Adult-Onset Growth Hormone and Insulin-Like Growth Factor I Deficiency Reduces Neoplastic Disease, Modifies Age-Related Pathology, and Increases Life Span (original) (raw)

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1Departments of Physiology and Pharmacology (W.E.S., C.S.C., C.B., R.I., T.M., M.R.), Wake Forest University Health Sciences, Winston-Salem, North Carolina 27012

3Roena Kulynych Center for Memory and Cognition Research (W.E.S.), Wake Forest University Health Sciences, Winston-Salem, North Carolina 27012

*Address all correspondence and requests for reprints to: William E. Sonntag, Ph.D., Department of Physiology and Pharmacology, Wake Forest University Health Sciences, 1 Medical Center Boulevard, Winston-Salem, North Carolina 27157-1083.

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1Departments of Physiology and Pharmacology (W.E.S., C.S.C., C.B., R.I., T.M., M.R.), Wake Forest University Health Sciences, Winston-Salem, North Carolina 27012

2Sticht Center on Aging (C.S.C.), Wake Forest University Health Sciences, Winston-Salem, North Carolina 27012

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4Department of Cellular and Structural Biology (Y.I., S.L.), University of Texas Health Science Center at San Antonio, Audie Murphy Veteran’s Administration Hospital, San Antonio, Texas 78229

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6Department of Veterinary Population Medicine (K.E., C.S.C.), College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota 55108

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6Department of Veterinary Population Medicine (K.E., C.S.C.), College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota 55108

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7Departments of Medicine and Biochemistry (R.F.L.), Rush Medical College, Chicago, Illinois 60612

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8Department of Obstetrics and Gynecology (S.C.), University of Texas Medical Branch at Galveston, Galveston, Texas 77555

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4Department of Cellular and Structural Biology (Y.I., S.L.), University of Texas Health Science Center at San Antonio, Audie Murphy Veteran’s Administration Hospital, San Antonio, Texas 78229

5Research Service (S.L.), Audie Murphy Veteran’s Administration Hospital, San Antonio, Texas 78229

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1Departments of Physiology and Pharmacology (W.E.S., C.S.C., C.B., R.I., T.M., M.R.), Wake Forest University Health Sciences, Winston-Salem, North Carolina 27012

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1Departments of Physiology and Pharmacology (W.E.S., C.S.C., C.B., R.I., T.M., M.R.), Wake Forest University Health Sciences, Winston-Salem, North Carolina 27012

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14 January 2005

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William E. Sonntag, Christy S. Carter, Yuji Ikeno, Kari Ekenstedt, Cathy S. Carlson, Richard F. Loeser, Shilla Chakrabarty, Shuko Lee, Colleen Bennett, Rhonda Ingram, Tracy Moore, Melinda Ramsey, Adult-Onset Growth Hormone and Insulin-Like Growth Factor I Deficiency Reduces Neoplastic Disease, Modifies Age-Related Pathology, and Increases Life Span, Endocrinology, Volume 146, Issue 7, 1 July 2005, Pages 2920–2932, https://doi.org/10.1210/en.2005-0058
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Abstract

Disruption of the insulin/IGF-I pathway increases life span in invertebrates. However, effects of decreased IGF-I signaling in mammalian models remain controversial. Using a rodent model with a specific and limited deficiency of GH and IGF-I, we report that GH and IGF-I deficiency throughout life [GH deficiency (GHD)] has no effect on life span compared with normal, heterozygous animals. However, treatment of GHD animals with GH from 4–14 wk of age [adult-onset (AO) GHD] increased median and maximal life span by 14% and 12%, respectively. Analysis of end-of-life pathology indicated that deficiency of these hormones decreased tumor incidence in GHD and AO-GHD animals (18 and 30%, respectively) compared with heterozygous animals and decreased the severity of, and eliminated deaths from, chronic nephropathy. Total disease burden was reduced by 24% in GHD and 16% in AO-GHD animals. Interestingly, the incidence of intracranial hemorrhage increased by 154 and 198% in GHD and AO-GHD animals, respectively, compared with heterozygous animals. Deaths from intracranial hemorrhage in AO-GHD animals were delayed by 14 wk accounting for the increased life span compared with GHD animals. The presence of GH and IGF-I was necessary to maximize reproductive fitness and growth of offspring early in life and to maintain cognitive function and prevent cartilage degeneration later in life. The diverse effects of GH and IGF-I are consistent with a model of antagonistic pleiotropy and suggest that, in response to a deficiency of these hormones, increased life span is derived at the risk of functional impairments and tissue degeneration.

Copyright © 2005 by The Endocrine Society

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