DNA methylation proxies of senescence markers track human disease and mortality
The new blood-based tools estimate senescence gene activity to predict incident diseases, all-cause mortality, and clinical treatment responses.
medRxiv · 1 Oct · Simpson DJ, Crofts SJ, Mavrommatis C et al.
In a preprint analyzing 18,859 human participants from the Generation Scotland cohort, researchers evaluated Methylation-associated Gene Expression (MaGE) predictors. These tools use whole-blood DNA methylation proxies for p14ARF, p16INK4A, and p21CIP1 expression, as well as a composite score. Across the cohort, MaGE identified 45 Bonferroni-significant associations spanning 18 incident diseases and all-cause mortality. The two strongest links reflected the known tissue specificity of senescence activation: MaGE-p21 associated with incident alcoholic liver disease, while MaGE-p16 associated with pulmonary fibrosis. In a separate study, MaGE tracked clinical disease severity and treatment response in patients with Crohn's disease.
Why it matters
Cellular senescence is a key driver of aging, but studying it has traditionally required invasive, tissue-specific biopsies. Scalable blood-based markers allow researchers to monitor senescence at population scale and may aid patient selection in senolytic clinical trials.
Caveats
The study is an observational preprint that has not yet undergone peer review. The findings rely on blood-derived proxies rather than direct tissue measurements of senescence-marker expression.
The paper
Methylation-associated Gene Expression (MaGE): a non-invasive, in vivo measure of cellular senescence
Simpson DJ, Crofts SJ, Mavrommatis C et al.
medRxiv
doi.org/10.64898/2026.09.29.26364335