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Lysosome Lipid Signaling from the Periphery to Neurons Regulates Longevity

ABSTRACT:

Lysosomes are key cellular organelles that metabolize extra- and intra-cellular substrates. Alterations in lysosomal metabolism are implicated in aging-associated metabolic and neurodegenerative diseases. However, how lysosomal metabolism actively coordinates the metabolic and nervous systems to regulate aging remains unclear. Here, we report a fat-to-neuron lipid signaling pathway induced by lysosomal metabolism and its longevity promoting role in Caenorhabditis elegans. We discovered that induced lysosomal lipolysis in peripheral fat storage tissue up-regulates the neuropeptide signaling pathway in the nervous system to promote longevity. This cell-non-autonomous regulation is mediated by a 47 specific polyunsaturated fatty acid, dihomo-gamma-linolenic acid (DGLA) and LBP-3 lipid chaperone protein transporting from the fat storage tissue to neurons. LBP-3 binds to DGLA, and acts through NHR-49 nuclear receptor and NLP-11 neuropeptide in neurons to extend lifespan. These results reveal lysosomes as a signaling hub to coordinate metabolism and aging, and lysosomal signaling mediated inter-tissue communication in promoting longevity.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Marzia Savini

PROVIDER: MTBLS4654 | MetaboLights | 2022-05-06

REPOSITORIES: MetaboLights

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