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