Habitual aerobic exercise and circulating proteomic patterns in healthy adults: relation to indicators of healthspan

Abstract

Habitual aerobic exercise enhances physiological function and reduces risk of morbidity and mortality throughout life, but the underlying molecular mechanisms are largely unknown. The circulating proteome reflects the intricate network of physiological processes maintaining homeostasis and may provide insight into the molecular transducers of the health benefits of physical activity. In this exploratory study, we assessed the plasma proteome (SOMAscan proteomic assay; 1,129 proteins) of healthy sedentary or aerobic exercise-trained young women and young and older men ( n = 47). Using weighted correlation network analysis to identify clusters of highly co-expressed proteins, we characterized 10 distinct plasma proteomic modules (patterns). In healthy young (24 ± 1 yr) men and women, 4 modules were associated with aerobic exercise status and 1 with participant sex. In healthy young and older (64 ± 2 yr) men, 5 modules differed with age, but 2 of these were partially preserved at young adult levels in older men who exercised; among all men, 4 modules were associated with exercise status, including 3 of the 4 identified in young adults. Exercise-linked proteomic patterns were related to pathways involved in wound healing, regulation of apoptosis, glucose-insulin and cellular stress signaling, and inflammation/immune responses. Importantly, several of the exercise-related modules were associated with physiological and clinical indicators of healthspan, including diastolic blood pressure, insulin resistance, maximal aerobic capacity, and vascular endothelial function. Overall, these findings provide initial insight into circulating proteomic patterns modulated by habitual aerobic exercise in healthy young and older adults, the biological processes involved, and their relation to indicators of healthspan. NEW & NOTEWORTHY This is the first study to assess the relation between plasma proteomic patterns and aerobic exercise status in healthy adults. Weighted correlation network analysis identified 10 distinct proteomic modules, including 5 patterns specific for exercise status. Additionally, 5 modules differed with aging in men, two of which were preserved in older exercising men. Exercise-associated modules included proteins related to inflammation, stress pathways, and immune function and correlated with clinical and physiological indicators of healthspan.

Keywords: SomaLogic; blood pressure; inflammation; weighted correlation network analysis.

Figures

Fig. 1.

Modules different with exercise status in young inactive (INAC) and aerobic exercise-trained (AEX) men and women. Data are means ± SE; *P < 0.05.

Fig. 2.

Modules associated with sex (A) or exercise-sex interaction (B) in young inactive (INAC) and aerobic exercise-trained (AEX) men (M) and women (W). Data are means ± SE; AEX*S, aerobic exercise-trained status by sex; *P < 0.05.

Fig. 3.

Modules influenced by age in young and older men. Data are means ± SE; *P < 0.05: young vs. older men. O-AEX, older aerobic exercise-trained men; O-INAC, older inactive men; Y-AEX, young aerobic exercise-trained men; Y-INAC, young inactive men.

Fig. 4.

Modules different with exercise status in men. Data are means ± SE; *P < 0.05: inactive vs. exercise-trained men. O-AEX, older aerobic exercise-trained men; O-INAC, older inactive men; Y-AEX, young aerobic exercise-trained men; Y-INAC, young inactive men.

Fig. 5.

Modules associated with age (Y-INAC vs. O-INAC) and partially preserved in older exercise-trained (O-AEX) men. Data are means ± SE; *P < 0.05. ns, not significant; O-INAC, older inactive men; Y-INAC, young inactive men.

Fig. 6.

GO biological processes implicated by proteins in modules associated with habitual aerobic exercise status. GO, Gene Ontology.

Fig. 7.

GO biological processes implicated by proteins in modules associated with sex (blue) or age (brown). GO, Gene Ontology.

Fig. 8.

GO biological processes implicated by proteins in modules partially preserved in habitually trained older men to levels of young men. GO, Gene Ontology.

Fig. 9.

Modules influenced by exercise or age-related modules preserved with exercise associated with select indicators of healthspan [diastolic blood pressure (A), HOMA-IR (B), V̇o2max (C), endothelial function (D)] in all participants. FMD, flow-mediated dilation; HOMA-IR, homeostasis model assessment-insulin resistance; V̇o2max, maximal aerobic capacity.