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Cellular senescence is increasingly recognized as a fundamental driver of aging and age-related diseases. Studies in peripheral tissues have revealed that senescence is not a uniform cellular state, but a highly heterogeneous phenotype shaped by distinct combinations of DNA damage, mitochondrial dysfunction, chromatin remodeling, impaired proteostasis, and diverse senescence-associated secretory phenotype. This heterogeneity critically influences both the identification and therapeutic targeting...

CONCLUSIONS: CSF TIMP2 levels primarily reflect ageing-related processes associated with neurodegeneration rather than disease-specific effects. Genetic variation in TIMP2 may contribute to clinical heterogeneity. These findings support a role of extracellular matrix-related ageing mechanisms in PD and related disorders.

Caloric restriction (CR) extends lifespan and delays age-related diseases in model organisms, yet its effects on biological aging in humans remain unclear. We pooled data from seven randomized CR trials (n = 829) and examined randomization to CR and change in weight with a biomarker index composed of CRP, IL-6, cystatin C, insulin, GDF-15, and TNF-R1. CR improved the composite biomarker index. The effect of CR decreased from -2.2 to -1.2 (95% CI -2.0 to -0.3) after adjustment for weight, while...

Understanding cognitive aging requires approaches that capture individual variability while enabling integration across studies. In rodent models, behavioral data are central to this effort, yet cross-laboratory differences in experimental design limit comparability and constrain secondary analysis. To address this gap, we developed the Individual Differences in Cognitive Aging Rodent Datasets (ID-CARD), a first-of-its-kind collaborative repository aggregating trial-level Morris water maze data...

Resilience has become an integral component of theory and research in brain aging. Recent frameworks have provided guidelines for identifying and investigating resilience in the context of diversity (e.g., sex and risk exposure differences). We leverage a multi-factorial longitudinal approach to operationalize and predict pathways of resilience, stability and vulnerability as a function of differential within-person trajectory patterns of hippocampal volume and cognitive change. Participants...

CONCLUSION: Epigenetic clocks may improve the assessment of biological aging in people living with HIV and could support risk stratification, early identification of frailty, and evaluation of interventions. However, longitudinal validation, standardized methods, adjustment for immune-cell composition, and evidence linking clock changes with meaningful clinical outcomes are required before these biomarkers can be used routinely in HIV care.

CONCLUSION: PIS provides a compact, interpretable proteomic measure of inflammaging and captures mortality, multisystem disease burden, and aging-related biology in population-scale cohorts.

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Researchers found that blocking IL1RAP could disrupt a powerful inflammatory network that helps pancreatic cancer survive treatment. In preclinical experiments, the approach reduced tumor-protecting cells and fibrosis while boosting the activity of cancer-fighting T cells. That could make chemotherapy and immunotherapy more effective.

Long-lived bats appear to combine powerful immune defenses with unusual strategies for eliminating damaged cells, potentially helping them avoid cancer and disease for decades. Researchers hope these genetic tricks could eventually reveal new ways to protect human health during aging.

Geologist and officials were acquitted last week, but scientists fear future liability for failing to predict similar disasters

A major Ontario study found 24 common medication chains in which one drug’s side effects can be mistaken for a new medical problem, leading to another prescription. Researchers say closer medication reviews, pharmacist involvement, and automated alerts could help prevent these potentially harmful prescribing cascades.

Researchers analyzing data from more than 1.9 million people found that ADHD is associated with substantially higher rates of digestive problems. People with ADHD had nearly double the odds of constipation, 58% higher odds of irritable bowel syndrome, and more than four times the odds of encopresis.

An evolutionary trade-off may have helped a mutation linked to auto-immune disease persist in human populations

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder in which neuroinflammation, vascular dysfunction, metabolic disturbances, and impaired tissue resilience contribute to disease progression. Aerobic exercise is a widely applicable lifestyle intervention that has been increasingly investigated in AD; however, the mechanisms linking peripheral exercise adaptations to brain outcomes remain incompletely understood. This review evaluates the potential contribution of gut-derived...

CONCLUSION: Deep learning models hold considerable potential for predicting MCI-to-AD conversion, yet substantial barriers remain to their translation into routine clinical practice. Greater emphasis on longitudinal analysis, intelligent multimodal fusion, and interpretable architectures is essential for clinical impact. Future research should prioritize the development of diverse, multicenter datasets, advancement of explainable AI (XAI) techniques, and the design of personalized time-to-event...

Cellular senescence is a key driver of age-related pathologies. Our study focuses on PTCHD4, a transmembrane protein with previously undefined physiological functions in aging processes. We found that PTCHD4 expression was increased across multiple cellular senescence models and showed an age-associated increase in mouse tissues and human lung transcriptomic datasets. Functionally, PTCHD4 deficiency attenuated senescence progression, whereas its overexpression promoted this process. In vivo,...

As societies age, a deeper understanding of ageing-related factors that contribute to longevity is needed. We therefore investigated possible longevity factors (social, medical, and biological) in relation to parental longevity (PL) and polygenic longevity scores (PGLSs). We examined 1126 70-year-olds from the Swedish population-based Gothenburg H70 Birth Cohort study in 2014-2016 (response rate 72%), with follow-up in 2019-2022 (response rate 77.6%). Comprehensive examinations included...

Long-term humoral immunity relies on long-lived plasma cells in the bone marrow (BM). However, the processes governing plasma cell transport, positioning, and longevity within the BM niche remain poorly understood, especially in humans. Most existing knowledge comes from mouse studies or limited human-based models, which makes translating findings to human biology challenging. Here, we introduce a physiologically relevant human bone marrow-on-a-chip (hBMOC) model to investigate the behavior and...

Ovarian aging leads to permanent reproductive senescence and systemic hormonal changes that predispose women to age-associated comorbidities. Despite these observations, the intrinsic mechanisms driving age-related ovarian decline are poorly defined. Mitochondrial DNA (mtDNA) mutations and instability are strongly associated with aging; however, it remains unknown if naturally occurring mitochondrial genetic variation influences the trajectory of ovarian aging. To address this, we compared two...