Suchergebnisse

Human prefrontal cortex (PFC) is a recently evolutionary emerged brain region involved in cognitive functions. Human cognitive abilities decline during aging. Yet the molecular mechanisms that sustain the preservation or deterioration of neurons and PFC functions are unknown. In this review, we focus on the role of lipids in human PFC aging. As the evolution of brain lipid concentrations is particularly accelerated in the human PFC, conferring a specific lipid profile, a brief approach to the lipidome of PFC was consider along with the relationship between lipids and lipoxidative damage, and the role of lipids in human PFC aging. In addition, the specific targets of lipoxidative damage in human PFC, the affected biological processes, and their potential role in the cognitive decline associated with aging are discussed. Finally, interventions designed to modify this process are considered. We propose that the dysfunction of key biological processes due to selective protein lipoxidation damage may have a role the cognitive decline of PFC during aging. ; Research by the authors was supported by the Spanish Ministry of Economy and Competitiveness, Institute of Health Carlos III (FIS grants PI14/00757 and PI14/00328), and the Autonomous Government of Catalonia (2017SGR696), to I.F. and R.P. and Instituto de Salud Carlos III and co-funded by FEDER [grant number PIE15/00013], SAF2016-75508-R from the Spanish Ministry of Education and Science (MEC), CB16/10/00435 (CIBERFES), PROMETEOII2014/056 de "Consellería, de Sanitat de la Generalitat Valenciana and EU Funded CM1001 and FRAILOMIC-HEALTH.2012.2.1.1-2 and ADVANTAGE-724099 Join Action (HP-JA) 3rd EU Health Programme to J.V. and PCIN-2017-117 of the Ministry of Economy and Competitiveness and the EU Joint Programming Initiative 'A Healthy Diet for a Healthy Life' (JPI HDHL INTIMIC-085) to C.B. This study was co-financed by FEDER funds from the European Union ('A way to build Europe').

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")

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.

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.