A preview of this full-text is provided by Springer Nature.
Content available from Reviews in Endocrine and Metabolic Disorders
This content is subject to copyright. Terms and conditions apply.
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 “little”mice 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.