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Open AccessArticle

Inter-Individual Variability in Xenobiotic-Metabolizing Enzymes: Implications for Human Aging and Longevity

Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, Italy
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Authors to whom correspondence should be addressed.
These authors equally contributed.
Genes 2019, 10(5), 403; https://doi.org/10.3390/genes10050403
Received: 29 April 2019 / Revised: 15 May 2019 / Accepted: 23 May 2019 / Published: 27 May 2019
(This article belongs to the Special Issue Genetic Determinants of Human Longevity)
Xenobiotic-metabolizing enzymes (XME) mediate the body’s response to potentially harmful compounds of exogenous/endogenous origin to which individuals are exposed during their lifetime. Aging adversely affects such responses, making the elderly more susceptible to toxics. Of note, XME genetic variability was found to impact the ability to cope with xenobiotics and, consequently, disease predisposition. We hypothesized that the variability of these genes influencing the interaction with the exposome could affect the individual chance of becoming long-lived. We tested this hypothesis by screening a cohort of 1112 individuals aged 20–108 years for 35 variants in 23 XME genes. Four variants in different genes (CYP2B6/rs3745274-G/T, CYP3A5/rs776746-G/A, COMT/rs4680-G/A and ABCC2/rs2273697-G/A) differently impacted the longevity phenotype. In particular, the highest impact was observed in the age group 65–89 years, known to have the highest incidence of age-related diseases. In fact, genetic variability of these genes we found to account for 7.7% of the chance to survive beyond the age of 89 years. Results presented herein confirm that XME genes, by mediating the dynamic and the complex gene–environment interactions, can affect the possibility to reach advanced ages, pointing to them as novel genes for future studies on genetic determinants for age-related traits. View Full-Text
Keywords: aging; longevity; survival; SNP; polymorphism; xenobiotic-metabolizing enzymes; xenobiotics aging; longevity; survival; SNP; polymorphism; xenobiotic-metabolizing enzymes; xenobiotics
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Crocco, P.; Montesanto, A.; Dato, S.; Geracitano, S.; Iannone, F.; Passarino, G.; Rose, G. Inter-Individual Variability in Xenobiotic-Metabolizing Enzymes: Implications for Human Aging and Longevity. Genes 2019, 10, 403.

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