Epigenetic age deceleration reflects exercise-induced cardiorespiratory fitness improvements.
Level 4 - case-series / case-control
Single-arm pre-post intervention pilot study without a control group
PubMed 41547677 · doi:10.1007/s11357-025-02076-9
What was done
A pilot intervention study investigated the effects of a 6-month cycling-based endurance exercise program in 42 adults aged 35–65 (38 completed; 33 adhered to >66% of the protocol). Researchers evaluated changes in cardiorespiratory fitness (VO2 max), body composition, and epigenetic aging measured by the GrimAge clock, while accounting for shifts in leukocyte composition.
What was found
VO2 max increased by 20% (P < 0.001) and body composition significantly improved (P < 0.001). GrimAge estimates were reproducible (<2 months measurement error) and correlated strongly with chronological age (R2 = 0.86, P < 0.001). Over the 6 months, GrimAge decreased by an average of 7.44 months relative to the expected trajectory (P = 0.012). This reduction correlated with improvements in VO2 max (R2 = 0.27, P = 0.002) but not with changes in body composition. GrimAge shifts strongly correlated with fluctuations in leukocyte composition, particularly the neutrophil fraction (R2 = 0.74, P < 0.001); adjusting for leukocyte composition explained up to 81% of GrimAge variance.
Why it matters
The study demonstrates that GrimAge is sensitive enough to capture biological aging changes from a 6-month exercise intervention and reflects improvements in aerobic fitness. It also highlights that adjusting for leukocyte composition is essential when interpreting epigenetic clock responses to physical activity.
Limits
The study had a small sample size (33 protocol-adherent participants) and lacked a non-exercising control group, making it impossible to isolate exercise effects from potential confounding factors. The cohort was limited to adults aged 35–65 engaged exclusively in cycling, limiting generalizability to other age groups or training modalities. Long-term durability of the epigenetic deceleration after training cessation was not evaluated.
Cited by
- supports A 2025 study by lead author Vanam found that 6 months of cycling for 4.5 hours per week improved VO2 max by 20% and reduced PC-GrimAge by approximately 7 to 7.4 months.