WHO-Recommended Exercise Dose Is Associated With Slower Epigenetic Aging in Older Adults
- 1Research Center for Molecular Exercise Science, Hungarian University of Sports Science, Alkotas U. 42-48, 1123, Budapest, Hungary
Abstract
The dose-response of six months of controlled exercise was studied in 72 subjects aged 50 to 70 years, with 1-4 training sessions per week, focusing on DNA methylation-based aging. Epigenetic age reduction increased with exercise dose, with about 255 MET-hours aligning with a one-year decrease in Robust PhenoAge acceleration - a volume consistent with WHO physical activity guidelines. The finding that relative ventricular posterior wall thickness and muscular quotient change in tandem with Robust PhenoAge acceleration suggests that epigenetic clocks reflect genuine organ-level rejuvenation. The DNA methylation-based protein prediction identified TGF-, TIMP1, and adrenomedullin as showing a dose-response relationship with exercise volume. The exercise intervention yielded systemic health benefits, improved some cardiac parameters measured by echocardiogram, increased HDL levels, lowered blood pressure, reduced android fat mass, and notably, enhanced physiological functions, including cognitive performance. The program increased the relative abundance of microbes supporting intestinal barrier integrity and decreased pro-inflammatory bacterial populations. Serum N-lactoyl-phenylalanine levels showed a downward trend after six months of exercise, while trimethylamine N-oxide levels rose in male participants. This single-arm exercise study identified a dose-response relationship between cumulative exercise dose and Robust PhenoAge or GrimAge acceleration, strengthening the evidence that the observed associations are attributable to exercise exposure rather than background factors or confounders. The results further support the idea that regular physical activity can influence biological age by improving cardiac structure and function, and indicate that PhenoAge and GrimAge effectively reflect age-related cardiac changes.
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BibTeX
@misc{torma2026whorecommended,
title = {{WHO-Recommended Exercise Dose Is Associated With Slower Epigenetic Aging in Older Adults}},
author = {F. Torma and M. Jokai and G. B. Babszky and Z. Babszky and G. Farkas and S. Mozaffaritabar and L. Zhou and E. Koltai and Z. Kneffel and G. Pavlik and I. Kalabiska and R. Olek and E. P. Juranyi and N. Szanto and P. Nagy and B. Ligeti and E. Z. M. Szatmari and C. Kerepesi and H. Vago and R. T. Brooke and S. Horvath and Z. Radak},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.26361502},
url = {https://www.medrxiv.org/content/10.64898/2026.09.02.26361502v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - WHO-Recommended Exercise Dose Is Associated With Slower Epigenetic Aging in Older Adults
AU - F. Torma
AU - M. Jokai
AU - G. B. Babszky
AU - Z. Babszky
AU - G. Farkas
AU - S. Mozaffaritabar
AU - L. Zhou
AU - E. Koltai
AU - Z. Kneffel
AU - G. Pavlik
AU - I. Kalabiska
AU - R. Olek
AU - E. P. Juranyi
AU - N. Szanto
AU - P. Nagy
AU - B. Ligeti
AU - E. Z. M. Szatmari
AU - C. Kerepesi
AU - H. Vago
AU - R. T. Brooke
AU - S. Horvath
AU - Z. Radak
PY - 2026
DA - 2026/09/02
PB - medRxiv
DO - 10.64898/2026.09.02.26361502
UR - https://www.medrxiv.org/content/10.64898/2026.09.02.26361502v1
AB - The dose-response of six months of controlled exercise was studied in 72 subjects aged 50 to 70 years, with 1-4 training sessions per week, focusing on DNA methylation-based aging. Epigenetic age reduction increased with exercise dose, with about 255 MET-hours aligning with a one-year decrease in Robust PhenoAge acceleration - a volume consistent with WHO physical activity guidelines. The finding that relative ventricular posterior wall thickness and muscular quotient change in tandem with Robust PhenoAge acceleration suggests that epigenetic clocks reflect genuine organ-level rejuvenation. The DNA methylation-based protein prediction identified TGF-, TIMP1, and adrenomedullin as showing a dose-response relationship with exercise volume. The exercise intervention yielded systemic health benefits, improved some cardiac parameters measured by echocardiogram, increased HDL levels, lowered blood pressure, reduced android fat mass, and notably, enhanced physiological functions, including cognitive performance. The program increased the relative abundance of microbes supporting intestinal barrier integrity and decreased pro-inflammatory bacterial populations. Serum N-lactoyl-phenylalanine levels showed a downward trend after six months of exercise, while trimethylamine N-oxide levels rose in male participants. This single-arm exercise study identified a dose-response relationship between cumulative exercise dose and Robust PhenoAge or GrimAge acceleration, strengthening the evidence that the observed associations are attributable to exercise exposure rather than background factors or confounders. The results further support the idea that regular physical activity can influence biological age by improving cardiac structure and function, and indicate that PhenoAge and GrimAge effectively reflect age-related cardiac changes.
ER -