RRC ID 53533
Author Seah NE, de Magalhaes Filho CD, Petrashen AP, Henderson HR, Laguer J, Gonzalez J, Dillin A, Hansen M, Lapierre LR.
Title Autophagy-mediated longevity is modulated by lipoprotein biogenesis.
Journal Autophagy
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.
Volume 12(2)
Pages 261-72
Published 2016-1-1
DOI 10.1080/15548627.2015.1127464
PMID 26671266
PMC PMC4836030
MeSH Animals Autophagy* Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism Caloric Restriction Gene Expression Regulation Gene Silencing Intestinal Mucosa / metabolism Lipase / metabolism Lipolysis Lipoproteins / biosynthesis* Longevity / physiology* Lysosomes / metabolism Transcription, Genetic Vitellogenesis / genetics Vitellogenins / metabolism
IF 11.059
Times Cited 43
C.elegans tm1011 tm4498 tm4417 tm1978