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Amor and colleagues previously developed chimeric antigen receptor (CAR) T cells that can target and eliminate senescent cells. The utility of these senolytic CAR T cells is now expanded to show that they can combat age-related metabolic dysfunction, and that they can be used prophylactically and have effects that persist for months, thus opening the door to the development of long-term senolytic approaches.
Using a data-driven proteomics strategy from a prospective community-based cohort with long-term follow-up, this study reports that plasma levels of glial fibrillary acidic protein (GFAP) can predict the risk of dementia, even 15 years before disease diagnosis. Our findings have important implications for early screening and interventions for dementia.
Using a multi-omics strategy, we uncovered location- and sex-specific aging heterogeneity of the large intestine in monkeys and identified a range of potential gut aging regulators. We explored the roles of several regulators in intestinal function and lifespan in Caenorhabditis elegans. Finally, we investigated potential links between gut aging and colorectal cancer.
Ying et al. integrate Mendelian randomization into epigenetic clock making and pioneer a strategy to develop aging biomarkers with stronger causal ties to healthspan. They distinguish signs of aging-related molecular damage from responses to it that might signal resilience.
Proteomics analysis of cerebrospinal fluid (CSF) from individuals with Alzheimer’s disease (AD) identified five subgroups with distinct underlying mechanisms and genetic risk profiles. These subtypes might be a step forward in realizing personalized treatment for AD.
Tagmentation-based methylation sequencing (TIME-seq) is an efficient and cost-effective solution for measuring and generating epigenetic clocks. We applied TIME-seq to over 2,800 mouse and human DNA samples to produce clocks that demonstrate accuracy and robustness; the method also outperforms conventional methods in speed and cost. The simple and practical design of TIME-seq facilitates large-scale epigenetic clock analysis, which makes it a valuable tool for advancing aging research.
Oleson et al. tackle the enduring question of the extent to which transient events during development shape our outcomes by studying the effects of early-life exposure to oxidative stress. They find that a cascade of changes initiated by the epigenetic-modifier COMPASS complex manifests in rearrangements in lipid metabolism in adulthood, which confers broad protection against amyloid-induced proteotoxicity.
Two recent studies discover a scaling law of mammalian lifespans: the speed at which DNA methylation drifts from a youthful state strongly associates with maximum lifespan.