Linking Peroxiredoxin and Vacuolar-ATPase Functions in Calorie Restriction-Mediated Life Span Extension

Calorie restriction (CR) is an intervention extending the life spans of many organisms. The mechanisms underlying CR-dependent retardation of aging are still poorly understood. Despite mechanisms involving conserved nutrient signaling pathways proposed, few target processes that can account for CR-mediated longevity have so far been identified. Recently, both peroxiredoxins and vacuolar-ATPases were reported to control CR-mediated retardation of aging downstream of conserved nutrient signaling pathways. In this review, we focus on peroxiredoxin-mediated stress-defence and vacuolar-ATPase regulated acidification and pinpoint common denominators between the two mechanisms proposed for how CR extends life span. Both the activities of peroxiredoxins and vacuolar-ATPases are stimulated upon CR through reduced activities in conserved nutrient signaling pathways and both seem to stimulate cellular resistance to peroxide-stress. However, whereas vacuolar-ATPases have recently been suggested to control both Ras-cAMP-PKA- and TORC1-mediated nutrient signaling, neither the physiological benefits of a proposed role for peroxiredoxins in H2O2-signaling nor downstream targets regulated are known. Both peroxiredoxins and vacuolar-ATPases do, however, impinge on mitochondrial iron-metabolism and further characterization of their impact on iron homeostasis and peroxide-resistance might therefore increase our understanding of the beneficial effects of CR on aging and age-related diseases.