Aging & Longevity

CONCLUSIONS: Our survey results indicate that older adults preferred to seek and receive HHC through traditional medical settings. These data were collected prior to the pandemic and before some of the recent OTC policy changes; nonetheless, they align with more recent findings and capture the attitudes of individuals who are likely still making HHC decisions today. These findings, therefore, provide contextual evidence about older adults' reported preferences against which future studies of...

Testosterone levels decline progressively with age from the third decade of life, impairing spermatogenesis and contributing to age-related disorders, underscoring the importance of enhancing endogenous testosterone production. DNA methyltransferase 1 (DNMT1) promotes testosterone synthesis in Leydig cells (LCs), yet the underlying mechanism remains unclear. Here, we found that DNMT1 expression is downregulated in aging rat testes and senescent LCs in vitro, correlating with reduced testosterone...

Cognitive impairment affects 30%-80% of patients with heart failure, yet the mechanisms beyond reduced brain blood flow remain poorly defined. Here we show that circulating factors released during heart failure trigger senescence of brain blood-vessel endothelial cells, which in turn drives synaptic loss and cognitive decline through crosstalk between endothelial cells and microglia, the brain's immune cells. Using a pressure-overload model (transverse aortic constriction) combined with plasma...

Chronic social deficits (persistent feelings of being lonely or isolated) have been linked to premature mortality, yet the underlying physical and mental pathways remain unclear. This study used data from 4,090 older adults in the English Longitudinal Study of Ageing, a longitudinal panel study. Using outcome-wide analyses, we assessed how the chronicity of social deficits was associated with 17 health outcomes across physical, mental, cognitive and behavioural health domains. Regression models...

The buried interface between the charge transport layer and the overlying perovskite absorber is critical yet difficult to probe in perovskite solar cells. Because light enters through the transparent substrate and is predominantly absorbed near this region, photo-induced degradation processes are partially initiated at the hidden buried interface. Here, we reveal that instability at the buried SnO(2)/perovskite interface triggers structural and chemical decomposition of the perovskite layer. To...

Alzheimer's disease (AD) disproportionately affects women, yet mechanisms underlying this sex difference remain unclear. Histone variants are overrepresented components of aging neuronal chromatin, but their contribution to AD is unknown. Here, we identify the histone variant H2A.Z as a sex-specific regulator of AD in the postmortem human hippocampus and in 5xFAD mice. H2A.Z occupancy decreased in female but increased in male AD patients. In females, reduced H2A.Z occupancy at the transcription...

Sepsis is a life-threatening syndrome defined by infection-triggered dysregulation of the host response, and its persistently high mortality and marked clinical heterogeneity remain major barriers to early risk stratification and individualized management. While the gut is increasingly recognized as a key modulator of the systemic sepsis response, current evidence does not support a universal, upstream causal role for intestinal alterations in the initiation of multi-organ injury. In this...

Heart failure with preserved ejection fraction (HFpEF) contributes to nearly 50% of the global heart failure (HF) cases, and remains a major clinical challenge because of its heterogeneous pathophysiology, substantial residual morbidity, and limited mechanism-based treatment options. HFpEF is increasingly recognized as a heterogeneous multisystem syndrome closely associated with aging, cardiometabolic comorbidities, and chronic low-grade inflammation. Cellular senescence and the...

Cellular senescence, characterized as a permanent arrest of cell proliferation, is triggered by various types of stress. Senescent cells are identified by markers, including senescence-associated β-galactosidase (SA-β-gal) activity and the secretion of senescence-associated secretory phenotype (SASP) factors. These senescent phenotypes have been observed in neurons, suggesting that cellular senescence may contribute to the pathogenesis of neurodegenerative diseases. Humanin (HN), an endogenous...

In mammals, a small population of spermatogonial stem cells (SSCs) is established shortly after birth. These cells self-renew and produce sperm for the male's reproductive lifespan, passing the genome on to the next generation. Establishment of a population of SSCs with high genomic integrity is essential. SSCs are derived from a much larger precursor population of male germ cells (MGCs) that differentiate during fetal life. During the last third of gestation, MGCs undergo a prolonged period of...

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.

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...

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,...

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...

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...

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...

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....