Prausn Kumar Dev1, Jacob L. Barber1, Guoshuai Cai1, Jeremy M. Robbins2, Prashant Rao2, Michael Mi2, Sujoy Ghosh3,4, Clary Clish5, Daniel H. Katz2, Robert E. Gerszten2, Claude Bouchard, FACSM4, Mark A. Sarzynski, FACSM1. 1University of South Carolina, Columbia, SC. 2Beth Israel Deaconess Medical Center, Boston, MA. 3Duke-National University of Singapore Medical School, Singapore. 4Pennington Biomedical Research Center, Baton Rouge, LA. 5Broad Institute of Harvard and MIT, Cambridge, MA.

Introduction: Identification of a robust molecular signature is a major goal in aging research. Recent studies have identified proteins that resemble a proteomic clock and can predict accelerated biological aging. Exercise is well known to mitigate the physiological and molecular changes associated with healthy biological aging. However, it is unknown whether regular exercise affects the predicted protein age. Hypothesis: We hypothesized that exercise training would attenuate proteomic age acceleration as evidenced by decreasing the difference between protein predicted age and actual age. Methods: We measured over 5,000 circulating proteins using an aptamer-affinity based platform (SomaScan) before and after 20 weeks of endurance exercise training in 647 Black (n=210) and White (n=417) adults from the HERITAGE Family Study. Proteomic age score was calculated by summing the weighted expression values across 360 proteins validated in previous proteomic age score studies. Delta age (or proteomic age acceleration) was quantified as the difference between predicted and chronological age. Change in delta age was calculated by subtracting baseline delta age from post-training delta age. Results: The proteomic age score was very strongly correlated with chronological age (r=0.94, p<0.0001). Proteomic age acceleration was associated with ethnicity, generation (parent vs offspring), and their interaction, but not sex. Specifically, baseline delta age (mean (SD)) was significantly lower in parents (5.2 (4.1) yrs) compared to offspring (10.6 (4.2) yrs) and in Blacks (8.0 (4.7) yrs) compared to Whites (9.2 (5.0) yrs). Exercise training resulted in a decrease in delta age in parents only (i.e., training attenuated proteomic age acceleration), with the decrease larger in White (-13.7 (8.0) yrs) compared to Black (-7.4 (9.0) yrs) parents.Conversely, offspring of both ethnic groups showed mean increases (+6.1 (4.1) yrs) in delta age with training (i.e., proteomic age acceleration increased). Conclusion:These results indicate that an established proteomic signature of age is sensitive to exercise training, but the magnitude of response differs by subgroups of age and ethnicity thereby limiting its potential clinical utility. Further studies are needed to examine whether reduced proteomic age acceleration with exercise training is associated with concomitant improvements in cardiometabolic traits related to healthy aging.

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