Aging Metabolism - Series

Step 1: Resveratrol
Resveratrol is a compound found in high concentrations in the skin of grapes, in red wine, and in plants, like giant knotweed. A potent antioxidant, resveratrol is naturally found in two configurations — a 'trans' isomer and its 'cis' counterpart. Research had demonstrated that the trans isomer is more biologically active; this form of resveratrol has recently gained attention because of its ability to increase lifespan in animal model studies.3 As a result, there is significant interest in resveratrol as a healthy aging nutrient for humans.

While the exact mechanism of action is uncertain, it is thought that resveratrol works primarily in two ways. First, it activates siRT1, a member of the sirtuin class of enzymes, an enzyme associated with longevity.4-7 By eliciting an active, highly conserved stress response, siRT1 prolongs lifespan by increasing the ability to survive adversity.8 Secondly — and most importantly from the perspective of the aging metabolism — resveratrol increases mitochondrial production and protects them from free radical damage.9-13

References:

4. Wood JG, Rogina B, Lavu S, et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004;430:686-9.
5. Valenzano DR, Cellerino A. Resveratrol and the pharmacology of aging: a new vertebrate model to validate an old molecule. Cell Cycle. 2006;5:1027-32.
6. Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, Cellerino A. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol. 2006;16:296-300.
7. Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006;127:1109-22.
8. Porth CM. Mitochondria and free radicals. Pathophysiology: Concepts of Altered Health States. 5th ed. Philadelphia, Pa: Lippincott; 2002:103-104.
9. Navarro A, Boveris A. The mitochondrial energy transduction system and the aging process. Am J Physiol Cell Physiol. 2007;292:C670-86.
10. Wood JG, Rogina B, Lavu S, et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004;430:686-9.
11. Sareen D, van Ginkel PR, Takach JC, et al. Mitochondria as the primary target of resveratrol-induced apoptosis in human retinoblastoma cells. Invest Ophthalmol Vis Sci. 2006;47:3708-16.
12. Goh SS, Woodman OL, Pepe S, Cao AH, Qin C, Ritchie RH. The red wine antioxidant resveratrol prevents cardiomyocyte injury following ischemia-reperfusion via multiple sites and mechanisms. Antioxid Redox Signal. 2007;9:101-13.
13. Kasdallah-Grissa A, Mornagui B, Aouani E, et al. Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stress in rat liver. Life Sci. 2007;80:1033-9.

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