Too Little Research into Relationships Between Exercise, Fitness, and Epigenetic Aging
Researchers here note that the state of research into the relationships between exercise, physical fitness, and epigenetic aging (or indeed, any other assessment of biological age provided by forms of aging clock) is patchy at best. There are at present too few studies and too little data for researchers to be able to confidently describe the degree to which various levels of exercise and fitness affect aging clocks, as compared to what it is possible to achieve for well-investigated outcomes such as risk of age-related disease and mortality.
The concept of an epigenetic clock is a predictive model based on DNA methylation patterns that provides a more accurate estimate of biological age than chronological age. Physical activity has emerged as a modifiable lifestyle factor that can influence the epigenetic clock and may serve as a geroprotective intervention to extend the health span and possibly the life span. However, some studies have discussed these effects without clearly distinguishing between physical activity, physical fitness, and exercise, which are closely related terms.
These foundational terms - physical activity, exercise, and physical fitness - are often used interchangeably in the general population; however, they have distinct physiological and epidemiological implications, particularly in aging research. For instance, while light-intensity physical activity, such as casual walking, contributes to energy expenditure and general health maintenance, it may not provide a sufficient stimulus to induce the molecular and cellular adaptations typically associated with geroprotective effects. In contrast, structured exercise programs, especially those incorporating moderate-to-vigorous intensity, are more likely to elicit systemic responses such as improved mitochondrial function, enhanced insulin sensitivity, and modulation of epigenetic markers. Furthermore, physical fitness, particularly cardiorespiratory fitness (CRF) and muscular strength, has been shown to be a robust predictor of morbidity and mortality in older adults. It is important to note that while physical activity and exercise are behaviors, physical fitness represents an integrated outcome influenced by genetics, training status, and overall health.
In human studies, one group showed that exercise training helps retain a more youthful methylome and gene expression profile in skeletal muscles. In another study, sedentary middle-aged and older females underwent eight weeks of combined (aerobic and strength) training. The group with a higher epigenetic age prior to the intervention showed a significant decrease in epigenetic age after the intervention. These findings suggest that structured exercise training can effectively reverse or rejuvenate blood- and skeletal muscle-based epigenetic clocks and the aging methylome.
Few studies have examined the relationship between physical fitness obtained through exercise and epigenetic aging. For example, researchers developed DNAmFitAge, which incorporates physical fitness measures into DNA methylation data, and found that bodybuilders had significantly lower DNAmFitAge compared to age-matched controls. These findings suggest that maintaining a high level of physical fitness delays epigenetic aging; however, these studies did not establish a causal relationship.
The effects of exercise on aging are difficult to study. They are difficult to study in animals because it is difficult to command the animal to exercise according to an exact exercise protocol. They are difficult to study in humans because randomized, blinded, placebo trials are impossible. So we can only theorize and hypothesize about the effects of different types of exercise on aging. Such theories and hypotheses are subjective and will vary from researcher to researcher.
Here are my suggestions on exercise and aging:
(1) As we age, the fast-twitch muscle fibers of our skeletal muscles are the first muscle fibers to disintegrate. I propose that fast-twitch muscle fibers secrete anti-inflammatory and anti-aging factors during and after exercise and are responsible for much of the rejuvenatory effects of High-Intensity Interval Training (HIIT).
(2) Most HIIT protocols generate too much lactic acid for too long a period of time, which leads to acidosis. A better protocol for exercising fast-twitch muscle fibers would be Anti-Glycolytic Training (AGT); or alternatively, to limit explosive, lightning-fast movements to only 10 seconds before fully resting. This activates the creatine system for energy.
(3) Exercising fast-twitch muscle fibers through explosive, lightning-fast movements engages the neurons of the brain. These neurons take on a firing rate of 40 Hz or more, which is gamma brainwave frequency (i.e. the super-awake state). Gamma brainwave frequency is known to decrease with aging and has been shown to dissipate amyloid beta in mice.
To my knowledge, I am the only one proposing that the biggest benefit of exercise (particularly fast-twitch muscle fiber exercise) to anti-aging is to exercise the neurons of the brain to fire at gamma brainwave frequency. Gamma brainwave frequency has an anti-aging effect on neurons and increases the neurons' resilience against external stress.
The brain controls the whole body. It controls the immune system, the bone marrow environment, the skeletal muscles, the involuntary muscles, the pituitary gland, the endocrine system, and the organs of the body.