In this paper, we examined whether meditation practice influences the epigenetic clock, a strong and reproducible biomarker of biological aging, which is accelerated by cumulative lifetime stress and with age-related chronic diseases. Using the Illumina 450K array platform, we analyzed the DNA methylome from blood cells of long-term meditators and meditation-naïve controls to estimate their Intrinsic Epigenetic Age Acceleration (IEAA), using Horvath’s calculator. IEAA was similar in both groups. However, controls showed a different IEAA trajectory with aging than meditators: older controls (age≥52) had significantly higher IEAAs compared with younger controls (age <52), while meditators were protected from this epigenetic aging effect. Notably, in the meditation group, we found a significant negative correlation between IEAA and the number of years of regular meditation practice. From our results, we hypothesize that the cumulative effects of a regular meditation practice may, in the long-term, help to slow the epigenetic clock and could represent a useful preventive strategy for age-related chronic diseases. Longitudinal randomized controlled trials in larger cohorts are warranted to confirm and further characterize these findings.