Comparing epigenetic puberty and epigenetic clocks as biomarkers of adult biological aging and health
Abstract
Recent lifespan frameworks of aging theorize that pubertal development and cellular aging are governed by overlapping pathways, but the time lag between adolescence and older adulthood complicates the study of shared molecular mechanisms. Here we compare a DNA-methylation-based epigenetic index of pubertal development to epigenetic clocks, which were designed to measure biological aging, as a putative biomarker of adult aging and health in two adult cohorts: 3,642 older Americans in the Health and Retirement Study (HRS; age range, 56 to 100 years; 2,106 females) and 18,676 adults from Generation Scotland (GS; age range, 18 to 98 years; 10,974 females). Epigenetic puberty was correlated with chronological age in both cohorts, moderately in the older HRS sample (r = 0.51 in females, r = 0.51 in males) and strongly across the wider adult age range of GS (r = 0.82 in females, r = 0.86 in males). In both cohorts, age-residualized epigenetic puberty was associated with accelerated biological aging as measured by epigenetic clocks and other aging biomarkers (standardized coefficients: HRS, 0.13 to 0.47, all P < 0.005; GS, 0.05 to 0.40, all P < 0.001). Epigenetic puberty was linked with multiple health outcomes: mortality in HRS in both sexes (ORs, 1.39 and 1.46, both P [≤] 0.001) and in GS among females (HR, 1.12, P = 0.003); 10-year onset of diabetes, any cancer and lung disease in GS (HRs, 1.12 to 1.19, all P < 0.005); and with multimorbidity, functional limitations and BMI in females in HRS (standardized coefficients, 0.10 to 0.16, all P < 0.001). It also accounted for a unique, albeit smaller, proportion of variance in aging-related outcomes beyond that explained by epigenetic clocks. These findings indicate that the epigenetic puberty index reflects pro-aging underlying biology, showing overlapping molecular pathways between pubertal development and cellular aging, and support a lifespan-based approach to studying biological aging.
Related
- Biological age measured by DNA methylation clocks and mortality: A systematic review and meta-analysis
- Biological age measured by DNA methylation clocks and neurodegenerative diseases: A systematic review and meta-analysis
- Speech clocks decode dementia phenotypes, social exposome, and biological aging
- Biomarkers of Individual Health Status Provide a Biological Signature of the Whole Person Living with Chronic Pain
- Circulating epigenetic and epitranscriptomic biomarkers identify EGFR status, predict TKI response and reveal therapeutic vulnerabilities in NSCLC
BibTeX
@misc{wu2026comparing,
title = {{Comparing epigenetic puberty and epigenetic clocks as biomarkers of adult biological aging and health}},
author = {Q. Wu and S. F. P. Gibbs and A. J. deSteiguer and S. Zarandooz and Y. E. Willems and T. Smith and J. A. Goode and C. Mitchell and E. M. Crimmins and K. P. Harden and R. E. Marioni and L. Raffington},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.26364286},
url = {https://www.medrxiv.org/content/10.64898/2026.09.29.26364286v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Comparing epigenetic puberty and epigenetic clocks as biomarkers of adult biological aging and health
AU - Q. Wu
AU - S. F. P. Gibbs
AU - A. J. deSteiguer
AU - S. Zarandooz
AU - Y. E. Willems
AU - T. Smith
AU - J. A. Goode
AU - C. Mitchell
AU - E. M. Crimmins
AU - K. P. Harden
AU - R. E. Marioni
AU - L. Raffington
PY - 2026
DA - 2026/09/29
PB - medRxiv
DO - 10.64898/2026.09.29.26364286
UR - https://www.medrxiv.org/content/10.64898/2026.09.29.26364286v1
AB - Recent lifespan frameworks of aging theorize that pubertal development and cellular aging are governed by overlapping pathways, but the time lag between adolescence and older adulthood complicates the study of shared molecular mechanisms. Here we compare a DNA-methylation-based epigenetic index of pubertal development to epigenetic clocks, which were designed to measure biological aging, as a putative biomarker of adult aging and health in two adult cohorts: 3,642 older Americans in the Health and Retirement Study (HRS; age range, 56 to 100 years; 2,106 females) and 18,676 adults from Generation Scotland (GS; age range, 18 to 98 years; 10,974 females). Epigenetic puberty was correlated with chronological age in both cohorts, moderately in the older HRS sample (r = 0.51 in females, r = 0.51 in males) and strongly across the wider adult age range of GS (r = 0.82 in females, r = 0.86 in males). In both cohorts, age-residualized epigenetic puberty was associated with accelerated biological aging as measured by epigenetic clocks and other aging biomarkers (standardized coefficients: HRS, 0.13 to 0.47, all P < 0.005; GS, 0.05 to 0.40, all P < 0.001). Epigenetic puberty was linked with multiple health outcomes: mortality in HRS in both sexes (ORs, 1.39 and 1.46, both P [≤] 0.001) and in GS among females (HR, 1.12, P = 0.003); 10-year onset of diabetes, any cancer and lung disease in GS (HRs, 1.12 to 1.19, all P < 0.005); and with multimorbidity, functional limitations and BMI in females in HRS (standardized coefficients, 0.10 to 0.16, all P < 0.001). It also accounted for a unique, albeit smaller, proportion of variance in aging-related outcomes beyond that explained by epigenetic clocks. These findings indicate that the epigenetic puberty index reflects pro-aging underlying biology, showing overlapping molecular pathways between pubertal development and cellular aging, and support a lifespan-based approach to studying biological aging.
ER -