From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing.
From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing.
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DOI：
10.1007/s00018-007-7123-x
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发表时间：
2007-10
影响因子：
8
通讯作者：
Faragher, R. G. A.
中科院分区：
文献类型：
--
作者：
Cox, L. S.;Faragher, R. G. A.
了解人类衰老的基本生物学是试图改善老年有害后果的一个重要里程碑。这是一个紧迫的研究重点，考虑到全球人口向老龄化的转变。虽然已经使用经典的生物化学和遗传学发现了一些被认为有助于衰老的分子途径，但衰老的复杂性、多基因性和随机性使得整个过程不能立即进行生物化学分析。因此，人们试图阐明单基因早老性疾病的原因，这些疾病概括了正常衰老的一些（如果不是全部）特征，希望这可能有助于我们对人类正常衰老的理解。两种典型的早老性疾病是沃纳综合征和哈钦森-吉尔福德早老性综合征（也称为早老症）。由于这些疾病本质上是衰老的表型，而不是衰老本身，因此在理解其发病机制方面取得的进展必须始终与提出的理论相结合，以帮助解释正常过程如何运作。一种可能的衰老机制被描述为细胞衰老假说。在这里，我们讨论了这一假设，并证明它提供了一个合理的解释，许多老化表型中看到沃纳综合征和哈钦森-吉尔福德早老综合征。最近取得的令人兴奋的进展，这两个综合征的潜在疗法也进行了审查。
Understanding the basic biology of human ageing is a key milestone in attempting to ameliorate the deleterious consequences of old age. This is an urgent research priority given the global demographic shift towards an ageing population. Although some molecular pathways that have been proposed to contribute to ageing have been discovered using classical biochemistry and genetics, the complex, polygenic and stochastic nature of ageing is such that the process as a whole is not immediately amenable to biochemical analysis. Thus, attempts have been made to elucidate the causes of monogenic progeroid disorders that recapitulate some, if not all, features of normal ageing in the hope that this may contribute to our understanding of normal human ageing. Two canonical progeroid disorders are Werner’s syndrome and Hutchinson-Gilford progeroid syndrome (also known as progeria). Because such disorders are essentially phenocopies of ageing, rather than ageing itself, advances made in understanding their pathogenesis must always be contextualised within theories proposed to help explain how the normal process operates. One such possible ageing mechanism is described by the cell senescence hypothesis of ageing. Here, we discuss this hypothesis and demonstrate that it provides a plausible explanation for many of the ageing phenotypes seen in Werner’s syndrome and Hutchinson-Gilford progeriod syndrome. The recent exciting advances made in potential therapies for these two syndromes are also reviewed.
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