Editors' ChoiceLipid Signaling

Lysosomes Signal the Nucleus to Control Aging

Sci. Signal.  06 Jan 2015:
Vol. 8, Issue 358, pp. ec6
DOI: 10.1126/scisignal.aaa5929

Folick et al. propose a mechanism by which a lysosomal enzyme influences nuclear events that control longevity in the worm (see the Perspective by Han and Brunet). Increased expression of the gene encoding the lysosomal acid lipase LIPL-4 increased longevity, and this effect depended on the presence of the lysosomal lipid-binding protein LBP-8. LBP-8 acts as a chaperone that helps carry lipids to the nucleus. The authors identified the fatty acid oleoylethanolamide (OEA) as a potential signaling molecule that when transported to the nucleus could activate nuclear hormone receptors and transcription factors NHR-49 and NHR-80. The transcriptional targets of NHR-49 and NHR-80 in turn regulate longevity.

A. Folick, H. D. Oakley, Y. Yu, E. H. Armstrong, M. Kumari, L. Sanor, D. D. Moore, E. A. Ortlund, R. Zechner, M. C. Wang, Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans. Science 347, 83–86 (2015). [Abstract] [Full Text]

S. Han, A. Brunet, Lysosomal lipid lengthens life span. Science 347, 32–33 (2015). [Summary] [Full Text]

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