Life Span Extension by Reduction in Growth Hormone-Insulin-Like Growth Factor-1 Axis in a Transgenic Rat Model

Shimokawa, Isao; Higami, Yoshikazu; Utsuyama, Masanori; Tuchiya, Tomoshi; Komatsu, Toshimitsu; Chiba, Takuya; Yamaza, Haruyoshi

doi:10.1016/s0002-9440(10)61173-x

Cited by 101 publications

(78 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because insulin levels were decreased in IF mice to levels even lower than in LDF mice, these two DR regimens reveal a dissociation in the mechanisms regulating IGF-1 and insulin levels. Transgenic rats with reduced levels of GH exhibit a transgene dose-dependent reduction in levels of IGF-1; rats with a moderate reduction in IGF-1 levels live longer, whereas those with a greater decrease in IGF-1 levels have a reduced life span (20). The latter results suggest that there is an optimal level of the GH-IGF-1 axis to maximize survival in mammals.…”

Section: Resultsmentioning

confidence: 94%

Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

Anson

Guo

Cabo

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

607

525

View full text Add to dashboard Cite

Dietary restriction has been shown to have several health benefits including increased insulin sensitivity, stress resistance, reduced morbidity, and increased life span. The mechanism remains unknown, but the need for a long-term reduction in caloric intake to achieve these benefits has been assumed. We report that when C57BL͞6 mice are maintained on an intermittent fasting (alternateday fasting) dietary-restriction regimen their overall food intake is not decreased and their body weight is maintained. Nevertheless, intermittent fasting resulted in beneficial effects that met or exceeded those of caloric restriction including reduced serum glucose and insulin levels and increased resistance of neurons in the brain to excitotoxic stress. Intermittent fasting therefore has beneficial effects on glucose regulation and neuronal resistance to injury in these mice that are independent of caloric intake.caloric restriction ͉ hippocampus ͉ insulin ͉ ␤-hydroxybutyrate ͉ ketosis

show abstract

Section: Resultsmentioning

confidence: 94%

Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

Anson

Guo

Cabo

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

607

525

View full text Add to dashboard Cite

show abstract

“…For example, IGF-1 has been shown to extend the in vitro replicative lifespan of satellite cells by modulating cell cycle regulatory molecules (Chakravarthy et al 2000), whereas repression of insulin/IGF-1 signalling by the deletion of the growth hormone receptor (Shimokawa et al 2002(Shimokawa et al , 2003 or IGF-1R (Holzenberger et al 2003, Holzenberger 2004 leads to an increased lifespan in vivo. The fact that IGFBPs can modulate the activity of IGF-1 adds further support to the idea that they play an important role in the ageing process.…”

Section: Igfbp5 and Senescencementioning

confidence: 99%

Epithelial injury induces an innate repair mechanism linked to cellular senescence and fibrosis involving IGF-binding protein-5

Allan¹,

Beattie²,

Flint³

2008

Journal of Endocrinology

View full text Add to dashboard Cite

Fibrosis is associated with epithelial repair. It involves the activation of fibroblasts, increased production of extracellular matrix proteins and transdifferentiation to contractile, myofibroblasts that aid in wound contraction. This provisional matrix plugs the injured epithelium and provides a scaffold for epithelial cell migration, involving an epithelial-mesenchymal transition (EMT). When epithelial injury involves blood loss, this leads to platelet activation, the production of several growth factors and an acute inflammatory response. Under normal circumstances, the epithelial barrier is repaired and the inflammatory response resolves. However, in fibrotic disease, the fibroblast response continues, resulting in unresolved wound healing. The fibrotic diseases range from scleroderma, where the problem may be restricted to the skin and where it is not life-threatening, through to systemic forms that can manifest as, for example, idiopathic pulmonary fibrosis, in which death is inevitable within 3-5 years. Anti-inflammatory treatments have failed to ameliorate the disease condition and focus has instead turned to transforming growth factor-b1 (TGFB1), since it induces many of the processes involved, including fibroblast activation and EMT. Most recently, however, a new player in this process has been described, IGF-binding protein-5 (IGFBP5). IGFBP5 has also been shown to induce similar effects to TGFB1, but, in addition, it is strongly implicated in the process of senescence which is now believed to be a significant factor in these diseases. We examine the evidence for this role of IGFBP5 and identify some of the therapeutic targets which might be used to ameliorate these diseases of unknown cause.

show abstract

“…Renal involvement was graded from 0-3 as determined by interstitial fibrosis and nephropathy. The severity of nephropathy was scored using the method of Maeda and colleagues with some modifications (14,15).…”

Section: Methodsmentioning

confidence: 99%

Fibrotic response to angiotensin II is blunted in the kidney, but not in the heart, in insulin-sensitive long-lived transgenic dwarf rats

Sato

Ashizawa²,

Ohtsuru³

et al. 2007

Int J Mol Med

Self Cite

View full text Add to dashboard Cite

Abstract. Insulin resistance is a characteristic feature of cardiovascular and renal diseases, and angiotensin II (Ang II) has been suggested to induce insulin resistance. The aims of this study were to elucidate the effect of chronic Ang II infusion on vascular reactivity and organ damage in insulinsensitive rats. We confirmed the following three points. First, there was no significant difference in pressor response to chronic Ang II infusion (600 ng/kg/min) between insulinsensitive transgenic rats (Tg) and control rats (C). Second, there was no significant difference in cardiac hypertrophy and fibrosis by chronic Ang II infusion between the two groups. However, third, fibrotic response to chronic Ang II infusion evaluated by histopathological scoring in the kidney was significantly decreased in insulin-sensitive transgenic rats (renal fibrosis and nephropathy score: C+Ang II vs Tg+Ang II; 2.5 vs 1.3; p<0.05). Furthermore, the expression of TGF-ß, a fibrosis indicator, was also significantly suppressed in the kidneys of the transgenic rats (TGF-ß1/ GAPDH ratio: C+Ang II vs Tg+Ang II; 1.15 vs 0.81; p<0.05). This result indicates that the growth hormone/insulin-like growth factor-1 axis is critically involved in the development of renal injury and fibrosis, rather than hypertension, cardiac hypertrophy, and cardiac fibrosis induced by chronic Ang II administration.

show abstract

Life Span Extension by Reduction in Growth Hormone-Insulin-Like Growth Factor-1 Axis in a Transgenic Rat Model

Cited by 101 publications

References 19 publications

Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

Epithelial injury induces an innate repair mechanism linked to cellular senescence and fibrosis involving IGF-binding protein-5

Fibrotic response to angiotensin II is blunted in the kidney, but not in the heart, in insulin-sensitive long-lived transgenic dwarf rats

Contact Info

Product

Resources

About