RESEARCH PERSPECTIVE


CYB5R3: a key player in aerobic metabolism and aging?

Rafael de Cabo1, Emilio Siendones2, Robin Minor1, and Plácido Navas2
1 Laboratory of Experimental Gerontology, National Institute on Aging, NIH, Baltimore, MD 21224, USA
2 Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC and Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, E-41013 Sevilla, Spain
Running title:
CYB5R3 and lifespan
Key words:
cytochrome b5 reductase, NAD+/NADH, NQR1, lifespan, respiration
Received:
11/30/09; accepted: 12/28/09; published on line: 12/29/09
Correspondence:
E-mail:

Abstract

Aging results from a complex and not completely understood chain of processes that are associated with various negative metabolic consequences and ultimately leads to senescence and death. The intracellular ratio of pyridine nucleotides (NAD+/NADH), has been proposed to be at the center stage of age-related biochemical changes in organisms, and may help to explain the observed influence of calorie restriction and energy-sensitive proteins on lifespan in model organisms. Indeed, the NAD+/NADH ratios affect the activity of a number of proteins, including sirtuins, which have gained prominence in the aging field as potential mediators of the beneficial effects of calorie restriction and mediating lifespan. Here we review the activities of a redox enzyme (NQR1 in yeast and CYB5R3 in mammals) that also influences the NAD+/NADH ratio and may play a regulatory role that connects aerobic metabolism with aging.