Decelerated Epigenetic Aging in Long Livers

Abstract

Epigenetic aging is a hot topic in the field of aging research. The present study estimated epigenetic age in long-lived individuals, who are currently actively being studied worldwide as an example of successful aging due to their longevity. We used Bekaert's blood-based age prediction model to estimate the epigenetic age of 50 conditionally "healthy" and 45 frail long-livers over 90 years old. Frailty assessment in long-livers was conducted using the Frailty Index. The control group was composed of 32 healthy individuals aged 20-60 years. The DNA methylation status of 4 CpG sites (ASPA CpG1, PDE4C CpG1, ELOVL2 CpG6, and EDARADD CpG1) included in the epigenetic clock was assessed through pyrosequencing. According to the model calculations, the epigenetic age of long-livers was significantly lower than their chronological age (on average by 21 years) compared with data from the group of people aged 20 to 60 years. This suggests a slowing of epigenetic and potentially biological aging in long livers. At the same time, the obtained results showed no statistically significant differences in delta age (difference between the predicted and chronological age) between "healthy" long livers and long livers with frailty. We also failed to detect sex differences in epigenetic age either in the group of long livers or in the control group. It is possible that the predictive power of epigenetic clocks based on a small number of CpG sites is insufficient to detect such differences. Nevertheless, this study underscores the need for further research on the epigenetic status of centenarians to gain a deeper understanding of the factors contributing to delayed aging in this population.

Keywords: DNA methylation; aging; epigenetic clock; long livers; pyrosequencing.

Figure 1

Scatter plots of the correlation between chronological age and DNA methylation of (a) ASPA CpG₁, (b) EDARADD CpG₁, (c) ELOVL2 CpG₆, and (d) PDE4C CpG₁. The control group is marked in orange, long livers—blue.

Figure 2

Comparison of the predicted and chronological age. (a) Scatterplot of the predicted age against chronological age for each group: CG—control group (green), HC—“healthy” long livers (blue), FC—frail long livers (orange). The line corresponds to the case when the predicted age is the same as the chronological age. (b) Boxplots of the delta age (difference between the predicted and chronological age) according to each group. ** p-value < 0.001, one-way ANOVA.