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