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Life-span Extension With Reduced Somatotrophic Signaling: Moderation of Aging Effect by Signal Type, Sex, and Experimental Cohort

Abstract

Reduced somatotrophic signaling through the growth hormone (GH) and insulin-like growth factor pathways (IGF1) can delay aging, although the degree of life-extension varies markedly across studies. By collating data from previous studies and using meta-analysis, we tested whether factors including sex, hormonal manipulation, body weight change and control baseline mortality quantitatively predict relative life-extension. Manipulations of GH signaling (including pituitary and direct GH deficiencies) generate significantly greater extension in median life span than IGF1 manipulations (including IGF1 production, reception, and bioactivity), producing a consistent shift in mortality risk of mutant mice. Reduced Insulin receptor substrate (IRS) expression produces more similar life-extension to reduced GH, although effects are more heterogeneous and appear to influence the demography of mortality differently. Life-extension with reduced IGF1 signaling, but neither GH nor IRS signaling, increases life span significantly more in females than males, and in cohorts where control survival is short. Our results thus suggest that reduced GH signaling has physiological benefits to survival outside of its actions on circulating IGF1. In addition to these biological moderators, we found an overrepresentation of small sample sized studies that report large improvements in survival, indicating potential publication bias. We discuss how this could potentially confound current conclusions from published work, and how this warrants further study replication.

Type Journal
ISBN 1758-535X (Electronic) 1079-5006 (Linking)
Authors Garratt, M.; Nakagawa, S.; Simons, M. J. P.
Responsible Garvan Author A/Prof Shinichi Nakagawa
Publisher Name JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
Published Date 2017-11-09
Published Volume 72
Published Issue 12
Published Pages 1620-1626
Status Published in-print
DOI 10.1093/gerona/glx010
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/28207064