Aging & Longevity
Appetite Loss, Inflammation, and Incident Functional Loss Among Community-Dwelling Older Adults
CONCLUSION: Impaired appetite and increased inflammatory biomarkers are independently linked to mobility loss. Appetite impairment might signal early nutritional and supportive care needs, but inflammation-targeted interventions require further study.
Robust and replicable effects of ageing on resting-state brain electrophysiology measured with MEG
Non-invasive recordings of brain electrophysiology provide credible insights into decline in neuronal functioning with age. New approaches are required to translate these results into compelling clinical metrics and meet the global challenge of preserving brain health in ageing. Changes in neuronal dynamics with ageing are observable in the power spectra of EEG and MEG recordings. Highly promising candidates for electrophysiological markers have been identified, but progress is hindered by...
Crosstalk Between the NRF2 Signaling Pathway and Heat Shock Proteins: Implications for Cellular Stress Response and Disease Therapy
Cells are continuously exposed to oxidative and proteotoxic stress that disrupt redox balance and protein homeostasis. Two major cytoprotective systems-the nuclear factor erythroid 2-related factor 2 (NRF2) pathway and the heat shock response (HSR) mediated by heat shock factor 1 (HSF1) and heat shock proteins (HSPs)-form an interconnected stress-adaptation network that coordinates redox defense, proteostasis, and cellular survival. Although historically viewed as largely independent pathways,...
Atlas of genetic architecture and exploratory temporal interaction networks of plasma protein-based organ and system aging
Organ-level investigations provide insights into inter-individual heterogeneity in health and disease, yet aging across organs and systems remains incompletely understood. Leveraging plasma proteomic data from 53,014 UK Biobank participants, we construct 16 organ- and system-specific aging clocks that show 5436 significant associations with 1059 diseases (i.e., 655 incident and 404 prevalent diseases) and widespread responses to 841 diverse environmental factors, highlighting organ-specific and...
Himito: a graph-based toolkit for mitochondrial genome analysis using long reads
Understanding the genetic and epigenetic regulation of mitochondrial DNA (mtDNA) is essential for elucidating mechanisms of aging and disease. Long-read sequencing can span the mitochondrial genome and capture base-modification signals, yet analytical tools remain limited. We developed Himito, a graph-based toolkit for analyzing mitochondrial genome using long reads. Himito filters reads originating from nuclear mitochondrial insertions (NUMTs), constructs a sequence graph to represent mtDNA...
Strengthening health systems to prioritise, provide care, and prevent osteoarthritis: a roadmap for global health policy
By 2050, almost 1 billion people are expected to live with osteoarthritis-a disabling musculoskeletal condition with currently no cure. Despite its burden and costs, osteoarthritis remains largely invisible in national and global health agendas, is poorly integrated within service models for other chronic health conditions, and is frequently perceived as inevitable with ageing and associated with limited therapeutic options. This context drives an osteoarthritis identity problem that fuels...
Interpreting ocular age estimates: source, output, evidence, and clinical meaning
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...
Balance control is more affected in older than younger adults by repeated visual perturbations during walking
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...
Ginsenoside Rg3 Promotes Healthy Aging Through Phosphoinositide-Associated Lysosomal Regulation in Caenorhabditis elegans
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...
Oxidative DNA damage drives centromere fragility and chromosome instability
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....
THE AGING PURINOME: A PURINERGIC FRAMEWORK LINKING THE HALLMARKS OF AGING TO INFLAMMAGING
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...
Driver or Passenger? A Bradford Hill Framework for Aging-Associated lncRNAs
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...
ZNF865 (BLST) a Novel Regulator of DNA Damage and Cell Senescence in Back Pain
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...
Magnetic Electroluminescent response as a predictive indicator of operational lifetime in phosphorescent blue OLEDs
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...
Menopause-associated proteomic changes link to brain ageing and dementia risk
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Author Correction: The kinase complex mTORC2 promotes the longevity of virus-specific memory CD4(+) T cells by preventing ferroptosis
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Publisher Correction: Sleep chart of biological ageing clocks in middle and late life
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Goals and challenges for senescence research
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Lymph node contraction links sex-biased naive CD8<sup>+</sup> T cell decline to compromised antigen recognition during middle age
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^(+)...
Mitochondrial dysfunction and inflammaging: a mechanistic bridge between bioenergetic failure and senescence
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...
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