Alterations of the gut microbiome are associated with epigenetic age acceleration and physical fitness.

Epigenetic clocks can measure aging and predict the incidence of diseases and mortality. Higher levels of physical fitness are associated with a slower aging process and a healthier lifespan. Microbiome alterations occur in various diseases and during the aging process, yet their relation to epigenetic clocks is not explored. To fill this gap, we collected metagenomic (from stool), epigenetic (from blood), and exercise-related data from physically active individuals and, by applying epigenetic clocks, we examined the relationship between gut flora, blood-based epigenetic age acceleration, and physical fitness. We revealed that an increased entropy in the gut microbiome of physically active middle-aged/old individuals is associated with accelerated epigenetic aging, decreased fitness, or impaired health status. We also observed that a slower epigenetic aging and higher fitness level can be linked to altered abundance of some bacterial species often linked to anti-inflammatory effects. Overall our data suggest that alterations in the microbiome can be associated with epigenetic age acceleration and physical fitness.

Associations between cardiorespiratory fitness and lifestyle-related factors with DNA methylation-based ageing clocks in older men: WASEDA'S Health Study.

DNA methylation-based age estimators (DNAm ageing clocks) are currently one of the most promising biomarkers for predicting biological age. However, the relationships between cardiorespiratory fitness (CRF), measured directly by expiratory gas analysis, and DNAm ageing clocks are largely unknown. We investigated the relationships between CRF and the age-adjusted value from the residuals of the regression of DNAm ageing clock to chronological age (DNAmAgeAcceleration: DNAmAgeAccel) and attempted to determine the relative contribution of CRF to DNAmAgeAccel in the presence of other lifestyle factors. DNA samples from 144 Japanese men aged 65-72 years were used to appraise first- (i.e., DNAmHorvath and DNAmHannum) and second- (i.e., DNAmPhenoAge, DNAmGrimAge, and DNAmFitAge) generation DNAm ageing clocks. Various surveys and measurements were conducted, including physical fitness, body composition, blood biochemical parameters, nutrient intake, smoking, alcohol consumption, disease status, sleep status, and chronotype. Both oxygen uptake at ventilatory threshold (VO2 /kg at VT) and peak oxygen uptake (VO2 /kg at Peak) showed a significant negative correlation with GrimAgeAccel, even after adjustments for chronological age and smoking and drinking status. Notably, VO2 /kg at VT and VO2 /kg at Peak above the reference value were also associated with delayed GrimAgeAccel. Multiple regression analysis showed that calf circumference, serum triglyceride, carbohydrate intake, and smoking status, rather than CRF, contributed more to GrimAgeAccel and FitAgeAccel. In conclusion, although the contribution of CRF to GrimAgeAccel and FitAgeAccel is relatively low compared to lifestyle-related factors such as smoking, the results suggest that the maintenance of CRF is associated with delayed biological ageing in older men.

What Determines the Competitive Success of Young Croatian Wrestlers: Anthropometric Indices, Generic or Specific Fitness Performance?

Identifying factors influencing wrestling performance is important for determining which capacities should be developed the most. This research aimed to investigate whether anthropometric indices, generic fitness, and specific fitness performance determine the competitive success of young wrestlers. This research included 49 Croatian Greco-Roman male wrestlers aged 17.75 ± 1.51 years. Variables included training and competing experience, anthropometric indices, generic fitness (countermovement jump and handgrip strength), and specific wrestling fitness test (SWFT). Wrestlers were separated into medallists and non-medallists (i.e., wrestlers who won a medal at the previous National Championship and wrestlers who did not win a medal, respectively). The t-test for independent samples was used to determine the differences between the two categories in all variables. Moreover, discriminant analysis was performed to identify differences in a multivariate manner. Medallists and non-medallists did not differ in anthropometric indices and wrestling experience. Medallists had better results in the countermovement jump (t = 2.55, p < 0.01), handgrip strength (t = 2.77, p < 0.01), and SWFT performance (t = 2.29, p < 0.05) than non-medallists. The discriminant analysis confirmed that performance categories differed in generic and specific fitness tests (Wilks' Lambda = 0.73, p < 0.05). It could be suggested that coaches should develop both the generic and specific fitness of their wrestlers to become more successful at competitions.

DNA methylation clock DNAmFitAge shows regular exercise is associated with slower aging and systemic adaptation.

DNAmPhenoAge, DNAmGrimAge, and the newly developed DNAmFitAge are DNA methylation (DNAm)-based biomarkers that reflect the individual aging process. Here, we examine the relationship between physical fitness and DNAm-based biomarkers in adults aged 33-88 with a wide range of physical fitness (including athletes with long-term training history). Higher levels of VO2max (ρ = 0.2, p = 6.4E - 4, r = 0.19, p = 1.2E - 3), Jumpmax (p = 0.11, p = 5.5E - 2, r = 0.13, p = 2.8E - 2), Gripmax (ρ = 0.17, p = 3.5E - 3, r = 0.16, p = 5.6E - 3), and HDL levels (ρ = 0.18, p = 1.95E - 3, r = 0.19, p = 1.1E - 3) are associated with better verbal short-term memory. In addition, verbal short-term memory is associated with decelerated aging assessed with the new DNAm biomarker FitAgeAcceleration (ρ: - 0.18, p = 0.0017). DNAmFitAge can distinguish high-fitness individuals from low/medium-fitness individuals better than existing DNAm biomarkers and estimates a younger biological age in the high-fit males and females (1.5 and 2.0 years younger, respectively). Our research shows that regular physical exercise contributes to observable physiological and methylation differences which are beneficial to the aging process. DNAmFitAge has now emerged as a new biological marker of quality of life.

The Circulating Level of Klotho Is Not Dependent upon Physical Fitness and Age-Associated Methylation Increases at the Promoter Region of the Klotho Gene.

(1) Background: Higher levels of physical fitness are believed to increase the physiological quality of life and impact the aging process with a wide range of adaptive mechanisms, including the regulation of the expression of the age-associated klotho (KL) gene and protein levels. (2) Methods: Here, we tested the relationship between the DNA methylation-based epigenetic biomarkers PhenoAge and GrimAge and methylation of the promoter region of the KL gene, the circulating level of KL, and the stage of physical fitness and grip force in two groups of volunteer subjects, trained (TRND) and sedentary (SED), aged between 37 and 85 years old. (3) Results: The circulating KL level is negatively associated with chronological age in the TRND group (r = -0.19; p = 0.0295) but not in the SED group (r = -0.065; p = 0.5925). The age-associated decrease in circulating KL is partly due to the increased methylation of the KL gene. In addition, higher plasma KL is significantly related to epigenetic age-deceleration in the TRND group, assessed by the biomarker of PhenoAge (r = -0.21; p = 0.0192). (4) Conclusions: The level of physical fitness, on the other hand, does not relate to circulating KL levels, nor to the rate of the methylation of the promoter region of the KL gene, only in males.

DNAmFitAge: biological age indicator incorporating physical fitness.

Physical fitness is a well-known correlate of health and the aging process and DNA methylation (DNAm) data can capture aging via epigenetic clocks. However, current epigenetic clocks did not yet use measures of mobility, strength, lung, or endurance fitness in their construction. We develop blood-based DNAm biomarkers for fitness parameters gait speed (walking speed), maximum handgrip strength, forced expiratory volume in one second (FEV1), and maximal oxygen uptake (VO2max) which have modest correlation with fitness parameters in five large-scale validation datasets (average r between 0.16-0.48). We then use these DNAm fitness parameter biomarkers with DNAmGrimAge, a DNAm mortality risk estimate, to construct DNAmFitAge, a new biological age indicator that incorporates physical fitness. DNAmFitAge is associated with low-intermediate physical activity levels across validation datasets (p = 6.4E-13), and younger/fitter DNAmFitAge corresponds to stronger DNAm fitness parameters in both males and females. DNAmFitAge is lower (p = 0.046) and DNAmVO2max is higher (p = 0.023) in male body builders compared to controls. Physically fit people have a younger DNAmFitAge and experience better age-related outcomes: lower mortality risk (p = 7.2E-51), coronary heart disease risk (p = 2.6E-8), and increased disease-free status (p = 1.1E-7). These new DNAm biomarkers provide researchers a new method to incorporate physical fitness into epigenetic clocks.

No strong association among epigenetic modifications by DNA methylation, telomere length, and physical fitness in biological aging.

Cellular senescence is greatly accelerated by telomere shortening, and the steps forward in human aging are strongly influenced by environmental and lifestyle factors, whether DNA methylation (DNAm) is affected by exercise training, remains unclear. In the present study, we investigated the relationships between physiological functions, maximal oxygen uptake (VO2max), vertical jump, working memory, telomere length (TL) assessed by RT-PCR, DNA methylation-based estimation of TL (DNAmTL), and DNA methylation-based biomarkers of aging of master rowers (N = 146) and sedentary subjects (N = 95), aged between 37 and 85 years. It was found that the TL inversely correlated with chronological age. We could not detect an association between telomere length and VO2max, vertical jump, and working memory by RT-PCR method, while these physiological test results showed a correlation with DNAmTL. DNAmGrimAge and DNAmPhenoAge acceleration were inversely associated with telomere length assessed by both methods. It appears that there are no strong beneficial effects of exercise or physiological fitness on telomere shortening, however, the degree of DNA methylation is associated with telomere length.

Blood flow restriction during the resting periods of high-intensity resistance training does not alter performance but decreases MIR-1 and MIR-133A levels in human skeletal muscle.

Blood flow restriction (BFR) during exercise bouts has been used to induce hypertrophy of skeletal muscle, even with low loads. However, the effects of BFR during the rest periods between sets are not known. We have tested the hypothesis that BFR during rest periods between sets of high-intensity resistance training would enhance performance. Twenty-two young adult male university students were recruited for the current study, with n = 11 assigned to BFR and n = 11 to a control group. The results revealed that four weeks training at 70% of 1 RM, five sets and 10 repetitions, three times a week with and without BFR, resulted in similar progress in maximal strength and in the number of maximal repetitions. The miR-1 and miR-133a decreased significantly in the vastus lateralis muscle of BFR group compared to the group without BFR, while no significant differences in the levels of miR133b, miR206, miR486, and miR499 were found between groups. In conclusion, it seems that BFR restrictions during rest periods of high-intensity resistance training, do not provide benefit for enhanced performance after a four-week training program. However, BFR-induced downregulation of miR-1 and miR-133a might cause different adaptive responses of skeletal muscle to high intensity resistance training.

The roles of microRNA in redox metabolism and exercise-mediated adaptation.

MicroRNAs (miRs) are small regulatory RNA transcripts capable of post-transcriptional silencing of mRNA messages by entering a cellular bimolecular apparatus called RNA-induced silencing complex. miRs are involved in the regulation of cellular processes producing, eliminating or repairing the damage caused by reactive oxygen species, and they are active players in redox homeostasis. Increased mitochondrial biogenesis, function and hypertrophy of skeletal muscle are important adaptive responses to regular exercise. In the present review, we highlight some of the redox-sensitive regulatory roles of miRs.

Exercise combined with a probiotics treatment alters the microbiome, but moderately affects signalling pathways in the liver of male APP/PS1 transgenic mice.

It has been demonstrated that physical exercise and probiotic supplementation delay the progress of Alzheimer's Disease (AD) in male APP/PS1TG mice. However, it has also been suggested that both exercise and AD have systemic effects. We have studied the effects of exercise training and probiotic treatment on microbiome and biochemical signalling proteins in the liver. The results suggest that liver is under oxidative stress, since SOD2 levels of APP/PS1 mice were decreased when compared to a wild type of mice. Exercise training prevented this decrease. We did not find significant changes in COX4, SIRT3, PGC-1a or GLUT4 levels, while the changes in pAMPK/AMPK, pmTOR/mTOR, pS6/S6 and NRF2 levels were randomly modulated. The data suggest that exercise and probiotics-induced changes in microbiome do not strongly affect mitochondrial density or protein synthesis-related AMPK/mTOR/S6 pathways in the liver of these animals.

High intensity interval training and molecular adaptive response of skeletal muscle.

Increased cardiovascular fitness, V ˙ O2max, is associated with enhanced endurance capacity and a decreased rate of mortality. High intensity interval training (HIIT) is one of the best methods to increase V ˙ O2max and endurance capacity for top athletes and for the general public as well. Because of the high intensity of this type of training, the adaptive response is not restricted to Type I fibers, as found for moderate intensity exercise of long duration. Even with a short exercise duration, HIIT can induce activation of AMPK, PGC-1α, SIRT1 and ROS pathway as well as by the modulation of Ca2+ homeostasis, leading to enhanced mitochondrial biogenesis, and angiogenesis. The present review summarizes the current knowledge of the adaptive response of HIIT.