Abstract 47: Five-Year Change in Biological Aging: Insights From the Age Gene-Environment Susceptibility-Reykjavik Study

Introduction: Epigenetic clocks help to establish a pace of biological aging. Many studies employ biologic aging scores but typically assume consistent aging pace as individuals age. We examined demographic differences in biologic aging over time in an older population. Methods: DNA methylation data are from the Age Gene/Environment Susceptibility-Reykjavik Study (AGES-RS) cohort (n=2,081 participants; 57.6% female; baseline mean [SD] age 75.5 [4.8]). The participants were examined in 2002-2006 (AGES-1) and after approximately 5-year follow-up (AGES-2). We calculated the AGES-1 and AGES-2 Epigenetic Age Acceleration (EAA) separately using the DunedinPACE clock. EAA >1 implies fast biological aging, EAA <1 implies slow aging, and EAA~1 suggests similar biological and chronological aging pace. Individuals were categorized as having slow (<1 SD of the mean), stable (within one SD), or fast (>1 SD) EAA. We investigated age (<76 vs. ≥76yrs) and sex differences in biological aging, as well as changes in biological aging pace. Results: Mean EAA (SD) at AGES-1 was 1.10 (0.11) and 1.13 (0.12) at AGES-2, with a strong correlation (r=0.83). While mean (SD) chronological age was comparable between women (75.4, [4.9]) and men (75.7 [4.7]) in AGES-1, women had lower EAA (1.07 [0.11]) than men (1.12 [0.10]; p < 2.2e-16). At AGES-1, people <76yrs had EAA 1.09 (0.11), while those aged ≥76yrs had 1.11 (0.11), p = 0.007. At AGES-1, 68.7% were stable, 15.1% slow, and 16.1% fast agers. At AGES-2, 74.6% maintained their pace, with 25.4% (n=528) changing categories. Of the 528, almost one-quarter (23.7%) went from fast to slow biological aging. Stratifying by sex, among the 314 (26.2%) women who switched categories, most (76.4%) transitioned from slow to fast, while 23.6% changed from fast to slow. Among males, 214 (24.2%) experienced EAA shifts, with 23.8% from fast to slow. When considering age groups, 297 individuals (24.3%) aged < 76yrs had shifts compared to 231 (26.8%) aged ≥76yrs. Notably, the shift from slow to fast was 75.8% among those < 76yrs compared to 77.1% in those ≥76yrs. Conclusion: In this older population cohort (>67 years), approximately a quarter (25.4%) displayed shifts in biological aging due to methylation signals. More women had EAA shifts, but men often showed a greater biological aging. Older individuals (≥76yrs) also shifted from slow to fast aging. These findings highlight the dynamic nature of biological aging and its susceptibility to environmental influences. Further research is needed to investigate what factors are associated with these changes over time and whether the changes have clinical significance.