Abstract 4366972: Endurance Exercise Modifies Organ-Specific Proteomic Aging Scores: Insights from the Heritage Family Study

Introduction: Plasma proteomics has been used to identify organ-specific aging signatures related to health and disease. It is unknown whether regular exercise can modulate predicted organ aging. Research Question: To examine whether proteomic aging signatures are modified by endurance exercise training (ET). Methods: We measured 4,979 plasma proteins (SomaScan assay) in the HERITAGE Family Study (N=657 adults) before and after 20 weeks of ET. Organ age was estimated for 11 major organs using different panels of proteins and age gap was calculated as the difference between predicted age and the LOWESS regression estimate of the population mean. Accelerated and decelerated aging were defined as an age gap value ≥ or < 2 SD from the mean, respectively. Paired t-tests examined changes in predicted organ age after ET. Results: The mean (SD) age of the study was 34.4 (13.5) years, and 55.1% were female. We found low-to-moderate correlations between predicted organ age and chronological age for 9 of 11 traits with the strongest correlations found in the conventional age score (r=0.81, p=2.1E-155), which included all proteins on the platform, and organismal age score, which incorporated organ-nonspecific proteins (r = 0.77, p=3.5E-132). Organismal age score was highly associated with several cardiometabolic traits including VO 2 max (r=-0.44, p=1.3E-37), body fat percentage (r=0.35, p=1.6E-21), and waist circumference (r=0.29, p=3.2E-13) after adjusting for sex and race; these associations were significant after adjustment for chronological age. We found 8 of the 11 organ age signatures changed (p<0.05) with ET ( Figure 1 ), with kidney, muscle, and pancreas the only organs to decrease age, while adipose, brain, heart, immune, and liver ages increased. Among the 23% of participants with accelerated and 15% with decelerated organ aging at baseline, 74% had fewer accelerated or decelerated organ ages after ET ( Figure 2 ). Conclusions: We found that organ age signatures replicated in the HERITAGE Family Study and were modified by ET in both positive and negative directions. These changes suggest that individuals with extreme aging tended to regress toward the mean, whereby those with accelerated aging decreased and those with decelerated aging increased organ aging.