Lipid Droplets and Peroxisomes Are Co-regulated to Drive Lifespan Extension in Response to Mono-unsaturated Fatty Acids

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2023 May 1

PMID 37127715

Authors

Katharina Papsdorf

Jason W Miklas

Amir Hosseini

Matias Cabruja

Christopher S Morrow

Marzia Savini

Yong Yu

Carlos G Silva-Garcia

Nicole R Haseley

Luke Meraz Murphy

Pallas Yao

Elisa de Launoit

Scott J Dixon

Michael P Snyder

Meng C Wang

William B Mair

Anne Brunet

Affiliations

Soon will be listed here.

Abstract

Dietary mono-unsaturated fatty acids (MUFAs) are linked to longevity in several species. But the mechanisms by which MUFAs extend lifespan remain unclear. Here we show that an organelle network involving lipid droplets and peroxisomes is critical for MUFA-induced longevity in Caenorhabditis elegans. MUFAs upregulate the number of lipid droplets in fat storage tissues. Increased lipid droplet number is necessary for MUFA-induced longevity and predicts remaining lifespan. Lipidomics datasets reveal that MUFAs also modify the ratio of membrane lipids and ether lipids-a signature associated with decreased lipid oxidation. In agreement with this, MUFAs decrease lipid oxidation in middle-aged individuals. Intriguingly, MUFAs upregulate not only lipid droplet number but also peroxisome number. A targeted screen identifies genes involved in the co-regulation of lipid droplets and peroxisomes, and reveals that induction of both organelles is optimal for longevity. Our study uncovers an organelle network involved in lipid homeostasis and lifespan regulation, opening new avenues for interventions to delay aging.

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