Iates the detection of salicin and other naturally occurring bitter compounds such as diphenidol, sodium benzoate, amygdalin, arbutin, helicin, Dsalicin, sinigrin, and phenyl beta-D-glucopyranoside [76,77]. Several of these compounds have been reported to have a pharmacologic effect and to be present in human food. For example, arbutin is present in pears, bearberries and wheat, and has been reported to be a strong inhibitor of bladder cancer proliferation [78]. Amygdalin, also known as Vitamin B17, is found in several fruit seeds and has been reported to have both apoptotic activity and to inhibit cell cycle genes [79] although its real effect on cancer remains controversial [80]. Sinigrin is found in plants of the Brassicaceae family such as broccoli, brussels sprouts, and the seeds of black mustard. It has been proposed to have a preventive effect on colorectal cancer and to inhibit bladder cancer [81]. The bark and leaf of willow species contain the prodrug salicin; following inhibitor absorption salicin is metabolized into various salicylate derivatives [82]. Salicin has effects similar to aspirin (acetylsalicylic acid) on analgesia and as an anti-inflammatory agent [82]. These reports point to a role for the TAS2R16 receptor in recognizing beneficial molecules with which the organism interacts during life. One can speculate that an impaired function of the receptor might affect the efficacy of the various compounds and that this could lead on the long term to a disadvantage for the organism. Polymorphic variants in TAS2R16 confer differential response in vitro via functional changes in the receptor [83] and have been suggested to influence the sensations, 
liking, or intake of common beverages that contain phytochemicals and other pharmacologically active ingredients linked to chronic diseases [84]. Moreover the functional polymorphism K172N (rs846664) appears to be a risk factor for alcohol intake [85] and dependence [86]. This variant is very rare in Caucasian populations and therefore its genotyping was not attempted in this sample set. TAS2R16 genetic variants have also been associated with the development of nicotine dependence in African Americans [67]. These observations point to a role of variation in the TAS2R16 receptor in recognizing and therefore modulating the effect of both beneficial and harmful molecules with which the organism interacts during life. It is possible that the fine tuning of the receptor function due to the genetic polymorphisms along with the environment may modulate how many beneficial and how manyharmful compounds are recognized by the receptor throughout the life span and that 
this could, in the long term, modify the chances to reach very old ages. However there is also another possible, even though highly speculative, explanation of the involvement of TAS2R16 genetic variability in healthy aging. Numerous recent reports investigated non-gustatory actions of taste receptors. They have been shown to be expressed in a plethora of tissues such as the respiratory system where they affect respiratory functions 16574785 in response to noxious stimuli [87], and the gastrointestinal tract where they are suspected to regulate the activation of metabolic and digestive functions [87]. Recently it has been shown that taste receptors are expressed also in the testis in mouse, where they can be involved in spermatogenesis [88]. The emerging picture is therefore that taste receptors could behave as pleiotropic genes, whose products.Iates the detection of salicin and other naturally occurring bitter compounds such as diphenidol, sodium benzoate, amygdalin, arbutin, helicin, Dsalicin, sinigrin, and phenyl beta-D-glucopyranoside [76,77]. Several of these compounds have been reported to have a pharmacologic effect and to be present in human food. For example, arbutin is present in pears, bearberries and wheat, and has been reported to be a strong inhibitor of bladder cancer proliferation [78]. Amygdalin, also known as Vitamin B17, is found in several fruit seeds and has been reported to have both apoptotic activity and to inhibit cell cycle genes [79] although its real effect on cancer remains controversial [80]. Sinigrin is found in plants of the Brassicaceae family such as broccoli, brussels sprouts, and the seeds of black mustard. It has been proposed to have a preventive effect on colorectal cancer and to inhibit bladder cancer [81]. The bark and leaf of willow species contain the prodrug salicin; following absorption salicin is metabolized into various salicylate derivatives [82]. Salicin has effects similar to aspirin (acetylsalicylic acid) on analgesia and as an anti-inflammatory agent [82]. These reports point to a role for the TAS2R16 receptor in recognizing beneficial molecules with which the organism interacts during life. One can speculate that an impaired function of the receptor might affect the efficacy of the various compounds and that this could lead on the long term to a disadvantage for the organism. Polymorphic variants in TAS2R16 confer differential response in vitro via functional changes in the receptor [83] and have been suggested to influence the sensations, liking, or intake of common beverages that contain phytochemicals and other pharmacologically active ingredients linked to chronic diseases [84]. Moreover the functional polymorphism K172N (rs846664) appears to be a risk factor for alcohol intake [85] and dependence [86]. This variant is very rare in Caucasian populations and therefore its genotyping was not attempted in this sample set. TAS2R16 genetic variants have also been associated with the development of nicotine dependence in African Americans [67]. These observations point to a role of variation in the TAS2R16 receptor in recognizing and therefore modulating the effect of both beneficial and harmful molecules with which the organism interacts during life. It is possible that the fine tuning of the receptor function due to the genetic polymorphisms along with the environment may modulate how many beneficial and how manyharmful compounds are recognized by the receptor throughout the life span and that this could, in the long term, modify the chances to reach very old ages. However there is also another possible, even though highly speculative, explanation of the involvement of TAS2R16 genetic variability in healthy aging. Numerous recent reports investigated non-gustatory actions of taste receptors. They have been shown to be expressed in a plethora of tissues such as the respiratory system where they affect respiratory functions 16574785 in response to noxious stimuli [87], and the gastrointestinal tract where they are suspected to regulate the activation of metabolic and digestive functions [87]. Recently it has been shown that taste receptors are expressed also in the testis in mouse, where they can be involved in spermatogenesis [88]. The emerging picture is therefore that taste receptors could behave as pleiotropic genes, whose products.
