Caloric Restriction Results in Decreased Expression of Peroxisome Proliferator-Activated Receptor Superfamily in Muscle of Normal and Long-Lived Growth Hormone Receptor/Binding Protein Knockout Mice

Masternak, Michał M.; Al-Regaiey, Khalid; Lim, Marc Michael Del Rosario; Bonkowski, Michael S.; Panici, Jacob A.; Przybylski, Grzegorz K.; Bartke, Andrzej

doi:10.1093/gerona/60.10.1238

Cited by 65 publications

(62 citation statements)

References 25 publications

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“…(N-AL 4.2±0.7, N-CR 1.4±0.2, KO-AL 0.9±0.1, and KO-CR 0.4±0.1, ng/ml) (35). The genotype (KO vs. N) and CR-induced increase in insulin sensitivity suggested by these findings was supported by the results of homeostasis model analysis (HOMA) (6). Studies in worms, flies and mice (including GHR-KO, Ames dwarfs and Snell dwarfs), as well as widely examined effects of CR in various animal species, strongly indicate insulin signaling as an important pathway in the control of aging (5).…”

Section: Discussionmentioning

confidence: 54%

“…However, these data clearly indicate that cardiac muscle responds differently than skeletal muscle with respect to this gene. In the skeletal muscle, both CR and GHR knockout caused down regulation of PPARγ gene expression (6). Concerning the possible cardio-protective effects of PPARγ agonists, decreased level of this nuclear receptor in aged hGH transgenic animals together with a trend for PPARγ RNA to be higher in old N-CR and KO-CR mice in comparison to their AL controls may imply anti-aging protection in the hearts of CR animals.…”

Section: Peroxisome Proliferator-activated Receptor γmentioning

confidence: 96%

“…The mRNA relative expression was analyzed by real-time PCR (RT-PCR) using the "Smart Cycler" instrument (Cepheid, Sunnyvale, CA) with iQ™ SYBR Green Supermix (BIO-RAD) (6,7). The three steps of the RT-PCR included denaturation at 94°C for 2 min, annealing at 62°C for 30 sec with fluorescence reading, and extension at 72°C for 30 sec.…”

Section: Real-time Pcrmentioning

confidence: 99%

“…Results obtained in animals subjected to CR and in various long-lived mutants suggest that perturbations in the insulin signaling pathway may play a key role in extended longevity (5). We have recently described the effects of long-term 30% CR on the expression of genes related to insulin and IGF1 signaling in the liver and skeletal muscle of these animals (6)(7)(8). Effects of insulin on protein metabolism in skeletal muscle and the liver are believed to be important in regulating the substrate availability for the heart (9).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 54%

Section: Peroxisome Proliferator-activated Receptor γmentioning

confidence: 96%

Section: Real-time Pcrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…All data presented used B2M as a housekeeping gene, while Actin was used as a second housekeeping gene for confirmation of results. Relative expression was calculated as previously described (Masternak et al 2005).…”

Section: Rt-pcrmentioning

confidence: 99%

Differential effects of early-life nutrient restriction in long-lived GHR-KO and normal mice

et al. 2017

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There is increasing evidence that growth hormone (GH) and insulin-like growth factor 1 (IGF-1) signaling (collectively referred to as somatotropic signaling) during development has a profound influence on aging and longevity. Moreover, the absence of GH action was shown to modify responses of adult mice to calorie restriction (CR) and other antiaging interventions. It was therefore of interest to determine whether GH resistance in GH receptor knockout (GHR-KO) mice would modify the effects of mild pre-weaning CR imposed by increasing the number of pups in a litter (the so-called litter crowding). In addition to the expected impact on body weight, litter crowding affected glucose homeostasis, hepatic expression of IGF-1 and genes related to lipid metabolism, and expression of inflammatory markers in white adipose tissue, with some of these effects persisting until the age of 2 years.Litter crowding failed to further extend the remarkable longevity of GHR-KO mice and, instead, reduced late life survival of GHR-KO females, an effect opposite to the changes detected in normal animals. We conclude that the absence of GH actions alters the responses to pre-weaning CR and prevents this intervention from extending longevity.

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Mouse models of growth hormone action and aging: A proteomic perspective

2012

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Growth hormone (GH) is a protein secreted by the anterior pituitary and circulates throughout the body to exert important actions on growth and metabolism. GH stimulates the secretion of insulin-like growth factor-I (IGF-I) which mediates some of the growth promoting actions of GH. The GH/IGF-I axis has recently been recognized as important in terms of longevity in organisms ranging from C. elegans to mice. For example, GH transgenic mice possess short lifespans while GH receptor null (GHR−/−) mice have extended longevity. Thus, the actions of GH (or IGF-I) or lack thereof impacts the aging process. In this review, we summarize the proteomic analyses of plasma and white adipose tissue in these two mouse models of GH action, i.e., GH transgenic and GHR−/− mice. At the protein level, we wanted to establish novel plasma biomarkers of GH action as a function of age and to determine differences in adipose tissue depots. We have shown that these proteomic approaches have not only confirmed several known physiological actions of GH, but also resulted in novel protein biomarkers and targets that may be indicative of the aging process and/or new functions of GH. These results may generate new directions for GH and/or aging research.

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Caloric Restriction Results in Decreased Expression of Peroxisome Proliferator-Activated Receptor Superfamily in Muscle of Normal and Long-Lived Growth Hormone Receptor/Binding Protein Knockout Mice

Cited by 65 publications

References 25 publications

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

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

Differential effects of early-life nutrient restriction in long-lived GHR-KO and normal mice

Mouse models of growth hormone action and aging: A proteomic perspective

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