Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial

Abstract

Manipulations to slow biological aging and extend healthspan are of interest given the societal and healthcare costs of our aging population. Herein we report on a randomized controlled clinical trial conducted among 43 healthy adult males between the ages of 50-72. The 8-week treatment program included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients. The control group received no intervention. Genome-wide DNA methylation analysis was conducted on saliva samples using the Illumina Methylation Epic Array and DNAmAge was calculated using the online Horvath DNAmAge clock (2013). The diet and lifestyle treatment was associated with a 3.23 years decrease in DNAmAge compared with controls (p=0.018). DNAmAge of those in the treatment group decreased by an average 1.96 years by the end of the program compared to the same individuals at the beginning with a strong trend towards significance (p=0.066). Changes in blood biomarkers were significant for mean serum 5-methyltetrahydrofolate (+15%, p=0.004) and mean triglycerides (-25%, p=0.009). To our knowledge, this is the first randomized controlled study to suggest that specific diet and lifestyle interventions may reverse Horvath DNAmAge (2013) epigenetic aging in healthy adult males. Larger-scale and longer duration clinical trials are needed to confirm these findings, as well as investigation in other human populations.

DNA methylation‐based biomarkers of aging were slowed down in a two‐year diet and physical activity intervention trial: the DAMA study

“…For example, Sae‐Lee and colleagues investigated folic acid and vitamin B12 supplementation in a randomized trial including 44 participants (+13 participants from a non‐randomized trial), concluding that the slowing down of the DNAm aging is gender‐ and MTHFR genotype‐specific (Sae‐Lee et al, 2018 ). More recently, Fitzgerald and colleagues provide evidence of reversal epigenetic clocks improving diet and lifestyle in a randomized trial including 38 participants (Fitzgerald et al, 2021 ). Although there is strong evidence that physical exercise has favorable effects on epigenetic mechanisms (Ferioli et al, 2019 ), there is a lack of intervention studies on increasing physical activity associated with longitudinal measures of epigenetic clocks and aging‐related epigenetic drift.…”

AltumAge: A Pan-Tissue DNA-Methylation Epigenetic Clock Based on Deep Learning

“…Horvath’s model has been widely used as it is seen as the state-of-the-art pan-tissue epigenetic clock for humans [13–16]. Therefore, it is essential to contrast it with AltumAge.…”

“…AltumAge is a better age predictor than state-of-the-art epigenetic clocks Horvath's model has been widely used as it is seen as the state-of-the-art pan-tissue epigenetic clock for humans [13][14][15][16]. Therefore, it is essential to contrast it with AltumAge.…”

“…Then Horvath showed epigenetic clocks could also accurately predict age across tissues, developing a predictor with 353 CpG sites [3]. Horvath's model has been widely used as it is seen as the state-of-the-art pan-tissue epigenetic clock for humans [4][5][6][7]. Both of these works used simple regularized linear regression (ElasticNet) for feature selection and prediction [8].…”

Biomarkers of geroprotection and cardiovascular health: An overview of omics studies and established clinical biomarkers in the context of diet

“…On the other hand, intrinsic epigenetic age acceleration, a measure of cell-intrinsic aging based on a modified version of Horvath's clock independent of blood cell composition (Chen et al 2016), is negatively associated with poultry intake (Quach et al 2018). Fitzgerald et al reported a reduction of Horvath's DNA methylation age of 1.96 years measured from saliva samples in a cohort that followed an 8-week diet and lifestyle intervention that targeted sleep, exercise, stress, and nutrition (Fitzgerald et al 2021).…”