The Genetics of Human Longevity
The Genetics of Human Longevity
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DOI：
10.1196/annals.1354.033
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Franceschi, Claudio
中科院分区：
文献类型：
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作者：
Capri, Miriam;Salvioli, Stefano;Franceschi, Claudio
衰老是由于遗传、表观遗传和环境因素的复杂相互作用造成的，但强大的遗传成分似乎对生存到极端年龄有影响。为了识别人类的“长寿基因”，现在有不同的策略可用。在我们的实验室里，我们对意大利百岁老人的各种“候选”多态进行了关联研究。许多基因/多态给出了否定的结果，而另一些基因/多态与人类寿命呈正相关，有时与不成功的衰老(心肌梗死、阿尔茨海默病和2型糖尿病)呈正相关。结果涉及炎症相关基因(IL-1簇、IL-6、IL-10、肿瘤坏死因子α、转化生长因子-β、TLR-4、PPAR-γ)、胰岛素/IGF-1信号通路及脂代谢(载脂蛋白、CETP、PON1)、氧化应激(P53、P66(SHC))。此外，核基因组和线粒体基因组(mtDNA单倍群和C150T突变)之间的相互作用也从我们的发现中显现出来。因此，在拮抗多效性可以发挥主要作用，基因在不同的年龄可以有不同的生物学作用的背景下，人类长寿的遗传学似乎相当独特。
Aging is due to a complex interaction of genetic, epigenetic, and environmental factors, but a strong genetic component appears to have an impact on survival to extreme ages. In order to identify "longevity genes" in humans, different strategies are now available. In our laboratory, we performed association studies on a variety of "candidate" polymorphisms in Italian centenarians. Many genes/polymorphisms gave negative results, while others showed a positive association with human longevity and a sometimes-positive association with unsuccessful aging (myocardial infarction, Alzheimer's disease, and type 2 diabetes). Results regarding genes involved in inflammation (IL-1 cluster, IL-6, IL-10, TNF alpha, TGF-beta, TLR-4, PPAR gamma), insulin/IGF-1 signaling pathway and lipid metabolism (apolipoproteins, CETP, PON1), and oxidative stress (p53, p66(shc)) will be described. In addition, a strong role of the interaction between nuclear and mitochondrial genomes (mtDNA haplogroups and the C150T mutation) emerged from our findings. Thus, the genetics of human longevity appears to be quite peculiar in a context where antagonistic pleiotropy can play a major role and genes can have a different biological role at different ages.