The somatotropic axis and aging: Benefits of endocrine defects

Bartke, Andrzej; List, Edward O.; Kopchick, John J.

doi:10.1016/j.ghir.2016.02.002

Cited by 47 publications

(40 citation statements)

References 79 publications

(114 reference statements)

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“…The reports of remarkably low cancer incidence and progression in the GHRKO mouse (97) as well as in LS individuals (14,102,103) coupled with human epidemiological studies reporting an increased risk for specific cancers (colorectal, thyroid) in patients with acromegaly (100,101,102,103,104,105,106,107,108,109,110,111) collectively offer an indication of the anti-cancer effects of attenuating GH-action. In GH treated patients with childhood-or adult-onset GHD, no association of GH treatment and development of primary cancer was found, based on available data (112,113).…”

Section: Cancermentioning

confidence: 99%

“…Additional factors that lead to the GHRKO mice being the longest-lived mouse in the world include the following -(i) increased stress resistance resulting from superior redox homeostasis due to upregulated expression and activity of glutaredoxin and thioredoxin detoxification systems (214,215,216,217) rather than changes in free-radical scavenging(218), (ii) reduced activity of TORC1 kinase complex (219, 220, 221), (iii) resistance to neoplastic incidence and growth(24, 97), (iv) suppressed hypothalamic inflammation(222) -an end-goal of anti-ageing drugs(223), (v) an anti-inflammatory adipokine profile, inverted liver-WAT lipid distribution and reduced senescent cell burden in WAT(62, 68, 70, 72), (vi) increased markers of mitochondrial biogenesis including higher levels of AMPK, SIRT1, and SIRT3 in heart and increased eNOS and PGC1α levels in skeletal muscle and kidney (224), (vii) detrimental effects of GH/IGF axis on very small embryonic-like stem cell pools in adult tissues (225,226) where age-related changes in DNA methylation patterns lead to increased sensitivity to circulating GH, IGF-1 and insulin with age with concomitant depletion of stem-cell pool and impaired tissue regeneration(225), (viii) resistance to diabetogenic effects of a HF diet (14), and (ix) improved insulin sensitivity(15).…”

Section: Factors For Extended Lifespan Of Ghrko Micementioning

confidence: 99%

“…Laron's seminal work with the Israeli cohort of LS patients (3,4,9,10) and Guevara's subsequent 22-year follow-up study on the Ecuadorian cohort (11,12) of LS patients along with extensive work with GHR knock-out (GHRKO) mice developed 25 years ago in our laboratory (13) have been instrumental in helping to define GH and insulin-like growth factor-1 (IGF-1) activities. Both human LS patients and GHRKO mice share several physical, metabolic, and cognitive similarities that will be described below (14,15,16,17).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Cancermentioning

confidence: 99%

Section: Factors For Extended Lifespan Of Ghrko Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…In addition to the direct effects of HGH on human metabolism, it is of utmost importance to emphasize that an association also exists between HGH activity and IGF-1 [2,4] because IGF-1 production is generally dependent on HGH in what is termed the HGH/IGF-1 somatotropic axis [10]. Thus, this aptly named HGH/IGF-1 paracrine axis constitutes a positive feedback loop for determining the level of HGH biological activity.…”

Section: Journal Of Steroids and Hormonal Sciencementioning

confidence: 99%

“…Moreover, in healthy individuals, the level of spontaneous as well as stimulated HGH secretion are significantly decreased with advanced aging [9]. However, these findings must now be re-evaluated in view of more recent findings reported by Bartke et al [10] who showed that reduced levels of HGH and insulin-like growth factor-1 (IGF-1) activity are associated with delayed or a "slower" rate of aging. Thus, a lower level of HGH was correlated with a reduction in frailty, age-related diseases and a decline in functional status, BUT most critically, in an extension of longevity.…”

mentioning

confidence: 96%

Growth Hormone: The Body Knows when to Quit

Malemud¹,

Denko²

2017

J Steroids Horm Sci

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The somatotropic axis and aging: Benefits of endocrine defects

Cited by 47 publications

References 79 publications

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

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

Growth Hormone: The Body Knows when to Quit

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