Exercise intervention differentially induces the expression of cystathionine beta synthase (CBS) in African American with MCI: Implication for endogenous H2S generation and component of aging pathway

Abstract

AbstractBackgroundDecline in metabolic fitness, accumulation of undesirable metabolic changes and cellular senescence are the hallmarks of aging [1,2]. The incorporation of lifespan‐extending platforms such as exercise can promote metabolic fitness and delay the process of aging [3]. However, the mechanisms involved are unclear. We hypothesized that exercise intervention can drive beneficial outcome by increasing expression of two enzymes; CBS and CTH involved in the production of H2S, glutathione and taurine as well as splice factors; SRSF2 and HNRNPD [4,5] in African American with MCI.MethodWe used TaqMan gene expression assay to investigate mechanistic link between exercise and components of aging pathway by evaluating CBS and CTH, enzymes metabolizing sulfur containing amino acid. We also evaluated if CBS and CTH expression correlate with SRSF2 and HNRNPD splice factors by virtue of endogenous H2S production.ResultComparison of CBS and CTH at baseline, 3‐ and 6‐month exercise time points revealed that 3‐month exercise intervention doubled the expression of CBS. However, CTH showed a decreasing trend, suggesting differential expression. Interestingly, expression of CBS correlated with SRSF2 splice factor whereas expression of CTH correlated with HNRNPD at all time points tested.ConclusionIn this study, we provided mechanistic insight through which exercise drive beneficial outcome by investigating component of aging pathway at baseline and exercise intervention in African American with MCI. Our data suggest differential effect of exercise on the expression of CBS, CTH; and the splice factors linked to delay pace of cellular senescence and aging by way of H2S [4,5]. Thus, our study implicates exercise‐induced CBS expression and endogenous H2S as drivers of benefit of fitness adaptation on metabolic fitness and life span with potential for clinical translation.