Exercise and gene expression: physiological regulation of the human genome through physical activity

Abstract

The current human genome was moulded and refined through generations of time. We propose that the basic framework for physiologic gene regulation was selected during an era of obligatory physical activity, as the survival of our Late Palaeolithic (50 000–10 000 BC) ancestors depended on hunting and gathering. A sedentary lifestyle in such an environment probably meant elimination of that individual organism. The phenotype of the present day Homo sapiens genome is much different from that of our ancient ancestors, primarily as a consequence of expressing evolutionarily programmed Late Palaeolithic genes in an environment that is predominantly sedentary. In this sense, our current genome is maladapted, resulting in abnormal gene expression, which in turn frequently manifests itself as clinically overt disease. We speculate that some of these genes still play a role in survival by causing premature death from chronic diseases produced by physical inactivity. We also contend that the current scientific evidence supports the notion that disruptions in cellular homeostasis are diminished in magnitude in physically active individuals compared with sedentary individuals due to the natural selection of gene expression that supports the physically active lifestyle displayed by our ancestors. We speculate that genes evolved with the expectation of requiring a certain threshold of physical activity for normal physiologic gene expression, and thus habitual exercise in sedentary cultures restores perturbed homeostatic mechanisms towards the normal physiological range of the Palaeolithic Homo sapiens. This hypothesis allows us to ask the question of whether normal physiological values change as a result of becoming sedentary. In summary, in sedentary cultures, daily physical activity normalizes gene expression towards patterns established to maintain the survival in the Late Palaeolithic era.

A Role for the Transcriptional Coactivator PGC-1α in Muscle Refueling

“…It has been suggested that molecular regulatory events triggered by exercise impart a protective effect against the effects of diabetes, heart failure, and aging (reviewed in Ref. 70). Indeed the development of insulin resistance and diabetes is associated with decreased muscle substrate flexibility (71) and an association between insulin resistance and reduced levels of muscle PGC-1␣ has been shown by several groups (6,72).…”

Towards the minimal amount of exercise for improving metabolic health: beneficial effects of reduced-exertion high-intensity interval training

“…In fact, it is now recognised that exercise, rather than just being a useful strategy for improving health, is actually essential for good metabolic and cardiovascular function, of which insulin action is a key component (Thyfault and Krogh-Madsen 2011;Booth et al 2002). With this in mind, the finding that ~6 out of 10 men and ~7 out of 10 women in the UK are currently not achieving the (low) minimum recommended levels of physical activity is a major concern (Allender et al 2008).…”

Grape Secondary Metabolites – Benefits for Human Health

“…Resveratrol treatment induces mitochondrial morphological changes in muscles and brown adipose tissue such as enlarging of mitochondrial structures and increasing presence of cristae and thus the polyphenol has a beneficial influence on the energy homeostasis and reduces the weight gaining in conditions of high fat diet. As far as resveratrol changes the morphological structure of mitochondria in muscles, this substance enhances the enzymatic activity of organelles and induces the muscle fiber-type switching resulting in increased resistance to muscle fatigue (Booth et al, 2002). All these data lead to the conclusion that resveratrol enhances mitochondrial activity resulting in suppression of ageing symptoms by increasing of fatty acid oxidation, amelioration of fat burning, maintaining of energy homeostasis and induction of muscle fatigue resistance.…”