Bitter Taste Receptor Polymorphisms and Human Aging, Francesco De, Maura Carrai, Paolina Crocco, Alberto Montesanto, Federico Canzian, Giuseppina Rose, Cosmeri Rizzato, Giuseppe Passarino, and Roberto Barale. 

Abstract: Several studies have shown that genetic factors account for 25% of the variation in human lifespan. Based on published molecular, genetic, and epidemiological data, we hypothesized that genetic polymorphisms of taste receptors - which modulate food preferences but are also expressed in various 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

Introduction: Epidemiological studies may find it difficult to obtain reliable information on diet style during early decades of life from elders who likely influenced later health status significantly. Since there are several indications that bitter taste gene polymorphisms can influence food choice, we considered it of interest to investigate the possible association between bitter taste and longevity. Based on 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 various 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 a significant familial and genetic component of longevity. Twin studies have highlighted that approximately 25% of the overall variation in human lifespan can be attributed to genetic factors, which become more relevant after 60 years of age. The research on the genetic component of human longevity has been focused on conserved pathways related to stress response signalling, DNA repair, and the storage and use of nutrients. Studies on centenarians or long-lived subjects allowed identifying specific genes and genotypes involved in these pathways that influence human lifespan. In particular, the variability and expression of genes involved in the storage and use of nutrients have shown to influence both longevity and the quality of aging.

For example, the TAS2R38 gene is characterized by three non-synonymous coding SNPs (rs713598 - G145C, Ala49Pro; rs1726866 - T785C, Val262Ala; rs10246939 - A886G, Ile296Val) that give rise to several haplotypes. Subjects possessing at least one copy of the PAV haplotype (i.e., 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. 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, and lettuce. Given the importance of diet in longevity, genetic variation in taste receptors could directly affect healthy aging by modulating food preference during life.

The importance of nutrients in the aging process is also witnessed by overwhelming epidemiological evidence 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. In particular, diets rich in vegetables seem to be associated with a significant increase in longevity and wellness. Taste receptor genes play a much broader role in human health. Genes of TAS1R-TAS2R gene family express membrane taste receptors in neuroendocrine cells of several organs of the system. These cells start the regulation of a variety of functions, including appetite, satiety, the proliferation of GI cells, secretory activity of the stomach, liver and intestine motility, and gall bladder contraction. A correlation has been observed between polymorphic variants in various taste receptors and homeThe following text has been processed: