Aging, Environment, & DiseaseImprinting and Inheritance

Offspring Reap the Benefits of Parent’s Exercise

Epigenetic inheritance exerciseThe epigenetic landscapes are vulnerable to many environmental insults, including unhealthy diet, famine, psychological stress and disease. Mounting evidence is indicating physical exercise can reprogram the epigenome and the epigenetic reprogramming of transcription is crucial for health and performance adaptations. Interestingly, environmental epigenetic reprogramming does not appear to be limited to the exposed individual and epigenetic inheritance can occur through germ cells. In rodents, toxins (BPA, pesticides, etc), psychological stress and high-fat diets are all environmental insults that perturb the epigenetic landscape that can lead to the inheritance of disease in subsequent generations – up to the 4th generation.4

In a recent review in Acta Physiologica ,1 I provid a synthesis of evidence supporting exercise as a lifestyle factor capable of influencing the epigenetic landscape of numerous tissues. These epigenetic changes may ultimately elicit the cardio-protection, metabolic, neurologic and cognitive performance adaptations from exercise training.

Furthermore, maternal and paternal exercise training may lead to environmental epigenetic inheritance of specific traits and also restore the aberrant inheritance of disease linked to diet-induced obesity in the subsequent generation. In mice, males given a high-fat diet prior to mating produced offspring with obese and metabolic syndrome phenotypes. However, an 8-week pre-mating diet and exercise intervention restored healthy phenotypes of offspring.5 Moreover, the aberrant expression of sperm-borne microRNAs (miR-503, miR-542-3p and miR-465b-5p) involved in cell cycle regulation, apoptosis and embryo development pathways were also restored by the lifestyle interventions and suggest a potential mechanism for the heritable reduction in metabolic dysfunction. Sperm-borne non-coding RNAs are also implicated in obesity in human subjects and are partly normalized by bariatric surgery-induced weight loss.3 The human sperm methylome is also reprogrammed by intense physical exercise, particularly in genes implicated in Parkinson’s disease and Schizophrenia.2

Notably, epigenetic inheritance is not limited to the effects of paternal exercise. Maternal exercise before, during and after gestation is linked to many of the same health benefits conferred by exercise in F1 pups. These include cognitive improvements (learning, ameliorated fear and anxiety), body weight and fat reduction, less metabolic dysfunction and tumour prevalence.1 Although there is lack of evidence demonstrating the precise epigenetic modification/s involved in the epigenetic inheritance of the aforementioned traits, these will likely be delineated in the not-so-distant future.

The area of exercise epigenetics is certainly in its infancy, but it does have the potential to explain how we respond to exercise training. The wide-spread accessibility of calorie-dense foods and physical inactivity plaguing modern societies is an enormous global issue that could be compounded by the possibility that these factors may lead to metabolic dysfunction and obesity in future generations. As such, it will be necessary to delineate whether maternal and paternal exercise training may be a therapeutic strategy capable of preventing the epigenetic inheritance of disease.


Original Article:
Denham J. Exercise and epigenetic inheritance of disease risk. Acta Physiol (Oxf) 2017.

1. Denham J. Exercise and epigenetic inheritance of disease risk. Acta Physiol (Oxf) 2017.
2. Denham J, O’Brien BJ, Harvey JT, and Charchar FJ. Genome-wide sperm DNA methylation changes after 3 months of exercise training in humans. Epigenomics 7: 717-731, 2015.
3. Donkin I, Versteyhe S, Ingerslev LR, Qian K, Mechta M, Nordkap L, Mortensen B, Appel EV, Jorgensen N, Kristiansen VB, Hansen T, Workman CT, Zierath JR, and Barres R. Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans. Cell Metab 23: 369-378, 2016.
4. Hanson MA, and Skinner MK. Developmental origins of epigenetic transgenerational inheritance. Environ Epigenet 2: 2016.
5. McPherson NO, Owens JA, Fullston T, and Lane M. Preconception diet or exercise intervention in obese fathers normalizes sperm microRNA profile and metabolic syndrome in female offspring. Am J Physiol Endocrinol Metab 308: E805-821, 2015.

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Joshua Denham

Joshua Denham