Life-span Extension With Reduced Somatotrophic Signaling: Moderation of Aging Effect by Signal Type, Sex, and Experimental Cohort.
Life-span Extension With Reduced Somatotrophic Signaling: Moderation of Aging Effect by Signal Type, Sex, and Experimental Cohort.
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DOI：
10.1093/gerona/glx010
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发表时间：
2017-11-09
期刊：
影响因子：
--
通讯作者：
Simons MJP
中科院分区：
文献类型：
--
作者：
Garratt M;Nakagawa S;Simons MJP
生长激素(GH)和胰岛素样生长因子(IGF1)途径的生长激素信号减少可以延缓衰老，尽管延长寿命的程度在不同的研究中明显不同。通过整理先前研究的数据并使用荟萃分析，我们检验了性别、激素操作、体重变化和控制基线死亡率等因素是否可以定量预测相对寿命的延长。与IGF1的操作(包括IGF1的产生、接收和生物活性)相比，GH信号的操作(包括垂体和直接的GH缺陷)在中位寿命方面产生了显著的延长，从而使突变小鼠的死亡风险发生了一致的转变。胰岛素受体底物(IRS)的表达减少会产生与GH减少更相似的寿命延长，尽管影响更异质性，似乎对死亡率的人口学影响不同。减少IGF1信号的延长寿命，但GH和IRS信号都不减少，在女性和对照生存时间较短的队列中，女性比男性显著延长寿命。因此，我们的结果表明，GH信号的减少除了对循环中的IGF1起作用外，还对生存有生理上的好处。除了这些生物主持人，我们发现小样本研究的代表性过高，这些研究报告了存活率的大幅改善，这表明潜在的发表偏见。我们讨论了这可能如何潜在地混淆已发表工作的当前结论，以及这如何证明有必要进一步研究复制。
Reduced somatotrophic signaling through the growth hormone (GH) and insulin-like growth factor pathways (IGF1) can delay aging, although the degree of life-extension varies markedly across studies. By collating data from previous studies and using meta-analysis, we tested whether factors including sex, hormonal manipulation, body weight change and control baseline mortality quantitatively predict relative life-extension. Manipulations of GH signaling (including pituitary and direct GH deficiencies) generate significantly greater extension in median life span than IGF1 manipulations (including IGF1 production, reception, and bioactivity), producing a consistent shift in mortality risk of mutant mice. Reduced Insulin receptor substrate (IRS) expression produces more similar life-extension to reduced GH, although effects are more heterogeneous and appear to influence the demography of mortality differently. Life-extension with reduced IGF1 signaling, but neither GH nor IRS signaling, increases life span significantly more in females than males, and in cohorts where control survival is short. Our results thus suggest that reduced GH signaling has physiological benefits to survival outside of its actions on circulating IGF1. In addition to these biological moderators, we found an overrepresentation of small sample sized studies that report large improvements in survival, indicating potential publication bias. We discuss how this could potentially confound current conclusions from published work, and how this warrants further study replication.
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影响因子：
7.8
作者：
Harrison DE;Strong R;Allison DB;Ames BN;Astle CM;Atamna H;Fernandez E;Flurkey K;Javors MA;Nadon NL;Nelson JF;Pletcher S;Simpkins JW;Smith D;Wilkinson JE;Miller RA
通讯作者：
Miller RA
DOI：
10.1098/rstb.2014.0379
发表时间：
2015-04-19
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Kirkwood TB
通讯作者：
Kirkwood TB
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：
Bartke, A;Wright, JC;Roth, GS
通讯作者：
Roth, GS
DOI：
10.1093/gerona/glt108
发表时间：
2014-04-01
影响因子：
5.1
作者：
Lorenzini, Antonello;Salmon, Adam B.;Sell, Christian
通讯作者：
Sell, Christian