title: Deletion of microRNA-80 activates dietary restriction to extend C. elegans healthspan and lifespan.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America.
authors.forename: Mehul
authors.initials: M
authors.lastname: Vora
authors.forename: Mitalie
authors.initials: M
authors.lastname: Shah
authors.forename: Silvana
authors.initials: S
authors.lastname: Ostafi
authors.forename: Brian
authors.initials: B
authors.lastname: Onken
authors.forename: Jian
authors.initials: J
authors.lastname: Xue
authors.forename: Julie Zhouli
authors.initials: JZ
authors.lastname: Ni
authors.forename: Sam
authors.initials: S
authors.lastname: Gu
authors.forename: Monica
authors.initials: M
authors.lastname: Driscoll
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D031204:Caloric Restriction; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D017384:Sequence Deletion; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; C587166:MIRN80 microRNA, C elegans; D035683:MicroRNAs; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C474710:heat shock factor-1, C elegans; C111709:CBP-1 protein, C elegans; D051548:Histone Acetyltransferases