title: 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.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor.
authors.forename: Michael
authors.initials: M
authors.lastname: Garratt
authors.affiliation: Evolution and Ecology Research Group and School of Biological, Earth and Environmental Sciences, The University of New South Wales, Sydney, Australia.|Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, Australia.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Department of Animal and Plant Sciences, University of Sheffield, UK.
authors.forename: Mirre J P
authors.initials: MJP
authors.lastname: Simons
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D005260:Female; D013006:Growth Hormone / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008017:Life Expectancy; D008297:Male; D051379:Mice; D012737:Sex Factors; D015398:Signal Transduction
chemical_list: D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone
keywords: Growth hormone; IGF1; Longevity; Mice