Growth Hormone and Aging: New Findings

Abstract

Complex relationships between growth hormone (GH) signaling and mammalian aging continue to attract attention of many investigators. Recent results include evidence that the impact of GH on genome maintenance (DNA damage and repair) is drastically different in normal as compared to cancer cells, consistent with GH promoting aging and cancer progression. Impact of GH on DNA methylation was studied as a possible mechanism linking actions of GH during early life to the trajectory of aging. Animals with reduced or enhanced GH signaling and novel animals with adipocyte-specific deletion of GH receptors were used to elucidate the effects of GH on white and brown adipose tissue, including the impact of this hormone on lipolysis, fibrosis, and thermogenesis. Effects of GH on adipose tissue related to lipid and energy metabolism emerge as mechanistic links between GH, healthspan, and lifespan. Treatment of healthy men with a combination of GH, dehydroepiandrosterone, and metformin was reported to restore thymus function and reduce epigenetic age. Studies of human subjects with deficiency of GH or GH receptors and studies of mice with the same endocrine syndromes identified several phenotypic changes related (positively or negatively) to the previously reported predisposition to healthy aging. Results of these and other recent studies advance present understanding of the mechanisms by which GH influences aging and longevity and of the trade-offs involved.

Cap‐independent translation of GPLD1 enhances markers of brain health in long‐lived mutant and drug‐treated mice

“…Similar data for the Snell dwarf pituitary mutant (Flurkey et al, 2001 ) and GH receptor knock‐out (GHRKO) mice (Zhou et al, 1997 ) suggested that healthy longevity was often increased in mice with deficits in GH production or response, which also had lower levels of insulin‐like growth factor 1 (IGF‐1), produced by liver in response to GH signals. Additional lifespan experiments in Ghrhr‐deficient (Flurkey et al, 2001 ; Sun et al, 2013 ) and Ghrh‐deficient mice (Bartke et al, 2021 ; Icyuz et al, 2020 ) were consistent with this idea. Increased longevity in mice with mutations in Pappa (Bale & Conover, 2005 ), an enzyme that can increase IGF‐1 action by cleavage of IGF‐1 binding proteins, implied that modulation of local IGF‐1 levels could be involved in the anti‐aging effects of GH and GHR mutants.…”

Aging under endocrine hormone regulation

“…GH has a regulatory role in terms of endocrine aspects for healthy longevity, metabolism associated with aging, and so on; thus, we explore future hormonal treatments for human aging. Fahy et al reported that treating people with GH in combination with dehydroepiandrosterone (a product of the adrenal cortex that serves as a precursor for sex hormone biosynthesis) and metformin (used to counteract the glucose-raising effects of GH) in healthy men aged 51-65 years induces protective immune changes and reduces epigenetic age to a rejuvenating level (28). GH has the potential to exert pro-and anti-aging effects at different stages of life.…”

Early Life Interventions Can Shape Aging

“…However, other actions of GH also could have been involved in partially rescuing (that is shortening) their longevity. Growth hormone has well documented effects on insulin signaling (44), immune function (45), stress resistance (46,47), and DNA repair (25), and each of these factors has important role in the regulation of aging and longevity (48). Our recent findings concerning histone modifications in Ames dwarf mice treated with GH (49) suggest that epigenetic mechanisms might have been involved in mediating the effects of this early life intervention on adult characteristics and longevity.…”