Skip to main content
Log in

Connecting serum IGF-1, body size, and age in the domestic dog

  • Published:
AGE Aims and scope Submit manuscript

Abstract

Many investigations in recent years have targeted understanding the genetic and biochemical basis of aging. Collectively, genetic factors and biological mechanisms appear to influence longevity in general and specifically; reduction of the insulin/IGF-1 signaling cascade has extended life span in diverse species. Genetic alteration of mammals for life extension indicates correlation to serum IGF-1 levels in mice, and IGF-1 levels have been demonstrated as a physiological predictor of frailty with aging in man. Longevity and aging data in the dog offer a close measure of the natural multifactorial longevity interactions of genetic influence, IGF-1 signaling, and environmental factors such as exposure, exercise, and lifestyle. The absence of genetic alteration more closely represents the human longevity status, and the unique species structure of the canine facilitates analyses not possible in other species. These investigations aimed to measure serum IGF-1 in numerous purebred and mixed-breed dogs of variable size and longevity in comparison to age, gender, and spay/neuter differences. The primary objective of this investigation was to determine plasma IGF-1 levels in the adult dog, including a wide range of breeds and adult body weight. The sample set includes animals ranging from just a few months of age through 204 months and ranging in size from 5 to 160 lb. Four groups were evaluated for serum IGF-1 levels, including intact and neutered males, and intact and spayed females. IGF-1 loss over time, as a function of age, decreases in all groups with significant differences between males and females. The relationship between IGF-1 and weight differs depending upon spay/neuter status, but there is an overall increase in IGF-1 levels with increasing weight. The data, currently being interrogated further for delineation of IGF-1 receptor variants and sex differences, are being collected longitudinally and explored for longevity associations previously unavailable in non-genetically modified mammals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Al-Regaiey KA, Masternak MM, Bonkowski M, Sun L, Bartke A (2005) Long-lived growth hormone receptor knockout mice: interaction of reduced insulin-like growth factor I/insulin signaling and caloric restriction. Endocrinology 146(2):851–860

    Article  PubMed  CAS  Google Scholar 

  • Antebi A (2007) Genetic of aging in Caenorhabditis elegans. PLoS Genet 3:1565–1571

    Article  PubMed  CAS  Google Scholar 

  • AVMA 2007: US Pet Ownership and Demographics Source Book; Center for Info. Management Staff; Center for Information Management American Veterinary Medical Association (June 15, 1997)

  • Barbieri M, Rizzo MR, Manzella D (2003) Glucose regulation and oxidative stress in healthy centenarians. Exp Gerontol 38:137–143

    Article  PubMed  CAS  Google Scholar 

  • Bartke A (2005) Minireview: role of the growth hormone/insulin-like growth factor system in mammalian aging. Endo 146:3718–3723

    CAS  Google Scholar 

  • Bartke A, Chandrashekar V, Dominici F, Turyn D, Kinney B, Steger R et al (2003) Insulin-like growth factor 1 (IGF-1) and aging: controversies and new insights. Biogerontology 4:1–8

    Article  PubMed  CAS  Google Scholar 

  • Blüher M, Kahn BB, Kahn CR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299:572

    Article  PubMed  Google Scholar 

  • Brown-Borg HM, Borg KE, Meliska CJ, Bartke A (1996) Dwarf mice and the ageing process. Nature 384(6604):33

    Article  PubMed  CAS  Google Scholar 

  • Campisi J (2008) Aging and cancer cell biology. Aging Cell 7:281–284

    Article  PubMed  CAS  Google Scholar 

  • Cheng I, Stram DO, Penney KL, Pike M, Le Marchand L, Kolonel LN, Hirschhorn J, Altshuler D, Henderson BE, Freedman ML (2006) Common genetic variation in IGF1 and prostate cancer risk in the Multiethnic Cohort. J Natl Cancer Inst 98(2):123–134

    Article  PubMed  CAS  Google Scholar 

  • Coile DC (2005) Encyclopedia of dog breeds. Barrons, New York

    Google Scholar 

  • Colao A, Di Somma C, Cascella T, Pivonello R, Vitale G, Grasso LFS, Lombardi G, Svastano (2008) Relationships between serum IGF1 levels, blood pressure, and glucose tolerance: an observational, exploratory study in 404 subjects. Eur J Endo 159(4):389–397

    Article  CAS  Google Scholar 

  • Coschigano KT, Clemmons D, Bellush LL, Kopchick JJ (2000) Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology 141(7):2608–2613

    Article  PubMed  CAS  Google Scholar 

  • Deeb B, Wolf NS (1994) Studying longevity and morbidity in giant and small breeds of dogs. Vet Med (Suppl, Geriatric Medicine) 89:702–713

    Google Scholar 

  • Eigenmann JE, Amador A, Patterson DF (1988) Insulin-like growth factor I levels in proportionate dogs, chondrodystrophic dogs and in giant dogs. Acta Endocrinol (Copenh) 118:105–108

    CAS  Google Scholar 

  • Eigenmann JE, Patterson DF, Froesch ER (1984) Body size parallels insulin-like growth factor I levels but not growth hormone secretory capacity. Acta Endocrinol (Copenh) 106:448–453

    CAS  Google Scholar 

  • Espinoza S, Walston JD (2005) Frailty in older adults: insights and interventions. Cleve Clin J Med 72:1105–1112

    Article  PubMed  Google Scholar 

  • Favier RP, Mol JA, Kooistra HS, Rijnberk A (2001) Large body size in the dog is associated with transient GH excess at a young age. J Endocrinol 170:479–484

    Article  PubMed  CAS  Google Scholar 

  • Flurkey K, Papaconstantinou J, Miller RA et al (2001) Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc Natl Acad Sci 98:6736–6741

    Article  PubMed  CAS  Google Scholar 

  • Galis F, Van der Sluijs I, Van Dooren TJ, Metz JA, Nussbaumer M (2007) Do large dogs die young? J Exp Zoolog B Mol Dev Evol 308:119–126

    Article  Google Scholar 

  • Garofalo RS (2002) Genetic analysis of insulin signaling in Drosophila. Trends Endocrinol Metab 13:156–162

    Article  PubMed  CAS  Google Scholar 

  • Greer KA, Canterberry SC, Murphy KE (2007) Statistical analysis regarding the effects of height and weight on life span of the domestic dog. Res Vet Sci 82:208–214

    Article  PubMed  Google Scholar 

  • Hsieh CC, DeFord JH, Flurkey K, Harrison DE, Papaconstantinou J (2002) Implications for the insulin signaling pathway in Snell dwarf mouse longevity: a similarity with the C. elegans longevity paradigm. Mech Ageing Dev 123:1229–1244

    Article  PubMed  CAS  Google Scholar 

  • Kapatkin AS, Arbittier G, Kass PH, Gilley RS, Smith GK (2007) Kinetic gait analysis of health dogs on two different surfaces. Vet Surg 36(6):605–608

    Article  PubMed  Google Scholar 

  • Kimura K, Tissenbaum HA, Liu Y, Ruvkun G (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277:942–946

    Article  PubMed  CAS  Google Scholar 

  • Menezes Oliveira JL, Marques-Santos C, Barreto-Filho JA, Ximenes Filho R et al (2006) Lack of evidence of premature aatherosclerosis in untreated severe isolated growth hormone (GH) deficiency due to a GH-releasing hormone receptor mutation. J Clin Endocrinol Metab 91:2093–2099

    Article  PubMed  Google Scholar 

  • Mihaylova VT, Borland CZ, Manjarrez L, Stern MJ, Sun H (1999) The PTEN tumor suppressor homolog in Caenorhabditis elegans regulates longevity and dauer formation in an insulin receptor-like signaling pathway. Proc Natl Acad Sci USA 96:7427–7432

    Article  PubMed  CAS  Google Scholar 

  • Miller RA, Harper JM, Galecki A, Burke DT (2002) Big mice die young: early life body weight predicts longevity in genetically heterogeneous mice. Aging Cel 1:22–29

    Article  CAS  Google Scholar 

  • Morris JZ, Tissenbaum HA, Ruvkun G (1996) A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382:536–539

    Article  PubMed  CAS  Google Scholar 

  • Nap RC, Hazewinkel HAW, Mol JA (1994) Growth and growth hormone in the dog. Vet Q 16(Suppl 1):31S–32S

    PubMed  Google Scholar 

  • Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, Ruvkun G (1997) The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389:994–999

    Article  PubMed  CAS  Google Scholar 

  • Paradis S, Ailion M, Toker A, Thomas JH, Ruvkun GA (1999) PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans. Genes Dev 13:1438–1

    Article  PubMed  CAS  Google Scholar 

  • Paradis S, Ruvkun G (1998) Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor. Genes Dev 12:2488–2498

    Article  PubMed  CAS  Google Scholar 

  • Samaras TT (2009) Should we be concerned over increasing body height and weight? Exp Gerontol 44:83–92

    Article  PubMed  Google Scholar 

  • Samaras TT, Elrick H, Storms LH (2003) Birthweight, rapid growth, cancer, and longevity: a review. J Natl Med Assoc 95:1170–1183

    PubMed  Google Scholar 

  • Shechter M, Ginsberg S, Scheinowitz M, Feinberg MS, Laron Z (2007) Obese adults with primary growth hormone resistance (Laron syndrome) have normal endothelial function. Growth Horm IGF Res 17:165–170

    Article  PubMed  CAS  Google Scholar 

  • Shevah O, Laron Z (2007) Patients with congenital deficiency of IGF-1 seem protected from the development of malignancies: a preliminary report. Growth Horm IGF Res 17:54–57

    Article  PubMed  CAS  Google Scholar 

  • Snibson KJ, Bhathal PS, Hardy CL, Brandon MR, Adams TE (1999) High, persistent hepatocellular proliferation and apoptosis precede hepatocarcinogenesis in growth hormone transgenic mice. Liver 19:242–252

    Article  PubMed  CAS  Google Scholar 

  • Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ et al (2008) Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci USA 105:3438–3442

    Article  PubMed  CAS  Google Scholar 

  • Sutter NB, Bustamante CD, Chase K, Gray MM, Zhao K, Zhu L et al (2007) A single IGF1 allele is a major determinant of small size in dogs. Science 316:112–115

    Article  PubMed  CAS  Google Scholar 

  • Taguchi A, White MF (2008) Insulin-like signaling, nutrient homeostasis, and life span. Annu Rev Physiol 70:191–212

    Article  PubMed  CAS  Google Scholar 

  • Tatar M (2003) The endocrine regulation of aging by insulin-like signals. Science 299:1346–1351

    Article  PubMed  CAS  Google Scholar 

  • Walston J (2004) Frailty—the search for underlying causes. Sci Aging Knowledge Environ 2004:pe4

    Article  PubMed  Google Scholar 

  • Warner HR (2004) Current status of efforts to measure and modulate the biological rate of aging. Jour Geron A Bio Sci 59(7):692–696

    Article  Google Scholar 

  • Waters DJ, Kengeri SS, Clever B, Booth JA, Maras AH, Schlittler DL, Hayek MG (2009) Exploring mechanisms of sex differences in longevity: lifetime ovary exposure and exceptional longevity in dogs. Aging Cell 8(6):752–755

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to extend special thanks to Drs. Jeff Logue and Mark Stickney for their contributions to sample collection pertaining to these studies.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kimberly A. Greer.

About this article

Cite this article

Greer, K.A., Hughes, L.M. & Masternak, M.M. Connecting serum IGF-1, body size, and age in the domestic dog. AGE 33, 475–483 (2011). https://doi.org/10.1007/s11357-010-9182-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-010-9182-4

Keywords

Navigation