Jorge Pinto Soares

How can age and lifestyle variables affect DNA damage, repair capacity and endogenous biomarkers of oxidative stress?

Age-related DNA damage has been regarded as one of the possible explanations of aging, and these age-related changes have been associated with lifestyle variables. Considering this, the purpose of this study was to investigate how age and lifestyle may affect DNA damage, DNA repair capacity and endogenous biomarkers of oxidative stress. Sixty-one healthy men (40 to 89 yrs) were enrolled in this study. The results showed that DNA strand breaks (DNA SBs) and DNA repair capacity were greater in the older group (>=65 yrs) compared to the younger group (<65 yrs) (p<0.05). FPG-sensitive sites, total antioxidant capacity and lipid peroxidation (MDA) were not statistically different between groups. The correlation test showed that DNA damage variables were not correlated with any lifestyle variable excepting DNA SBs which was correlated with aerobic capacity (6MWT). DNA SBs and DNA repair were positively correlated with age. The multiple regression analysis revealed that the aerobic capacity (6MWT) and MDA were the predictors for the variation of DNA SBs (41.9%). In conclusion these results suggest that DNA SB damage increases with age but not FPG-sensitive sites. Moreover, base excision repair capacity increases with age without the increase of oxidative damage to DNA. The most predictable variables of DNA SBs were the aerobic capacity and MDA.

Age-related increases in human lymphocyte DNA damage: is there a role of aerobic fitness?

Oxidative stress has been advanced as one of the major causes of damage to DNA and other macromolecules. Although physical exercise may also increase oxidative stress, an important role has been recognized for regular exercise in improving the overall functionality of the body, as indicated by an increase in maximal aerobic uptake ( V˙ O2max), and in resistance to cell damage. The aims of this study were 1) to evaluate the association between DNA damage in human lymphocytes and age and 2) to evaluate the association between DNA damage in human lymphocytes and V˙ O2max. The sample was composed of 36 healthy and nonsmoking males, aged from 20 to 84 years. V˙ O2max was evaluated through the Bruce protocol with direct measurement of oxygen consumption. The comet assay was used to evaluate the DNA damage, strand breaks and formamidopyrimidine DNA glycosylase (FPG)‐sensitive sites. We found a positive correlation of age with DNA strand breaks but not with FPG‐sensitive sites. V˙ O2max was significantly inversely related with DNA strand breaks, but this relation disappeared when adjusted for age. A significantly positive relation between V˙ O2max and FPG‐sensitive sites was verified. In conclusion, our results showed that younger subjects have lower DNA strand breaks and higher V˙ O2max compared with older subjects and FPG‐sensitive sites are positively related with V˙ O2max, probably as transient damage due to the acute effects of daily physical activity. Copyright

Efficacy of Exercise on Breast Cancer Outcomes: A Systematic Review and Meta-analysis of Preclinical Data

The use of preclinical models to investigate antitumor effects of exercise on breast tumor (BT) development and progression are critical. However, published results have not been quantitatively summarized or examined for potential exercise-moderating variables. We conducted this review to summarize and quantify the effect-size of exercise on BT outcomes in preclinical studies. A literature search was performed in MEDLINE, PubMed, Web of Science and System for Information on Grey Literature in Europe (SIGLE) databases. Risk of bias was assessed using SYRCLEs RoB tool. A total of 116 correlations were performed to analyze 28 preclinical studies published through December 2016, which included 2,085 animals and 51 exercise programs. Positive effects of small, medium and large magnitude were observed in tumor incidence, growth and multiplicity, respectively. In the tumor microenvironment, positive effects of large magnitude were also observed in proliferation and apoptosis but not in angiogenesis. Moderator variables correlated with higher intervention effects were identified along with a considerable heterogeneity in exercise protocols that precluded us from clearly perceiving the benefits of exercise exposure. In conclusion, exercise performed under specific conditions benefits BT outcomes. Preclinical studies with exercise designs mimicking exercise exposure that can be used in clinical contexts are needed.

Effects of physical exercise training in DNA damage and repair activity in humans with different genetic polymorphisms of hOGG1 (Ser326Cys)

The main purpose of this pilot study was to investigate the possible influence of genetic polymorphisms of the hOGG1 (Ser326Cys) gene in DNA damage and repair activity by 8‐oxoguanine DNA glycosylase 1 (OGG1 enzyme) in response to 16 weeks of combined physical exercise training. Thirty‐two healthy Caucasian men (40–74 years old) were enrolled in this study. All the subjects were submitted to a training of 16 weeks of combined physical exercise. The subjects with Ser/Ser genotype were considered as wild‐type group (WTG), and Ser/Cys and Cys/Cys genotype were analysed together as mutant group (MG). We used comet assay in conjunction with formamidopyrimidine DNA glycoslyase (FPG) to analyse both strand breaks and FPG‐sensitive sites. DNA repair activity were also analysed with the comet assay technique. Our results showed no differences between DNA damage (both strand breaks and FPG‐sensitive sites) and repair activity (OGG1) between genotype groups (in the pre‐training condition). Regarding the possible influence of genotype in the response to 16 weeks of physical exercise training, the results revealed a decrease in DNA strand breaks in both groups, a decrease in FPG‐sensitive sites and an increase in total antioxidant capacity in the WTG, but no changes were found in MG. No significant changes in DNA repair activity was observed in both genotype groups with physical exercise training. This preliminary study suggests the possibility of different responses in DNA damage to the physical exercise training, considering the hOGG1 Ser326Cys polymorphism. Copyright