Bitter taste receptors play crucial roles in detecting bitter compounds not only in the oral cavity, but also in extraoral tissues where they are involved in a variety of non‒tasting physiological processes. On the other hand, disorders or modifications in the sensitivity or expression of these extraoral 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. Differences in genotype distribution and haplotype frequency at the TAS2R38 gene between a cohort of centenarian and near-centenarian subjects and two control cohorts were determined. 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. In conclusion, our data providing evidence of an association between genetic variants of TAS2R38 gene and human longevity, suggest that TAS2R38 bitter receptor can be involved in the molecular physiological mechanisms implied in the biological process of aging.

Centenarians not only enjoy an extraordinary aging, but also show a compression of morbidity. Using functional transcriptomic analysis of peripheral blood mononuclear cells (PMBC) we identified 1721 mRNAs differentially expressed by centenarians when compared with septuagenarians and young people. Sub-network analysis led us to identify Bcl-xL as an important gene up-regulated in centenarians. It is involved in the control of apoptosis, cellular damage protection and also in modulation of immune response, all associated to healthy aging. Indeed, centenarians display lower plasma cytochrome C levels, higher mitochondrial membrane potential and also less cellular damage accumulation than septuagenarians. Leukocyte chemotaxis and NK cell activity are significantly impaired in septuagenarians compared with young people whereas centenarians maintain them. To further ascertain the functional role of Bcl-xL in cellular aging, we found that lymphocytes from septuagenarians transduced with Bcl-xL display a reduction in senescent-related markers. Finally, to demonstrate the role of Bcl-xL in longevity at the organism level, C. elegans bearing a gain of function mutation in the Bcl-xL ortholog ced-9, showed a significant increase in mean and maximal life span. These results show that mRNA expression in centenarians is unique and reveals that Bcl-xL plays an important role in exceptional aging.

(1) Background: Longevity Blue Zones (LBZs) are populations characterized by exceptional longevity. The purpose of this cross-sectional study was to compare the food habits of two representative samples of the oldest old subjects from the population residing in the LBZs of Nicoya peninsula (Costa Rica) and in the mountainous part of Ogliastra (Sardinia, Italy). (2) Methods: Data were collected using validated tools, including a food frequency questionnaire, Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL) scales for functional autonomy, body mass index, and waist and limbs circumferences. (3) Results: A total of 210 subjects, 60 (31 male) from Nicoya (age range 80–109 years), and 150 (61 male) from Ogliastra (age 90–101 years) were included in the study. In both populations, the highest frequencies of consumption were recorded for plant-derived foods (cereals 60–80% daily, legumes ≥ 80% daily in Nicoya, ≥ 60% 2–5 servings/week in Ogliastra), followed by those of animal origin (dairy products, meat) ≥60% and 80% daily, in Nicoya and Ogliastra, respectively. The frequency of milk consumption showed a positive correlation with BADL (ρ = 0.268 for Nicoya and ρ = 0.214 for Ogliastra) and IADL scores (ρ = 0.466 for Nicoya and ρ = 0.471 for Ogliastra), whereas legumes consumption correlated negatively with self-rated health (ρ = −0.264) and IADL (ρ = −0.332). (4) Conclusions: Our results indicate that the dominant dietary model among the elderly of Nicoya and Ogliastra is a plant-based diet complemented by a non-negligible consumption of animal products, mostly dairy products. Further prospective studies are needed to ascertain a possible cause–effect relationship between food habits and increased likelihood of reaching advanced age.