Reductions in serum IGF-1 during aging impair health span.
Reductions in serum IGF-1 during aging impair health span.
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DOI：
10.1111/acel.12188
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发表时间：
2014-06
期刊：
影响因子：
7.8
通讯作者：
Yakar S
中科院分区：
文献类型：
--
作者：
Gong Z;Kennedy O;Sun H;Wu Y;Williams GA;Klein L;Cardoso L;Matheny RW Jr;Hubbard GB;Ikeno Y;Farrar RP;Schaffler MB;Adamo ML;Muzumdar RH;Yakar S
在低等或简单的物种中，如蠕虫和苍蝇，胰岛素样生长因子（IGF）-1和胰岛素信号通路的破坏已被证明可以延长寿命。然而，在啮齿类动物中，生长激素（GH）调节血清和组织中的IGF-1水平，并可以通过/或独立于IGF-1调节寿命。先天性切除GH/IGF-1轴的啮齿动物模型显示寿命延长。然而，与血清IGF-1水平在整个生命中都很高的啮齿动物相反，在人类中，血清IGF-1在青春期达到峰值，然后在衰老期间下降。因此，GH/IGF-1轴先天性破坏的动物模型无法清楚地区分GH/IGF-1对健康的发育和年龄相关影响。为了克服这一警告，我们开发了一种可诱导的肝脏IGF-1缺陷（iLID）小鼠，允许血清IGF-1的时间控制。在一岁时肝脏IGF-1基因的缺失使iLID小鼠的血清IGF-1降低了70%，并显着损害了iLID小鼠的健康寿命。血清IGF-1的降低与iLID小鼠肝脏中GH水平的增加和基础STAT 5 B磷酸化的增加相结合。这些变化与肝脏重量增加、肝脏炎症增加、肝脏和肌肉中氧化应激增加以及肝脏肿瘤发生率增加相关。最后，尽管血清GH升高，但从1岁开始血清IGF-1水平低会损害骨骼完整性并加速骨丢失。我们的结论是，一个完整的GH/IGF-1轴是必不可少的，以保持健康的跨度和升高的GH，即使在生命的后期，与病理增加。
In lower or simple species, such as worms and flies, disruption of the insulin-like growth factor (IGF)-1 and the insulin signaling pathways has been shown to increase lifespan. In rodents, however, growth hormone (GH) regulates IGF-1 levels in serum and tissues and can modulate lifespan via/or independent of IGF-1. Rodent models, where the GH/IGF-1 axis was ablated congenitally, show increased lifespan. However, in contrast to rodents where serum IGF-1 levels are high throughout life, in humans, serum IGF-1 peaks during puberty and declines thereafter during aging. Thus, animal models with congenital disruption of the GH/IGF-1 axis are unable to clearly distinguish between developmental and age-related effects of GH/IGF-1 on health. To overcome this caveat, we developed an inducible liver IGF-1-deficient (iLID) mouse that allows temporal control of serum IGF-1. Deletion of liver Igf -1 gene at one year of age reduced serum IGF-1 by 70% and dramatically impaired health span of the iLID mice. Reductions in serum IGF-1 were coupled with increased GH levels and increased basal STAT5B phosphorylation in livers of iLID mice. These changes were associated with increased liver weight, increased liver inflammation, increased oxidative stress in liver and muscle, and increased incidence of hepatic tumors. Lastly, despite elevations in serum GH, low levels of serum IGF-1 from 1 year of age compromised skeletal integrity and accelerated bone loss. We conclude that an intact GH/IGF-1 axis is essential to maintain health span and that elevated GH, even late in life, associates with increased pathology.
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影响因子：
7.4
作者：
Page, Melissa M.;Salmon, Adam B.;Leiser, Scott F.;Robb, Ellen L.;Brown, Melanie F.;Miller, Richard A.;Stuart, Jeffrey A.
通讯作者：
Stuart, Jeffrey A.
DOI：
10.1126/science.1173635
发表时间：
2009-07-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Colman RJ;Anderson RM;Johnson SC;Kastman EK;Kosmatka KJ;Beasley TM;Allison DB;Cruzen C;Simmons HA;Kemnitz JW;Weindruch R
通讯作者：
Weindruch R
IGF1R +/-小鼠中IGF-1R信号的降低会改变衰老吗？
影响因子：
3.7
作者：
Bokov AF;Garg N;Ikeno Y;Thakur S;Musi N;DeFronzo RA;Zhang N;Erickson RC;Gelfond J;Hubbard GB;Adamo ML;Richardson A
通讯作者：
Richardson A
影响因子：
64.8
作者：
Mattison, Julie A.;Roth, George S.;Beasley, T. Mark;Tilmont, Edward M.;Handy, April M.;Herbert, Richard L.;Longo, Dan L.;Allison, David B.;Young, Jennifer E.;Bryant, Mark;Barnard, Dennis;Ward, Walter F.;Qi, Wenbo;Ingram, Donald K.;de Cabo, Rafael
通讯作者：
de Cabo, Rafael
影响因子：
3.7
作者：
Courtland HW;Elis S;Wu Y;Sun H;Rosen CJ;Jepsen KJ;Yakar S
通讯作者：
Yakar S