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, reduced adipose tissue, 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.
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Acknowledgments
Work described in this article was supported by NIH P01AG031736 and R01AG019899. We thank Dr. O. Arum, A. Spong, and other members of our laboratory who were importantly involved in various stages of this research and we apologize to those whose work pertinent to the discussed issues we have failed to mention or cite.
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Bartke, A. Healthspan and longevity can be extended by suppression of growth hormone signaling. Mamm Genome 27, 289–299 (2016). https://doi.org/10.1007/s00335-016-9621-3
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DOI: https://doi.org/10.1007/s00335-016-9621-3