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Growth hormone and aging

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Growth hormone (GH) actions impact growth, metabolism, and body composition and have been associated with aging and longevity. Lack of GH results in slower growth, delayed maturation, and reduced body size and can lead to delayed aging, increased healthspan, and a remarkable extension of longevity. Adult body size, which is a GH-dependent trait, has a negative association with longevity in several mammalian species. Mechanistic links between GH and aging include evolutionarily conserved insulin/insulin-like growth factors and mechanistic target of rapamycin signaling pathways in accordance with long-suspected trade-offs between anabolic/growth processes and longevity. Height and the rate and regulation of GH secretion have been related to human aging, but longevity is not extended in humans with syndromes of GH deficiency or resistance. However, the risk of age-related chronic disease is reduced in individuals affected by these syndromes and various indices of increased healthspan have been reported.
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Growth hormone and aging
Andrzej Bartke
1
Accepted: 11 September 2020
#Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract
Growth hormone (GH) actions impact growth, metabolism, and body composition and have been associated with aging and
longevity. Lack of GH results in slower growth, delayed maturation, and reduced body size and can lead to delayed aging,
increased healthspan, and a remarkable extension of longevity. Adult body size, which is a GH-dependent trait, has a negative
association with longevity in several mammalian species. Mechanistic links between GH and aging include evolutionarily
conserved insulin/insulin-like growth factors and mechanistic target of rapamycin signaling pathways in accordance with
long-suspected trade-offs between anabolic/growth processes and longevity. Height and the rate and regulation of GH secretion
have been related to human aging, but longevity is not extended in humans with syndromes of GH deficiency or resistance.
However, the risk of age-related chronic disease is reduced in individuals affected by these syndromes and various indices of
increased healthspan have been reported.
Keywords GH excess .GH resistance .Growth hormone .Human aging .Lifespan .Healthspan .Mice
1 Introduction
There is considerable evidence that actions of pituitary growth
hormone (GH) have an important impact on the process of
aging in mammals. However, there are quantitative differ-
ences in this role of GH in different species. In this article,
we will review the effects of GH on aging in laboratory pop-
ulations of mice (Mus musculus), the mechanisms believed to
link GH signaling to aging and longevity in this species, and
the relationship of GH and GH-dependent traits to age-related
disease, healthspan and lifespan in other mammalian species,
including humans. We will close with a discussion of trade-
offs between growth, reproduction, and aging. We will high-
light the remarkable evolutionary conservation of signaling
mechanisms that underlie these trade-offs and determine the
trajectoryof aging in organisms ranging from unicellular yeast
and simple microscopic worms to insects and vertebrates.
2 GH signaling impacts aging in
laboratory mice
Long survival of mice with hereditary dwarfism was described
almost 50 years ago in a study of age-related osteoarthritis [1].
Studies conducted in the 90s provided evidence that two
types of dwarf mice with deficiency of GH, prolactin, and
thyroid-stimulating hormone (TSH) live much longer than
their normal siblings [2,3]. Altered endocrine function in
these mutants is due to the loss of function of the Pituitary-1
(Pit-1) or Prophet of Pit-1 (Prop1) transcription factors and the
resulting defects in the differentiation of the corresponding
cell lineages in the anterior pituitary [4,5]. Extended longevity
of Ames dwarf (Prop1
df
) mice was believed to be due primar-
ily to GH deficiency [2] and this interpretation is now sup-
ported by considerable evidence. Flurkey and his colleagues
reported that littlemice with isolated GH deficiency due to
mutation of a gene encoding for the GH releasing hormone
(GHRH) receptor are also long-lived [3], although extension
of longevity in these mutants was relatively modest and diet-
dependent. In 2000, Coschigano et al. [6] reported major ex-
tension of longevity in GH-resistant mice produced in the
Kopchick laboratory by disruption of the GH receptor
(GHR) gene [7]. Further work of Coschigano and her
*Andrzej Bartke
abartke@siumed.edu
1
Southern Illinois University School of Medicine, 801 N. Rutledge,
P.O. Box 19628, Springfield, IL 62794-9628, USA
https://doi.org/10.1007/s11154-020-09593-2
/ Published online: 1 October 2020
Reviews in Endocrine and Metabolic Disorders (2021) 22:71–80
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... While circulating GH declines with age (Bartke, 2017(Bartke, , 2020Bartke et al., 2016;Colon et al., 2019;Masternak & Bartke, 2012), local nonpituitary GH (npGH) is induced with aging in colon tissue (Chesnokova et al., 2021) and in senescent cells (Chesnokova et al., 2013). Aging, associated with telomere shortening and increased DNA damage, leads to senescence, which also occurs in response to genotoxic stressors, followed by depletion of viable functioning cells (McHugh & Gil, 2018;Sharpless & Sherr, 2015). ...
... In light of the increased murine lifespan associated with GH deficiency (Bartke, 2020;Colon et al., 2019;Young et al., 2021) as well as the observed cancer absence in patients harboring a GHR mutation that disrupts GH signaling (Guevara-Aguirre et al., 2011; ...
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... When white adipose was transplanted from HFD-fed Ames dwarf mice to HFD-fed WT mice, improvements in insulin sensitivity and reduced IL-6 levels were reported in the WT mice (Hill et al., 2016). The enhanced lifespan of our GHRH-KO mice through high-fat feeding is consistent with these reports as reduced inflammation and enhanced insulin sensitivity have been associated with increased lifespan (Bartke, 2021;Marín-Aguilar et al., 2020;Spadaro et al., 2016). ...
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... GHRH/IGF1 axis plays key roles in regulating growth, metabolism, and aging. GHRH stimulates the release of growth hormone (GH), which in turn stimulates hepatic IGF-1 expression [67]. Growth hormone (GH) secretion declines with aging, but the aging pituitary remains responsive to GH-releasing hormone (GHRH) [68]. ...
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... These findings reinforce the idea that decreases in GH secretion contribute to a slower/delayed aging process. Accordingly, GH is usually negatively associated with longevity [47] and maintenance of cognitive function with age [48,49] (Fig. 1). The attenuated neuroinflammation seen in animals with GH deficiency can improve cognitive function, possibly via increased insulin sensitivity, which is also strongly associated with longevity. ...
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... Genetically modified mice with changes in GH signaling have been used to assess the interaction of the somatotrophic system with aging, including the brain. Most of these studies show that impairing GH signaling results in delayed aging, including of the brain, with increased lifespan and healthspan, i.e., the period of life free from important morbidities (16). Accordingly, GH deficient GHRH knockout mice show cognitive decline markedly later than control animals (17). ...
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... Studies have shown that alterations in insulin and insulin-like growth factor 1 (IGF-1) signaling can affect healthspan and lifespan in a large number of organisms ranging from worms to humans (Min and Tatar, 2018; Aguiar-Oliveira and Bartke, 2019;Bartke, 2021;Bartke, 2022). The lifespan extending effects in mammals are believed to occur through the actions of growth hormone (GH) signaling through the somatotropic axis. ...
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