Serum Proteomic and Metabolomic Signatures of High Versus Low Physical Function in Octogenarians

ABSTRACT Physical function declines with aging, yet there is considerable heterogeneity, with some individuals declining very slowly while others experience accelerated functional decline. To gain insight into mechanisms promoting high physical function with aging, we performed proteomics, targeted metabolomics, and targeted kynurenine‐focused metabolomic analyses on serum specimens from three groups of octogenarians: High‐functioning master athletes (HF, n  = 16), healthy normal‐functioning non‐athletes (NF, n  = 12), and lower functioning non‐athletes (LF, n  = 11). Higher performance status was associated with evidence consistent with: Lower levels of circulating proinflammatory markers, as well as unperturbed tryptophan metabolism, with the normal function of the kynurenic pathway; higher circulating levels of lysophosphatidylcholines that have been previously associated with better mitochondrial oxidative capacity; lower activity of the integrated stress response; lower levels of circulating SASP protein members; and lower levels of proteins that reflect neurodegeneration/denervation. Extending the observations of previous studies focused on the biomarkers of aging that predict poor function, our findings show that many of the same biomarkers associated with poor function exhibit attenuated changes in those who maintain a high function. Because of the cross‐sectional nature of this study, results should be interpreted with caution, and bidirectional causality, where physical activity behavior is both a cause and outcome of differences in the biomarker changes, remains a possible interpretation.