Mechanisms underlying caloric restriction and lifespan regulation: implications for vascular aging

Abstract

This review focuses on the emerging evidence that attenuation of the production of reactive oxygen species and inhibition of inflammatory pathways play a central role in the antiaging cardiovascular effects of caloric restriction. Particular emphasis is placed on the potential role of the plasma membrane redox system in caloric restriction-induced pathways responsible for sensing oxidative stress and increasing cellular oxidative stress resistance. We propose that caloric restriction increases bioavailability of NO, decreases vascular reactive oxygen species generation, activates the Nrf2/antioxidant response element pathway, inducing reactive oxygen species detoxification systems, exerts antiinflammatory effects, and, thereby, suppresses initiation/progression of vascular disease that accompany aging.

Figure 1

A diagram of the plasma membrane redox system. The redox cycle is shown in blue. CoQ, oxidized form of coenzyme Q; CoQ^.−,semiquinone radical; CoQH₂, reduced form of coenzyme Q; NQO1, NADH-quinone oxidoreductase. Modified from Hyun et al. (2006a).

Figure 2

Dilations in response to step increases in intraluminal flow (Panel A) or administration of acetylcholine (Panel B) in isolated, cannulated, first order gracilis muscle arterioles (d: ~100 μm; pressurized to 80 mmHg74) of aged (24 month old) F344 rats fed a standard diet (SD) are impaired, as compared to young vessels. Lifelong caloric restriction (CR) preserved microvascular endothelial function. *P<0.05 vs. aged SD. Data are mean±S.D. (n=4 in each group). Panel C: Original Western blots showing that expression of eNOS is up-regulated in carotid arteries of aged CR rats. Bar graphs (Panel D) are summary densitometry data. #P<0.05 vs. SD. Panel E: Lucigenin chemiluminescence measurements revealed that age-related increases in O₂.- production in the aorta of F344 rats are prevented by lifelong caloric restriction (CR). *P<0.05 vs. young, #P<0.05 vs. standard diet (SD)-fed rats.