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Development and validation of a simplified time-dependent interpretable machine learning-based survival model for older adults with multimorbidity

1 month 3 weeks ago
Multimorbidity elevates late-life mortality, yet existing tools remain complex. Using two nationally representative Chinese cohorts-the Chinese Longitudinal Healthy Longevity and Happiness Family Study (CLHLS-HF; n = 8675) and the China Health and Retirement Longitudinal Study (CHARLS, n = 4171)-we developed and externally validated a simplified, time-dependent, interpretable survival model. A four-stage feature-selection pipeline (univariate Cox, L1-penalized Cox, multi-model importance with...
Junmin Zhu

Mitochondrial RNA cytosolic leakage drives the SASP

1 month 3 weeks ago
Senescent cells secrete proinflammatory factors known as the senescence-associated secretory phenotype (SASP), contributing to tissue dysfunction and aging. Mitochondrial dysfunction is a key feature of senescence, influencing SASP via mitochondrial DNA (mtDNA) release and cGAS/STING pathway activation. Here, we demonstrate that mitochondrial RNA (mtRNA) also accumulates in the cytosol of senescent cells, activating RNA sensors RIG-I and MDA5, leading to MAVS aggregation and SASP induction....
Stella Victorelli

Persistent pneumococcal colonisation in antiretroviral-treated HIV infection is associated with nasal inflammation

1 month 3 weeks ago
Despite systemic viral suppression, people living with HIV (PLHIV) on antiretroviral therapy (ART) remain highly susceptible to pneumococcal colonisation and disease. Here, we show that long-term ART does not restore nasal mucosal immunity. Using flow cytometry, single-cell transcriptomics, and neutrophil functional assays, we identify a persistent mucosal immune signature in PLHIV-ART > 1 yr marked by epithelial-driven neutrophilic inflammation, T cell exhaustion, and cellular senescence....
Joseph Aston Phiri

University students' perspectives on delivering health education interventions to underprivileged older adults in the community: a qualitative study of a large-scale community-based research project

1 month 3 weeks ago
CONCLUSIONS: Older adult's functional limitations and negative generalization of ageing may have prevented them from actively seeking health information and health-promoting behaviors. To enhance the intervention's effectiveness, the health education contents should be customized based on their health needs, functional capabilities, and readiness to change health behaviors.
Siu Long Chau

A urinary microRNA aging clock accurately predicts biological age

1 month 3 weeks ago
We aimed to develop and validate a urinary miRNA aging clock, positioning urine as a scalable, non-invasive aging-biomarker source. Using machine learning on 6331 adults, our clock achieved MAE ≈ 4.4 years (R² ≈ 0.79) in independent validation. The clock's key biomarkers included well-established geromiRs miR-34a-5p, miR-31-5p, miR-146a-5p, and miR-155-5p. While slightly less accurate than DNA-methylation clocks, our model outperformed blood-based miRNA and mRNA clocks, underscoring urinary...
Milos Havelka

GDF3 promotes adipose tissue macrophage-mediated inflammation via altered chromatin accessibility during aging

1 month 3 weeks ago
Aging is characterized by amplified inflammation, including proinflammatory macrophages and increased susceptibility to endotoxemia. Here we uncover a mechanism by which macrophages maintain their inflammatory phenotype through autocrine GDF3-SMAD2/3 signaling, which ultimately exacerbates endotoxemia. We show that inflammatory adipose tissue macrophages display an age-dependent increase in GDF3, a TGFβ-family cytokine. Lifelong systemic or myeloid-specific Gdf3 deletion leads to reduced...
In Hwa Jang

Oxytocin varies across the life course in a sex-specific way in a human subsistence population

1 month 3 weeks ago
Oxytocin, a hormone linked to reproduction and health, may mediate life-history trade-offs across the human life course. Yet, how oxytocin naturally varies with age remains poorly understood. Here, working with the Tsimane, forager-horticulturalists of lowland Bolivia, we collected the largest sample of oxytocin measurements to date (n = 1,242 samples, n = 405 individuals, age = 2 to 84 y, 51% female), and i) examined how oxytocin varies throughout the life course in females and males, and ii)...
Abigail E Colby

Association between Klotho levels in cerebrospinal fluid and choroid plexus enlargement in neurodegeneration

1 month 3 weeks ago
CONCLUSION: In this preliminary study, we observed a strong association between CSF Klotho levels and CP enlargement. Reduced CSF Klotho levels, due to CP dysfunction, may contribute to neurodegeneration. If confirmed in larger cohorts, this association suggests that CSF Klotho may serve as a biomarker for CP enlargement, possibly reflecting its underlying dysfunction.
Luca Sacchi

Discrimination of normal from slow-aging mice by plasma metabolomic and proteomic features

1 month 3 weeks ago
Tests that can predict whether a drug is likely to extend mouse lifespan could speed up the search for anti-aging drugs. We have applied a machine learning algorithm, XGBoost regression, to seek sets of plasma metabolites (n = 12,000) and peptides (n = 17,000) that can discriminate control mice from mice treated with one of five anti-aging interventions (n = 278 mice). When the model is trained on any four of these five interventions, it predicts significantly higher lifespan extension in mice...
Bretton Badenoch

Wnt signaling pathway in lung aging and aging-related chronic lung diseases

1 month 3 weeks ago
As a target organ in direct contact with external air, lung tissue is more susceptible to aging, and lung aging is closely related to the development of chronic lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis. Evolutionarily speaking, the Wnt signaling pathway is highly conserved and plays an important role in embryonic development, tissue homeostasis, as well as cell proliferation, differentiation, apoptosis, and migration of a variety of cells. Alterations in...
Wu Jirong