Somatotropic Signaling: Trade-Offs Between Growth, Reproductive Development, and Longevity

Abstract

Growth hormone (GH) is a key determinant of postnatal growth and plays an important role in the control of metabolism and body composition. Surprisingly, deficiency in GH signaling delays aging and remarkably extends longevity in laboratory mice. In GH-deficient and GH-resistant animals, the "healthspan" is also extended with delays in cognitive decline and in the onset of age-related disease. The role of hormones homologous to insulin-like growth factor (IGF, an important mediator of GH actions) in the control of aging and lifespan is evolutionarily conserved from worms to mammals with some homologies extending to unicellular yeast. The combination of reduced GH, IGF-I, and insulin signaling likely contributes to extended longevity in GH or GH receptor-deficient organisms. Diminutive body size and reduced fecundity of GH-deficient and GH-resistant mice can be viewed as trade-offs for extended longevity. Mechanisms responsible for delayed aging of GH-related mutants include enhanced stress resistance and xenobiotic metabolism, reduced inflammation, improved insulin signaling, and various metabolic adjustments. Pathological excess of GH reduces life expectancy in men as well as in mice, and GH resistance or deficiency provides protection from major age-related diseases, including diabetes and cancer, in both species. However, there is yet no evidence of increased longevity in GH-resistant or GH-deficient humans, possibly due to non-age-related deaths. Results obtained in GH-related mutant mice provide striking examples of mutations of a single gene delaying aging, reducing age-related disease, and extending lifespan in a mammal and providing novel experimental systems for the study of mechanisms of aging.

VCAM‐1 upregulation accompanies muscle remodeling following resistance‐type exercise in Snell dwarf (Pit1dw/dw) mice

“…This demonstrated the trade‐off between growth vs. longevity with anterior pituitary hormone deficiency (Bartke et al, 2013; Sharples et al, 2015). Such a trade‐off is consistent with reports regarding IGF‐1, a key hormone regulated by growth hormone.…”

“…The finding of a high muscle mass to body mass ratio concomitant with low muscle quality and compromised fatigue recovery for nontrained muscles of Snell dwarf mice demonstrates a distinct phenotype and that anterior pituitary hormones regulate these outcomes. The low muscle quality and fatigue recovery in the nontrained state demonstrated an instance of the trade‐off between vigor vs. longevity inherent in Snell dwarf mice (Bartke, Sun, & Longo, 2013). Following resistance‐type training, maximum static and dynamic performance of agonist GTN muscles improved by 20% for control mice although such measures were unaltered for Snell dwarf mice.…”

Growth hormone modulates hypothalamic inflammation in long‐lived pituitary dwarf mice

“…Food consumption, O2 utilization, when adjusted for body mass, is higher in dwarf and GHR −/− mice, and these mice also have higher adiposity (Meyer et al ., 2004; Bonkowski et al ., 2006). It is possible that their elevations in adiponectin and leptin, or reduced body temperature, contribute to their extended longevity (Bartke et al ., 2013) and may themselves be influenced by alterations in hypothalamic status.…”

“…There is growing evidence that the first few weeks of life may be a period in which GH action can influence the course of aging and that the time window for this developmental programming of aging may be relatively short (Bartke et al ., 2013). Ames dwarf mice injected with GH between 2 and 8 weeks of age do not live longer than littermate control mice (Panici et al ., 2010), suggesting that the extended lifespan of Ames dwarf mice depends upon lower availability of GH during the first few weeks of life, rather than on the level of GH action after the 8th week of life.…”

Impacts of metformin and aspirin on life history features and longevity of crickets: trade-offs versus cost-free life extension?

“…This is consistent with a general trade-off between production (growth and reproduction) versus stress resistance (Rollo 2010(Rollo , 2012. This may be the most fundamental of life history trade-offs and the best understood at hormonal, cellular, and molecular levels (see Rollo 2010Rollo , 2012Bartke et al 2013).…”