Extended Data Table 3 Treatment effects of vitamin D, omega-3 and SHEP (simple home exercise program) individually and in combination on the change of DNAm measures from baseline to year 3

From: Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial

  1. Treatment effects are expressed as standardized estimates of the change in DNAm measure from baseline to year three at the respective 95%CI. All analyses show main effects under the assumption of additive effects between treatments in the 2x2x2 factorial trial design, that is comparing all individuals treated with vitamin D across the 8 treatment arms of the trial compared with those who did not receive vitamin D (same for omega-3 and SHEP compared to control SHEP). Only for GrimAge2 each treatment arm is compared to placebo, because of treatment interactions. There is consistency for omega-3 slowing biological aging as measured by PhenoAge, GrimAge2 and Pace of Aging. PhenoAge additionally shows the additive benefit between treatments. There was no significant treatment effect on the change in DNAmFitAge61 over three years. Additionally, the combination of Vitamin D and omega-3 (0.21(0.01;0.41)), the combination of SHEP and omega-3 (0.30 (0.1;0.5)), as well as the combination of all three treatments (0.33 (0.09;0.58)) significantly increases PC-DNAmTL over three years. DNAmTL it is not a good proxy for telomere length (weak correlation of around 0.35). However, DNAmTL has a stronger relationship to age, smoking, obesity, mortality risk) than actual leukocyte telomere length based on Southern blotting or PRC measures62. The table shows regression coefficients, and their 95% CI derived from analysis of covariance adjusted for chronological age (continuous + spline at 85 years), sex, falls before study, body mass index, study site, respective baseline biological age measure. All analyses were done in n = 777 participants sampled at baseline and at 3-year follow-up, without technical replicates
  2. To derive the effect of each treatment in month the respective estimate needs to be multiplied by the standard deviation and by 12. To translate effect units to months: (Standardized estimate* SD + mean)*12; that is (−0.16*0.49-0.16)*12* = 2.9 months; (−0.32*0.49-0.16)*12 = −3.8 months. See Fig. 2 – visual display of the same findings.
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