Low Circulating IGF-I Bioactivity is Associated with Human Longevity: Findings in Centenarians' Offspring

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2012 Sep 18

PMID 22983440

Citations 38

Authors

Giovanni Vitale

Michael P Brugts

Giulia Ogliari

Davide Castaldi

Letizia M Fatti

Aimee J Varewijck

Steven W Lamberts

Daniela Monti

Laura Bucci

Elisa Cevenini

Francesco Cavagnini

Claudio Franceschi

Leo J Hofland

Daniela Mari

Joseph Janssen

Affiliations

Soon will be listed here.

Abstract

Unlabelled: Centenarians' offspring represent a suitable model to study age-dependent variables (e.g. IGF-I) potentially involved in the modulation of the lifespan. The aim of the present study was to investigate the role of the IGF-I in human longevity. We evaluated circulating IGF-I bioactivity measured by an innovative IGF-I Kinase Receptor Activation (KIRA) Assay, total IGF-I, IGFBP-3, total IGF-II, insulin, glucose, HOMA2-B% and HOMA2-S% in 192 centenarians' offspring and 80 offspring-controls of which both parents died relatively young. Both groups were well-matched for age, gender and BMI with the centenarians' offspring. IGF-I bioactivity (p〈0.01), total IGF-I (p〈0.01) and the IGF-I/IGFBP-3 molar ratio (p〈0.001) were significantly lower in centenarians' offspring compared to offspring matched-controls. Serum insulin, glucose, HOMA2-B% and HOMA2-S% values were similar between both groups. In centenarians' offspring IGF-I bioactivity was inversely associated to insulin sensitivity.

In Conclusion: 1) centenarians' offspring had relatively lower circulating IGF-I bioactivity compared to offspring matched-controls; 2) IGF-I bioactivity in centenarians' offspring was inversely related to insulin sensitivity. These data support a role of the IGF-I/insulin system in the modulation of human aging process.

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References

Suh Y, Atzmon G, Cho M, Hwang D, Liu B, Leahy D . Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci U S A. 2008; 105(9):3438-42. PMC: 2265137. DOI: 10.1073/pnas.0705467105. View

Longo V, Finch C . Evolutionary medicine: from dwarf model systems to healthy centenarians?. Science. 2003; 299(5611):1342-6. DOI: 10.1126/science.1077991. View

Sharma N, Castorena C, Cartee G . Tissue-specific responses of IGF-1/insulin and mTOR signaling in calorie restricted rats. PLoS One. 2012; 7(6):e38835. PMC: 3368930. DOI: 10.1371/journal.pone.0038835. View

Clemmons D . Metabolic actions of insulin-like growth factor-I in normal physiology and diabetes. Endocrinol Metab Clin North Am. 2012; 41(2):425-43, vii-viii. PMC: 3374394. DOI: 10.1016/j.ecl.2012.04.017. View

Janssen J, Stolk R, Pols H, Grobbee D, Lamberts S . Serum total IGF-I, free IGF-I, and IGFB-1 levels in an elderly population: relation to cardiovascular risk factors and disease. Arterioscler Thromb Vasc Biol. 1998; 18(2):277-82. DOI: 10.1161/01.atv.18.2.277. View

Parr T . Insulin exposure controls the rate of mammalian aging. Mech Ageing Dev. 1996; 88(1-2):75-82. DOI: 10.1016/0047-6374(96)01723-x. View

Paolisso G, Ammendola S, Del Buono A, Gambardella A, Riondino M, Tagliamonte M . Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function. J Clin Endocrinol Metab. 1997; 82(7):2204-9. DOI: 10.1210/jcem.82.7.4087. View

Galderisi M, Vitale G, Lupoli G, Barbieri M, Varricchio G, Carella C . Inverse association between free insulin-like growth factor-1 and isovolumic relaxation in arterial systemic hypertension. Hypertension. 2001; 38(4):840-5. DOI: 10.1161/hy1001.091776. View

Newman A, Glynn N, Taylor C, Sebastiani P, Perls T, Mayeux R . Health and function of participants in the Long Life Family Study: A comparison with other cohorts. Aging (Albany NY). 2011; 3(1):63-76. PMC: 3047140. DOI: 10.18632/aging.100242. View

10.

Atzmon G, Schechter C, Greiner W, Davidson D, Rennert G, Barzilai N . Clinical phenotype of families with longevity. J Am Geriatr Soc. 2004; 52(2):274-7. DOI: 10.1111/j.1532-5415.2004.52068.x. View

11.

Rozing M, Westendorp R, Frolich M, de Craen A, Beekman M, Heijmans B . Human insulin/IGF-1 and familial longevity at middle age. Aging (Albany NY). 2010; 1(8):714-22. PMC: 2806046. DOI: 10.18632/aging.100071. View

12.

Franceschi C, Bonafe M . Centenarians as a model for healthy aging. Biochem Soc Trans. 2003; 31(2):457-61. DOI: 10.1042/bst0310457. View

13.

DCosta A, Lenham J, Ingram R, Sonntag W . Moderate caloric restriction increases type 1 IGF receptors and protein synthesis in aging rats. Mech Ageing Dev. 1993; 71(1-2):59-71. DOI: 10.1016/0047-6374(93)90035-p. View

14.

van Heemst D, Beekman M, Mooijaart S, Heijmans B, Brandt B, Zwaan B . Reduced insulin/IGF-1 signalling and human longevity. Aging Cell. 2005; 4(2):79-85. DOI: 10.1111/j.1474-9728.2005.00148.x. View

15.

Kuk J, Saunders T, Davidson L, Ross R . Age-related changes in total and regional fat distribution. Ageing Res Rev. 2009; 8(4):339-48. DOI: 10.1016/j.arr.2009.06.001. View

16.

Barbieri M, Rizzo M, Manzella D, Paolisso G . Age-related insulin resistance: is it an obligatory finding? The lesson from healthy centenarians. Diabetes Metab Res Rev. 2001; 17(1):19-26. DOI: 10.1002/dmrr.178. View

17.

Rajpathak S, Gunter M, Wylie-Rosett J, Ho G, Kaplan R, Muzumdar R . The role of insulin-like growth factor-I and its binding proteins in glucose homeostasis and type 2 diabetes. Diabetes Metab Res Rev. 2009; 25(1):3-12. PMC: 4153414. DOI: 10.1002/dmrr.919. View

18.

Mohn A, Marcovecchio M, de Giorgis T, Pfaeffle R, Chiarelli F, Kiess W . An insulin-like growth factor-I receptor defect associated with short stature and impaired carbohydrate homeostasis in an Italian pedigree. Horm Res Paediatr. 2011; 76(2):136-43. DOI: 10.1159/000324957. View

19.

Mooijaart S, van Heemst D, Noordam R, Rozing M, Wijsman C, de Craen A . Polymorphisms associated with type 2 diabetes in familial longevity: The Leiden Longevity Study. Aging (Albany NY). 2010; 3(1):55-62. PMC: 3047139. DOI: 10.18632/aging.100250. View

20.

Arafat A, Weickert M, Frystyk J, Spranger J, Schofl C, Mohlig M . The role of insulin-like growth factor (IGF) binding protein-2 in the insulin-mediated decrease in IGF-I bioactivity. J Clin Endocrinol Metab. 2009; 94(12):5093-101. DOI: 10.1210/jc.2009-0875. View