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Disentangling shifting demographic and treatment effects on years of life lost to cancer in Denmark

3 days 8 hours ago
Cancer is increasingly relevant to ageing societies, yet progress in cancer control is difficult to assess when population years of life lost (YLL) to cancer appear stable. Using Danish registers, we followed 4.26 million residents aged ≥50 years (1980-2019) and estimated YLL under observed and counterfactual scenarios, separating demography and incidence from post-diagnosis outcomes. From the 1980s to the 2010s, YLL per individual changed little (men 2.3 to 2.1; women 2.5 to 2.2), while YLL per...
Ólafur Birgir Davíðsson

Cell-to-cell variability and gain of methylation at polycomb CpG islands as a hallmark of aging

3 days 8 hours ago
Aging is a complex multifactorial process that affects cellular function and tissue homeostasis over time. Despite substantial research, the molecular mechanisms driving cellular aging remain poorly understood. Many studies focused on changes in DNA methylation as an indicator of aging. In particular, methylation at polycomb CpG islands was shown to be predictive of phenotypic changes associated with aging. Since many age-related pathological processes are thought to originate from single cells,...
Hagit Masika

Corylin promotes healthy aging via RAGA-mTOR suppression and sex-dependent activation of SIRT3

3 days 8 hours ago
Aging is accompanied by progressive physiological decline and an increased risk of chronic disease, motivating the search for interventions that promote healthy longevity. We found that mid-life administration of Corylin, a flavonoid derived from Psoralea corylifolia, improves metabolic function, muscle integrity, and physical performance in mice maintained on a standard diet. Corylin significantly extends median lifespan in female mice, with an 11.9% increase and a 33% higher survival rate at...
Shu-Fang Cheng

Targeted plasma proteomics reveals a central role of upregulated TNFRSF proteins in HIV-associated stroke

3 days 8 hours ago
Chronic inflammation drives vascular aging and stroke risk, yet circulating proteins linking immune activation to cerebrovascular events remain elusive. People with HIV (PWH) face elevated stroke risk beyond traditional vascular risk factors, even under antiretroviral therapy. We aimed to identify circulating proteomic signatures of HIV-associated stroke, characterize underlying biological pathways, and assess their longitudinal stability. We conducted a nested case-control study of 135 PWH with...
Tailin Chen

A damage accumulation model identifies distinct aging regimes across species

3 days 8 hours ago
Different species age in similar ways but their lifespans differ by orders of magnitude. It is not clear how these similarities and differences arise from the accumulation of damage that underlies aging. Does long lifespan arise from reduced damage production, increased removal or enhanced robustness to damage? Here we apply the saturating removal model-a stochastic model of damage accumulation and removal-and fit it to survival data from well-studied species. Several parameters have...
Naveh Raz

Single-nucleus interrogation of primate small intestinal aging reveals NCoR1 decline as a conserved feature that is reversed by metformin

3 days 8 hours ago
How the small intestine ages at the cellular and molecular level has been unclear. Here we profile single nuclei from young and aged primate small intestine and find that aging brings barrier dysfunction, chronic inflammation and a shift in stem cell differentiation away from absorptive cells toward secretory cells. Through integrative multimodal analysis, we identify the transcriptional corepressor NCoR1 as a key player whose decline is conserved in the aging human gut. In human intestinal...
Jingyi Li

Urate-Related Genetic Risk Modulates the Anti-Aging Effects of Exogenous Nucleotides: Multi-Omics Evidence From Older Adults

3 days 8 hours ago
Nucleotides-essential substrates for DNA repair, energy metabolism, and redox regulation-are emerging as nutritional modulators of biological aging. Yet, individual responses to exogenous nucleotide (NTs) supplementation remain poorly understood. Given that urate metabolism governs systemic oxidative balance, this study investigated whether genetic variability in urate regulation modifies the anti-aging effects of NTs. In this secondary analysis of the TALENTs randomized controlled trial (121...
Ruisheng Fu

iLDA-SGCN: Identifying Associations Between Age-Related Diseases and Long Non-Coding RNAs Using Dual Graph Convolutional Networks

3 days 8 hours ago
Aging reshapes global disease burdens, yet the regulatory roles of long non-coding RNAs (lncRNAs) in age-related disorders remain incompletely characterized. We developed iLDA-SGCN, a graph-based computational framework that integrates singular value decomposition (SVD) with dual graph convolutional networks (GCNs) to predict lncRNA-disease associations. SVD first derives compact low-dimensional representations from the lncRNA-disease association matrix. Two complementary GCN modules then learn...
Yu Guo

Capsaicin acts as a novel NRF2 agonist to suppress ethanol induced gastric mucosa oxidative damage by directly disrupting the KEAP1-NRF2 interaction

3 days 8 hours ago
Excessive alcohol consumption poses significant health risks and is closely associated with oxidative damage. The KEAP1-NRF2-ARE signaling pathway serves as the primary antioxidant system. However, current small molecule inhibitors are all covalently bound to KEAP1, meaning that once bound, they are not easily dissociated, while continuous inhibition of KEAP1 exhibits severe side effects. In this study, BLI, CETSA, Pull-down, Co-IP, and HDX-MS assay analysis were conducted to detect the KEAP1...
Xiaoning Gao

Association between trajectories of physical activity and depressive symptoms among Chinese older adults with chronic disease: evidence from the Chinese Longitudinal Healthy Longevity Survey

3 days 8 hours ago
CONCLUSIONS: Maintaining favorable long-term patterns of PA, even with gradual decline, is associated with reduced odds of DS among older adults with chronic diseases. These findings support PA as a potentially cost-effective strategy for secondary prevention and highlight the importance of sustained behavioral patterns in mitigating mental health risks in aging populations.
Jinghong Huang