Skip to main content

Advertisement

SpringerLink
Log in

Do long-lived mutant and calorie-restricted mice share common anti-aging mechanisms?—a pathological point of view

  • Published:
AGE Aims and scope Submit manuscript

Abstract

Rodent models are an invaluable resource for studying the mechanism of mammalian aging. In recent years, the availability of transgenic and knockout mouse models has facilitated the study of potential mechanisms of aging. Since 1996, aging studies with several long-lived mutant mice have been conducted. Studies with the long-lived mutant mice, Ames and Snell dwarf, and growth hormone receptor/binding protein knockout mice, are currently providing important clues regarding the role of the growth hormone/insulin like growth factor-1 axis in the aging process. Interestingly, these studies demonstrate that these long-lived mutant mice have physiological characteristics that are similar to the effects of calorie restriction, which has been the most effective experimental manipulation capable of extending lifespan in various species. However, a question remains to be answered: do these long-lived mutant and calorie-restricted mice extend their lifespan through a common underlying mechanism?

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CR:

caloric restriction

GH:

growth hormone

GHR:

growth hormone receptor

GHR/BP:

growth hormone receptor/binding protein

KO:

knockout

PRL:

prolactin

IGF-1:

insulin-like growth factor-1

TSH:

thyroid stimulating hormone

T3:

triiodo-thyronnine

T4:

thyroxine

AL:

ad libitum

References

  • Bartke A (1964) Histology of the anterior hypohysis, thyroid and gonads of two types of dwarf mice. Anat Rec 149:225–235

    Article  CAS  PubMed  Google Scholar 

  • Bartke A (1965) The response of two types of dwarf mice to growth hormone, thyrotropin, and thyroxine. Gen Comp Endocrinol 5:418–426

    Article  CAS  PubMed  Google Scholar 

  • Bartke A (2000) Delayed aging in Ames dwarf mice. Relationships to endocrine function and body size. In: Hekimi S (ed) The molecular genetics of aging. Springer, Berlin Heidelberg New York, pp 181–202

    Google Scholar 

  • Bartke A, Coschigano K, Kopchick J, Chandrashekar V, Mattison J, Kinney B, Hauck S (2001a) Genes that prolong life: relationships of growth hormone and growth to aging and life span. J Gerontol Biol Sci 56A:B340–B349

    CAS  Google Scholar 

  • Bartke A, Wright JC, Mattison J, Ingram DK, Miller RA, Roth GS (2001b) Extending the lifespan of long-lived mice. Nature 414:412

    Article  CAS  PubMed  Google Scholar 

  • Berryman DE, List EO, Coschigano KT, Behar K, Kim JK, Kopchick JJ (2004) Comparing adiposity profiles in three mouse models with altered GH signaling. Growth Horm IGF Res 14:309–318

    Article  CAS  PubMed  Google Scholar 

  • Bronson RT, Lipman RD (1991) Reduction in rate of occurrence of age related lesions in dietary restricted laboratory mice. Growth Dev Aging 55:169–184

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Burroughs KD, Dunn SE, Barrett JC, Taylor JA (1999) Insulin-like growth factor-1: a key regulator of human cancer risk? J Natl Cancer Inst 91:579–581

    Article  CAS  PubMed  Google Scholar 

  • Bustin SA, Jenkins PJ (2001) The growth hormone-insulin-like growth factor-I axis and colorectal cancer. Trends Mol Med 7:447–454

    Article  CAS  PubMed  Google Scholar 

  • Chandrashekar V, Bartke A, Coschigano KT, Kopchick JJ (1999) Pituitary and testicular function in growth hormone receptor gene knockout mice. Endocrinology 140:1082–1088

    Article  CAS  PubMed  Google Scholar 

  • Chen HW, Meier H, Heiniger HJ, Heubner RJ (1972) Tumorigenesis in strain DW/J mice and induction by prolactin of the group-specific antigen of endogenous C-type RNA tumor virus. J Natl Cancer Inst 49:1145–1154

    CAS  PubMed  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 14:2608–2613

    Article  Google Scholar 

  • Coschigano KT, Holland AN, Riders ME, List EO, Flyvbjerg A, Kopchick JJ (2003) Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Endocrinology 144:3799–3810

    Article  CAS  PubMed  Google Scholar 

  • De Mello-Coelho V, Savino W, Postel-Vinay MC, Dardenne M (1998) Role of prolactin and growth hormone on thymus physiology. Dev Immunol 6:317–323

    Article  PubMed  Google Scholar 

  • Doi T, Striker LJ, Quaife C, Conti FG, Palmiter R, Behringer R, Brinster R, Striker GE (1988) Progressive glomerulosclerosis develops in transgenic mice chronically expressing growth hormone and growth hormone releasing factor but not in those expressing insulinlike growth factor-1. Am J Pathol 131:398–403

    CAS  PubMed  Google Scholar 

  • Dominici FP, Hauck S, Argentino DP, Bartke A, Turyn D (1999) Increased insulin sensitivity and upregulation of insulin receptor, insulin receptor substrate (IRS)-1 and IRS-2 in liver of Ames dwarf mice. J Endocrinol 173:81–94

    Article  Google Scholar 

  • Esquifino AI, Villanúa MA, Szary A, Yau J, Bartke A (1991) Ectopic pituitary transplants restore immunocompetence in Ames dwarf mice. Acta Endocrinol 125:67–72

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Flurkey K, Papaconstantinou J, Harrison DE (2002) The Snell dwarf mutation Pit1(dw) can increase lifespan in mice. Mech Ageing Dev 123:121–130

    Article  CAS  PubMed  Google Scholar 

  • Hauck SJ, Hunter WS, Danilovich N, Kopchick JJ, Bartke A (2001) Reduced levels of thyroid hormones, insulin, and glucose, and lower body core temperature in the growth hormone receptor/binding protein knockout mouse. Exp Biol Med 226:552–558

    CAS  Google Scholar 

  • Ikeno Y, Bronson RT, Hubbard GB, Lee S, Bartke A (2003) The delayed occurrence of fatal neoplastic diseases in Ames dwarf mice: correlation to the extended longevity. J Gerontol Ser A Biol Sci Med Sci 58:291–296

    Google Scholar 

  • Ikeno Y, Hubbard GB, Lee S, Richardson A, Strong R, Fernandez E, Diaz V, Nelson JF (2005) Housing density does not influence the longevity effect of calorie restriction. J Gerontol 60A: 1510–1517

    Google Scholar 

  • Iwasaki K, Gleiser CA, Masoro EJ, McMahn CA, Seo E, Yu BP (1988) The influence of dietary protein source on longevity and age-related disease processes of Fischer 344 rats. J Gerontol Biol Sci 43:B5–B12

    CAS  Google Scholar 

  • Li S, Crenshaw BE III, Rawson EJ, Simmons DM, Swanson LW, Rosenfeld MG (1990) Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1. Nature 347:528–533

    Article  CAS  PubMed  Google Scholar 

  • Maeda H, Gleiser CA, Masoro EJ, Murata I, McMahan CA, Yu BP (1985) Nutritional influences on aging of Fischer 344 rats: II. Pathology. J Gerontol 40:671–688

    CAS  PubMed  Google Scholar 

  • Masoro EJ (1988) Food restriction in rodents: an evaluation of its role in the study of aging. J Gerontol 43:B59–B64

    CAS  PubMed  Google Scholar 

  • Masoro EJ, Yu BP, Bertrand HA (1982) Action of food restriction in delaying the aging process. Proc Natl Acad Sci USA 79:4239–4241

    Article  CAS  PubMed  Google Scholar 

  • Masternak M, Al-Regaiey K, Bonkowski M, Panici J, Sun L, Wang J, Przybylski GK, Bartke A (2004) Divergent effects of caloric restriction on gene expression in normal and long-lived mice. J Gerontol Ser A Biol Sci Med Sci 59:784–788

    Google Scholar 

  • Mattison JA, Wright C, Bronson RT, Roth GS, Ingram DK, Bartke A (2000) Studies of aging in Ames dwarf mice: effects of caloric restriction. J Am Aging Assoc 23:9–16

    Google Scholar 

  • McCay CM, Crowell MF, Maynard LA (1935) The effect of retarded growth upon length of life span and upon ultimate body size. J Nutr 10:63–79

    CAS  Google Scholar 

  • Miller RA (1996) Aging and immune response. In: Schneider EL, Rowe JW (eds) Handbook of the biology of aging. Academic, New York, pp 157–180

    Google Scholar 

  • Miller RA, Chang Y, Galecki AT, Al-Regaiey K, Kopchick JJ, Bartke A (2002) Gene expression patterns in calorically restricted mice: partial overlap with long-lived mutant mice. Mol Endocrinol 16:2657–2666

    Article  CAS  PubMed  Google Scholar 

  • Montecino-Rodriguez E, Clark R, Johnson A, Collins L, Dorshkind K (1996) Defective B cell development in Snell dwarf (dw/dw) mice can be corrected by thyroxine treatment. J Immunol 157:3334–3340

    CAS  PubMed  Google Scholar 

  • Silberberg R (1972) Articular aging and osteoarthrosis in dwarf mice. Pathol Microbiol 38:417–430

    CAS  Google Scholar 

  • Snell GD (1929) Dwarf, a new Mendelian recessive character of the house mouse. Proc Natl Acad Sci USA 15:733–734

    Article  CAS  PubMed  Google Scholar 

  • Sonntag WE, Xu X, Ingram RL, D’Costa A (1995) Moderate caloric restriction alters the subcellular distribution of somatostatin mRNA and increases growth hormone pulse amplitude in aged animals. Neuroendocrinology 61:601–608

    Article  CAS  PubMed  Google Scholar 

  • Sornson MW, Wu W, Dasen JS, Flynn SE, Norman DJ, O’Connell SM, Gukovsky I, Carriere C, Ryan AK, Miller AP, Zuo L, Gleiberman AS, Anderson B, Beamer WG, Rosenfeld MG (1996) Pituitary lineage determination by the prophet of pit-1 homeodomain factor defective in Ames dwarfism. Nature 384:327–333

    Article  CAS  PubMed  Google Scholar 

  • Swerdlow AJ, Higgins CD, Adlard P, Preece MA (2002) Risk of cancer in patients treated with human pituitary growth hormone in the UK, 1959–1985: a cohort study. Lancet 60:273–277

    Article  Google Scholar 

  • Tsuchiya T, Dhahbi JM, Cui X, Mote PL, Bartke A, Spindler SR (2004) Additive regulation of hepatic gene expression by dwarfism and caloric restriction. Physiol Genomics 17:307–315

    Article  CAS  PubMed  Google Scholar 

  • Vergara M, Smith-Wheelock M, Harper JM, Sigler R, Miller RA (2004) Hormone-treated Snell dwarf mice regain fertility but remain long lived and disease resistant. J Gerontol Ser A Biol Sci Med Sci 59:1244–1250

    Google Scholar 

  • Volk MJ, Pugh TD, Kim M-J, Frith CH, Daynes RA, Ershler WB, Weindruch R (1994) Dietary restriction from middle age attenuates age-associated lymphoma development and interleukin 6 dysregulation in C57BL/6 mice. Cancer Res 54:3054–3061

    CAS  PubMed  Google Scholar 

  • Wanke R, Wolf E, Hermannns W, Folger S, Buchmuller T, Brem G (1992) The GH-transgenic mouse as an experimental model for growth research: clinical and pathological studies. Horm Res 37:74–87

    Article  PubMed  Google Scholar 

  • Weindruch R, Walford RL (1988) The Retardation of Aging and Disease by Dietary Restriction, Thomas, Springfield, IL

    Google Scholar 

  • Yang CW, Striker LJ, Pesce C, Chen WY, Paten EP, Elliot S, Doi T, Kopchick JJ, Striker GE (1993) Glomerulosclerosis and body growth are mediated by different portions of bovine growth hormone: studies in transgenic mice. Lab Invest 68:62–70

    CAS  PubMed  Google Scholar 

  • Yu H, Rohan T (2000) Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 92:1472–1489

    Article  CAS  PubMed  Google Scholar 

  • Yu BP, Masoro EJ, Murata I, Bertrand HA, Lynd FT (1982) Life span study for SPF Fischer 344 male rats fed ad libitum or restricted diets: longevity, growth, lean body mass and disease. J Gerontol 37: 130–141

    CAS  PubMed  Google Scholar 

  • Zhou Y, Xu BC, Maheshwari HG, He L, Reed M, Lozykowski M, Okada S, Cataldo L, Coschigano K, Wagner TE, Baumann G, Kopchick JJ (1997) A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). Proc Natl Acad Sci USA 94:13215–13220

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA

    Yuji Ikeno, Christie M. Lew, Lisa A. Cortez & Celeste R. Webb

  2. Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA

    Yuji Ikeno, Christie M. Lew, Lisa A. Cortez & Celeste R. Webb

  3. Research Service, Audie Murphy VA Hospital (STVHCS), San Antonio, TX, 78229, USA

    Yuji Ikeno & Shuko Lee

  4. Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, TX, 78245, USA

    Gene B. Hubbard

Authors
  1. Yuji Ikeno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christie M. Lew
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lisa A. Cortez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Celeste R. Webb
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shuko Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gene B. Hubbard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuji Ikeno.

About this article

Cite this article

Ikeno, Y., Lew, C.M., Cortez, L.A. et al. Do long-lived mutant and calorie-restricted mice share common anti-aging mechanisms?—a pathological point of view. AGE 28, 163–171 (2006). https://doi.org/10.1007/s11357-006-9007-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-006-9007-7

Key words

Search

Navigation