Further support to the uncoupling-to-survive theory: The genetic variation of human UCP genes is associated with longevity

PLoS ONE

Volumn 6, Issue 12, 2011, Pages

  Rose, Giuseppina ^a   Crocco, Paolina ^a   de Rango, Francesco ^a   Montesanto, Alberto ^a   Passarino, Giuseppe ^a  

^a UNIVERSITY OF CALABRIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; REACTIVE OXYGEN METABOLITE; UNCLASSIFIED DRUG; UNCOUPLING PROTEIN; UNCOUPLING PROTEIN 2; UNCOUPLING PROTEIN 3; UNCOUPLING PROTEIN 4; VALINE; MITOCHONDRIAL PROTEIN;

ADIPOSE TISSUE; ADULT; AGE; AGED; AGING; ARTICLE; BRAIN TISSUE; BROWN ADIPOSE TISSUE; COHORT ANALYSIS; CONTROLLED STUDY; ENERGY EXPENDITURE; ENERGY METABOLISM; FEMALE; GENE; GENE LINKAGE DISEQUILIBRIUM; GENETIC VARIABILITY; HEART; HUMAN; HUMAN CELL; LONGEVITY; MAJOR CLINICAL STUDY; MALE; MUSCLE TISSUE; NERVE CELL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; SINGLE NUCLEOTIDE POLYMORPHISM; SURVIVAL RATE; UCP2 GENE; UCP3 GENE; UCP4 GENE; CHEMISTRY; GENETICS; HAPLOTYPE;

GENETIC VARIATION; HAPLOTYPES; HUMANS; LONGEVITY; MITOCHONDRIAL PROTEINS; POLYMORPHISM, SINGLE NUCLEOTIDE; UNCOUPLING AGENTS;

EID: 84455161659     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0029650     Document Type: Article

References (94)

1. Cannon B, Nedergaard J, (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84: 277-359.
2. Pecqueur C, Couplan E, Bouillaud F, Ricquier D, (2001) Genetic and physiological analysis of the role of uncoupling proteins in human energy homeostasis. J Mol Med 79: 48-56.
3. Boss O, Samec S, Paoloni-Giacobino A, Rossier C, Dulloo A, et al. (1997) Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression. FEBS Lett 408: 39-42.
4. Vidal-Puig A, Solanes G, Grujic D, Flier JS, Lowell BB, (1997) UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue. Biochem Biophys Res Commun 235: 79-82.
5. Yang X, Pratley RE, Tokraks S, Tataranni PA, Permana PA, (2002) UCP5/BMCP1 transcript isoforms in human skeletal muscle: relationship of the short-insert isoform with lipid oxidation and resting metabolic rates. Mol Genet Metab 75: 369-373.
6. Smorodchenko A, Rupprecht A, Sarilova I, Ninnemann O, Bräuer AU, et al. (2009) Comparative analysis of uncoupling protein 4 distribution in various tissues under physiological conditions and during development. Biochim Biophys Acta 1788: 2309-2319.
7. Nègre-Salvayre A, Hirtz C, Carrera G, Cazenave R, Troly M, et al. (1997) A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation. FASEB J 11: 809-815.
8. Mailloux RJ, Harper ME, (2011) Uncoupling proteins and the control of mitochondrial reactive oxygen species production. Free Radic Biol Med 51: 1106-1115.
9. Arsenijevic D, Onuma H, Pecqueur C, Raimbault S, Manning BS, et al. (2000) Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat Genet 26: 435-439.
10. Vidal-Puig AJ, Grujic D, Zhang CY, Hagen T, Boss O, et al. (2000) Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem 275: 16258-16266.
11. Brand MD, Pamplona R, Portero-Otin M, Requena JR, Roebuck SJ, et al. (2002) Oxidative damage and phospholipids fatty acyl composition in skeletal muscle mitochondria from mice underexpressing or overexpressing uncoupling protein 3. Biochem J 368: 597-603.
12. Echtay KS, Roussel D, St-Pierre J, Jekabsons MB, Cadenas S, et al. (2002) Superoxide activates mitochondrial uncoupling proteins. Nature 415: 96-99.
13. Brand MD, Buckingham JA, Esteves TC, Green K, Lambert AJ, et al. (2004) Mitochondrial superoxide and ageing: uncoupling-protein activity and superoxide production. Biochem Soc Symp 71: 203-213.
14. Brand MD, Esteves TC, (2005) Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3. Cell Metab 2: 85-93.
15. Nübel T, Ricquier D, (2006) Respiration under control of uncoupling proteins: Clinical perspective. Horm Res 65: 300-310.
16. Echtay KS, (2007) Mitochondrial uncoupling proteins--what is their physiological role? Free Radic Biol Med 43: 1351-1371.
17. MacLellan JD, Gerrits MF, Gowing A, Smith PJ, Wheeler MB, et al. (2005) Physiological increases in uncoupling protein 3 augment fatty acid oxidation and decrease reactive oxygen species production without uncoupling respiration in muscle cells. Diabetes 54: 2343-2350.
18. Chan CB, Kashemsant N, (2006) Regulation of insulin secretion by uncoupling protein. Biochem Soc Trans 34: 802-805.
19. Bézaire V, Seifert EL, Harper ME, (2007) Uncoupling protein-3: clues in an ongoing mitochondrial mystery. FASEB J 21: 312-324.
20. Mattson MP, Kroemer G, (2003) Mitochondria in cell death: novel targets for neuroprotection and cardioprotection. Trends Mol Med 9: 196-205.
21. Wilson MM, Morley JE, (2003) Invited review: Aging and energy balance. J Appl Physiol 95: 1728-1736.
22. Frisard M, Ravussin E, (2006) Energy metabolism and oxidative stress: impact on the metabolic syndrome and the aging process. Endocrine 29: 27-32.
23. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, et al. (2001) Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56: 146-56.
24. Roberts SB, Rosenberg I, (2006) Nutrition and ageing: changes in the regulation of energy metabolism with ageing. Physiol Rev 86: 651-667.
25. Frisard MI, Broussard A, Davies SS, Roberts LJ, Rood J, et al. (2007) Ageing, resting metabolic rate, and oxidative damage: results from the Louisiana Healthy Ageing Study. J Gerontol A Biol Sci Med Sci 62: 752-759.
26. Brand MD, (2000) Uncoupling to survive? The role of mitochondrial inefficiency in ageing. Exp Gerontol 35: 811-820.
27. Wolkow CA, Iser WB, (2006) Uncoupling protein homologs may provide a link between mitochondria, metabolism and lifespan. Ageing Res Rev 5: 196-208.
28. Mookerjee SA, Divakaruni AS, Jastroch M, Brand MD, (2010) Mitochondrial uncoupling and lifespan. Mech Ageing Dev 131: 463-472.
29. Harper ME, Bevilacqua L, Hagopian K, Weindruch R, Ramsey JJ, (2004) Ageing, oxidative stress, and mitochondrial uncoupling. Acta Physiol Scand 182: 321-331.
30. Dietrich MO, Horvath TL, (2010) The role of mitochondrial uncoupling proteins in lifespan. Eur J Physiol 459: 269-275.
31. Fridell YW, Sánchez-Blanco A, Silvia BA, Helfand SL, (2004) Functional characterization of a Drosophila mitochondrial uncoupling protein. J Bioenerg Biomembr 36: 219-228.
32. Fridell YW, Hoh M, Kréneisz O, Hosier S, Chang C, et al. (2009) Increased uncoupling protein (UCP) activity in Drosophila insulin-producing neurons attenuates insulin signaling and extends lifespan. Ageing 1: 699-713.
33. Speakman JR, Talbot DA, Selman C, Snart S, McLaren JS, et al. (2004) Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer. Ageing Cell 3: 87-95.
34. Conti B, Sanchez-Alavez M, Winsky-Sommerer R, Morale MC, Lucero J, et al. (2006) Transgenic mice with a reduced core body temperature have an increased life span. Science 314: 825-828.
35. Andrews ZB, Horvath TL, (2009) Uncoupling protein-2 regulates lifespan in mice. Am J Physiol Endocrinol Metab 96 (E): 621-627.
36. Caldeira da Silva CC, Cerqueira FM, Barbosa LF, Medeiros MH, Kowaltowski AJ, (2008) Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity. Ageing Cell 7: 552-560.
37. Bevilacqua L, Ramsey JJ, Hagopian K, Weindruch R, Harper ME, (2005) Long-term caloric restriction increases UCP3 content but decreases proton leak and reactive oxygen species production in rat skeletal muscle mitochondria. Am J Physiol Endocrinol Metab 289 (E): 429-438.
38. McDonald RB, Walker KM, Warman DB, Griffey SM, Warden CH, et al. (2008) Characterization of survival and phenotype throughout the life span in UCP2/UCP3 genetically altered mice. Exp Gerontol 43: 1061-1068.
39. Li Y, Maedler K, Shu L, Haataja L, (2008) UCP-2 and UCP-3 proteins are differentially regulated in pancreatic beta-cells. PLoS One 3: e1397.
40. Salopuro T, Pulkkinen L, Lindström J, Kolehmainen M, Tolppanen AM, et al. (2009) Variation in the UCP2 and UCP3 genes associates with abdominal obesity and serum lipids: the Finnish Diabetes Prevention Study. BMC Med Genet 10: 94.
41. Jia JJ, Zhang X, Ge CR, Jois M, (2009) The polymorphisms of UCP2 and UCP3 genes associated with fat metabolism, obesity and diabetes. Obes Rev 10: 519-552.
42. Crocco P, Montesanto A, Passarino G, Rose G, (2011) A common polymorphism in the UCP3 promoter influences hand grip strength in elderly people. Biogerontology 12 (3): 265-271.
43. Rose G, Crocco P, D'Aquila P, Montesanto A, Bellizzi D, et al. (2011) Two variants located in the upstream enhancer region of human UCP1 gene affect gene expression and are correlated with human longevity. Exp Gerontol [Epub ahead of print].
44. Passarino G, Montesanto A, Dato S, Giordano S, Domma F, et al. (2006) Sex and age specificity of susceptibility genes modulating survival at old age. Hum Hered 62: 213-220.
45. Wigginton JE, Cutler DJ, Abecasis GR, (2005) A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet 76: 887-893.
46. Freidlin B, Zheng G, Li Z, Gastwirth JL, (2002) Trend tests for case-control studies of genetic markers: power, sample size and robustness. Hum Hered 53: 146-152.
47. Zang Y, Fung WK, (2010) Robust tests for matched case-control genetic association studies. BMC Genet 11: 91.
48. Zang Y, Fung WK, Zheng G, (2010) Simple algorithms to calculate asymptotic null distribution for robust tests in case-control genetic association studies in R. Journal of Statistical Software 33: 1-24.
49. So HC, Sham PC, (2011) Robust Association Tests Under Different Genetic Models, Allowing for Binary or Quantitative Traits and Covariates. Behav Genet 41: 768-75.
50. Barrett JC, Fry B, Maller J, Daly MJ, (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21: 263-265.
51. Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA, (2002) "Score tests for association of traits with haplotypes when linkage phase is ambiguous. " Amer J Hum Genet 70: 425-434.
52. Calle ML, Urrea V, Vellalta G, Malats N, Steen KV, (2008) Improving strategies for detecting genetic patterns of disease susceptibility in association studies. Stat Med 27 (30): 6532-6546.
53. Bouchard C, Perusse L, Chagnon YC, Warden C, Ricquier D, (1997) Linkage between markers in the vicinity of the uncoupling protein 2 gene and resting metabolic rate in humans. Hum Mol Genet 6: 1887-1889.
54. Fleury C, Neverova M, Collins S, Raimbault S, Champigny O, et al. (1997) Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet 15: 269-272.
55. Bézaire V, Spriet LL, Campbell S, Sabet N, Gerrits M, et al. (2005) Constitutive UCP3 overexpression at physiological levels increases mouse skeletal muscle capacity for fatty acid transport and oxidation. FASEB J 19: 977-979.
56. Xu K, Zhang M, Cui D, Fu Y, Qian L, et al. (2011) UCP2-866G/A and Ala55Val, and UCP3-55C/T polymorphisms in association with type 2 diabetes susceptibility: a meta-analysis study. Diabetologia DOI 10.1007/s00125-011-2245-y [Epub ahead of print].
57. Astrup A, Toubro S, Dalgaard LT, Urhammer SA, Sorensen TI, et al. (1999) Impact of the v/v 55 polymorphism of the uncoupling protein 2 gene on 24-h energy expenditure and substrate oxidation. Int J Obes Relat Metab Disord 23: 1030-1034.
58. Buemann B, Schierning B, Toubro S, Bibby BM, Sorensen T, et al. (2001) The association between the Val/Ala-55 polymorphism of the uncoupling protein 2 gene and exercise efficiency. Int J Obes Relat Metab Disord 25: 467-471.
59. Walder K, Norman RA, Hanson RL, Schrauwen P, Neverova M, et al. (1998) Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metabolism/obesity in Pima Indians. Hum Mol Genet 7: 1431-1435.
60. Yu X, Jacobs DR, Schreiner PJ, Gross MD, Steffes MW, et al. (2005) The uncoupling protein 2 Ala55Val polymorphism is associated with diabetes mellitus: the CARDIA Study. Clin Chem 51: 1451-1456.
61. Willig AL, Casazza KR, Divers J, Bigham AW, Gower BA, et al. (2009) Uncoupling protein 2 Ala55Val polymorphism is associated with a higher acute insulin response to glucose. Metabolism 58: 877-881.
62. Chen HH, Lee W, Wang W, Huang MT, Lee YC, et al. (2007) Ala55Val polymorphism on UCP2 gene predicts greater weight loss in morbidly obese patients undergoing gastric banding. Obes Surg 17: 926-933.
63. Dalgaard LT, Andersen G, Larsen LH, Sorensen TI, Andersen T, et al. (2003) Mutational analysis of the UCP2 core promoter and relationships of variants with obesity. Obes Res 11: 1420-1427.
64. Wang H, Chu WS, Lu T, Hasstedt SJ, Kern PA, et al. (2004) Uncoupling protein-2 polymorphisms in type 2 diabetes, obesity, and insulin secretion. Am J Physiol Endocrinol Metab 286: E1-E7.
65. Hsu YH, Niu T, Song Y, Tinker L, Kuller LH, et al. (2008) Genetic variants in the UCP2- UCP3 gene cluster and risk of diabetes in the women's health initiative observational study. Diabetes 57: 1101-1107.
66. Lee YH, Kim W, Yu BC, Lae Park BL, Kim LH, et al. (2008) Association of the Ins/Del polymorphisms of uncoupling protein 2 (UCP2) with BMI in a Korean population. Biochem Biophys Res Commun 371: 767-771.
67. Paradis E, Clavel S, Bouillaud F, Ricquier D, Richard D, (2003) Uncoupling protein 2: A novel player in neuroprotection. Trends Mol Med 9: 522-525.
68. Horvath TL, Diano S, Barnstable C, (2003) Mitochondrial uncoupling protein 2 in the central nervous system: Neuromodulator and neuroprotector. Biochem Pharmacol 65: 1917-1921.
69. Cortez-Pinto H, Yang SQ, Lin HZ, Costa S, Hwang CS, et al. (1998) Bacterial lipopolysaccharide induces uncoupling protein-2 expression in hepatocytes by a tumor necrosis factor-alpha-dependent mechanism. Biochem Biophys Res Commun 251: 313-319.
70. Murray AJ, Anderson RE, Watson GC, Radda GK, Clarke K, (2004) Uncoupling proteins in human heart. Lancet 364: 1786-1788.
71. Kopecky J, Rossmeisl M, Flachs P, Brauner P, Sponarova J, et al. (2004) Energy metabolism of adipose tissue--physiological aspets and target in obesity treatment. Physiol Res 53: S225-S232.
72. Samec S, Seydoux J, Dulloo AG, (1999) nSkeletal muscle UCP3 and UCP2 gene expression in response to inhibition of free fatty acid flux through mitochondrial beta-oxidation. Pflugers Arch 438: 452-457.
73. Saleh MC, Wheeler MB, Chan CB, (2002) Uncoupling protein-2: Evidence for its function as a metabolic regulator. Diabetologia 45: 74-187.
74. Diao J, Allister EM, Koshkin V, Lee SC, Bhattacharjee A, et al. (2008) UCP2 is highly expressed in pancreatic alpha-cells and influences secretion and survival. PNAS 105: 12057-1262.
75. Andrews ZB, (2010) Uncoupling protein-2 and the potential link between metabolism and longevity. Curr Aging Sci 3: 102-112.
76. Barbieri M, Boccardi V, Esposito A, Papa M, Vestini F, et al. (2011) A/ASP/VAL allele combination of IGF1R, IRS2, and UCP2 genes is associated with better metabolic profile, preserved energy expenditure parameters, and low mortality rate in longevity. Age DOI:10.1007/s11357-011-9210-z [Epub ahead of print].
77. Manini TM, (2010) Energy expenditure and aging. Ageing Res Rev 9: 1-11.
78. Barbieri M, Gambardella A, Paolisso G, Varricchio M, (2008) Metabolic aspects of the extreme longevity. Exp Gerontol 43: 74-78.
79. Rizzo MR, Mari D, Barbieri M, Ragno E, Grella R, et al. (2005) Resting Metabolic Rate and Respiratory Quotient in Human Longevity. J Clin Endocrinol Metab 90: 409-413.
80. Rolfe DF, Brown GC, (1997) Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev 77: 731-758.
81. Schrauwen P, Xia J, Walder K, Snitker S, Ravussin E, (1999) A novel polymorphism in the proximal UCP3 promoter region: effect on skeletal muscle UCP3 mRNA expression and obesity in male non-diabetic Pima Indians. Int J Obes Relat Metab Disord; 23: 1242-1245.
82. Schrauwen P, Xia J, Bogardus C, Pratley R, Ravussin E, (1999) Skeletal muscle UCP3 expression is a determinant of energy expenditure in Pima Indians. Diabetes 48: 146-149.
83. Nabben M, Hoeks J, Briede JJ, Glatz JF, Moonen-Kornips E, et al. (2008) The effect of UCP3 overexpression on mitochondrial ROS production in skeletal muscle of young versus aged mice. FEBS Lett 582: 4147-4152.
84. Karakelides H, Nair KS, (2005) Sarcopenia of ageing and its metabolic impact. Curr Top Dev Biol 68: 123-148.
85. Rossi P, Marzani B, Giardina S, Negro M, Marzatico F, (2008) Human skeletal muscle ageing and the oxidative system: cellular events. Curr Ageing Sci 1: 182-191.
86. Amara CE, Shankland EG, Jubrias SA, Marcinek DJ, Kushmerick MJ, et al. (2007) Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo. PNAS 104: 1057-62.
87. Dalgaard LT, (2011) Genetic Variance in Uncoupling Protein 2 in Relation to Obesity, Type 2 Diabetes, and Related Metabolic Traits: Focus on the Functional-866G&A Promoter Variant (rs659366). J Obes doi:10.1155/2011/340241 [Epub ahead of print].
88. Andrews ZB, Diano S, Horvath TL, (2005) Mitochondrial uncoupling proteins in the CNS: in support of function and survival. Nat Rev Neurosci 6: 829-840.
89. Liu D, Chan SL, De Souza-Pinto NC, Slevin JR, Wersto RP, et al. (2006) Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress. Neuromolecular Med 8: 389-414.
90. Wei Z, Chigurupati S, Bagsiyao P, Henriquez A, Chan SL, (2009) The brain uncoupling protein UCP4 attenuates mitochondrial toxin-induced cell death: role of extracellular signal-regulated kinases in bioenergetics adaptation and cell survival. Neurotox Res 16: 14-29.
91. de la Monte SM, Wands JR, (2006) Molecular indices of oxidative stress and mitochondrial dysfunction occur early and often progress with severity of Alzheimer's disease. J Alzheimers Dis 9: 167-181.
92. Szolnoki Z, Kondacs A, Mandi Y, Bodor A, Somogyvari F, (2009) A homozygous genetic variant of mitochondrial uncoupling protein 4 exerts protection against the occurrence of multiple sclerosis. Neuromolecular Med 11: 101-105.
93. Szolnoki Z, Kondacs A, Mandi Y, Bodor A, Somogyvari F, (2011) A homozygous genetic variant of mitochondrial uncoupling protein 4 affects the occurrence of leukoaraiosis. Acta Neurol Scand 123: 352-357.
94. Girousse A, Tavernier G, Tiraby C, Lichtenstein L, Iacovoni JS, et al. (2009) Transcription of the human uncoupling protein 3 gene is governed by a complex interplay between the promoter and intronic sequences. Diabetologia 52: 1638-1646.