Abstract
Evaluation of biological age, as opposed to chronological age, is of high relevance for interventions to increase healthy ageing. Highly reproducible age-associated DNA methylation (DNAm) changes can be integrated into algorithms for epigenetic age predictions. These predictors have mostly been trained to correlate with chronological age, but they are also indicative for biological ageing. For example, accelerated epigenetic age of blood is associated with higher risk of all-cause mortality in later life. The perceived age of facial images (face-age) is also associated with all-cause mortality and other ageing-associated traits. In this study, we therefore tested the hypothesis that an epigenetic predictor for biological age might be trained on face-age as a surrogate for biological age rather than on chronological age. Our data demonstrate that facial ageing does not correlate with either the epigenetic clock or blood-based DNAm measures.
Highlights
We analysed data from the Lothian Birth Cohort 1921 (LBC1921), a longitudinal study of ageing in a 1921 birth cohort followed up at five assessment waves between ages 79 and 92 years (Additional file 1) [1]
DNA methylation profiles were analysed in whole blood collected at mean age 79.1 (SD 0.55) years using Illumina HumanMethylation450BeadChips as previously described [2]
Perceived facial age was assessed from neutral expression facial photographs taken at mean age 83.3 years (SD 0.52; blood samples were not collected at this time point) [3]
Summary
We analysed data from the Lothian Birth Cohort 1921 (LBC1921), a longitudinal study of ageing in a 1921 birth cohort followed up at five assessment waves between ages 79 and 92 years (Additional file 1) [1]. In the LBC1921 training sample (n = 235, ndeaths = 198), the epigenetic predictor of facial age was correlated with measured facial age (r = 0.66) and predicted increased risk for mortality (HR 1.31 [1.12, 1.53] per SD increase in face-age, p = 8.2 × 10−4; Fig. 1b). The association with mortality risk was in the same direction but had a much smaller effect-size and was not statistically significant in the out-of-sample analysis in the independent Lothian Birth Cohort 1936 (n = 920, ndeaths = 215; HR 1.07 [0.94, 1.23], p = 0.32; Additional file 1; Fig. 1c) This is the first study on epigenome-wide association of DNAm with perceived facial age. Our results indicate that face-age is uncorrelated with both blood-based individual CpG levels and epigenetic clock estimates, despite face-age itself being proposed as a measure of biological age
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