Regular exercise can upgrade the efficiency of the immune system and beneficially alter the composition of the gastro-intestinal microbiome. We tested the hypothesis that active athletes have a more diverse microbiome than sedentary subjects, which could provide better protection against COVID-19 during infection. Twenty active competing athletes (CA) (16 male and 4 females of the national first and second leagues), aged 24.15 ± 4.7 years, and 20 sedentary subjects (SED) (15 male and 5 females), aged 27.75 ± 7.5 years, who had been diagnosed as positive for COVID-19 by a PCR test, served as subjects for the study. Fecal samples collected five to eight days after diagnosis and three weeks after a negative COVID-19 PCR test were used for microbiome analysis. Except for two individuals, all subjects reported very mild and/or mild symptoms of COVID-19 and stayed at home under quarantine. Significant differences were not found in the bacterial flora of trained and untrained subjects. On the other hand, during COVID-19 infection, at the phylum level, the relative abundance of Bacteroidetes was elevated during COVID-19 compared to the level measured three weeks after a negative PCR test (p < 0.05) when all subjects were included in the statistical analysis. Since it is known that Bacteroidetes can suppress toll-like receptor 4 and ACE2-dependent signaling, thus enhancing resistance against pro-inflammatory cytokines, it is suggested that Bacteroidetes provide protection against severe COVID-19 infection. There is no difference in the microbiome bacterial flora of trained and untrained subjects during and after a mild level of COVID-19 infection.

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.

Alzheimer’s disease (AD) is a progressive degenerative disorder and a leading cause of dementia in the elderly. The etiology of AD is multifactorial, including an increased oxidative state, deposition of amyloid plaques, and neurofibrillary tangles of the tau protein. The formation of amyloid plaques is considered one of the first signs of the illness, but only in the central nervous system (CNS). Interestingly, results indicate that AD is not just localized in the brain but is also found in organs distant from the brain, such as the cardiovascular system, gut microbiome, liver, testes, and kidney. These observations make AD a complex systemic disorder. Still, no effective medications have been found, but regular physical activity has been considered to have a positive impact on this challenging disease. While several articles have been published on the benefits of physical activity on AD development in the CNS, its peripheral effects have not been discussed in detail. The provocative question arising is the following: is it possible that the beneficial effects of regular exercise on AD are due to the systemic impact of training, rather than just the effects of exercise on the brain? If so, does this mean that the level of fitness of these peripheral organs can directly or indirectly influence the incidence or progress of AD? Therefore, the present paper aims to summarize the systemic effects of both regular exercise and AD and point out how common exercise-induced adaptation via peripheral organs can decrease the incidence of AD or attenuate the progress of AD.

DNAmPhenoAge, DNAmGrimAge, and the newly developed DNAmFitAge are DNA methylation (DNAm) based biomarkers that reflect the individual aging process. Furthermore, physical fitness is known to relate to the aging process, but its relationship to the gut microbiome has not yet been studied. Here, we examine the relationship among physical fitness, DNAm based biomarkers, and the microbiome 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 is able to 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). The microbiomal pathways are associated with VO2max, redox balance, and DNAmPhenoAge. PhenoAge Acceleration is influenced by pyruvate producing microbiomal pathways, where higher activity of these pathways lead to suppressed PhenoAge acceleration. Our research shows that regular physical exercise contributes to observable physiological, methylation, and microbiota differences which are beneficial to the aging process. DNAmFitAge emerged as a biological marker of the quality of life.

Despite the intensive investigation of the molecular mechanism of skeletal muscle hypertrophy, the underlying signaling processes are not completely understood. Therefore, we used an overload model, in which the main synergist muscles (gastrocnemius, soleus) of the plantaris muscle were surgically removed, to cause a significant overload in the remaining plantaris muscle of 8-month-old Wistar male rats. SIRT1-associated pro-anabolic, pro-catabolic molecular signaling pathways, NAD and H2S levels of this overload-induced hypertrophy were studied. Fourteen days of overload resulted in a significant 43% (p < 0.01) increase in the mass of plantaris muscle compared to sham operated animals. Cystathionine-β-synthase (CBS) activities and bioavailable H2S levels were not modified by overload. On the other hand, overload-induced hypertrophy of skeletal muscle was associated with increased SIRT1 (p < 0.01), Akt (p < 0.01), mTOR, S6 (p < 0.01) and suppressed sestrin 2 levels (p < 0.01), which are mostly responsible for anabolic signaling. Decreased FOXO1 and SIRT3 signaling (p < 0.01) suggest downregulation of protein breakdown and mitophagy. Decreased levels of NAD+, sestrin2, OGG1 (p < 0.01) indicate that the redox milieu of skeletal muscle after 14 days of overloading is reduced. The present investigation revealed novel cellular interactions that regulate anabolic and catabolic processes in the hypertrophy of skeletal muscle.

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.

(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.

Cellular senescence is greatly accelerated by telomere shortening, and the steps forward in human aging is strongly influenced by environmental and life-style 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, DNAmethylation based estimation of TL (DNAmTL) and DNA methylation based biomarkers of aging of master rowers (N = 151) and sedentary subjects (N = 90), aged between 37–85 years. It was found that the TL inversely correlated with chronological age, while no gender dependent difference was found. We could not detect association between telomere length and VO2max, vertical jump and working memory by RT-PCR method, while these physiological test results showed correlation with DNAmTL. DNAmGrimAge and DNAmPhenoAge acceleration were inversely associated with telomere length assessed by both methods. It appears that there is no powerful beneficial effects of exercise or physiological fitness on telomere shortening, however the degree of DNA methylation is associated with telomere length. DNAm based estimation of TL shows stronger relationships with physiological functions than RT-PCR measured data.