed inflammaging, which contributes to the development of neurodegenerative, cardiometabolic, and neoplastic disorders. Although inflammaging represents a convergence point of multiple hallmarks of aging, the molecular networks linking these processes remain incompletely understood. Here, we propose the Aging Purinome as a systems-level framework describing the...

Transcriptomic surveys of aging tissues routinely report hundreds to thousands of differentially expressed long non-coding RNAs (lncRNAs), and the field has no agreed way of separating causal drivers from passengers that merely track the aging phenotype. I translate Sir Austin Bradford Hill's nine criteria for causal inference, formulated in 1965, into operational tests for aging-associated lncRNAs. Each criterion is recorded as 0, 1 or 2, and the per-criterion profile is the result: no sum or...

Senescence has been shown to contribute to the progression of aging-related diseases including degenerative disc disease (DDD). However, the mechanisms regulating senescence in the intervertebral disc (IVD) and other tissues/diseases remain poorly understood. Recently, ZNF865 (BLST) was identified as a previously uncharacterized zinc finger protein that regulates a wide array of genes related to protein processing, cell senescence, and DNA damage repair. Here, we show that ZNF865 expression...

Chronic diabetic wounds may fail to heal because immune cells remain locked in damaging inflammatory states instead of transitioning toward tissue repair. Researchers are exploring treatments that reprogram these immune responses, raising hopes for more targeted and effective therapies for diabetic ulcers.

Depression may not be one biological condition, but several distinct patterns of brain activity hiding under the same diagnosis. Researchers studying 263 people with depression identified five brain profiles, each showing different patterns of communication between brain regions and associations with symptoms such as anxiety, trauma, and substance abuse.

Teams led by physicist used “BootLoops” software to produce 36 papers in weeks on everything from linguistics to health policy

A six-month study suggests that high-intensity interval training (HIIT) may offer older adults a powerful advantage: losing body fat while keeping their muscle. Unlike moderate-intensity workouts, which led to a small loss of lean muscle, HIIT preserved it while also improving body composition around the waist.

Improving operational lifetime remains a major challenge for blue organic light-emitting diodes (OLEDs) harvesting triplet excitons. Achieving substantial lifetime enhancement requires analytical techniques that elucidate degradation mechanisms. Because conventional lifetime analysis involves destructive aging tests, developing non-invasive methods that correlate strongly with device longevity is highly desirable. Here, we show that the operational lifetime of blue phosphorescent OLEDs...

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The abundance of diverse naive CD8^(+) T cell clones is essential for broad protection against infection and cancer, but how sex and aging jointly shape this compartment remains poorly understood. Here, using mouse models with supporting human data, we uncover a sex-biased mechanism of immune aging in which early male-biased depletion of naive CD8^(+) T cells driven by accelerated, antigen-agnostic differentiation into virtual memory cells combines with thymic involution, limiting naive CD8^(+)...

Ageing is characterized by a progressive decline in mitochondrial integrity that extends beyond impaired energy production to include redox imbalance, defective quality control, altered organelle dynamics, and persistent inflammatory signalling. This review examines mitochondrial dysfunction as a mechanistic bridge linking bioenergetic failure to cellular senescence and inflammaging, two central features of biological ageing. We discuss how impaired oxidative phosphorylation, loss of...

CONCLUSION: This study defines a cognitive impairment subtype primarily driven by education poverty and digital exclusion, which is prone to be missed in routine memory-centric screenings. The findings suggest that biomedical interventions alone may be insufficient to prevent such decline; promoting digital inclusion among older adults should be regarded as a critical public health strategy to compensate for early-life educational deficits and prevent the decline of calculation and executive...

Parkinson's disease (PD) is a systemic disorder linked to gut dysbiosis, yet key microbiota-regulated metabolites remain unclear. Here, we observe elevated taurochenodeoxycholic acid (TCDCA) in patients with PD that correlates with disease severity. Reduced bile salt hydrolase (BSH) gene abundance correlates inversely with circulating TCDCA, consistent with altered bile acid deconjugation. Exogenous TCDCA correlates with aggravated motor and gastrointestinal deficits, impaired blood-brain...

Tau phosphorylation is classically associated with neurodegeneration, yet similar phosphorylation patterns emerge during physiological states and acute stress responses. How these overlapping patterns of phosphorylated Tau (pTau) relate to neuronal adaptation and Alzheimer's disease pathology remains unresolved. We synthesize findings from human to rodent and fly brains and from neuronal cell models, across neurodevelopment, sleep, hibernation, cellular stress, and disease. Across these...

Alzheimer's disease (AD) presents distinct extracellular, intracellular and vascular delivery targets, yet brain exposure of candidate therapeutics remains difficult to establish. This narrative review compares hyaluronic acid, chitosan, cyclodextrin, dextran, alginate and pectin systems by construct architecture, route, blood-brain barrier (BBB) evidence, cargo release and biological response. The literature includes covalent drug conjugates, loaded or coated carriers, host-guest complexes and...

Human immune aging is heterogeneous, with immune responses becoming increasingly variable over the lifespan. Here, we integrated seven large-scale public single-cell peripheral blood mononuclear cell (PBMC) datasets and a newly generated cohort, encompassing 2,609 ostensibly healthy individuals across diverse ages, ancestries, and biological sexes. We identified both conserved and cohort-associated age-associated remodeling across 59 immune populations, together with sex- and ancestry-dependent...