Lysosomes within cells recycle cellular waste and damaged cellular structures, ingesting them and then breaking them down with a range of enzymes. Over time, however, lysosomes in long-lived cells such as those of the central nervous system become bloated with a buildup of comparatively rare waste products that they cannot recycle and their functional activity declines. This certainly has a serious impact on the ability of an older cell to function, but is this only because of the growing level of unrecycled garbage in the cell? Researchers here uncover another way in which lysosomes are influencing longevity in a lower animal, and it will be interesting to see if comparable mechanisms also operate in mammals:
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.