Aging & Longevity

Ocular age estimates derived from fundus photographs, optical coherence tomography, ocular fluids, systemic omics, and multimodal models are increasingly reported in years. The eye is unusually tractable for organ-specific aging research because it is paired, repeatedly imageable, locally treatable, and linked to quantitative function. The familiar scale can obscure differences in what was measured, what the model was developed to predict, which quantity is reported, and what the study design...

Sensory degradation with aging can impair balance control, partly by disrupting visual contributions to self-motion estimation. We investigated age-related differences in center of mass (CoM) trajectories controlling in the frontal plane during exposure to repeated visual perturbations in walking. We hypothesized that the older adults would show larger responses to visual perturbations and less adaptation to repeated visual perturbation exposure. We applied three visual perturbations to 14...

Lysosomal decline and proteostasis collapse are defining features of aging and major contributors to neurodegenerative vulnerability, yet interventions that preserve neuronal lysosomal function across aging remain poorly defined. Here, we identify 20(S)-ginsenoside Rg3, a ginseng-derived natural product, as a geroprotective small molecule in Caenorhabditis elegans. Rg3 extended lifespan and preserved key physiological outputs, including locomotion and pharyngeal pumping, indicating that Rg3...

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...

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...

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...

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...

A growing body of preclinical research is demonstrating the therapeutic potential of chronic, continuous hypoxia (11% FIO(2)) for rare and common diseases. However, the chronic delivery of hypoxic gas poses both practical challenges and long-term safety concerns. We previously introduced a small-molecule, "hypoxia-in-a-pill" combining a hemoglobin affinity enhancer (GBT440) to limit oxygen delivery with a HIF-2α inhibitor (PT2399) to prevent detrimental compensatory erythropoiesis. Although this...

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are standard therapies for estrogen receptor-positive breast cancer, but their efficacy is limited by drug resistance. While dysregulation of alternative splicing has been implicated in cancer progression, the underlying mechanisms remain unclear. Here, we uncover a splicing-mediated mechanism whereby exon 2 inclusion in SUV39H2 drives its overexpression in CDK4/6i-resistant breast cancer cells. Clinically, elevated exon 2 inclusion in SUV39H2...

As an important component of biomimetic drug delivery systems, cell membrane-coated nanoparticles are widely used for subcellular delivery. However, the influence of cell membranes at different life cycles on subcellular delivery remains unexplored. Our previous study demonstrated that senescent tumor cell membrane-coated nanoparticles (SNP) displayed superior endoplasmic reticulum (ER) targeting efficiency in tumor cells. After inducing tumor cells into senescence, SNP showed greater...