Skip to main content
Top
Published in: BMC Geriatrics 1/2009

Open Access 01-12-2009 | Research article

A polymorphic variant of the insulin-like growth factor 1 (IGF-1) receptor correlates with male longevity in the Italian population: a genetic study and evaluation of circulating IGF-1 from the "Treviso Longeva (TRELONG)" study

Authors: Diego Albani, Sara Batelli, Letizia Polito, Angelica Vittori, Marzia Pesaresi, Giovanni Battista Gajo, Sergio De Angeli, Andrea Zanardo, Maurizio Gallucci, Gianluigi Forloni

Published in: BMC Geriatrics | Issue 1/2009

Login to get access

Abstract

Background

An attenuation of the insulin-like growth factor 1 (IGF-1) signaling has been associated with elongation of the lifespan in simple metazoan organisms and in rodents. In humans, IGF-1 level has an age-related modulation with a lower concentration in the elderly, depending on hormonal and genetic factors affecting the IGF-1 receptor gene (IGF-1R).

Methods

In an elderly population from North-eastern Italy (n = 668 subjects, age range 70–106 years) we investigated the IGF-1R polymorphism G3174A (rs2229765) and the plasma concentration of free IGF-1. Frequency distributions were compared using χ2-test "Goodness of Fit" test, and means were compared by one-way analysis of variance (ANOVA); multiple regression analysis was performed using JMP7 for SAS software (SAS Institute, USA). The limit of significance for genetic and biochemical comparison was set at α = 0.05.

Results

Males showed an age-related increase in the A-allele of rs2229765 and a change in the plasma level of IGF-1, which dropped significantly after 85 years of age (85+ group). In the male 85+ group, A/A homozygous subjects had the lowest plasma IGF-1 level. We found no clear correlation between rs2229765 genotype and IGF-1 in the females.

Conclusion

These findings confirm the importance of the rs2229765 minor allele as a genetic predisposing factor for longevity in Italy where a sex-specific pattern for IGF-1 attenuation with ageing was found.
Appendix
Available only for authorised users
Literature
1.
go back to reference Herskind A, McGue M, Holm N, Sørensen T, Harvald B, Vaupel J: The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870–1900. Hum Genet. 1996, 97: 319-323. 10.1007/BF02185763.CrossRefPubMed Herskind A, McGue M, Holm N, Sørensen T, Harvald B, Vaupel J: The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870–1900. Hum Genet. 1996, 97: 319-323. 10.1007/BF02185763.CrossRefPubMed
2.
go back to reference vB Hjelmborg J, Iachine I, Skytthe A, Vaupel JW, McGue M, Koskenvuo M, Kaprio J, Pedersen NL, Christensen K: Genetic influence on human lifespan and longevity. Hum Genet. 2006, 119: 312-321. 10.1007/s00439-006-0144-y.CrossRefPubMed vB Hjelmborg J, Iachine I, Skytthe A, Vaupel JW, McGue M, Koskenvuo M, Kaprio J, Pedersen NL, Christensen K: Genetic influence on human lifespan and longevity. Hum Genet. 2006, 119: 312-321. 10.1007/s00439-006-0144-y.CrossRefPubMed
3.
go back to reference Antebi A: Genetics of aging in Caenorhabditis elegans. PLoS Genet. 2007, 3: 1565-1571. 10.1371/journal.pgen.0030129.CrossRefPubMed Antebi A: Genetics of aging in Caenorhabditis elegans. PLoS Genet. 2007, 3: 1565-1571. 10.1371/journal.pgen.0030129.CrossRefPubMed
4.
go back to reference Herndon LA, Schmeissner PJ, Dudaronek JM, Brown PA, Listner KM, Sakano Y, Paupard MC, Hall DH, Driscoll M: Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature. 2002, 419: 808-814. 10.1038/nature01135.CrossRefPubMed Herndon LA, Schmeissner PJ, Dudaronek JM, Brown PA, Listner KM, Sakano Y, Paupard MC, Hall DH, Driscoll M: Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature. 2002, 419: 808-814. 10.1038/nature01135.CrossRefPubMed
5.
go back to reference Kim SK: Common aging pathways in worms, flies, mice and humans. J Exp Biol. 2007, 210: 1607-1612. 10.1242/jeb.004887.CrossRefPubMed Kim SK: Common aging pathways in worms, flies, mice and humans. J Exp Biol. 2007, 210: 1607-1612. 10.1242/jeb.004887.CrossRefPubMed
6.
go back to reference Samuelson AV, Carr CE, Ruvkun G: Gene activities that mediate increased life span of C. elegans insulin-like signaling mutants. Genes Dev. 2007, 21: 2976-2994. 10.1101/gad.1588907.CrossRefPubMedPubMedCentral Samuelson AV, Carr CE, Ruvkun G: Gene activities that mediate increased life span of C. elegans insulin-like signaling mutants. Genes Dev. 2007, 21: 2976-2994. 10.1101/gad.1588907.CrossRefPubMedPubMedCentral
7.
go back to reference Selman C, Lingard S, Choudhury AI, Batterham RL, Claret M, Clements M, Ramadani F, Okkenhaug K, Schuster E, Blanc E, Piper MD, Al-Qassab H, Speakman JR, Carmignac D, Robinson IC, Thornton JM, Gems D, Partridge L, Withers DJ: Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J. 2008, 22: 807-818. 10.1096/fj.07-9261com.CrossRefPubMed Selman C, Lingard S, Choudhury AI, Batterham RL, Claret M, Clements M, Ramadani F, Okkenhaug K, Schuster E, Blanc E, Piper MD, Al-Qassab H, Speakman JR, Carmignac D, Robinson IC, Thornton JM, Gems D, Partridge L, Withers DJ: Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J. 2008, 22: 807-818. 10.1096/fj.07-9261com.CrossRefPubMed
8.
go back to reference Cameron AR, Anton S, Melville L, Houston NP, Dayal S, McDougall GJ, Stewart D, Rena G: Black tea polyphenols mimic insulin/insulin-like growth factor-1 signalling to the longevity factor FOXO1a. Aging Cell. 2008, 7: 69-77. 10.1111/j.1474-9726.2007.00353.x.CrossRefPubMed Cameron AR, Anton S, Melville L, Houston NP, Dayal S, McDougall GJ, Stewart D, Rena G: Black tea polyphenols mimic insulin/insulin-like growth factor-1 signalling to the longevity factor FOXO1a. Aging Cell. 2008, 7: 69-77. 10.1111/j.1474-9726.2007.00353.x.CrossRefPubMed
9.
go back to reference Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, Li H, Kenyon C: Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature. 2003, 424: 277-283. 10.1038/nature01789.CrossRefPubMed Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, Li H, Kenyon C: Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature. 2003, 424: 277-283. 10.1038/nature01789.CrossRefPubMed
10.
go back to reference Pinkston-Gosse J, Kenyon C: DAF-16/FOXO targets genes that regulate tumor growth in Caenorhabditis elegans. Nat Genet. 2007, 39: 1403-1409. 10.1038/ng.2007.1.CrossRefPubMed Pinkston-Gosse J, Kenyon C: DAF-16/FOXO targets genes that regulate tumor growth in Caenorhabditis elegans. Nat Genet. 2007, 39: 1403-1409. 10.1038/ng.2007.1.CrossRefPubMed
11.
go back to reference van Heemst D, Beekman M, Mooijaart SP, Heijmans BT, Brandt BW, Zwaan BJ, Slagboom PE, Westendorp RG: Reduced insulin/IGF-1 signalling and human longevity. Aging Cell. 2005, 4: 79-85. 10.1111/j.1474-9728.2005.00148.x.CrossRefPubMed van Heemst D, Beekman M, Mooijaart SP, Heijmans BT, Brandt BW, Zwaan BJ, Slagboom PE, Westendorp RG: Reduced insulin/IGF-1 signalling and human longevity. Aging Cell. 2005, 4: 79-85. 10.1111/j.1474-9728.2005.00148.x.CrossRefPubMed
12.
go back to reference Hall K, Hilding A, Thorén M: Determinants of circulating insulin-like growth factor-I. J Endocrinol Invest. 1999, 22: 48-57.CrossRefPubMed Hall K, Hilding A, Thorén M: Determinants of circulating insulin-like growth factor-I. J Endocrinol Invest. 1999, 22: 48-57.CrossRefPubMed
13.
go back to reference Münzer T, Rosen CJ, Harman SM, Pabst KM, St Clair C, Sorkin JD, Blackman MR: Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men. Am J Physiol Endocrinol Metab. 2006, 290: E1006-1013. 10.1152/ajpendo.00166.2005.CrossRefPubMed Münzer T, Rosen CJ, Harman SM, Pabst KM, St Clair C, Sorkin JD, Blackman MR: Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men. Am J Physiol Endocrinol Metab. 2006, 290: E1006-1013. 10.1152/ajpendo.00166.2005.CrossRefPubMed
14.
go back to reference Ruiz-Torres A, Soares de Melo Kirzner M: Ageing and longevity are related to growth hormone/insulin-like growth factor-1 secretion. Gerontology. 2002, 48: 401-407. 10.1159/000065507.CrossRefPubMed Ruiz-Torres A, Soares de Melo Kirzner M: Ageing and longevity are related to growth hormone/insulin-like growth factor-1 secretion. Gerontology. 2002, 48: 401-407. 10.1159/000065507.CrossRefPubMed
15.
go back to reference Garcia J, Ahmadi A, Wonnacott A, Sutcliffe W, Nagga K, Soderkvist P, Marcusson J: Association of insulin-like growth factor-1 receptor polymorphism in dementia. Dement Geriatr Cogn Disord. 2006, 22: 439-444. 10.1159/000095803.CrossRefPubMed Garcia J, Ahmadi A, Wonnacott A, Sutcliffe W, Nagga K, Soderkvist P, Marcusson J: Association of insulin-like growth factor-1 receptor polymorphism in dementia. Dement Geriatr Cogn Disord. 2006, 22: 439-444. 10.1159/000095803.CrossRefPubMed
16.
go back to reference Kojima T, Kamei H, Aizu T, Arai Y, Takayama M, Nakazawa S, Ebihara Y, Inagaki H, Masui Y, Gondo Y, Sakaki Y, Hirose N: Association analysis between longevity in the Japanese population and polymorphic variants of genes involved in insulin and insulin-like growth factor 1 signaling pathways. Exp Gerontol. 2004, 39: 1595-1598. 10.1016/j.exger.2004.05.007.CrossRefPubMed Kojima T, Kamei H, Aizu T, Arai Y, Takayama M, Nakazawa S, Ebihara Y, Inagaki H, Masui Y, Gondo Y, Sakaki Y, Hirose N: Association analysis between longevity in the Japanese population and polymorphic variants of genes involved in insulin and insulin-like growth factor 1 signaling pathways. Exp Gerontol. 2004, 39: 1595-1598. 10.1016/j.exger.2004.05.007.CrossRefPubMed
17.
go back to reference Lunetta KL, D'Agostino RB, Karasik D, Benjamin EJ, Guo CY, Govindaraju R, Kiel DP, Kelly-Hayes M, Massaro JM, Pencina MJ, Seshadri S, Murabito JM: Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study. BMC Med Genet. 2007, 8 (Suppl 1): S13-10.1186/1471-2350-8-S1-S13.CrossRefPubMedPubMedCentral Lunetta KL, D'Agostino RB, Karasik D, Benjamin EJ, Guo CY, Govindaraju R, Kiel DP, Kelly-Hayes M, Massaro JM, Pencina MJ, Seshadri S, Murabito JM: Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study. BMC Med Genet. 2007, 8 (Suppl 1): S13-10.1186/1471-2350-8-S1-S13.CrossRefPubMedPubMedCentral
18.
go back to reference Rodriguez S, Gaunt TR, Day IN: Molecular genetics of human growth hormone, insulin-like growth factors and their pathways in common disease. Hum Genet. 2007, 122: 1-21. 10.1007/s00439-007-0378-3.CrossRefPubMed Rodriguez S, Gaunt TR, Day IN: Molecular genetics of human growth hormone, insulin-like growth factors and their pathways in common disease. Hum Genet. 2007, 122: 1-21. 10.1007/s00439-007-0378-3.CrossRefPubMed
19.
go back to reference Bonafè M, Barbieri M, Marchegiani F, Olivieri F, Ragno E, Giampieri C, Mugianesi E, Centurelli M, Franceschi C, Paolisso G: Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. J Clin Endocrinol Metab. 2003, 88: 3299-3304. 10.1210/jc.2002-021810.CrossRefPubMed Bonafè M, Barbieri M, Marchegiani F, Olivieri F, Ragno E, Giampieri C, Mugianesi E, Centurelli M, Franceschi C, Paolisso G: Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. J Clin Endocrinol Metab. 2003, 88: 3299-3304. 10.1210/jc.2002-021810.CrossRefPubMed
20.
go back to reference Cheng J, Liu J, Li X, Peng J, Han S, Zhang R, Xu Y, Nie S: Insulin-like growth factor-1 receptor polymorphism and ischemic stroke: a case-control study in Chinese population. Acta Neurol Scand. 2008, 118: 333-8. 10.1111/j.1600-0404.2008.01040.x.CrossRefPubMed Cheng J, Liu J, Li X, Peng J, Han S, Zhang R, Xu Y, Nie S: Insulin-like growth factor-1 receptor polymorphism and ischemic stroke: a case-control study in Chinese population. Acta Neurol Scand. 2008, 118: 333-8. 10.1111/j.1600-0404.2008.01040.x.CrossRefPubMed
21.
go back to reference Gallucci M, Ongaro F, Bresolin F, Bernardi U, Salvato C, Minello A, Amici GP, Barasciutti E, Mazzuco S, Gajo GB, De Angeli S, Forloni GL, Albani D, Zanardo A, Regini C: The Treviso Longeva (Trelong) study: a biomedical, demographic, economic and social investigation on people 70 years and over in a typical town of North-East of Italy. Arch Gerontol Geriatr. 2007, 44: 173-192. 10.1016/j.archger.2007.01.025.CrossRefPubMed Gallucci M, Ongaro F, Bresolin F, Bernardi U, Salvato C, Minello A, Amici GP, Barasciutti E, Mazzuco S, Gajo GB, De Angeli S, Forloni GL, Albani D, Zanardo A, Regini C: The Treviso Longeva (Trelong) study: a biomedical, demographic, economic and social investigation on people 70 years and over in a typical town of North-East of Italy. Arch Gerontol Geriatr. 2007, 44: 173-192. 10.1016/j.archger.2007.01.025.CrossRefPubMed
22.
go back to reference Yashin AI, De Benedictis G, Vaupel JW, Tan Q, Andreev KF, Iachine IA, Bonafe' M, De Luca M, Valensin S, Carotenuto L, Franceschi C: Genes, demography and life span: the contribution of demographic data and genetic studies on ageing and longevity. Am J Hum Genet. 1999, 65: 1178-1193. 10.1086/302572.CrossRefPubMedPubMedCentral Yashin AI, De Benedictis G, Vaupel JW, Tan Q, Andreev KF, Iachine IA, Bonafe' M, De Luca M, Valensin S, Carotenuto L, Franceschi C: Genes, demography and life span: the contribution of demographic data and genetic studies on ageing and longevity. Am J Hum Genet. 1999, 65: 1178-1193. 10.1086/302572.CrossRefPubMedPubMedCentral
23.
go back to reference Barbieri M, Bonafè M, Rizzo MR, Ragno E, Olivieri F, Marchegiani F, Franceschi C, Paolisso G: Gender specific association of genetic variation in peroxisome proliferator-activated receptor (PPAR)gamma-2 with longevity. Exp Gerontol. 2004, 39: 1095-1100. 10.1016/j.exger.2004.03.034.CrossRefPubMed Barbieri M, Bonafè M, Rizzo MR, Ragno E, Olivieri F, Marchegiani F, Franceschi C, Paolisso G: Gender specific association of genetic variation in peroxisome proliferator-activated receptor (PPAR)gamma-2 with longevity. Exp Gerontol. 2004, 39: 1095-1100. 10.1016/j.exger.2004.03.034.CrossRefPubMed
24.
go back to reference Cederholm T, Persson M, Andersson P, Stenvinkel P, Nordfors L, Madden J, Vedin I, Wretlind B, Grimble RF, Palmblad J: Polymorphisms in cytokine genes influence long-term survival differently in elderly male and female patients. J Intern Med. 2007, 262: 215-223. 10.1111/j.1365-2796.2007.01803.x.CrossRefPubMed Cederholm T, Persson M, Andersson P, Stenvinkel P, Nordfors L, Madden J, Vedin I, Wretlind B, Grimble RF, Palmblad J: Polymorphisms in cytokine genes influence long-term survival differently in elderly male and female patients. J Intern Med. 2007, 262: 215-223. 10.1111/j.1365-2796.2007.01803.x.CrossRefPubMed
25.
go back to reference Lio D, Scola L, Crivello A, Colonna-Romano G, Candore G, Bonafè M, Cavallone L, Franceschi C, Caruso C: Gender-specific association between -1082 IL-10 promoter polymorphism and longevity. Genes Immun. 2002, 3: 30-33. 10.1038/sj.gene.6363827.CrossRefPubMed Lio D, Scola L, Crivello A, Colonna-Romano G, Candore G, Bonafè M, Cavallone L, Franceschi C, Caruso C: Gender-specific association between -1082 IL-10 promoter polymorphism and longevity. Genes Immun. 2002, 3: 30-33. 10.1038/sj.gene.6363827.CrossRefPubMed
26.
go back to reference Passarino G, Montesanto A, Dato S, Giordano S, Domma F, Mari V, Feraco E, De Benedictis G: Sex and age specificity of susceptibility genes modulating survival at old age. Hum Hered. 2006, 62: 213-220. 10.1159/000097305.CrossRefPubMed Passarino G, Montesanto A, Dato S, Giordano S, Domma F, Mari V, Feraco E, De Benedictis G: Sex and age specificity of susceptibility genes modulating survival at old age. Hum Hered. 2006, 62: 213-220. 10.1159/000097305.CrossRefPubMed
27.
go back to reference Harper JM, Wolf N, Galecki AT, Pinkosky SL, Miller RA: Hormone levels and cataract scores as sex-specific, mid-life predictors of longevity in genetically heterogeneous mice. Mech Ageing Dev. 2003, 124: 801-810. 10.1016/S0047-6374(03)00133-7.CrossRefPubMed Harper JM, Wolf N, Galecki AT, Pinkosky SL, Miller RA: Hormone levels and cataract scores as sex-specific, mid-life predictors of longevity in genetically heterogeneous mice. Mech Ageing Dev. 2003, 124: 801-810. 10.1016/S0047-6374(03)00133-7.CrossRefPubMed
28.
go back to reference McCulloch D, Gems D: Sex-specific effects of the DAF-12 steroid receptor on aging in Caenorhabditis elegans. Ann N Y Acad Sci. 2007, 1119: 253-259. 10.1196/annals.1404.018.CrossRefPubMedPubMedCentral McCulloch D, Gems D: Sex-specific effects of the DAF-12 steroid receptor on aging in Caenorhabditis elegans. Ann N Y Acad Sci. 2007, 1119: 253-259. 10.1196/annals.1404.018.CrossRefPubMedPubMedCentral
29.
go back to reference Shved N, Berishvili G, D'Cotta H, Baroiller JF, Segner H, Eppler E, Reinecke M: Ethinylestradiol differentially interferes with IGF-I in liver and extrahepatic sites during development of male and female bony fish. J Endocrinol. 2007, 195: 513-523. 10.1677/JOE-07-0295.CrossRefPubMed Shved N, Berishvili G, D'Cotta H, Baroiller JF, Segner H, Eppler E, Reinecke M: Ethinylestradiol differentially interferes with IGF-I in liver and extrahepatic sites during development of male and female bony fish. J Endocrinol. 2007, 195: 513-523. 10.1677/JOE-07-0295.CrossRefPubMed
30.
go back to reference Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ, Barzilai N, Cohen P: Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci USA. 2008, 105: 3438-3842. 10.1073/pnas.0705467105.CrossRefPubMedPubMedCentral Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ, Barzilai N, Cohen P: Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci USA. 2008, 105: 3438-3842. 10.1073/pnas.0705467105.CrossRefPubMedPubMedCentral
Metadata
Title
A polymorphic variant of the insulin-like growth factor 1 (IGF-1) receptor correlates with male longevity in the Italian population: a genetic study and evaluation of circulating IGF-1 from the "Treviso Longeva (TRELONG)" study
Authors
Diego Albani
Sara Batelli
Letizia Polito
Angelica Vittori
Marzia Pesaresi
Giovanni Battista Gajo
Sergio De Angeli
Andrea Zanardo
Maurizio Gallucci
Gianluigi Forloni
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Geriatrics / Issue 1/2009
Electronic ISSN: 1471-2318
DOI
https://doi.org/10.1186/1471-2318-9-19

Other articles of this Issue 1/2009

BMC Geriatrics 1/2009 Go to the issue