Regular, Intense Exercise Training as a Healthy Aging Lifestyle Strategy: Preventing DNA Damage, Telomere Shortening and Adverse DNA Methylation Changes Over a Lifetime.

Maha Sellami,Nicola Bragazzi,Mohamed Elrayess,Joshua Denham,Mohammad Shoaib Prince

doi:10.3389/fgene.2021.652497

Abstract

Exercise training is one of the few therapeutic interventions that improves health span by delaying the onset of age-related diseases and preventing early death. The length of telomeres, the 5′-TTAGGGn-3′ tandem repeats at the ends of mammalian chromosomes, is one of the main indicators of biological age. Telomeres undergo shortening with each cellular division. This subsequently leads to alterations in the expression of several genes that encode vital proteins with critical functions in many tissues throughout the body, and ultimately impacts cardiovascular, immune and muscle physiology. The sub-telomeric DNA is comprised of heavily methylated, heterochromatin. Methylation and histone acetylation are two of the most well-studied examples of the epigenetic modifications that occur on histone proteins. DNA methylation is the type of epigenetic modification that alters gene expression without modifying gene sequence. Although diet, genetic predisposition and a healthy lifestyle seem to alter DNA methylation and telomere length (TL), recent evidence suggests that training status or physical fitness are some of the major factors that control DNA structural modifications. In fact, TL is positively associated with cardiorespiratory fitness, physical activity level (sedentary, active, moderately trained, or elite) and training intensity, but is shorter in over-trained athletes. Similarly, somatic cells are vulnerable to exercise-induced epigenetic modification, including DNA methylation. Exercise-training load, however, depends on intensity and volume (duration and frequency). Training load-dependent responses in genomic profiles could underpin the discordant physiological and physical responses to exercise. In the current review, we will discuss the role of various forms of exercise training in the regulation of DNA damage, TL and DNA methylation status in humans, to provide an update on the influence exercise training has on biological aging.

Highlights

It is well-established that physical activity and regular exercise can significantly improve overall health and mental wellbeing
The research group found that more intense resistance training resulted in increases of oxidative stress expressed by higher urine 8-OHdG levels and lower antioxidant tripeptide GSH, while moderate training allow reduction in DNA damage with no alteration in GSH or the GSSG/GSH ratio despite improvement in physical performances in both groups
Most studies have shown that regular physical activity increases the activity of telomerase and attenuates telomere shortening in human leukocytes

Summary

INTRODUCTION

It is well-established that physical activity and regular exercise can significantly improve overall health and mental wellbeing. Barres et al (2012) studied the exercise intensity effect (40% of VO2max vs 80% of VO2max) on DNA methylation level in biopsies of vastus lateralis skeletal muscle and gene activation in young sedentary men and women before and after an acute exercise. The intense training and in combination with aerobic exercise attenuated DNA SBs, FPG-sensitive sites, and Malondialdehyde (MDA) levels, without changes in OGG1 activity, the main enzyme regulating the excision of 8-oxoguanine (8-oxoG) Such results were assumed to be due to reductions in oxidative stress levels through decreased ROS and lower production of oxidants. The research group found that more intense resistance training resulted in increases of oxidative stress expressed by higher urine 8-OHdG levels and lower antioxidant tripeptide GSH, while moderate training allow reduction in DNA damage with no alteration in GSH or the GSSG/GSH ratio despite improvement in physical performances in both groups. Shorter TL is linked to higher adiposity (Gardner et al, 2005) and resistance training has been shown to improve body weight and composition in young and adult subjects

Findings

DISCUSSION AND SUMMARY

CONCLUSION