Deletion of microRNA-80 activates dietary restriction to extend C. elegans healthspan and lifespan

PLoS Genet. 2013 Aug;9(8):e1003737. doi: 10.1371/journal.pgen.1003737. Epub 2013 Aug 29.


Caloric/dietary restriction (CR/DR) can promote longevity and protect against age-associated disease across species. The molecular mechanisms coordinating food intake with health-promoting metabolism are thus of significant medical interest. We report that conserved Caenorhabditis elegans microRNA-80 (mir-80) is a major regulator of the DR state. mir-80 deletion confers system-wide healthy aging, including maintained cardiac-like and skeletal muscle-like function at advanced age, reduced accumulation of lipofuscin, and extended lifespan, coincident with induction of physiological features of DR. mir-80 expression is generally high under ad lib feeding and low under food limitation, with most striking food-sensitive expression changes in posterior intestine. The acetyltransferase transcription co-factor cbp-1 and interacting transcription factors daf-16/FOXO and heat shock factor-1 hsf-1 are essential for mir-80(Δ) benefits. Candidate miR-80 target sequences within the cbp-1 transcript may confer food-dependent regulation. Under food limitation, lowered miR-80 levels directly or indirectly increase CBP-1 protein levels to engage metabolic loops that promote DR.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Caloric Restriction*
  • Forkhead Transcription Factors
  • Gene Expression Regulation
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism
  • Longevity / genetics*
  • MicroRNAs / genetics*
  • Sequence Deletion
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • MIRN80 microRNA, C elegans
  • MicroRNAs
  • Transcription Factors
  • daf-16 protein, C elegans
  • heat shock factor-1, C elegans
  • CBP-1 protein, C elegans
  • Histone Acetyltransferases