Epigenetic clock analysis of diet, exercise, education, and lifestyle factors

Abstract

Behavioral and lifestyle factors have been shown to relate to a number of health-related outcomes, yet there is a need for studies that examine their relationship to molecular aging rates. Toward this end, we use recent epigenetic biomarkers of age that have previously been shown to predict all-cause mortality, chronic conditions and age-related functional decline. We analyze cross-sectional data from 4,173 postmenopausal female participants from the Women's Health Initiative, as well as 402 male and female participants from the Italian cohort study, Invecchiare nel Chianti.Extrinsic epigenetic age acceleration (EEAA) exhibits significant associations with fish intake (p=0.02), moderate alcohol consumption (p=0.01), education (p=3×10-5), BMI (p=0.01), and blood carotenoid levels (p=1×10-5)—an indicator of fruit and vegetable consumption, whereas intrinsic epigenetic age acceleration (IEAA) is associated with poultry intake (p=0.03) and BMI (p=0.05). Both EEAA and IEAA were also found to relate to indicators of metabolic syndrome, which appear to mediate their associations with BMI. Metformin—the first-line medication for the treatment of type 2 diabetes—does not delay epigenetic aging in this observational study. Finally, longitudinal data suggests that an increase in BMI is associated with increase in both EEAA and IEAA.Overall, the epigenetic age analysis of blood confirms the conventional wisdom regarding the benefits of eating a high plant diet with lean meats, moderate alcohol consumption, physical activity, and education, as well as the health risks of obesity and metabolic syndrome.

Traumatic Stress and Accelerated Cellular Aging: From Epigenetics to Cardiometabolic Disease

“…These correlations could suggest that reductions in the integrity of the immune and inflammation systems drive accelerated aging in DNAm (or vice versa), or the convergence of these metrics of cellular aging could be due to a distinct and more basic biological process. Related to this, Chen et al [55], Quach et al [79], and Horvath et al [80] combined data from DNAm age and white blood cell counts to create a new index of immune system aging in blood. They showed that this new metric out-performed other age-adjusted DNAm age estimates in predicting important outcomes, such as time until death [55], and a variety of cardiometabolic measures [79].…”

“…Related to this, Chen et al [55], Quach et al [79], and Horvath et al [80] combined data from DNAm age and white blood cell counts to create a new index of immune system aging in blood. They showed that this new metric out-performed other age-adjusted DNAm age estimates in predicting important outcomes, such as time until death [55], and a variety of cardiometabolic measures [79]. Though chronological age was regressed out of this combined metric of DNAm age and immune system age, one concern about this approach was that the immune system components used to form this index were selected on, and weighted by, their univariate associations with chronological age (in a separate dataset).…”

“…There is preliminary evidence that healthy diet, moderate alcohol use, exercise, and educational attainment may be protective against accelerated aging [79] and these are logical behavioral targets for intervention. It is unknown if successful PTSD treatment (e.g., psychotherapy) might have a far reaching effect on reducing the pace of cellular aging, but the addition of DNAm data to clinical trials could begin to address this question.…”

Interindividual epigenetic variability: Sound or noise?

“…Some types of cancer are associated with increased epigenetic aging rates (e.g. Moreover, although the clock may reflect the potential consequences of intrinsic and programmed cellular events during the aging process, it is affected by other external factors such as viral infections, including HIV [59], obesity [60], and metabolic syndromes [61]. basal breast cancer) [19,56].…”

Is Cellular Heterogeneity Merely a Confounder to be Removed from Epigenome-Wide Association Studies?

“…Regardless, recently researchers have begun to question whether the methylation signal determined by cell mix should be discarded as a merely a technical artefact. Horvath et al [19] and Quach et al [49] found their intrinsic and extrinsic signals of aging in blood correlated with different lifestyle factors and outcomes. Cell mix driven DNA methylation signal may be extremely relevant to prognostic biomarkers and trackers of intervention efficacy.…”