Healthspan and longevity can be extended by suppression of growth hormone signaling

Abstract

Average and maximal lifespan are important biological characteristics of every species, but can be modified by mutations and by a variety of genetic, dietary, environmental, and pharmacological interventions. Mutations or disruption of genes required for biosynthesis or action of growth hormone (GH) produce remarkable extension of longevity in laboratory mice. Importantly, the long-lived GH-related mutants exhibit many symptoms of delayed and/or slower aging, including preservation of physical and cognitive functions and resistance to stress and age-related disease. These characteristics could be collectively described as “healthy aging” or extension of the healthspan. Extension of both the healthspan and lifespan in GH-deficient and GH-resistant mice appears to be due to multiple interrelated mechanisms. Some of these mechanisms have been linked to healthy aging and genetic predisposition to extended longevity in humans. Enhanced insulin sensitivity combined with reduced insulin levels, cell senescence in the adipose tissue and central nervous system inflammation, and increased levels of adiponectin represent such mechanisms. Further progress in elucidation of mechanisms that link reduced GH action to delayed and healthy aging should identify targets for lifestyle and pharmacological interventions that could benefit individuals as well as society.

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

“…In mice and men, the somatotropic axis occupy a central position in the study of ageing, health-span, and longevity (195,196,197,198,199,200,201). GHD mouse models have consistently shown an extended lifespan, while the results are inconsistent in GHD humans (200,202,203).…”

“…This marked protection from cancer was also consistent in the Israeli cohort of LS patients (99) and, therefore, display one of the most prominent factors underlying lifespan extension due to GHR deficiency in humans (227). For now, a conclusive answer to the question whether the link between GHR dysfunction and extended longevity observed in GHRKO mice holds in GH resistant humans (198,201) remains unknown.…”

Somatic growth, aging, and longevity

“…These include pleiotropic actions of GH which affect both body size and aging, acting through different, but likely physiologically related mechanisms. Growth hormone is a key regulator of hepatic IGF-1 expression, circulating IGF-1 levels, growth and adult body size, but it also appears to promote aging by a variety of actions such as inducing insulin resistance 35 , 42 promoting cell senescence 74 and chronic low grade inflammation, 75 , 76 as well as favoring differentiation and depletion of at least one type of stem cell. 77 Thus, the spectrum of known biological actions of GH could explain why growth and adult body size would tend to be negatively associated with longevity.…”

Comparing the Behavioural Effects of Exogenous Growth Hormone and Melatonin in Young and Old Wistar Rats

“…As Bartke (2016) [139] recently affirmed, the extension of healthspan and longevity depend on suppressing the GH signaling. However, it is evident that old subjects have in fact reached longevity.…”