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

Abstract

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.

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

“…In addition, comparisons across the tertiles indicated that GrimAgeAccel in the high VO2/kg at Peak groups (31.5 ± 3.3 mL/kg/min) decelerated by approximately 1.6 years, compared to that of low group (21.8 ± 1.9 mL/kg/min) (Figure 2e, Table S4). Similarly, in the recent report, a study of 303 men and women aged 33-88 years, including participants in the World Rowing Masters Regatta in Velence, Hungary, showed that DNAmAgeAccel (i.e., FitAgeAccel) was decelerated by 1.5 years in women and 2.0 years in men in the group with higher indirectly calculated VO2max levels (Women: 42.5 ± 7.5 mL/kg/min; Men: 50.2 ± 10.0 mL/kg/min) compared to those with medium-low group (Women: 28.1 ± 5.4 mL/kg/min; Men: 35.1 ± 6.1 mL/kg/min) (Jokai et al, 2022). Although both studies differ in terms of participants, age range, race, and fitness levels, these findings suggest that retaining a high cardiorespiratory fitness is associated with slowing down the biological aging process.…”

“…Epigenome-wide DNA methylation was measured using the same procedure as previously reported (Jokai et al, 2022). Briefly, genomic DNA bisulfite conversion was performed by using the EZ DNA Methylation Kit (Zymo Research, Irvine, CA, USA), followed by hybridization using Infinium MethylationEPIC BeadChip Kit (Illumina Inc., San Diego, CA, USA).…”

“…Briefly, genomic DNA bisulfite conversion was performed by using the EZ DNA Methylation Kit (Zymo Research, Irvine, CA, USA), followed by hybridization using Infinium MethylationEPIC BeadChip Kit (Illumina Inc., San Diego, CA, USA). Sample-and probe-based quality checking were performed using R version 4.0.5 and they involved the use of minfi, Meffil, and ewastools R packages (Jokai et al, 2022). In this study, no samples were excluded as all 144 DNA samples passed the criteria set by Illumina.…”

“…However, whether DNAmAgeAccel is related to physical functions such as grip strength, walking speed, and pulmonary function is controversial (Belsky et al, 2018;Föhr et al, 2022;Maddock et al, 2020;Marioni et al, 2015;McCrory et al, 2021;Petersen et al, 2021;Sillanpaä et al, 2018;Sillanpää et al, 2021;Simpkin et al, 2017). In addition, there is insufficient evidence on the relationships between DNAmAgeAccel and VO2max, a strong predictor of all-cause mortality (Jokai et al, 2022;Sillanpää et al, 2021). In sum, it is essential to clarify the relationship between objectively measured physical fitness and DNAmAgeAccel, including VO2max measurements, to develop a basis for establishing an efficient exercise intervention against biological aging.…”

Wearable-ome meets epigenome: A novel approach to measuring biological age with wearable devices

“…Increased arterial stiffness, measured by impedance cardiography, has been shown to associate with an increase in epigenetic age acceleration 19 , validating our finding. Estimation of VO2max has been shown to negatively associate with a fitness specific DNAm clock, FitAge 60 , but not PhenoAge acceleration 61 . This speaks to a hypothesis that different epigenetic clocks capture different portions of aging.…”