This paper is chiefly interesting for the discussion on possible mechanisms by which variants in a taste receptor gene might be modestly influencing the odds of living a longer, healthier life. Calorie restriction, practiced to even a lesser degree, has such as a strong effect on aging in comparison to most other factors that one has to consider whether alterations in mechanisms of taste can be influential on aging via consequent alterations in dietary preferences.
Yet taste is complicated, and these genes also have other functions that seem clearly relevant to health over the long term. As this paper illustrates, even when provided with a very specific taste-related mechanism to discuss, and data on its prevalence in centenarians versus the rest of the population, it is far from straightforward to arrive at a robust conclusion. Of course it remains the case that, even given that robust conclusion, the size of this effect would not be large enough to care about in a world in which rejuvenation therapies are presently under development.
Bitter taste receptors play crucial roles in detecting bitter compounds not only in the oral cavity, but also in other tissues where they are involved in a variety of non-tasting physiological processes. Disorders or modifications in the sensitivity or expression of these receptors can affect physiological functions. Here we evaluated the role of the bitter receptor TAS2R38 in attainment of longevity, since it has been widely associated with individual differences in taste perception, food preferences, diet, nutrition, immune responses and pathophysiological mechanisms.
Our results show that the genetically homogeneous cohort of subjects ranging in age from 90 to 105 years of an area recognised as one of the world's longevity hot spots, differed based on the genotype distribution and haplotype frequencies of TAS2R38 gene from the two genetically heterogeneous cohorts from the South of Sardinia where the longevity level is distinctly lower. Results show in the centenarian cohort an increased frequency of subjects carrying the homozygous genotype for the functional variant of TAS2R38 (PAV/PAV) and a decreased frequency of those having homozygous genotype for the non-functional form (AVI/AVI), as compared to those determined in the two control cohorts.
A number of studies on human nutrition have suggested that the TAS2R38 variants and the related 6-n-propylthioural (PROP) phenotype may influence dietary behaviour and nutritional status. The possible association between PROP responsiveness and perception and intake of fats has been extensively studied, but with controversial results. The widely accepted hypothesis is that PROP non-tasters, compared to PROP super-tasters, show a reduced ability to perceive dietary fat which could lead them to increase the consumption of high-fat foods to compensate the reduced perception. In agreement with this assumption, the high frequency of the tasting homozygous genotype (PAV/PAV) and the low frequency of the non-tasting one (AVI/AVI), that we found in centenarian subjects, suggest that these individuals may have reached an exceptional longevity because of their genetic predisposition to a low-fat diet.
On the other hand, the extreme bitterness intensity of PROP super-tasters has been shown to be the primary reason for avoiding bitter-tasting fruits and vegetables. Since many bitter-tasting compounds in foods (e.g., flavonoids, phenols, glucosinolates) have benefit effects for health, our results in the centenarian cohort seem to be in contrast with the possibility that TAS2R38 genotype is a genetic factor that favour an adequate intake of fruits and vegetables or other bitter foods recommended for a healthy life. However, only a few studies have investigated the relationship between TAS2R38 variants and vegetable intake obtaining controversial results. The notion that TAS2R38 might serve to govern food intake is interesting, but eating behaviour is a complex phenomenon influenced by a broad range of environmental factors.
In addition, it is known that TAS2R38 receptor serves other genotype-dependent roles which are relevant for health, with the PAV form associated with an efficient immune response, a favourable body composition, as well as with physiological processes. On the contrary, the AVI group is associated with a higher risk to develop many dysfunctions and diseases. Therefore, it is not surprising that we find in the centenarian cohort an increased frequency of homozygous subjects for the functional variant of TAS2R38 (PAV) and above all a decreased frequency of those having homozygous genotype for the non-functional form (AVI).