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.We acknowledge funding from the Spanish Ministry of Education and Science (ref. SAF2013–44663-R), and from the ‘Red Tematica de Investigación Cooperativa en Envejecimiento y Fragilidad’ (RETICEF) (ref. ISCIII2012-RED-43-029) to J.V.; and from the Spanish Ministry of Economy and Competitiveness/Institute of Health Carlos III (ref. PI14/00328), and the Autonomous Government of Catalonia, Department of Health (ref. SLT002/16/00250) and Department of Business and Knowledge (ref. 2017SGR696) to R.P. This study has been co-financed by FEDER funds from the European Union (“Una manera de hacer Europa”). I.P. was supported by a University of Lleida Predoctoral Fellowship. K.H. was supported by a Dementia Australia Research Foundation Scholarship