Autophagy-mediated longevity is modulated by lipoprotein biogenesis

Autophagy. 2016;12(2):261-72. doi: 10.1080/15548627.2015.1127464.


Autophagy-dependent longevity models in C. elegans display altered lipid storage profiles, but the contribution of lipid distribution to life-span extension is not fully understood. Here we report that lipoprotein production, autophagy and lysosomal lipolysis are linked to modulate life span in a conserved fashion. We find that overexpression of the yolk lipoprotein VIT/vitellogenin reduces the life span of long-lived animals by impairing the induction of autophagy-related and lysosomal genes necessary for longevity. Accordingly, reducing vitellogenesis increases life span via induction of autophagy and lysosomal lipolysis. Life-span extension due to reduced vitellogenesis or enhanced lysosomal lipolysis requires nuclear hormone receptors (NHRs) NHR-49 and NHR-80, highlighting novel roles for these NHRs in lysosomal lipid signaling. In dietary-restricted worms and mice, expression of VIT and hepatic APOB (apolipoprotein B), respectively, are significantly reduced, suggesting a conserved longevity mechanism. Altogether, our study demonstrates that lipoprotein biogenesis is an important mechanism that modulates aging by impairing autophagy and lysosomal lipolysis.

Keywords: C. elegans; TOR; apolipoprotein B; autophagy; fat storage; intestine; life span; lipid metabolism; lipoprotein; vitellogenin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autophagy*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / metabolism
  • Caloric Restriction
  • Gene Expression Regulation
  • Gene Silencing
  • Intestinal Mucosa / metabolism
  • Lipase / metabolism
  • Lipolysis
  • Lipoproteins / biosynthesis*
  • Longevity / physiology*
  • Lysosomes / metabolism
  • Transcription, Genetic
  • Vitellogenesis / genetics
  • Vitellogenins / metabolism


  • Caenorhabditis elegans Proteins
  • Lipoproteins
  • Vitellogenins
  • Lipase