Pleiotropic Effects of Growth Hormone and Insulin-like Growth Factor (IGF)-1 on Biological Aging: Inferences From Moderate Caloric-Restricted Animals

Sonntag, W. E.; Lynch, C. D.; Cefalu, W. T.; Ingram, R. L.; Bennett, S. A.; Thornton, P. L.; Khan, A. S.

doi:10.1093/gerona/54.12.b521

Cited by 229Genetics, Aging, and Longevity in Model OrganismsGrowth Hormone and Insulin-like Growth FactorsDietary Effects on Health

Pleiotropic Effects of Growth Hormone and Insulin-like Growth Factor (IGF)-1 on Biological Aging: Inferences From Moderate Caloric-Restricted Animals

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Sonntag, W. E., Lynch, C. D., Cefalu, W. T., Ingram, R. L., Bennett, S. A., Thornton, P. L., Khan, A. S.·1999·The Journals of Gerontology Series A: Biological Sciences and Medical Sciences

DOI 10.1093/gerona/54.12.b521

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Abstract

Moderate caloric restriction (60% of ad libitum intake) is an important model to investigate potential mechanisms of biological aging. This regimen has been reported to decrease the number of pathologies and increase life span in all species tested to date. Although moderate caloric restriction induces a wide range of physiological changes within the organism, adaptive changes within the endocrine system are evident and serve to maintain blood levels of glucose. These alterations include an increase in growth hormone secretory dynamics and a decline in plasma levels of IGF-1. These endocrine compensatory mechanisms can be induced at any age, and we have proposed that these alterations mediate some of the beneficial aspects of moderate caloric restriction. Numerous studies indicate that growth hormone and IGF-1 decrease with age and that administration of these hormones ameliorates the deterioration of tissue function evident in aged ad libitum-fed animals, suggesting that the absence of these hormones contributes to the phenotype of aging. Nevertheless, IGF-1 is an important risk factor in age-related pathologies including lung, breast, and prostate cancer. From these studies, we propose that endocrine compensatory mechanisms induced by moderate caloric restriction (including increased growth hormone and decreased IGF-1) decrease the stimulus for cellular replication, resulting in a decline in pathologies and increased life span observed in these animals. These findings have important implications for potential mechanisms of moderate caloric restriction and suggest that neuroendocrine compensatory mechanisms exert a key role on the actions of moderate caloric restriction on life span.

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Caloric restriction lowers IGF-1 secretion.
“CR reportedly reduces IGF-1 secretion (114)”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [114]
Caloric restriction may raise growth hormone levels.
“CR may also increase GH levels (114)”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [114]

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Decreases in growth hormone receptor signal transduction contribute to the decline in insulin-like growth factor I gene expression with age
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Insulin/insulin‐like growth factor I and other epigenetic modulators of myelin basic protein expression in isolated oligodendrocyte progenitor cells
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Effects of moderate caloric restriction on cortical microvascular density and local cerebral blood flow in aged rats☆
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Moderate caloric restriction increases type 1 IGF receptors and protein synthesis in aging rats
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Effect of Age and IGF-I Administration on Elastin Gene Expression in Rat Aorta
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Molecular biology of the insulin-like growth factors
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Somatostatin gene expression in hypothalamus and cortex of aging male rats
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Increased Pituitary Response to Somatostatin in Aging Male Rats: Relationship to Somatostatin Receptor Number and Affinity
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Presence of a Somatomedin-C-Immunoreactive Substance in the Central Nervous System: Immunohistochemical Mapping Studies
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Insulin-like growth factor-I and human lung fibroblast-derived insulin-like growth factor-I stimulate the proliferation of human lung carcinoma cells in vitro.
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Effect of age and dietary restriction on protein synthesis by isolated kidney cells
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Effect of Hypophysectomy on Hypothalamic Growth Hormone-Releasing Factor Content and Release in the Rat*
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Feedback effects of growth hormone on growth hormone-releasing hormone and somatostatin are not evident in aged rats
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GH Binding to Liver in Young and Old Female Rats: Relation to Somatomedin-C Secretion
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Postreceptor signaling mechanisms for growth hormone
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Growth hormone-induced nuclear translocation of Stat-3 decreases with age: modulation by caloric restriction
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Growth promoting effects of IGF‐I on fetal hypothalamic cell lines under serum‐free culture conditions
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Partial characterization of insulin-like growth factor I in primary human lung cancers using immunohistochemical and receptor autoradiographic techniques.
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Moderate Caloric Restriction Prevents the Age-Related Decline in Growth Hormone Receptor Signal Transduction
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Inhibition of the mitogenic effects of plasma by a monoclonal antibody to somatomedin C.
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Chronic [DAla2] GHRH Administration Increases Working Memory in Aged Animals
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Authors: Sonntag, W. E., Lynch, C. D., Cefalu, W. T., Ingram, R. L., Bennett, S. A., Thornton, P. L., & Khan, A. S.
Affiliations: Wake Forest University Health Sciences (US)
ORCID: Sonntag, W. E.
Cefalu, W. T.
Venue: The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
Publisher: Oxford University Press (OUP)
Published: 1999-12-01
Volume: 54
Issue: 12
Pages: B521-B538
ISSN: 1079-5006 (ISSN-L)
1758-535X
DOI: 10.1093/gerona/54.12.b521
OpenAlex: W2166656167
Cited by: 229
References: 131
Citations by year: 2026: 2 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 12 · 2020: 10 · 2019: 14 · 2018: 3 · 2017: 7 · 2016: 12 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 9
FWCI: 1.41
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journals of Gerontology Series A (publishedVersion)
PubMed (publishedVersion)
DigitalCommons-Cedarville (Cedarville University) (submittedVersion)
Funders: Wake Forest University
National Institutes of Health (5r01ag007752-07)
National Institute on Aging (AG-11370, P01AG011370, AG 07752)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Health Sciences › Medicine › Physiology › Dietary Effects on Health
Keywords: biological aging, growth hormone, insulin-like growth factor I, lifespan extension, age-related diseases, cancer risk, neuroendocrine adaptation, glucose homeostasis
MeSH terms: Aging, Animals, Blood Glucose, Energy Intake, Cell Division, Disease Models, Animal, Female, Insulin-Like Growth Factor I, Longevity, Lung Neoplasms, Male, Mammary Neoplasms, Experimental, Neurosecretory Systems, Phenotype, Prostatic Neoplasms, Risk Factors, Growth Hormone

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Pleiotropic Effects of Growth Hormone and Insulin-like Growth Factor (IGF)-1 on Biological Aging: Inferences From Moderate Caloric-Restricted Animals

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