Muscle loss associated changes of oxylipin signatures during biological aging: an exploratory study from the PROOF cohort

Characterizations of the multiple mechanisms determining biological aging are required to better understand the etiology and identify early biomarkers of sarcopenia. Oxylipins are a large family of signaling lipids involved in the regulation of various biological processes that become dysregulated during aging. To investigate whether comprehensive oxylipin profiling could provide an integrated and fine characterisation of the early phases of sarcopenia, we performed a quantitative targeted metabolomics of oxylipins in plasma of 81-year old subjects from the PROOF cohort with decreased (n=12), stable (n=16) or increased appendicular muscle mass (n=14). Multivariate and univariate analyses identified significant and concordant changes of oxylipin profiles according to the muscle status. Of note, 90% of the most discriminant oxylipins were derived from EPA and DHA and were increased in the sarcopenic subjects. The oxylipins signatures of sarcopenic subjects revealed subtle activation of inflammatory resolution pathways, coagulation processes and oxidative stress and the inhibition of angiogenesis. Heat maps highlighted relationships between oxylipins and the cardiometabolic health parameters which were mainly lost in sarcopenic subjects. This exploratory study supports that targeted metabolomics of oxylipins could provide relevant and subtle characterization of early disturbances associated with muscle-loss during aging.