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Science. 2015 Jan 2;347(6217):83-6. doi: 10.1126/science.1258857.

Aging. Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans.

Author information

1
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
2
Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
3
Department of Biochemistry, Discovery and Developmental Therapeutics, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.
4
Institute of Molecular Biosciences, University of Graz, Graz, A-8010, Austria.
5
Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA.
6
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
7
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA. Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. wmeng@bcm.edu.

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.

PMID:
25554789
PMCID:
PMC4425353
DOI:
10.1126/science.1258857
[Indexed for MEDLINE]
Free PMC Article

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