Local expression of GH and IGF-1 in the hippocampus of GH-deficient long-lived mice

Sun, Liou Y.; Al-Regaiey, Khalid; Masternak, Michał M.; Wang, Jian; Bartke, Andrzej

doi:10.1016/j.neurobiolaging.2004.07.010

Cited by 153 publications

(123 citation statements)

References 58 publications

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“…liver and kidney) while preserving it elsewhere, including the brain and the heart [71,72]. Differences between the phenotypes of 'GH-related' and 'IGF-1-related' mutants may also stem from the fact that they are based on comparisons of the effects of complete blockade of GH signals and partial suppression of IGF-1 levels and actions.…”

Section: Discussion and Relevance To Other Mammalian Speciesmentioning

confidence: 99%

Single-gene mutations and healthy ageing in mammals

Bartke

2011

Phil. Trans. R. Soc. B

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103

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Studies of the effects of single-gene mutations on longevity in Caenorhabditis elegans, Drosophila melanogaster and Mus musculus identified homologous, highly conserved signalling pathways that influence ageing. In each of these very distantly related species, single mutations which lead—directly or indirectly—to reduced insulin, insulin-like growth factor (IGF) or insulin/IGF-like signalling (IIS) can produce significant increases in both average and maximal lifespan. In mice, most of the life-extending mutations described to date reduce somatotropic (growth hormone (GH) and IGF-1) signalling. The reported extensions of longevity are most robust in GH-deficient and GH-resistant mice, while suppression of somatotropic signalling ‘downstream’ of the GH receptor produces effects that are generally smaller and often limited to female animals. This could be due to GH influencing ageing by both IGF-1-mediated and IGF-1-independent mechanisms. In mutants that have been examined in some detail, increased longevity is associated with various indices of delayed ageing and extended ‘healthspan’. The mechanisms that probably underlie the extension of both lifespan and healthspan of these animals include increased stress resistance, improved antioxidant defences, alterations in insulin signalling (e.g. hypoinsulinaemia combined with improved insulin sensitivity in some mutants and insulin resistance in others), a shift from pro- to anti-inflammatory profile of circulating adipokines, reduced mammalian target of rapamycin-mediated translation and altered mitochondrial function including greater utilization of lipids when compared with carbohydrates.

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Section: Discussion and Relevance To Other Mammalian Speciesmentioning

confidence: 99%

Single-gene mutations and healthy ageing in mammals

Bartke

2011

Phil. Trans. R. Soc. B

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103

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“…A previous study which used an independently derived line of GHR (−/−) mutant mice showed that hepatic and kidney IGF1 RNA levels were decreased without changes in IGF1 expression in other organs including the heart (40). The levels of IGF1 RNA in the hippocampus of Ames dwarf mice do not differ from the levels measured in normal siblings, although Ames dwarf mice are characterized by suppressed hepatic IGF1 expression and circulating IGF1 levels (41). However, the cardiac expression of IGF1 in young KO mice was decreased in comparison to their normal siblings, which is closer to the findings in the skeletal muscle (7).…”

Section: Insulin-like Growth Factor-1 and Insulin-like Growth Factor-mentioning

confidence: 93%

Caloric restriction and growth hormone receptor knockout: Effects on expression of genes involved in insulin action in the heart

Masternak¹,

Al-Regaiey²,

Lim³

et al. 2006

Experimental Gerontology

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Blockade of growth hormone (GH), decreased insulin-like growth factor-1 (IGF1) action and increased insulin sensitivity are associated with life extension and an apparent slowing of the aging process. We examined expression of genes involved in insulin action, IR, IRS1, IRS2, IGF1, IGF1R, GLUT4, PPARs and RXRs in the hearts of normal and GHR−/− (KO) mice fed ad libitum or subjected to 30% caloric restriction (CR). CR increased the cardiac expression of IR, IRS1, IGF1, IGF1R and GLUT4 in normal mice and IRS1, GLUT4, PPARα and PPARβ/δ in GHR-KO animals. Expression of IR, IRS1, IRS2, IGF1, GLUT4, PPARγ and PPARα did not differ between GHR-KO and normal mice. These unexpected results suggest that CR may lead to major modifications of insulin action in the heart, but high insulin sensitivity of GHR-KO mice is not associated with alterations in the levels of most of the examined molecules related to intracellular insulin signaling.

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“…IGF1 is mostly secreted into the blood by the liver where its synthesis is regulated by the pituitary growth hormone (GH). However, many other tissues, including the brain, are also able to synthesize IGF1 locally where it is not under the control of GH [26,100,144]. The proof that brain IGF1 is not under the control of circulating GH comes essentially from Ghr −/− and Ames dwarf (Prop 1 df ) mice.…”

Section: Insulin/igf1 Receptors: a Signaling Pathway For The Generalmentioning

confidence: 99%

Aging of the brain, neurotrophin signaling, and Alzheimer's disease: Is IGF1-R the common culprit?

Puglielli¹

2008

Neurobiology of Aging

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The last decade has revealed that the lifespan of an organism can be modulated by the signaling pathway that acts downstream of the insulin/insulin-like growth factor 1 receptors (IR/IGF1-R), indicating that there is a "program" that drives the process of aging. New results have now linked the same pathway to the neurogenic capacities of the aging brain, to neurotrophin signaling, and to the molecular pathogenesis of Alzheimer's disease. Therefore, a common signaling cascade now seems to link aging to age-associated pathologies of the brain, suggesting that pharmacologic approaches aimed at the modulation of this pathway can serve to delay the onset of age-associated disorders and improve the quality of life. Work from a wide range of fields performed with different approaches has already identified some of the signaling molecules that act downstream of IGF1-R, and has revealed that a delicate checkpoint exists to balance excessive growth/"immortality" and reduced growth/"senescence" of a cell. Future research will determine how far the connection goes and how much of it we can influence.

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Local expression of GH and IGF-1 in the hippocampus of GH-deficient long-lived mice

Cited by 153 publications

References 58 publications

Single-gene mutations and healthy ageing in mammals

Single-gene mutations and healthy ageing in mammals

Caloric restriction and growth hormone receptor knockout: Effects on expression of genes involved in insulin action in the heart

Aging of the brain, neurotrophin signaling, and Alzheimer's disease: Is IGF1-R the common culprit?

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