The Impact of 8 Weeks of Combined Physical Exercise Training on SIRT3 and mTOR in Lymphocytes, and on Lipid Peroxidation.

The sirtuins (SIRT) protein family and the mechanistic/mammalian target of rapamycin (mTOR) are intracellular molecules that have been involved in the regulation of several biological processes, as well as in various aging-related processes. This pilot study, in small scale, aimed to analyze the effects of an 8-week physical exercise program on SIRT3 and mTOR levels in lymphocytes, as well as on lipid peroxidation in middle aged and older men. A total of 9 participants aged between 56 and 73 years were enrolled in an 8-week physical exercise program comprising cardiovascular and high-intensity interval training. The program involved three sessions per week, each lasting 45-60 min, conducted on non-consecutive days. Tests were conducted before and after the experimental period (pre- and post-training). Assessments included a vertical jump, 20 m velocity, ball throwing, and an aerobic capacity test. Lipid peroxidation (MDA) was measured in plasma as an oxidative stress biomarker. Additionally, sirtuin 3 (SIRT3/ß-actin) and mTOR (mTOR/ß-actin) levels were measured in isolated lymphocytes extracted from venous blood. Following the exercise training period, our results demonstrated a significant improvement in aerobic capacity (pre-training: 615.4 ± 45.3 m; post-training: 687.2 ± 34.6 m; t = -2.521; p = 0.012) and 20 m velocity (pre-training: 4.6 ± 0.5 s; post-training: 4.3 ± 0.3 s; t = -2.023; p = 0.04). Concerning blood variables, there was a significant decrease in mTOR levels (pre-training: 0.857 ± 0.593; post-training: 0.214 ± 0.097; t = -2.547; p = 0.011), while no changes were observed in SIRT3 (pre-training: 0.608 ± 0.404; post-training: 0.516 ± 0.390; t = 0.533; p = 0.594) and MDA (pre-training: 8420 ± 4615; post-training: 8800 ± 3163; t = -0.533; p = 0.594). The notable reduction in mTOR levels in lymphocytes following the 8-week physical exercise program suggests a potential role of exercise in modulating immune cell dynamics, particularly in middle-aged and older individuals. Furthermore, the exercise regimen resulted in improvements in physical function, including enhanced aerobic capacity and walking velocity.

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 SYRCLE's 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.

Effects of combined physical exercise training on DNA damage and repair capacity: role of oxidative stress changes.

Regular physical exercise has been shown to be one of the most important lifestyle influences on improving functional performance, decreasing morbidity and all causes of mortality among older people. However, it is known that acute physical exercise may induce an increase in oxidative stress and oxidative damage in several structures, including DNA. Considering this, the purpose of this study was to identify the effects of 16 weeks of combined physical exercise in DNA damage and repair capacity in lymphocytes. In addition, we aimed to investigate the role of oxidative stress involved in those changes. Fifty-seven healthy men (40 to 74 years) were enrolled in this study. The sample was divided into two groups: the experimental group (EG), composed of 31 individuals, submitted to 16 weeks of combined physical exercise training; and the control group (CG), composed of 26 individuals, who did not undergo any specifically orientated physical activity. We observed an improvement of overall physical performance in the EG, after the physical exercise training. A significant decrease in DNA strand breaks and FPG-sensitive sites was found after the physical exercise training, with no significant changes in 8-oxoguanine DNA glycosylase enzyme activity. An increase was observed in antioxidant activity, and a decrease was found in lipid peroxidation levels after physical exercise training. These results suggest that physical exercise training induces protective effects against DNA damage in lymphocytes possibly related to the increase in antioxidant capacity.

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.

Aging and DNA damage in humans: a meta­analysis study.

Age­related DNA damage is regarded as one of the possible explanations of aging. Although a generalized idea about the accumulation of DNA damage with age exists, results found in the literature are inconsistent. To better understand the question of age­related DNA damage in humans and to identify possible moderator variables, a metaanalysis was conducted. Electronic databases and bibliographies for studies published since 2004 were searched. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for age­related DNA damage were calculated in a random­effects model. A total of 76 correlations from 36 studies with 4676 participants were included. Based on our analysis, a correlation between age and DNA damage was found (r=0.230, p=0.000; 95% confidence interval=0.111­0.342). The test for heterogeneity of variance indicates that the study´s results are significantly high (Q (75)=1754.831, p=0.000). Moderator variables such as smoking habits, technique used, and the tissue/sample analyzed, are shown to influence age­related DNA damage (p=0.026; p=0.000; p=0.000, respectively). Nevertheless, sex did not show any influence on this relation (p=0.114). In conclusion, this meta­analysis showed an association between age and DNA damage in humans. It was also found that smoking habits, the technique used, and tissue/sample analyzed, are important moderator variables in age­related DNA damage.

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.