Bitter Taste Receptor Polymorphisms and Human Aging

Several studies have shown that genetic factors account for 25% of the variation in human life span. On the basis of published molecular, genetic and epidemiological data, we hypothesized that genetic polymorphisms of taste receptors, which modulate food preferences but are also expressed in a number of 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.

[1]  Feng Li,et al.  Depletion of bitter taste transduction leads to massive spermatid loss in transgenic mice. , 2012, Molecular human reproduction.

[2]  B. Tepper.  The taste for fat: new discoveries on the role of fat in sensory perception, metabolism, sensory pleasure, and beyond. , 2012, Journal of food science.

[3]  J. de Magalhães,et al.  Genome-Environment Interactions That Modulate Aging: Powerful Targets for Drug Discovery , 2012, Pharmacological Reviews.

[4]  Anat Levit,et al.  BitterDB: a database of bitter compounds , 2011, Nucleic Acids Res..

[5]  S. Chrubasik,et al.  Willow Species and Aspirin: Different Mechanism of Actions , 2011, Phytotherapy research : PTR.

[6]  M. Kloor,et al.  Association Between TAS2R38 Gene Polymorphisms and Colorectal Cancer Risk: A Case-Control Study in Two Independent Populations of Caucasian Origin , 2011, PloS one.

[7]  K. Kidd,et al.  Selection on the Human Bitter Taste Gene, TAS2R16, in Eurasian Populations , 2011, Human biology.

[8]  C. González,et al.  Adherence to the Mediterranean diet reduces mortality in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain) , 2011, British Journal of Nutrition.

[9]  Giancarlo Logroscino,et al.  Diet and Alzheimer’s disease risk factors or prevention: the current evidence , 2011, Expert review of neurotherapeutics.

[10]  H. Tissenbaum,et al.  PDP-1 Links the TGF-β and IIS Pathways to Regulate Longevity, Development, and Metabolism , 2011, PLoS genetics.

[11]  S. Y. Kim,et al.  Arbutin inhibits TCCSUP human bladder cancer cell proliferation via up-regulation of p21. , 2011, Die Pharmazie.

[12]  G. Passarino,et al.  The genetic component of human longevity: analysis of the survival advantage of parents and siblings of Italian nonagenarians , 2011, European Journal of Human Genetics.

[13]  J. Fischer,et al.  Nutrition in centenarians. , 2011, Maturitas.

[14]  J. Hayes,et al.  Allelic variation in TAS2R bitter receptor genes associates with variation in sensations from and ingestive behaviors toward common bitter beverages in adults. , 2011, Chemical senses.

[15]  B. Tepper,et al.  Greater energy intake from a buffet meal in lean, young women is associated with the 6-n-propylthiouracil (PROP) non-taster phenotype , 2011, Appetite.

[16]  M. Beekman,et al.  Genomics of human longevity , 2011, Philosophical Transactions of the Royal Society B: Biological Sciences.

[17]  J. Fahey,et al.  Allyl isothiocyanate-rich mustard seed powder inhibits bladder cancer growth and muscle invasion. , 2010, Carcinogenesis.

[18]  L. Lissner,et al.  Does the Mediterranean diet predict longevity in the elderly? A Swedish perspective , 2010, AGE.

[19]  Paolo Gasparini,et al.  Insights into the Binding of Phenyltiocarbamide (PTC) Agonist to Its Target Human TAS2R38 Bitter Receptor , 2010, PloS one.

[20]  W. Chung,et al.  The role of genetic variants in human longevity , 2010, Ageing Research Reviews.

[21]  N. Martin,et al.  The perception of quinine taste intensity is associated with common genetic variants in a bitter receptor cluster on chromosome 12 , 2010, Human molecular genetics.

[22]  Linda Partridge,et al.  Extending Healthy Life Span—From Yeast to Humans , 2010, Science.

[23]  C. Kenyon.  The genetics of ageing , 2010, Nature.

[24]  J. Hayes.  Response to “Lack of Relation Between Bitter Taste Receptor TAS2R38 and BMI in Adults” , 2010, Obesity.

[25]  V. Longo,et al.  Insulin/IGF-I and Related Signaling Pathways Regulate Aging in Nondividing Cells: from Yeast to the Mammalian Brain , 2010, TheScientificWorldJournal.

[26]  J. Ford.  Saturated fatty acid metabolism is key link between cell division, cancer, and senescence in cellular and whole organism aging , 2010, AGE.

[27]  Pascale Barberger-Gateau,et al.  Mediterranean diet and cognitive function in older adults , 2010, Current opinion in clinical nutrition and metabolic care.

[28]  Bowang Chen,et al.  SNP_tools: A compact tool package for analysis and conversion of genotype data for MS-Excel , 2009, BMC Research Notes.

[29]  D. Willcox,et al.  The Okinawan Diet: Health Implications of a Low-Calorie, Nutrient-Dense, Antioxidant-Rich Dietary Pattern Low in Glycemic Load , 2009, Journal of the American College of Nutrition.

[30]  H. Wichmann,et al.  Lack of Relation Between Bitter Taste Receptor TAS2R38 and BMI in Adults , 2009, Obesity.

[31]  S. Bingham,et al.  Biomarkers in nutritional epidemiology: applications, needs and new horizons , 2009, Human Genetics.

[32]  Ahmed El-Sohemy,et al.  Genetic variation in taste and its influence on food selection. , 2009, Omics : a journal of integrative biology.

[33]  L. Fontana.  The scientific basis of caloric restriction leading to longer life , 2009, Current opinion in gastroenterology.

[34]  M. Bonafè,et al.  Genetic polymorphism in long-lived people: Cues for the presence of an insulin/IGF-pathway-dependent network affecting human longevity , 2009, Molecular and Cellular Endocrinology.

[35]  Braxton D. Mitchell,et al.  Bitter Taste Receptors Influence Glucose Homeostasis , 2008, PloS one.

[36]  P. Gasparini,et al.  Variation in the Bitter‐taste Receptor Gene TAS2R38, and Adiposity in a Genetically Isolated Population in Southern Italy , 2008, Obesity.

[37]  B. Tepper,et al.  Nutritional implications of genetic taste variation: the role of PROP sensitivity and other taste phenotypes. , 2008, Annual review of nutrition.

[38]  L. Ferguson,et al.  Nutrition and mutagenesis. , 2008, Annual review of nutrition.

[39]  Kent L Thornburg,et al.  Effect of in Utero and Early-life Conditions on Adult Health and Disease Epidemiol Ogic a Nd Clinic a L Observations , 2022 .

[40]  J. Lumeng,et al.  Ability to Taste 6‐n‐Propylthiouracil and BMI in Low‐income Preschool‐aged Children , 2008, Obesity.

[41]  Ming D. Li,et al.  Bitter taste receptor gene polymorphisms are an important factor in the development of nicotine dependence in African Americans , 2008, Journal of Medical Genetics.

[42]  Eden R Martin,et al.  A multiple testing correction method for genetic association studies using correlated single nucleotide polymorphisms , 2008, Genetic epidemiology.

[43]  P. Gluckman,et al.  Developmental origins of health and disease: new insights. , 2008, Basic & clinical pharmacology & toxicology.

[44]  M. Mattson.  Dietary factors, hormesis and health , 2008, Ageing Research Reviews.

[45]  G. Beauchamp,et al.  Taste receptor genes. , 2007, Annual review of nutrition.

[46]  V. Duffy,et al.  Variation in oral sensation: implications for diet and health , 2007, Current opinion in gastroenterology.

[47]  C. Sternini.  Taste receptors in the gastrointestinal tract. IV. Functional implications of bitter taste receptors in gastrointestinal chemosensing. , 2007, American journal of physiology. Gastrointestinal and liver physiology.

[48]  L. Bierut,et al.  Functional variants in TAS2R38 and TAS2R16 influence alcohol consumption in high-risk families of African-American origin. , 2007, Alcoholism, clinical and experimental research.

[49]  E. Riboli,et al.  Diet and Cancer Prevention: Where We Are, Where We Are Going , 2006, Nutrition and cancer.

[50]  K. Kim,et al.  Amygdalin induces apoptosis through regulation of Bax and Bcl-2 expressions in human DU145 and LNCaP prostate cancer cells. , 2006, Biological & pharmaceutical bulletin.

[51]  E. Rozengurt.  Taste receptors in the gastrointestinal tract. I. Bitter taste receptors and alpha-gustducin in the mammalian gut. , 2006, American journal of physiology. Gastrointestinal and liver physiology.

[52]  M. Behrens,et al.  Bitter taste receptors and human bitter taste perception. , 2006, Cellular and molecular life sciences : CMLS.

[53]  B. Tepper,et al.  Short-term vegetable intake by young children classified by 6-n-propylthoiuracil bitter-taste phenotype. , 2006, The American journal of clinical nutrition.

[54]  Kaare Christensen,et al.  The quest for genetic determinants of human longevity: challenges and insights , 2006, Nature Reviews Genetics.

[55]  M. Behrens,et al.  Signaling in chemosensory systems , 2006, Cellular and Molecular Life Sciences CMLS.

[56]  D. Willcox,et al.  Siblings of Okinawan centenarians share lifelong mortality advantages. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[57]  J. Hayes,et al.  Bitter taste markers explain variability in vegetable sweetness, bitterness, and intake , 2006, Physiology & Behavior.

[58]  Kaare Christensen,et al.  Genetic influence on human lifespan and longevity , 2006, Human Genetics.

[59]  Megan E. Piper,et al.  Associations between phenylthiocarbamide gene polymorphisms and cigarette smoking. , 2005, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[60]  S. Gabriel,et al.  Efficiency and power in genetic association studies , 2005, Nature Genetics.

[61]  L. Jorde,et al.  Worldwide haplotype diversity and coding sequence variation at human bitter taste receptor loci , 2005, Human mutation.

[62]  Pardis C Sabeti,et al.  Positive Selection on a High-Sensitivity Allele of the Human Bitter-Taste Receptor TAS2R16 , 2005, Current Biology.

[63]  F. Panza,et al.  Dietary fatty acids intake: possible role in cognitive decline and dementia , 2005, Experimental Gerontology.

[64]  J. Slack,et al.  The Molecular Basis of Individual Differences in Phenylthiocarbamide and Propylthiouracil Bitterness Perception , 2005, Current Biology.

[65]  Mark Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[66]  K. Kidd,et al.  Bitter receptor gene (TAS2R38), 6-n-propylthiouracil (PROP) bitterness and alcohol intake. , 2004, Alcoholism, clinical and experimental research.

[67]  Jason H Moore,et al.  Computational analysis of gene-gene interactions using multifactor dimensionality reduction , 2004, Expert review of molecular diagnostics.

[68]  D. Drayna,et al.  Genetics of individual differences in bitter taste perception: lessons from the PTC gene , 2004, Clinical genetics.

[69]  D. Drayna,et al.  Bitter taste study in a sardinian genetic isolate supports the association of phenylthiocarbamide sensitivity to the TAS2R38 bitter receptor gene. , 2004, Chemical senses.

[70]  Michael J Bamshad,et al.  Natural selection and molecular evolution in PTC, a bitter-taste receptor gene. , 2004, American journal of human genetics.

[71]  Kaare Christensen,et al.  Longevity studies in GenomEUtwin. , 2003, Twin research : the official journal of the International Society for Twin Studies.

[72]  Dietmar Krautwurst,et al.  The human TAS2R16 receptor mediates bitter taste in response to β-glucopyranosides , 2002, Nature Genetics.

[73]  L. Kunkel,et al.  Life-long sustained mortality advantage of siblings of centenarians , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[74]  S. Gabriel,et al.  The Structure of Haplotype Blocks in the Human Genome , 2002, Science.

[75]  M. Thun,et al.  American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention: Reducing the Risk of Cancer With Healthy Food Choices and Physical Activity , 2002, CA: a cancer journal for clinicians.

[76]  T. Kirkwood,et al.  If you would live long, choose your parents well. , 2001, Trends in genetics : TIG.

[77]  R. Cawthon,et al.  Familial excess longevity in Utah genealogies. , 2001, The journals of gerontology. Series A, Biological sciences and medical sciences.

[78]  L. Kunkel,et al.  Exceptional Familial Clustering for Extreme Longevity in Humans , 2000, Journal of the American Geriatrics Society.

[79]  Kári Stefánsson,et al.  Inheritance of human longevity in Iceland , 2000, European Journal of Human Genetics.

[80]  G. Mcclearn,et al.  The effect of genetic factors for longevity: a comparison of identical and fraternal twins in the Swedish Twin Registry. , 1998, The journals of gerontology. Series A, Biological sciences and medical sciences.

[81]  B. Tepper.  6-n-Propylthiouracil: a genetic marker for taste, with implications for food preference and dietary habits. , 1998, American journal of human genetics.

[82]  James W. Vaupel,et al.  The heritability of human longevity: A population-based study of 2872 Danish twin pairs born 1870–1900 , 1996, Human Genetics.

[83]  C. Osmond,et al.  INFANT MORTALITY, CHILDHOOD NUTRITION, AND ISCHAEMIC HEART DISEASE IN ENGLAND AND WALES , 1986, The Lancet.

[84]  M. Culpin,et al.  PREVENTION OF ACCIDENTS , 1938, British medical journal.

[85]  D. Mozaffarian,et al.  Estimating the global and regional burden of suboptimal nutrition on chronic disease: methods and inputs to the analysis , 2012, European Journal of Clinical Nutrition.

[86]  M. Thun,et al.  American Cancer Society guidelines on nutrition and physical activity for cancer prevention , 2002, CA: a cancer journal for clinicians.

[87]  M. Behrens,et al.  Oral and extraoral bitter taste receptors. , 2010, Results and problems in cell differentiation.

[88]  Marian Beekman,et al.  Evidence of genetic enrichment for exceptional survival using a family approach: the Leiden Longevity Study , 2006, European Journal of Human Genetics.

[89]  L. Bierut,et al.  Functional variant in a bitter-taste receptor (hTAS2R16) influences risk of alcohol dependence. , 2006, American journal of human genetics.

[90]  S. Lejeune,et al.  Laetrile treatment for cancer. , 2006, The Cochrane database of systematic reviews.

[91]  C. Carlson,et al.  Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium. , 2004, American journal of human genetics.

[92]  M. Daly,et al.  Centenarians and the genetics of longevity. , 2000, Results and problems in cell differentiation.