Modulation of redox-sensitive transcription factors by calorie restriction during aging

Oxidative stress is considered to be a major cause of aging and many age-related diseases. Calorie restriction (CR) is known to retard deleterious, age-related processes. Recent studies document that CR retards the aging process by regulating the redox environment through its anti-oxidative properties. Among the key cellular components exquisitely sensitive to redox status are transcriptions factors such as nuclear factor kappa B (NF-kappaB), activator protein-1 (AP-1), and hypoxia inducible factor-1 (HIF-1). Based on available findings and our recent supporting evidence, we proposed to use a new term, 'molecular inflammation' to emphasize the importance of molecular reaction mechanisms distinct from chronic and fully expressed inflammatory phenomena. Currently, limited information is available on the age-related and dietary modulations of these factors. In this review, we place a major focus on the age effects of NF-kappaB, AP-1, and HIF-1 regulation, and further delineate how age-related changes are modulated by CR. Age-related increases in redox-sensitive NF-kappaB, AP-1, and HIF-1 binding activities are concluded to be associated with increased ROS and CR to modulate their activations by suppressing oxidative stress. Data on cellular regulation provide better molecular insights into the mechanisms underlying cellular redox maintenance, which may be the cross-talk between normal aging and age-associated pathogenic processes.