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To verify whether DNA repair is regulated by FOXO3a, a tet-on flag-h-FOXO3a transgenic mice were used. RT-q-PCR and western blot analysis showed that the mRNA and protein levels of flag-h-FOXO3a, XRCC4, XPC, APE1 and MSH2 increased dose dependently by doxycycline. DNA repair activities like non-homologous end joining (NHEJ), nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR) also increased in a doxycycline dose dependent manner. MEF (mouse embryonic fibroblast)...

This study critically reevaluates the utility of brain-age models within the context of detecting neurological and psychiatric disorders, challenging the conventional emphasis on maximizing chronological age prediction accuracy. Our analysis of T1 MRI data from 46,381 UK Biobank participants reveals that simpler machine learning models, and notably those with excessive regularization, demonstrate superior sensitivity to disease-relevant changes compared to their more complex counterparts,...

Decreased telomerase expression, telomere shortening, senescence-associated markers, and inflammation have all been independently observed in the ageing brain and associated with disease. However, causality between limited telomerase expression and brain senescence and neuro-inflammation in the natural ageing setting is yet to be established. Here, we address these questions using the zebrafish as an ageing model. Akin to humans, zebrafish display premature ageing and death in the absence of...

Clonally expanded CD8^(+) T cells may contribute to Alzheimer's disease (AD) pathology through interactions with brain-resident cells. However, the functional impact of AD-specific T cell receptor (TCR) clonotypes remains unclear. Here, we demonstrate that CD8^(+) T cells undergo clonal expansion in early-stage AD mouse models, App^(NL-G-F) and 5xFAD, and that their depletion reduces amyloid plaque accumulation. Expanded TCR-expressing CD8^(+) T cells preferentially infiltrate the brain,...

The biological mechanisms underlying the increased prevalence of Alzheimer's disease (AD) in women remain undefined. While previous case/control studies have identified sex-biased molecular pathways, the sex-specific relationships between gene expression and AD endophenotypes, particularly involving sex chromosomes, are underexplored. With bulk transcriptomic data across 3 brain regions from 767 decedents, we investigated sex-specific associations between gene expression and post-mortem...

Decreased trabecular meshwork (TM) cellularity is a critical pathogenic cause of primary open-angle glaucoma, yet therapies to regenerate the decellularized TM are very limited. Induced pluripotent stem cell-derived TM-like cells (iPSC-TM) can efficiently restore aqueous humor outflow. Here, we conducted a multi-modal RNA sequencing analysis to characterize the molecular mechanisms underlying TM regeneration. Our clustering analysis identified a group of iPSC-derived alpha6 integrin-positive...

Trees are integral to ecosystems and hold considerable economic importance. Their exceptional longevity and modular structure also make them valuable models for studying the long-term accumulation of somatic mutations and epimutations in plants. Empirical evidence indicates that the annual rate of these stochastic events correlates negatively with generation time, suggesting that species with long lifespans have evolved mechanisms to mitigate the build-up of deleterious somatic variants. It has...

Aging research has primarily focused on adult aging clocks, leaving a critical gap in understanding a biological clock across the full life cycle, particularly during infancy and childhood. Here we introduce LifeClock, a biological clock model that predicts biological age across all life stages using routine electronic health records and laboratory test data. To enhance individualized predictions, we integrated virtual patient representations from 24,633,025 heterogeneous longitudinal clinical...

The 70-kDa heat shock protein (Hsp70) chaperone is essential to maintain cellular protein homeostasis, facilitating the folding, assembly, membrane translocation and quality control of proteins. Hsp70s achieve their functions through 'selective promiscuity', interacting with a wide range of substrate proteins while minimizing undesired interactions. J-domain proteins (JDPs) and nucleotide exchange factors (NEFs) are key to substrate recognition, remodelling and release from chaperone complexes....

Across the evolutionary spectrum, sexual interactions can significantly influence the physiology and somatic aging in various species. In Caenorhabditis, male pheromones, sperm, and seminal fluid shorten the lifespan of hermaphrodites through different mechanisms. However, the specific male seminal fluid proteins responsible for this effect remain unidentified. Here, we find that several of the previously observed physiological changes in mated hermaphrodites require a newly-identified seminal...

CONCLUSION: In this study, it was found that quality of life decreased with increasing kinesiophobia, whereas quality of life increased with increasing level of successful aging. Longitudinal studies on quality of life in the elderly are recommended.

CONCLUSION: Our results imply that for those born small, having lower educational level is associated with having worse physical function at late-life, partly through less physical activity throughout the life-course.

CONCLUSIONS: Government-procured pDXA enables cost-effective universal OP screening in resource-limited rural areas. Scaling this model requires culturally adapted education (e.g., Wu Chinese dialect audiovisual materials) and tiered medication subsidies for groups with low medical payment capacity, aligning with the UN Decade of Healthy Aging (United Nations, UN Decade of Healthy Aging 2021-2030, World Health Organization, 2020).