Molecular mechanisms of calorie restriction's protection against age-related sclerosis.
The current knowledge on the molecular mechanisms of the protective effect of calorie restriction (CR) against age-related fibrosclerosis is tentatively reviewed with specific reference to the role of oxidative stress in aging. The effects of oxidative stress are often mediated by its own final products. Of these, 4-hydroxy-2,3-nonenal (HNE) induces the expression and synthesis of transforming growth factor beta1 (TGFbeta1) and activates nuclear binding of transcription factor activator protein 1 (AP-1) thus stimulating fibrogenesis. Several studies have shown that, as well as extending mean and maximum life span in a variety of species, CR delays the onset and slows the progression of a variety of age-associated diseases, including diabetes, cardiovascular diseases and neoplasia. However, the anti-aging mechanisms of CR are still not clearly understood. Of the numerous hypotheses put forward, one that still remains popular is protection against the age-associated increase of oxidative stress and consequent cell damage. CR protects the rat aorta from the age-related increase of both oxidative damage and fibrosis; as regards the possible mechanism/s of CR's protection against fibrosclerosis, it is conceivable that, by decreasing oxidative stress, CR reduces HNE levels and consequently TGFbeta1 expression and collagen deposition, likely by down-regulating the activation of Jun-N terminal kinase and of AP-1. Through the modulation of reactive oxygen species and oxidative stress CR may also attenuate the age-associated increase in the inflammatory milieu, thus preserving vascular functional integrity by suppressing the age-associated increase in inflammatory enzyme activities and prostanoids.
Chiarpotto
Elena
E
Department of Clinical and Biological Sciences, University of Torino, Italy. elena.chiarpotto@unito.it
Bergamini
Ettore
E
Poli
Giuseppe
G
D000367:Age Factors; D000447:Aldehydes / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D031204:Caloric Restriction; D006801:Humans; D008136:Longevity / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D012598:Sclerosis / Q000517:prevention & control*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000447:Aldehydes; D018808:Transcription Factor AP-1; D053773:Transforming Growth Factor beta1; C462359:tert-4-hydroxy-2-nonenal