Abstract

The overall objective is to test the hypothesis that age-related changes in the neuroendocrine system are potential biomarkers for mammalian aging. The focus of our research will be to study the decline in growth hormone secretory dynamics, plasma levels of somatomedin-C, and skeletal muscle protein synthesis as an integrated system. Previous research from our laboratory, and others, has clearly established that these variables decrease with age in rodents, monkeys and man. Administration of growth hormone has been shown to increase plasma levels of somatomedin-C in man, protein synthesis in rats, and immune function in several species with age. This comprehensive approach is designed to develop and verify a non-invasive index of neuroendocrine aging which will eventually be applicable to man. Our working hypothesis in developing an integrated approach to this area is that the age-related declines in protein synthesis and somatomedin-C are the result of a cascading effect initiated within the hypothalamic-hypophysial system. We will test this hypothesis by: (1) Assessing age-related changes in growth hormone secretory dynamics and plasma levels of somatomedin-C in 3 strains of rats and 4 strains of mice at 5 month intervals throughout the lifespan of these animals; (2) correlating measures described in (1) with the age-related decline in skeletal muscle protein synthesis and mean lifespan of the animal; (3) Determining the effects of dietary restriction on growth hormone, somatomedin-C, and protein synthesis; and (4) Assessing whether an increase in pituitary somatostatin receptors (recently observed by our laboratory in aging Fischer rats) is present in other aging rodents and is influenced by dietary restriction. To our knowledge there have been no studies of the growth hormone/ somatomedin- C system using moderate dietary restriction and this information is necessary to assess the role of these hormones as biomarkers of aging. The integrated/comprehensive approach of this application should provide data of high reliability (because of the inter- relationship between the measures) and validity (because of the use of several strains of rats/mice) on the relationship between the age-related decline in growth hormone and aging and its modification by dietary restriction.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG007752-05
Application #
3119041
Study Section
Aging Review Committee (AGE)
Project Start
1988-04-01
Project End
1993-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Wake Forest University Health Sciences
Department
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106

  Publications

Khan, Amir S; Sane, David C; Wannenburg, Thomas et al. (2002) Growth hormone, insulin-like growth factor-1 and the aging cardiovascular system. Cardiovasc Res 54:25-35
Wannenburg, T; Khan, A S; Sane, D C et al. (2001) Growth hormone reverses age-related cardiac myofilament dysfunction in rats. Am J Physiol Heart Circ Physiol 281:H915-22
Lynch, C D; Cooney, P T; Bennett, S A et al. (1999) Effects of moderate caloric restriction on cortical microvascular density and local cerebral blood flow in aged rats. Neurobiol Aging 20:191-200
Sonntag, W E; Lynch, C D; Cefalu, W T et al. (1999) Pleiotropic effects of growth hormone and insulin-like growth factor (IGF)-1 on biological aging: inferences from moderate caloric-restricted animals. J Gerontol A Biol Sci Med Sci 54:B521-38
Xu, X; Sonntag, W E (1996) Moderate caloric restriction prevents the age-related decline in growth hormone receptor signal transduction. J Gerontol A Biol Sci Med Sci 51:B167-74
Xu, X; Sonntag, W E (1996) Growth hormone-induced nuclear translocation of Stat-3 decreases with age: modulation by caloric restriction. Am J Physiol 271:E903-9
Sonntag, W E; Xu, X; Ingram, R L et al. (1995) Moderate caloric restriction alters the subcellular distribution of somatostatin mRNA and increases growth hormone pulse amplitude in aged animals. Neuroendocrinology 61:601-8
D'Costa, A P; Xu, X; Ingram, R L et al. (1995) Insulin-like growth factor-1 stimulation of protein synthesis is attenuated in cerebral cortex of aging rats. Neuroscience 65:805-13
Xu, X; Bennett, S A; Ingram, R L et al. (1995) Decreases in growth hormone receptor signal transduction contribute to the decline in insulin-like growth factor I gene expression with age. Endocrinology 136:4551-7
Breese, C R; Sonntag, W E (1995) Effect of ethanol on plasma and hepatic insulin-like growth factor regulation in pregnant rats. Alcohol Clin Exp Res 19:867-73

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