DNA Damage Following Acute Aerobic Exercise: A Systematic Review and Meta-analysis

Abstract

Background Exercise is widely recognised for its health enhancing benefits. Despite this, an overproduction of reactive oxygen and nitrogen species (RONS), outstripping antioxidant defence mechanisms, can lead to a state of (chronic) oxidative stress. DNA is a vulnerable target of RONS attack and, if left unrepaired, DNA damage may cause genetic instability. Objective This meta-analysis aimed to systematically investigate and assess the overall effect of studies reporting DNA damage following acute aerobic exercise. Methods Web of Science, PubMed, MEDLINE, EMBASE, and Scopus were searched until April 2019. Outcomes included (1) multiple time-points (TPs) of measuring DNA damage post-exercise, (2) two different quantification methods (comet assay and 8-oxo-2′-deoxyguanosine; 8-OHdG), and (3) protocols of high intensity (≥ 75% of maximum rate of oxygen consumption; VO 2-max) and long distance (≥ 42 km). Results Literature search identified 4316 non-duplicate records of which 35 studies were included in the meta-analysis. The evidence was strong, showcasing an increase in DNA damage immediately following acute aerobic exercise with a large-effect size at TP 0 (0 h) (SMD = 0.875; 95% CI 0.5, 1.25; p < 0.05). When comparing between comet assay and 8-OHdG at TP 0, a significant difference was observed only when using the comet assay. Finally, when isolating protocols of long-distance and high-intensity exercise, increased DNA damage was only observed in the latter. (SMD = 0.48; 95% CI − 0.16, 1.03; p = 0.15 and SMD = 1.18; 95% CI 0.71, 1.65; p < 0.05 respectively). Conclusions A substantial increase in DNA damage occurs immediately following acute aerobic exercise. This increase remains significant between 2 h and 1 day, but not within 5-28 days post-exercise. Such an increase was not observed in protocols of a long-distance. The relationship between exercise and DNA damage may be explained through the hormesis theory, which is somewhat one-dimensional, and thus limited. The hormesis theory describes how exercise modulates any advantageous or harmful effects mediated through RONS, by increasing DNA oxidation between the two end-points of the curve: physical inactivity and overtraining. We propose a more intricate approach to explain this relationship: a multi-dimensional model, to develop a better understanding of the complexity of the relationship between DNA integrity and exercise.

The mitochondria-targeted antioxidant MitoQ, attenuates exercise-induced mitochondrial DNA damage

“…To date, knowledge of how exercise impacts mtDNA damage is lacking [ 7 , 9 ]. Recently, it has been proposed that the simultaneous, beneficial (e.g., signal) and harming (e.g., damage to macromolecules) effects of exercise induce a state of oxidative eustress, which is largely dependent on the local microenvironment (pH, temperature, solvent accessibility, and vicinal interactome) [ 51 ].…”

“…Presence of this commonly quantified base adduct following exercise is indicative of hydroxyl radical addition to guanine's eighth position, as guanine is the most readily oxidised base [ 8 ]. To date, the literature surrounding exercise-induced DNA damage has focused on nuclear DNA damage [ 9 ]; however, the lack of complex chromatin organisation and histone proteins [ 10 , 11 ], the accumulation of vicinal transition metal ions (e.g., ferrous iron), and the potential activation of secondary DNA- and lipid-oxidation products collectively make mtDNA more susceptible to oxidative attack compared to nuclear DNA [ 12 , 13 ]. Understanding and manipulating exercise-induced mtDNA damage is important for avoiding mtDNA heteroplasmy and maintaining genome integrity [ 14 ].…”

Changes in γH2AX and H4K16ac levels are involved in the biochemical response to a competitive soccer match in adolescent players

“…An increase in serum 8-OHdG level, such as observed in this study, may also result from the release of DNA from damaged cells 47 . Other studies have also documented physical activity-induced increases in 8-OHdG concentrations 25,26 .…”

“…Although the role of γH2AX in the response to DNA damage produced by a wide range of chemical and physical agents, such as high doses of ionizing radiation and oxidative stress, is well established 49 , the link between γH2AX and physical activity is still very poorly documented. While there are reports documenting an impact of physical activity on DNA damage 26 or exercise-dependent kinetics of DNA damage repair mechanisms 25 , they focus on other, non-epigenetic components of the DDR pathway.…”

Quantitative Redox Biology of Exercise

“…1). In our opinion, these models are clear examples of insufficient quantitative thinking, largely because they are not expressed in numbers in a universal way [11,12]. Moreover, both models are rather outdated, not because they are simple (even a mathematical model is necessarily simple), but because their underlying biology seems unsubstantiated.…”