title: Exogenous insulin can reverse the effects of caloric restriction on mitochondria.
abstract: It has been proposed that part of the anti-aging mechanism of caloric restriction (CR) involves a reduction in both the generation rate of reactive oxygen species (ROS) by mitochondria, and a reduction in peroxidizability of mitochondrial membranes. It was hypothesized that these effects may be due to upstream changes in hormonal status, since certain hormones (such as insulin) are stimulatory for ROS production, effect fatty acid composition, and are lowered by CR. To investigate this hypothesis, young male Brown-Norway rats on 55% CR (4 months duration) were subjected to insulin replacement by use of mini-osmotic pumps. ROS and free radical-induced malondialdehdye production were significantly lower in mitochondria from CR animals compared to those from fully fed, and these effects were reversed by insulin. It is concluded that the beneficial changes induced by CR, as seen at the mitochondrion, may in part be downstream effects of alterations in hormonal signalling.
authors.affiliation: School of Biological Sciences, Biosciences Building, Crown Street, University of Liverpool, Liverpool L69 7ZB, UK. adrian.lambert@mrc-dunn.cam.ac.uk
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Lambert
authors.forename: Bohan
authors.initials: B
authors.lastname: Wang
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Merry
mesh_terms: D000818:Animals; D031204:Caloric Restriction / Q000379:methods*; D002478:Cells, Cultured; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D007328:Insulin; D017382:Reactive Oxygen Species; D008315:Malondialdehyde