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Longevity GenesIn terms of aging and genes, researchers have found that there is a family of genes involved in an organism's ability to withstand a stressful environment, and if these remain activated long enough, they can also dramatically extend its life span. Of the genes found so far, several that are shared among very different species appear to function in the insulin-signaling pathway, offering a signal that there might be a relationship between life span and the regulation of metabolism. Other genes appear to be related to caloric restriction, which has radically extended life span in mammals. In animal studies, the genes found so far to have longevity profile include: Age-1/Daf-23, Amp-1/AMPK, Chico, Clk-1, Ctl-1, Daf-2, Daf-16, Eat-2, Ghr, Ghrhr, Hsp70, Indy, InR, Klotho, Methuselah/CD97, MsrA, Mth, Old-1/old-2, P53, P66shc, Pcmt, Pit1/Prop1, SIR2/SIRT1, Sod-1, Sod-2, TOR, Upa. In humans, one ongoing approach is to study families that exhibit exceptional longevity. So far, one gene that has been found to have an effect on longevity is a mutation of a gene involved in lipoprotein metabolism, known as CETP (cholesteryl ester transfer protein, plasma). The same research group (Atzmon G, Rincon M, Schechter CB, et al.) that found that gene also identified another longevity-linked gene associated with lipoprotein levels and sizes. Longevity Genes - StudiesButler RN, Austad SN, Barzilai N, et al. Longevity genes: from primitive organisms to humans. J Gerontol A Biol Sci Med Sci. 2003 Jul;58(7):581-4. Atzmon G, Schechter C, Greiner W, et al. Clinical phenotype of families with longevity. J Am Geriatr Soc. 2004 Feb;52(2):274-7. Atzmon G, Rincon M, Rabizadeh P, Barzilai N. Biological evidence for inheritance of exceptional longevity. Mech Ageing Dev. 2005 Feb;126(2):341-5. Atzmon G, Rincon M, Schechter CB, et al. Lipoprotein genotype and conserved pathway for exceptional longevity in humans. PLoS Biol. 2006 Apr;4(4):e113. Sinclair DA, Guarente L. Unlocking the secrets of longevity genes. Sci Am. 2006 Mar;294(3):48-7. Chen J, Zhou Y, Mueller-Steiner S, et al. SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling. J Biol Chem. 2005 Dec 2;280(48):40364-74. Dhahbi JM, Tsuchiya T, Kim HJ, Mote PL, Spindler SR. Gene expression and physiologic responses of the heart to the initiation and withdrawal of caloric restriction. J Gerontol A Biol Sci Med Sci. 2006 Mar;61(3):218-31. Dhahbi JM, Mote PL, Fahy GM, Spindler SR. Identification of potential caloric restriction mimetics by microarray profiling. Physiol Genomics. 2005 Nov 17;23(3):343-50.
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