Pioglitazone: an anti-diabetic compound with anti-aging properties
Pioglitazone: an anti-diabetic compound with anti-aging properties
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DOI：
10.1007/s10522-007-9105-7
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发表时间：
2007-12-01
期刊：
影响因子：
4.5
通讯作者：
Mueller, Laurence D.
中科院分区：
文献类型：
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作者：
Jafari, Mahtab;Khodayari, Behnood;Mueller, Laurence D.
胰岛素和胰岛素生长因子样（IGF）信号通路是线虫、昆虫和哺乳动物中众所周知的长寿途径。据我们所知，尚无系统的药理学研究评估针对果蝇这一途径的药物的抗衰老特性。虽然没有发表的数据表明这些化合物在果蝇中具有抗衰老作用，但我们假设它们有希望的药理特征可能会降低死亡率。然而，死亡率的下降可能是由于许多潜在的人为因素和混杂因素，如生殖力下降、代谢率下降或中枢神经系统抑制。因此，仅仅发现一种化合物降低死亡率并不能使其成为抗衰老化合物。在这项研究中，我们评估了四种可能针对果蝇胰岛素信号通路的化合物的抗衰老特性。一旦确定该化合物降低了死亡率，我们就开始评估可能导致死亡率降低的混杂因素。我们发现只有吡格列酮具有抗衰老特性。目前，我们还没有对这种药理差异的机制解释。
Insulin and Insulin-Growth-Factor-like (IGF) signaling pathways are well known longevity pathways in nematodes, insects and mammals. To our knowledge, there are no systematic pharmacological studies evaluating the anti-aging properties of medications that target this pathway in Drosophila. Although there are no published data implicating an anti-aging role for these compounds in Drosophila, we hypothesized that their promising pharmacological profile might decrease mortality. However, the decrease in mortality could be due to a number of potential artifacts and confounds such as fecundity depression, decrease in metabolic rate, or CNS depression. Therefore, the mere finding that a compound decreases mortality does not qualify it as an anti-aging compound. In this study, we evaluated the anti-aging properties of four compounds that might target the insulin signaling pathway in Drosophila. Once it was established that the compound decreased mortality, we proceeded to evaluate possible confounding factors that could have contributed to the mortality reduction. We show that only piolglitazone displayed anti-aging properties. At present, we do not have a mechanistic explanation for this pharmacological disparity.