Short communicationEpigenetic clock analysis in long-term meditators
Introduction
Recently, DNA methylation has emerged as a robust biomarker of biological aging. The methylation level of a large number of genomic sites are highly associated with age, to such a point that methods based on a small number of these sites can predict the chronological age with an average error of only 4 years (Hannum et al., 2013, Horvath, 2013). More precisely, the DNA methylation (DNAm) age can be estimated from the methylation levels of 353 CpG sites of the genome and has been found to highly correlate to chronological age and to be stable across most tissues and cell types (i.e. whole blood, peripheral mononuclear cells, brain cells, breast, kidney, liver, lung and saliva) (Horvath, 2013). The deviation between the DNAm age and the chronological age of an individual provides information regarding his epigenetic aging rate (Chen et al., 2016). Faster-running epigenetic clocks have been negatively associated with longevity (Horvath et al., 2015), and positively associated with chronic diseases (Horvath et al., 2014, Horvath and Ritz, 2015, Levine et al., 2015a, Levine et al., 2015b, Perna et al., 2016), frailty (Breitling et al., 2016), cognitive and physical fitness in the elderly (Marioni et al., 2015b) and all cause mortality even after adjusting for chronological age and a variety of known risk factors (Christiansen et al., 2016, Marioni et al., 2015a, Perna et al., 2016). The epigenetic clock therefore may represent an accurate tool to measure the effectiveness of lifestyle-based interventions for the prevention of age-related diseases. This is a health priority area today as revealed by data from the Centers for Disease Control and Prevention indicating that 78% of adults aged 55 years and over present one or more chronic diseases (www.cdc.gov).
Consistent with previous work describing the noxious impact of psychological stress on health span (Juster et al., 2010), it has recently been shown that cumulative lifetime chronic stress (Zannas et al., 2015) and trauma (Boks et al., 2015) predict accelerated epigenetic aging. Meditation-based stress reduction interventions have increasingly become a focus of scientific interest to promote healthy aging. Recent research suggests that meditation has beneficial effects in stress and age-related neuroplastic changes, and mood and cognitive disorders (Acevedo et al., 2016, Luders, 2014). Molecular mechanisms involved in the aging process, such as inflammation, immune and epigenetic pathways (Black and Slavich, 2016, Kaliman et al., 2014), as well as telomere maintenance (Epel et al., 2009; Alda et al., 2016), are also sensitive to contemplative practices. However, it remains unexplored whether meditation experience modulates the rate of the epigenetic aging. Given the well-characterized effect of meditation practice on stress reduction (McEwen, 2016), we tested the hypothesis that long-term practitioners would show slower rates of epigenetic aging than age and sex matched controls. To do so, we analyzed DNA methylome data from blood cells of long-term meditators and meditation-naïve controls.
Section snippets
Participants
Long-term meditators (n = 18) and meditation-naïve controls (n = 20) were studied. The recruitment strategy, and inclusion and exclusion criteria, are described in detail in supplementary information S1. The two groups had similar group distribution of age, sex, body mass index and ethnicity (S2). Participant's written informed consent was approved by the UW-Madison. Meditators had more than 3 years of practice (with a minimum of 30 min of daily sitting meditation and at least 3 intensive retreats),
DNA methylation (DNAm) age and Intrinsic epigenetic age acceleration (IEAA) estimation
We measured the DNA methylation (DNAm) ages in long-term meditators and meditation-naïve controls. DNAm and chronological ages were highly correlated to each other (Pearson r = 0.88 in controls, r = 0.79 in meditators, r = 0.83 overall, p-value < 10−3 in all cases) (Fig. 1A), confirming the accuracy of the epigenetic clock model (Horvath, 2013).
We calculated the Intrinsic Epigenetic Age Aceleration (IEAA) which adjusts the epigenetic aging rate for blood cell count estimates, leading to a measure
Discussion
The current study was designed to determine if the rate of epigenetic aging in long-term meditators was different than in meditation-naïve controls (the meditators recruited for this study had between 5 and 30 years of continuous regular practice). We found no difference in the intrinsic epigenetic aging acceleration (IEAA) between long-term meditators and meditation-naïve controls. However, we found a different IEAA trajectory in controls and meditators as a function of age, with an increase
Funding
This work was supported by CNRS PEPS INEE 2015 (RC), NCCAM (NIH) (P01-AT004952 (RJD and AL), Fetzer Institute, John Templeton Foundation, anonymous donor (RJD), LABEX CORTEX ANR-11- LABX-0042, Université de Lyon ANR-11-IDEX-0007 and ERCConsolidator 617739-BRAINandMINDFULNESS (AL). We thank Claire Dandine, Hervé Perdry and Alice Urvoy for helpful discussions.
Authors’ contributions
RC, RJD, AL and PK designed the study; MJA and PK generated the samples; BR and LL produced the methylation data; RC, MF and BR analyzed the data; RC and PK wrote the manuscript. All authors declare that they have no conflicts of interest.
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2021, Ageing Research ReviewsCitation Excerpt :Interestingly, these structures are known to be particularly sensitive to ageing and AD. MM training has also been associated with increased telomerase activity in blood cells (Schutte and Malouff, 2014), and reduced molecular, genetic and epigenetic markers of inflammation(Chaix et al., 2017; Kaliman et al., 2014). Preliminary evidence also comes from cross-sectional studies in expert meditators.