Aging. Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans

Area of Science:

• Cell Biology
• Aging Research
• Molecular Biology

Background:

• Lysosomes are vital organelles involved in cellular digestion and recycling.
• Their role in cellular signaling, particularly in aging, is an emerging area of research.
• Understanding lysosome function is crucial for human health and longevity.

Purpose of the Study:

• To investigate a novel signaling pathway involving lysosomes that influences aging.
• To identify molecular mechanisms by which lysosomes regulate longevity.
• To explore the function of lysosomes as signaling organelles in metazoans.

Main Methods:

• Utilized the model organism Caenorhabditis elegans.
• Investigated the role of lysosomal acid lipase LIPL-4 and lysosomal lipid-binding protein LBP-8.
• Employed high-throughput metabolomic analysis to identify key lipids.
• Examined the activation of nuclear hormone receptors NHR-49 and NHR-80.

Main Results:

• Lysosomal lipase LIPL-4 triggers nuclear translocation of chaperone LBP-8.
• LBP-8 activates nuclear hormone receptors NHR-49 and NHR-80, promoting longevity.
• Oleoylethanolamide was identified as a lipid that directly binds LBP-8 and NHR-80, enhancing longevity.

Conclusions:

• Discovered a lysosome-to-nucleus signaling pathway that regulates aging.
• Lysosomes function as signaling organelles, impacting longevity.
• This pathway involves specific lipids and nuclear hormone receptors, offering potential targets for aging interventions.