Exceptional human longevity is associated with a specific plasma phenotype of ether lipids

A lipid profile resistant to oxidative damage is an inherent trait associated with animal lifespan. However, there is a lack of lipidomic studies on human longevity. Here we use mass spectrometry based technologies to detect and quantify 137 ether lipids to define a phenotype of healthy humans with exceptional lifespan. Ether lipids were chosen because of their antioxidant properties and ability to modulate oxidative stress. Our results demonstrate that a specific ether lipid signature can be obtained to define the centenarian state. This profile comprises higher level of alkyl forms derived from phosphatidylcholine with shorter number of carbon atoms and double bonds; and decreased content in alkenyl forms from phosphatidylethanolamine with longer chain length and higher double bonds. This compositional pattern suggests that ether lipids from centenarians are more resistant to lipid peroxidation, and that ether lipid signature expresses an optimized feature associated with exceptional human longevity. These results are in keeping with the free radical theory of aging. • Centenarians have higher level of alkyl forms derived from phosphatidylcholine. • Centenarians show decreased alkenyl forms from phosphatidylethanolamine. • Ether lipids from centenarians are more resistant to lipid peroxidation. • Ether lipid signature expresses an optimized trait associated with exceptional human longevity.