Ljubuncic Predrag, Reznick Abraham Z
Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Gerontology. 2009;55(2):205-16. doi: 10.1159/000200772. Epub 2009 Feb 7.
This short review portrays the evolutionary theories of aging in the light of the existing discoveries from genomic and molecular genetic studies on aging and longevity. At the outset, an historical background for the development of the evolutionary theories of aging is presented through the works of August Weismann (programmed death and the germ plasm theories) including his exceptional theoretical postulation, later experimentally validated by the existence of cell division limits. Afterwards, the theory of mutation accumulation of Peter Medawar and the theory modification by Charlesworth (late-life mortality plateau) are presented as well as the antagonistic pleiotropy hypothesis of George Williams, and the disposable soma theory of Kirkwood and Holliday. These theories are discussed in the light of the different research studies, which include studies on insulin signaling and longevity, the possibility that nuclear factor kappa B may be a major mediator of aging, studies of anti-aging Sirtuins and studies on heat shock proteins and longevity and on gene sets as biomarkers of aging. Finally, the proposals for future research in biogerontology, such as studies on the control of protein synthesis, validation of biomarkers of aging, understanding the biochemistry of longevity and research in the field of gerontologic pathology are presented. Likewise, further attention is suggested regarding the work on telomere shortening, stem cells and studies on understanding the biochemical and molecular basis for longevity in centenarians.
这篇简短的综述根据基因组和分子遗传学研究中关于衰老和长寿的现有发现,阐述了衰老的进化理论。首先,通过奥古斯特·魏斯曼(程序性死亡和种质理论)的著作,介绍了衰老进化理论发展的历史背景,包括他独特的理论假设,该假设后来通过细胞分裂极限的存在得到了实验验证。之后,介绍了彼得·梅达沃的突变积累理论以及查尔斯沃思的理论修正(晚年死亡率平台期),还有乔治·威廉姆斯的拮抗多效性假说,以及柯克伍德和霍利迪的可抛弃体细胞理论。这些理论结合不同的研究进行了讨论,这些研究包括胰岛素信号与长寿的研究、核因子κB可能是衰老主要调节因子的可能性、抗衰老沉默调节蛋白的研究、热休克蛋白与长寿以及基因集作为衰老生物标志物的研究。最后,提出了生物老年学未来研究的建议,如蛋白质合成控制的研究、衰老生物标志物的验证、长寿生物化学的理解以及老年病理学领域的研究。同样,建议进一步关注端粒缩短、干细胞的研究以及百岁老人长寿生化和分子基础理解方面的工作。