Volume 4 Issue 2, February 2024

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.

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.

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.

This study reveals that many previously reported changes in gene expression in aging hematopoietic stem cells (HSCs) may be linked to extraction stress rather than aging itself and has implications for future HSC aging research.

An inflammatory profile is associated with aging and senescence. Here, Hao et al. show that TXNRD1 drives the senescence-associated secretory phenotype through the cGAS–STING pathway, independently of its enzymatic activity, during senescence and that the TXNRD1–cGAS interaction may be a target for selectively suppressing inflammaging.

Yang et al. demonstrate that inhibition of early-acting autophagy genes in neurons extend C. elegans lifespan, improve neuronal proteostasis and increase exopher formation mediated by the autonomous WD40 domain-related function of ATG-16.2.

He et al. demonstrate a noncanonical role for the TRMT6–TRMT61A methyltransferase complex in hematopoietic stem cell (HSC) aging, where its enrichment activates necroptosis signaling. Blocking necroptosis counters features of HSC aging, suggesting a therapeutic strategy.

The authors identify causality-enriched CpGs linked to aging using Mendelian randomization. They develop new epigenetic clocks, DamAge and AdaptAge, that more reliably track age-related changes, offering insights into aging mechanisms and interventions.

Large-scale proteomics data hold promise for individual disease risk prediction. Here the authors use data from more than 50,000 adults without dementia in the UK Biobank to predict the future risk of dementia and highlight GFAP as an important protein elevated in individuals more likely to develop dementia.

Griffin et al. present a versatile method for scalable and low-cost sequencing for the construction of epigenetic clocks. They assay 2,892 human or mouse samples, benchmark their method and assess diverse interventions.