Abstract

Aging causes physiological dysfunction, some of which can be prevented or reduced by habitual aerobic exercise (AE). However, the molecular mechanisms underlying these effects remain largely unknown, particularly in humans. We used a novel high‐throughput molecular assay (SOMAscan v3.0, SomaLogic Inc., Boulder, CO) to characterize the effects of age and regular AE on the plasma proteome of healthy adult humans. From 1129 analytes, the expression of 48 proteins was greater and 37 lower in older (O; 64±6 yr; n=16) vs. young (Y; 24±4 yr; n=16) healthy men (false discovery rate [FDR] < 15%, p<0.01). Expression of the non‐collagenous extracellular matrix (ECM) protein dermatopontin was greater in O vs. Y (P=0.007), but was lower in older AE‐trained men (63±7 yr; n=8; VO2max = 49.6±3.7 mL/kg⋅min) compared with their sedentary counterparts (VO2max = 27.4±2.4 mL/kg⋅min) (FDR < 1.28%, p<0.001). Within O, no other group differences in plasma protein expression associated with exercise status met our FDR threshold (>35%). These preliminary results suggest that normal human aging is associated with several changes to the plasma proteome that may serve as molecular biomarkers of physiological dysfunction or disease risk. Regular AE status influences age‐related changes in circulating dermatopontin, a possible mediator of age‐related ECM remodeling.Grant Funding Source: Supported by NIH AG013038 and RR025780

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