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Turning back the clock: Can exercise and a healthy diet reduce your biological age?

This was a secondary analysis of a 24-month randomized controlled trial in healthy, postmenopausal women. Judging by DNA methylation and epigenetic mutation load, biological age was reduced by physical activity (−2.06 years) and a healthy, plant-based diet (−0.66 years).

Background

“Biological age” represents the idea that different people see their bodies age at different speeds. It is a reflection of quality of life and physical and mental functioning.

DNAm clocks are epigenetic clocks based on DNA methylation. They can assess a person’s biological age with increasing accuracy.[1] DNAmGrimAge is a “next-generation clock” based on a linear combination of sex, chronological age, smoking pack-years, and 7 plasma proteins associated with mortality and morbidity.[2]

Another indicator of biological age is the epigenetic mutation load (EML), defined as the sum of stochastic epigenetic mutations (SEMs: the outlier DNAm values) per sample. A higher EML has been associated with different types of cancer.[3][4]

DNAm clocks and EML can be used to identify interventions that may slow the aging process. A healthy diet and high levels of physical activity seem like a good place to start.

Age: biological vs. chronological
The study

This secondary analysis of a 24-month randomized controlled trial investigated whether better dietary habits and higher levels of physical activity improved biomarkers of aging in 219 postmenopausal women (aged 50–69) from the “Diet, Physical Activity, and Mammography” (DAMA[5]) study. The participants in the DAMA study were assigned to 1 of 4 interventions:

  • Dietary intervention: ad libitum, low-glycemic-load, plant-based diet high in antioxidants and low in saturated fat, trans fat, and alcohol

  • Exercise intervention: 1 hour of moderate-intensity exercise per day, 6–10 metabolic equivalent (MET[6]) hours of strenuous activity per week, and a weekly 1-hour session with a physical-activity expert at a fitness facility

  • Both of the above

  • Control: general advice on a healthy diet and healthy levels of physical activity, based on the 2007 recommendations of the World Cancer Research Fund

The primary outcomes were DNAmGrimAge and EML, which were measured at baseline and at the end of the study.

The results

At baseline, DNAmGrimAge was positively associated with obesity and former smoking and negatively associated with both fruit and vegetable intakes, whereas EML was positively associated with processed-meat intake. (For both DNAmGrimAge and EML, positive associations are undesirable.)

Compared to control, the dietary intervention led to a reduction in DNAmGrimAge (−0.66 years). Of the plasma proteins measured, only PAI-1 was significantly reduced: it accounted for more than 30% of the variability. (PAI-1 is associated with type 2 diabetes, hypertension, and time-to-coronary heart disease.[2][7]) Reductions in leptin and GDF-15 proteins, while not statistically significant, contributed to 20% and 15% of the variability, respectively.

Compared to control, the exercise intervention led to a reduction in EML (−2.06 years). A further analysis found that SEMs critical in cancer-related pathways were reduced.

No change in DNAmGrimAge was associated with the exercise intervention, and no change in EML was associated with the dietary intervention.

Note

A strength of this study is that the sample was composed of healthy, nonsmoking women, so the results were not confounded by the presence of diseases or smoking. Moreover, over the 2 years of the study, the participants’ body weight was relatively stable, with an average weight loss of 0.38 kg (the control group lost the least, 0.20 kg, while the diet + exercise group lost the most, 0.54 kg; the authors didn’t specify how much weight the two other groups lost).

All the participants were postmenopausal women. The study’s findings may not apply to other populations.

The big picture

Several studies support the link between DNAm clocks and biological age. DNAm age acceleration (i.e., the difference between DNAm age and chronological age) is associated with HIV,[8] Down syndrome,[9] and the following age-related issues: Alzheimer’s disease,[10] Parkinson disease,[11] amyotrophic lateral sclerosis,[12] and mortality.[13]

Different DNAm clocks have different strengths and weaknesses, but some are overall better than others.[14] For example, second-generation clocks such as DNAmGrimAge and DNAmPhenoAge are better indicators of various age-related health and functional outcomes than first-generation clocks such as Hannum’s blood-specific clock and Horvath’s pan-tissue clock.[15][16][17]

DNAGrimAge, in particular, has outperformed other DNAm clocks, including its second-generation peers. DNAGrimAge has shown to be a reliable predictor of type 2 diabetes, chronic obstructive pulmonary disease, cardiovascular disease, time-to-coronary heart disease, time-to-cancer, and time-to-death.[18][2] It’s also strongly associated with brain health and age-related clinical phenotypes (e.g., polypharmacy,[19] frailty, walking speed).[20][15]

DNAm clocks have a lot of potential; however, most studies were cross-sectional in design (they looked at population data at a specific point in time) and so could neither establish causation nor follow the changes over time of people’s DNAm clocks and other health parameters. The present study was the first to investigate longitudinal changes in DNAmGrimAge. More longitudinal intervention studies are needed to clarify causality and accurately quantify the benefits, at a molecular level, of various changes in lifestyle.

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