Autophagy-mediated Longevity is Modulated by Lipoprotein Biogenesis

Overview

Journal Autophagy

Specialty Cell Biology

Date 2015 Dec 17

PMID 26671266

Citations 63

Authors

Nicole E Seah

C Daniel De Magalhaes Filho

Anna P Petrashen

Hope R Henderson

Jade Laguer

Julissa Gonzalez

Andrew Dillin

Malene Hansen

Louis R Lapierre

Affiliations

Soon will be listed here.

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.

Citing Articles

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