Autophagy-mediated longevity is modulated by lipoprotein biogenesis |
| |
| Authors: | Nicole E Seah C Daniel de Magalhaes Filho Anna P Petrashen Hope R Henderson Jade Laguer Julissa Gonzalez |
| |
| Institution: | 1. Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA;2. The Howard Hughes Medical Institute, The Glenn Center for Aging Research, The Salk Institute for Biological Studies, La Jolla, CA, USA;3. The Howard Hughes Medical Institute, Molecular and Cell Biology Department, Li Ka Shing Center, University of California Berkeley, Berkeley, CA, USA;4. The Howard Hughes Medical Institute, Molecular and Cell Biology Department, Li Ka Shing Center, University of California Berkeley, Berkeley, CA, USA;5. Del E. Webb Neuroscience, Aging and Stem Cell Research Center, Program of Development and Aging, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA;6. Del E. Webb Neuroscience, Aging and Stem Cell Research Center, Program of Development and Aging, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA |
| |
| Abstract: | Autophagy-dependent longevity models in C. elegans display altered lipid storage profiles, but the contribution of lipid distribution to life-span extension is not fully understood. Here we report that lipoprotein production, autophagy and lysosomal lipolysis are linked to modulate life span in a conserved fashion. We find that overexpression of the yolk lipoprotein VIT/vitellogenin reduces the life span of long-lived animals by impairing the induction of autophagy-related and lysosomal genes necessary for longevity. Accordingly, reducing vitellogenesis increases life span via induction of autophagy and lysosomal lipolysis. Life-span extension due to reduced vitellogenesis or enhanced lysosomal lipolysis requires nuclear hormone receptors (NHRs) NHR-49 and NHR-80, highlighting novel roles for these NHRs in lysosomal lipid signaling. In dietary-restricted worms and mice, expression of VIT and hepatic APOB (apolipoprotein B), respectively, are significantly reduced, suggesting a conserved longevity mechanism. Altogether, our study demonstrates that lipoprotein biogenesis is an important mechanism that modulates aging by impairing autophagy and lysosomal lipolysis. |
| |
| Keywords: | apolipoprotein B autophagy C elegans fat storage intestine life span lipid metabolism lipoprotein TOR vitellogenin |
|
|
