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In conclusion, while some studies have found associations between certain genetic polymorphisms and aging or age-related diseases, there is not enough evidence to support the idea that metabolic susceptibility genes play a strong role in these processes. Random variation due to small sample sizes or multiple comparisons may also affect the significance of some findings. However, rare sequence variants have been strongly associated with some diseases.Circular forms may limit the lifespan of somatic cells due to the inability of conventional DNA polymerases to replicate their ends (Takahashi et al., 2000). Two examples of candidate genes in the aging process are the Werner syndrome gene, where the corresponding protein acts as a transcriptional activation factor (Oshima, 2000), and the telomerase gene, which is expressed both in cancer cells and germ cells to overcome the limited proliferation capacity of somatic cells. Are risk factors worth reassessing? Cancer Biomarkers Prev., Garte, S., Gaspari, L., Alexandrie, A.K., Ambrosone, Autrup, H., Autrup, J.L., Baranova, H., Bathum, Benhamou, S., Boffetta, P., et al. Metabolic polymorphism frequencies in control populations. Epidemiol. Biomarkers Prev., Gudmundsdottir, K., Tryggvadottir, L., Eyfjord, J.E. GSTM, GSTT, and GSTP genotypes in relation to cancer risk and frequency of mutations in the p gene. Epidemiol. Biomarkers Prev., Gudmundsson, H., Gudbjartsson, D.F., Frigge, M., Gulcher, Stefansson, K. Inheritance of human longevity Iceland. Eur. J. Hum. Genet., Hart, R.W., Keenan, K., Turturro, A., Abdo, K.M., Leakey, J., Cook, B. Caloric restriction and toxicity. Fund. Toxicol., Heijmans, B.T., Westendorp, R.G., Slagboom P.E. Gene variants, mortality and extreme longevity in Exp. Gerontol., Horwitz B.A., Blanton C.A., McDonald R.B. Determinants of the anorexia of aging: insights from studies. Annu. Rev. Nutr., Ji, X., Tordova, M., O'Donnell, R., Parsons, J.F., Hayden, Gilliland G.L., Zimniak, P. Structure and location of the xenobiotic substrate-binding site and potential non-substrate-binding site in a class pi S-transferase. Biochemistry, Ko, Y., Abel, J., Harth, V., Brde, P., Antony, C., Donat, S., H.P., Ortiz-Pallardo, M.E., Thier R., Sachinidis A., Vetter Bolt H.M., Herberhold C., Brning T. Association of CYPB codon mutant allele in head and neck cell cancer is reflected by somatic mutations of p in tissue. Cancer Res., Li D.N., Seidel A., Pritchard M.P., Wolf C.R., Friedberg Polymorphisms in P CYPB affect the conversion of estradiol to the potentially carcinogenic metabolite hydroxyestradiol. Pharmacogenetics, Lottermoser K., Dsing R., Ervens P., Koch B. Brning Sachinidis A. Vetter H. Ko Y. The activator inhibitor G/G polymorphism is not associated with longevity: a study in octogenarians. J. Mol. Med. Lu C.Y., Lee H.C., Fahn H.J., Wie Y.H. Oxidative stress elicited by an imbalance of free radical scavenging enzymes associated with large-scale mRNA deletions in aging skin. Mutat. Res., Mantosh C., Morley J.E. Chapman I.M. The biology of aging Nutrition, Miyanishi K., Takayama T., Ohi M., Hayashi T., Nobuoka Nakajima T. Takimoto R.Kogawa K.Kato J. S. Niitsu Y. Glutathione S-transferase-pi is closely associated with K-ras mutation during human carcinogenesis. Gastroenterology, Muiras M.L., Verasdonck P., Cottet F., Schachter F. In particular, sequence variations in metabolic susceptibility genes could be associated with longevity given the relevance of oxidative stress for many chronic diseases. References Alexander D.L., Ganem L.G., Fernandez-Salguero P., Gonzalez F., Jefcoate C.R. Aryl-hydrocarbon receptor is an inhibitory regulator of lipid synthesis and commitment to adipogenesis. J. Cell Sci., Ali-Osman F., Akande O., Antoun G., Mao J.X., Buolamwini J. Molecular cloning, characterization, and expression in Escherichia coli of full-length NAs of three human glutathione S-transferase Pi gene variants. Evidence for differential catalytic activity of the encoded proteins. J. Biol. Chem., Bailey L.R., Roodi N., Dupont W.D., Parl F.F. Association of cytochrome PB (CYP