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.

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.

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.