Aging. Lysosomal Signaling Molecules Regulate Longevity in Caenorhabditis Elegans

Overview

Journal Science

Specialty Science

Date 2015 Jan 3

PMID 25554789

Citations 148

Authors

Andrew Folick

Holly D Oakley

Yong Yu

Eric H Armstrong

Manju Kumari

Lucas Sanor

David D Moore

Eric A Ortlund

Rudolf Zechner

Meng C Wang

Affiliations

Soon will be listed here.

Abstract

Lysosomes are crucial cellular organelles for human health that function in digestion and recycling of extracellular and intracellular macromolecules. We describe a signaling role for lysosomes that affects aging. In the worm Caenorhabditis elegans, the lysosomal acid lipase LIPL-4 triggered nuclear translocalization of a lysosomal lipid chaperone LBP-8, which promoted longevity by activating the nuclear hormone receptors NHR-49 and NHR-80. We used high-throughput metabolomic analysis to identify several lipids in which abundance was increased in worms constitutively overexpressing LIPL-4. Among them, oleoylethanolamide directly bound to LBP-8 and NHR-80 proteins, activated transcription of target genes of NHR-49 and NHR-80, and promoted longevity in C. elegans. These findings reveal a lysosome-to-nucleus signaling pathway that promotes longevity and suggest a function of lysosomes as signaling organelles in metazoans.

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