The somatotropic axis and longevity in mice

Brown‐Borg, Holly M.

doi:10.1152/ajpendo.00262.2015

Cited by 66 publications

(64 citation statements)

References 124 publications

(104 reference statements)

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“…IGF-1, acting as a classic anabolic hormone and growth factor, has the capacity to influence cellular growth and tissue organization during development and regulate normal cellular and tissue function in adults. There are three mouse models of GH/IGF-1 deficiency that have consistently shown increased lifespan across multiple studies: Ames (prop1 mutation), Snell (pit1 mutation), and ghr knockout mice (as reviewed by Brown-Borg (2015) and Ladiges et al (2009)). Each of these models demonstrates a profound reduction in GH and/or IGF-1 initiated early during development.…”

Section: Discussionmentioning

confidence: 99%

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan

et al. 2017

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Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging mechanism that contributes to increased lifespan in diverse experimental models. However, IGF-1 has also been shown to be essential for normal development and the maintenance of tissue function late into the lifespan. These disparate findings suggest that IGF-1 may be a pleiotropic modulator of health and aging, as reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental for another. We postulated that the effects of IGF-1 on tissue health and function in advanced age are dependent on the tissue, the sex of the animal, and the age at which IGF-1 is manipulated. In this study, we examined how alterations in IGF-1 levels at multiple stages of development and aging influence overall lifespan, healthspan, and pathology. Specifically, we investigated the effects of perinatal, post-pubertal, and late-adult onset IGF-1 deficiency using genetic and viral approaches in both male and female igf f/f C57Bl/6 mice. Our results support the concept that IGF-1 levels early during lifespan establish the conditions necessary for subsequent healthspan and pathological changes that contribute to aging. Nevertheless, these changes are specific for each sex and tissue. Importantly, late-life IGF-1 deficiency (a time point relevant for human studies) reduces cancer risk but does not increase lifespan. Overall, our results indicate that the levels of IGF-1 during development influence late-life pathology, suggesting that IGF-1 is a developmental driver of healthspan, pathology, and lifespan.

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Section: Discussionmentioning

confidence: 99%

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan

et al. 2017

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“…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).…”

Section: Ageing and Longevitymentioning

confidence: 99%

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

Basu

Qian

Kopchick

2018

European Journal of Endocrinology

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Growth hormone (GH) is produced primarily by anterior pituitary somatotroph cells. Numerous acute human (h) GH treatment and long-term follow-up studies and extensive use of animal models of GH action have shaped the body of GH research over the past 40-50 years. Work on the GH receptor (R) knock-out (GHRKO) mice and results of studies on GH resistant Laron Syndrome (LS) patients have helped define many physiological actions of GH including those dealing with metabolism, obesity, cancer, diabetes, cognition, and aging/longevity. In this review, we have discussed several issues dealing with these biological effects of GH and attempt to answer the question of whether decreased GH action may be beneficial.

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“…These include improved anti-oxidant defense mechanisms, stress resistance, reduced chronic low-grade inflammation in the adipose tissue and in the central nervous system, reduced mTOR signaling, reduced cell senescence and improved maintenance of stem cells and multiple metabolic adjustments [25,26]. Among the metabolic alterations in these mutants, enhanced insulin sensitivity (combined with reduced insulin levels) [25–27] increased thermogenesis and oxygen consumption [19,28] and increased reliance on fatty acids as metabolic fuel [28] attracted our particular attention as potential anti-aging mechanisms.…”

Section: Growth Hormone and Agingmentioning

confidence: 99%

Growth hormone actions during development influence adult phenotype and longevity

Bartke

Sun

Fang

et al. 2016

Experimental Gerontology

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There is considerable evidence that exposure to undernutrition, overnutrition, stress or endocrine disruptors during fetal development can increase the probability of obesity, hypertension, cardiovascular disease and other problems in adult life. In contrast to these findings, reducing early postnatal growth by altering maternal diet or number of pups in a litter can increase longevity. In hypopituitary Ames dwarf mice, which are remarkably long lived, a brief period of growth hormone therapy starting at 1 or 2 weeks of age reduces longevity and normalizes (“rescues”) multiple aging-related traits. Collectively, these findings indicate that nutritional and hormonal signals during development can have profound impact on the trajectory of aging. We suspect that altered “programming” of aging during development may represent one of the mechanisms of the Developmental Origins of Health and Disease (DOHaD) and the detrimental effects of “catch-up” growth.

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The somatotropic axis and longevity in mice

Abstract: Brown-Borg HM. The somatotropic axis and longevity in mice.

Cited by 66 publications

References 124 publications

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan

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

Growth hormone actions during development influence adult phenotype and longevity

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