Rose Michael R
Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697-2525, USA.
Aging (Albany NY). 2009 May 21;1(5):444-50. doi: 10.18632/aging.100053.
Aging is not simply an accumulation of damage or inappropriate higher-order signaling, though it does secondarily involve both of these subsidiary mechanisms. Rather, aging occurs because of the extensive absence of adaptive genomic information required for survival to, and function at, later adult ages, due to the declining forces of natural selection during adult life. This absence of information then secondarily leads to misallocations and damage at every level of biological organization. But the primary problem is a failure of adaptation at later ages. Contemporary proposals concerning means by which human aging can be ended or cured which are based on simple signaling or damage theories will thus reliably fail. Strategies based on reverse-engineering age-extended adaptation using experimental evolution and genomics offer the prospect of systematically greater success.
衰老并非仅仅是损伤的积累或不适当的高阶信号传导,尽管它确实在次要层面涉及这两种辅助机制。相反,衰老是由于成年期自然选择的力量下降,导致在成年后期生存和发挥功能所需的适应性基因组信息大量缺失。这种信息的缺失进而在生物组织的各个层面导致资源分配不当和损伤。但主要问题是后期适应能力的失效。因此,基于简单信号传导或损伤理论的有关人类衰老可以被终结或治愈的当代提议必然会失败。基于利用实验进化和基因组学对延长寿命的适应性进行逆向工程的策略,有望取得系统性更强的成功。