Lifestyle factors and DNA methylation-based aging clocks: cross-sectional and longitudinal associations in the Singapore diet and healthy aging cohort.
Shan J, Tay J, et al. • The journal of prevention of Alzheimer's disease • 2026
Cross-sectional analyses revealed robust associations between smoking, physical activity, and cognitive engagement with epigenetic aging clocks in older Asian adults, while no significant longitudinal associations were detected over a mean follow-up of 3.96 years.
Key Findings
Results
Smoking history showed robust positive associations with accelerated epigenetic aging on both DNAm clocks in cross-sectional analyses.
GrimAge AgeDev association: β = 1.45, 95% CI 1.13–1.77, p < 0.0001
DunedinPACE association: β = 0.63, 95% CI 0.22–1.05, p = 0.003
Analysis included 631 participants (median age 70.0 years; 72.6% female) from the Singapore Diet and Healthy Aging (DaHA) cohort
Models were adjusted for sociodemographic covariates, health status, and immune cell-type proportions
Results
Weekly physical activity was associated with slower epigenetic aging as measured by GrimAge acceleration.
GrimAge AgeDev association: β = -0.22, 95% CI -0.40 to -0.04, p = 0.02
Association was assessed in the cross-sectional sample of 631 participants
Lifestyle exposures were assessed using validated self-administered questionnaires
No significant association with DunedinPACE was reported for physical activity
Results
Daily engagement in cognitively stimulating activities was associated with slower epigenetic aging as measured by GrimAge acceleration.
GrimAge AgeDev association: β = -0.16, 95% CI -0.31 to -0.01, p = 0.04
Association was detected in cross-sectional analyses of 631 older adults
No significant association with DunedinPACE was reported for cognitive engagement
Results
Weekly feelings of stress were initially associated with greater GrimAge AgeDev, but this relationship was attenuated after full adjustment.
The stress-aging association did not survive full multivariable adjustment including sociodemographic covariates, health status, and immune cell-type proportions
The attenuation suggests potential confounding by other covariates in the model
This finding was from the cross-sectional analysis of 631 participants
Results
No significant longitudinal associations between lifestyle factors and DNAm aging clocks were detected.
Longitudinal analysis included 114 participants with a mean follow-up of 3.96 years
Peripheral blood DNAm profiles were generated using the Illumina MethylationEPIC array
The absence of significant findings may reflect limited statistical power and the stability of long-standing lifestyle behaviors over the follow-up period
The authors note the need for larger prospective studies with longer follow-up to confirm these relationships
Methods
The study examined 15 modifiable lifestyle factors in relation to two DNAm clocks in older Asian adults.
The two clocks examined were GrimAge acceleration (AgeDev) and DunedinPACE
The cohort consisted of 631 participants with median age 70.0 years and 72.6% female in the cross-sectional analysis
The study population was drawn from the Singapore Diet and Healthy Aging (DaHA) cohort
Multivariable linear regression models were applied to evaluate associations
Shan J, Tay J, Ye K, Guo J, Cao L, Zeng Y, et al.. (2026). Lifestyle factors and DNA methylation-based aging clocks: cross-sectional and longitudinal associations in the Singapore diet and healthy aging cohort.. The journal of prevention of Alzheimer's disease. https://doi.org/10.1016/j.tjpad.2026.100522