Methylation-associated Gene Expression (MaGE): a non-invasive, in vivo measure of cellular senescence.
- 1Mayo Clinic, Rochester MN
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 Crohns 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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BibTeX
@misc{simpson2026methylationassociated,
title = {{Methylation-associated Gene Expression (MaGE): a non-invasive, in vivo measure of cellular senescence.}},
author = {D. J. Simpson and S. J. Crofts and C. Mavrommatis and T. A. White and Y. J. Suwanlikit and K. Loyva and W. A. Rocca and K. Kantarci and M. Mielke and A. Richmond and R. E. Marioni and K. Kirschner and N. K. LeBrasseur and T. Chandra},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.26364335},
url = {https://www.medrxiv.org/content/10.64898/2026.09.29.26364335v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Methylation-associated Gene Expression (MaGE): a non-invasive, in vivo measure of cellular senescence.
AU - D. J. Simpson
AU - S. J. Crofts
AU - C. Mavrommatis
AU - T. A. White
AU - Y. J. Suwanlikit
AU - K. Loyva
AU - W. A. Rocca
AU - K. Kantarci
AU - M. Mielke
AU - A. Richmond
AU - R. E. Marioni
AU - K. Kirschner
AU - N. K. LeBrasseur
AU - T. Chandra
PY - 2026
DA - 2026/09/29
PB - medRxiv
DO - 10.64898/2026.09.29.26364335
UR - https://www.medrxiv.org/content/10.64898/2026.09.29.26364335v1
AB - 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 Crohns 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.
ER -