Charakterisierung der alterungsbedingten Veränderungen im Proteom des Afrikanischen Killifischs
Zusammenfassung der Projektergebnisse
Fat was long thought to be detrimental for health, but new evidence has revealed that specific lipids can be beneficial for lifespan. In many species, long-lived mutants store more fat. Diets that are rich in certain lipids (e.g. oleic acid), such as the Mediterranean diet, correlate with longevity in humans. A key question is how do specific lipids influence longevity and could lipids be leveraged as an intervention? We and others have found that the supplementation of specific lipids can extend lifespan in the nematode worm C. elegans. For example, oleic acid, which is a monounsaturated fatty acid and the main component of olive oil, extends lifespan in C. elegans. The goal of my research was to understand how monounsaturated fatty acids (MUFAs) promote longevity. One exciting possibility is that MUFAs could benefit health by being packed as triglycerides into lipid droplets. Lipid droplets are conserved organelles that contain diverse lipids and interact with other organelles (e.g. mitochondria and peroxisome) to modulate metabolism. My work so far has revealed that long-lived MUFA-enriched C. elegans exhibit a striking increase in lipid droplet number in the intestine. Excitingly, I showed that lipid droplet synthesis is required for longevity and that lipid droplet number can even predict remaining lifespan. I also made the intriguing discovery that peroxisomal enzymes are necessary for lifespan extension by MUFAs in C. elegans. Peroxisomes are central organelles in lipid metabolism, and they can interact with lipid droplets. One hypothesis is that packaging monounsaturated fatty acids into lipid droplets and switching metabolism towards peroxisomal lipid degradation is a critical mechanism for longevity. Results from this work could provide novel insights into how lipid metabolism is regulated to become beneficial and how aging can be delayed by lipidbased dietary interventions.
Projektbezogene Publikationen (Auswahl)
- (2018) Cross-Platform Comparison of Untargeted and Targeted Lipidomics Approaches on Aging Mouse Plasma. Sci. Rep. 8, 1–9
Contrepois, K. et al.
(Siehe online unter https://doi.org/10.1038/s41598-018-35807-4) - (2019) Linking Lipid Metabolism to Chromatin Regulation in Aging. Trends Cell Biol. 29, 97–116
Papsdorf, K. and Brunet, A.
(Siehe online unter https://doi.org/10.1016/j.tcb.2018.09.004)
