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RESEARCH PRODUCT

Long-lived Humans Have a Unique Plasma Sphingolipidome

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A species-specific lipidome profile is an inherent feature linked to longevity in the animal kingdom. However, there is a lack of lipidomic studies on human longevity. Here, we use mass spectrometry-based lipidomics to detect and quantify 151 sphingolipid molecular species and use these to define a phenotype of healthy humans with exceptional life span. Our results demonstrate that this profile specifically comprises a higher content of complex glycosphingolipids (hexosylceramides and gangliosides), and lower levels of ceramide species from the de novo pathway, sphingomyelin and sulfatide; while for ceramide-derived signaling compounds, their content remains unchanged. Our findings suggest that structural glycosphingolipids may be more relevant to achieve the centenarian condition than signaling sphingolipids. We acknowledge funding from the Spanish Ministry of Science, Innovation and Universities (RTI2018-099200-B-I00) and the Generalitat of Catalonia, Agency for management of University and Research Grants (2017SGR696) and Department of Health (SLT002/16/00250) to R.P., and Spanish Ministry of Education and Science (SAF2013-44663-R) and the ‘Red Tematica de Investigación Cooperativa en Envejecimiento y Fragilidad’ (RETICEF) (ISCIII2012-RED-43-029) to J.V. This study has been co-financed by FEDER funds from the European Union (“A way to build Europe”). I.P. was supported by a University of Lleida Predoctoral Fellowship. K.H. was supported by a Dementia Australia Research Foundation Scholarship.