Open AccessDeletion of microRNA-80 Activates Dietary Restriction to Extend C. elegans Healthspan and Lifespan
Author(s) -
Mehul Vora,
Mitalie B. Shah,
Silvana Ostafi,
Brian Onken,
Jian Xue,
Julie Ni,
Sam Guoping Gu,
Monica Driscoll
Publication year - 2013
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1003737
Subject(s) - caenorhabditis elegans , biology , transcription factor , microrna , microbiology and biotechnology , longevity , heat shock factor , regulator , genetics , heat shock protein , hsp70 , gene
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.