Aging & Longevity

Lifestyle factors and DNA methylation-based aging clocks: cross-sectional and longitudinal associations in the Singapore diet and healthy aging cohort.

TL;DR

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

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

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

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

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

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

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

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Citation

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