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Methylation-associated Gene Expression (MaGE): a non-invasive, in vivo measure of cellular senescence.

Simpson, D. J.; Crofts, S. J.; Mavrommatis, C.; White, T. A.; Suwanlikit, Y. J.; Loyva, K.; Rocca, W. A.; Kantarci, K.; Mielke, M.; Richmond, A.; Marioni, R. E.; Kirschner, K.; LeBrasseur, N. K.; Chandra, T.

2026-10-01 epidemiology
10.64898/2026.09.29.26364335 medRxiv
Show abstract

Cellular senescence is a central hallmark of aging, yet its measurement in humans remains invasive, low-throughput and tissue-specific, precluding population-scale study. We developed Methylation-associated Gene Expression (MaGE) predictors: whole-blood DNA methylation proxies of p14ARF, p16INK4A and p21CIP1 expression, plus a composite score, providing the first scalable measure of senescence-marker expression. Deployed across Generation Scotland (n=18,859), MaGE yielded 45 Bonferroni-significant associations spanning 18 incident diseases and all-cause mortality. The two strongest associations recapitulated the established tissue specificity of p21CIP1 and p16INK4A activation, with MaGE-p21 associating with incident alcoholic liver disease and MaGE-p16 with pulmonary fibrosis. In a separate study, MaGE tracked disease severity and treatment response in Crohn's disease. MaGE is a scalable, interpretable biomarker of senescence that enables its study at population scale and offers a route to patient stratification in senolytic trials.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.