Associations of taste receptor gene variants with Body Mass Index (BMI) and longevity

Taste receptors are expressed in the oral cavity and numerous extra-oral tissues, where they share signaling mechanisms. Within this broad context, taste receptors regulate feeding behavior and metabolic homeostasis, potentially contributing to exceptional longevity. We evaluated differences in genotype and allele frequencies at the TAS1R2, TAS1R3, TAS2R38, and CD36 single-nucleotide polymorphisms (SNPs) and their associations with BMI and sex in two genetically and environmentally distinct populations: a cohort of near centenarian participants (LBZ) and a control cohort (CYME). Significant differences were observed in the genotype and allele distributions of the TAS1R3, TAS2R38, and CD36 SNPs. In the LBZ cohort, specific genotypes, such as TAS1R3 CC, TAS2R38 PAV/PAV, and CD36 AA, were most frequent, and likely contributed to favorable phenotypes, whereas they showed no effect in the more heterogeneous urban CYME population. The BMI was significantly higher in the LBZ cohort, particularly among females. The TAS1R2, TAS1R3, TAS2R38, and CD36 variants modulated BMI in a population- and sex-dependent manner. These results contribute to expanding the understanding of taste receptors as multifunctional chemosensors, with roles that extend beyond gustatory perception to influence systemic physiology, energy balance, and potentially contribute to phenotypic profiles associated with longevity.