Statins Induce a DAF-16/Foxo-dependent Longevity Phenotype via JNK-1 through Mevalonate Depletion in C. elegans.

ABSTRACT: Statins belong to the most pre-scribed cholesterol lowering drugs in western countries. Their competitive inhibition of the HMG-CoA reductase causes a reduction in the mevalonate pool, resulting in reduced cholesterol biosynthesis, impaired protein prenylation and glycosylation. Recently, a cohort study showed a decreased mortality rate in humans between age 78-90 going along with statin therapy, which is independent of blood cholesterol levels. As C. elegans harbors the mevalonate pathway, but is cholesterol-auxotroph, it is particularly suitable to study cholesterol-independent effects of statins on aging-associated phenotypes. Here, we show that low doses of lovastatin or a mild HMG-CoA reductase knockdown via hmgr-1(RNAi) in C. elegans substantially attenuate aging

SUBMITTER: Jahn A 

PROVIDER: S-EPMC6961767 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature