Bitter Taste Receptor Polymorphisms and Human Aging

, Francesco De , Maura Carrai3, Paolina Crocco2, Alberto Montesanto2, Canzian1, Giuseppina Rose2, Cosmeri Rizzato1, Giuseppe Passarino2" , Roberto Barale3"

1Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany, 2Department of Cell Biology, University of Calabria, Rende, 3Department of Biology, University of Pisa, Pisa, Italy

Abstract

Several studies have shown that genetic factors account for 25% of the variation in human life span. On the basis of published molecular, genetic and epidemiological data, we hypothesized that genetic polymorphisms of taste receptors, which modulate food preferences but are also expressed in a number of organs and regulate food absorption processing and metabolism, could modulate the aging process. Using a tagging approach, we investigated the possible associations between longevity and the common genetic variation at the three bitter taste receptor gene clusters on chromosomes 5, 7 and 12 in a population of 941 individuals ranging in age from 20 to 106 years from the South of Italy. We found that one polymorphism, rs978739, situated 212 bp upstream of the TAS2R16 gene, shows a statistically significant association (p= 0.001) with longevity. In particular, the frequency of A/A homozygotes increases gradually from 35% in subjects aged 20 to 70 up to 55% in centenarians. These data provide suggestive evidence on the possible correlation between human longevity and taste genetics.

Citation: Campa D, De Rango F, Carrai M, Crocco P, Montesanto A, et al. (2012) Bitter Taste Receptor Polymorphisms and Human Aging. PLoS ONE 7(11): doi:10.1371/journal.pone.0045232 Editor: John I. Glendinning, Barnard College, Columbia University, United States of America Received April 2, 2012; Accepted August 17, 2012; Published November 2, 2012 Copyright:   2012 Campa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This research was partially funded from the European Union’s Seventh Framework Programme (FP7/2007–2011) under the grant agreement The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study. Competing Interests: The authors have declared that no competing interests exist.

Introduction

epidemiological studies it could be difficult to obtain, by elders, reliable information on diet style in their early decades of life, which, likely, significantly influenced later health status. Since there are several indications that bitter taste gene polymorphisms can influence food choice [39,41,42,43,44,45], we considered of some interest to investigate the possible association between bitter taste and longevity. On the basis of these molecular, genetic and epidemiological data from the literature we hypothesized that genetic polymorphisms of taste receptors, which modulate food preferences but are also expressed in a number of organs and regulate food absorption and processing, could modulate the aging process.

Several studies including various genome wide association studies have demonstrated the existence of an important familial and genetic component of longevity [1,2,3,4,5,6,7,8,9]. Twin studies have highlighted that approximately 25% of the overall variation in human lifespan can be attributed to genetic factors [10,11,12], which becomes more relevant after 60 years of age [13]. Based on the results obtained in model organisms, the research on the genetic component of human longevity has been focused on conserved pathways related to stress response signalling, DNA repair and to the storage and the use of nutrients [14,15]. Studies on centenarians or long-lived subjects allowed indeed to identify specific genes and genotypes involved in these pathways that influence human lifespan (for reviews see [16,17,18,19]). In particular, the variability and the expression of the genes involved in the storage and the use of the nutrients showed to influence both longevity and the quality of the aging [14,20].

For example, the TAS2R38 gene is characterized by three non synonymous coding SNPs (rs713598 – G145C, Ala49Pro; rs1726866 – T785C, Val262Ala; rs10246939 – A886G, Ile296Val) which give rise to several haplotypes [46]. Subjects possessing at least one copy of the PAV haplotype (i.e. the alleles coding for proline at rs713598, alanine at rs1726866 and valine at rs10246939) are significantly more responsive to the bitter tastants PROP, PTC, and chemically similar compounds [47,48,49,50,51,52,53,54,55]. Such individuals display the so-called taster phenotype, and are distinct from those who are homozygous for the AVI haplotype and display the so-called non-taster phenotype. Tasters show a reduction in their intake of several vegetables such as cabbage, spinach, lettuce [56,57]. Given the importance of diet in longevity, genetic variation in taste receptor could directly affect a healthy aging by modulating food preference during life.

The importance of nutrients in the aging process is also witnessed by overwhelming epidemiologic evidences that diet and nutrition can affect growth, the development of the body during childhood, the risk of acute and chronic diseases during adulthood, the maintenance of physiological processes and the biological process of aging [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38]. In particular, diets rich in vegetables seem to be associated with a significant increase in longevity and wellness [23,39,40]. In