Garratt, M., Nakagawa, S. and Simons, M.J. orcid.org/0000-0001-7406-7708 (2017) Life-span Extension With Reduced Somatotrophic Signaling: Moderation of Aging Effect by Signal Type, Sex, and Experimental Cohort. Journals of Gerontology, Series A. ISSN 1079-5006
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 lifeextension. 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. 1 Journals of Gerontology: Biological Sciences cite as: J Gerontol A Biol Sci Med Sci, 2017, Vol. 00, No. 00, 1–8 doi:10.1093/gerona/glx010 Advance Access publication February 16, 2017 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
Keywords: | IGF1; Growth hormone; Longevity; Mice |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Animal and Plant Sciences (Sheffield) |
Funding Information: | Funder Grant number WELLCOME TRUST (THE) 107400/Z/15/Z NATURAL ENVIRONMENT RESEARCH COUNCIL NE/N013832/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 23 Feb 2017 15:06 |
Last Modified: | 23 Feb 2017 15:06 |
Published Version: | http://doi.org/10.1093/gerona/glx010 |
Status: | Published |
Publisher: | Oxford University Press |
Refereed: | Yes |
Identification Number: | 10.1093/gerona/glx010 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:112537 |