Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom.
Annu Rev Physiol. 2013;75:621-44. doi: 10.1146/annurev-physiol-030212-183712. Epub 2012 Nov 26.
Discovering the biological basis of aging is one of the greatest remaining challenges for science. Work on the biology of aging has discovered a range of interventions and pathways that control aging rate. A picture is emerging of a signaling network that is sensitive to nutritional status and that controls growth, stress resistance, and aging. This network includes the insulin/IGF-1 and target of rapamycin (TOR) pathways and likely mediates the effects of dietary restriction on aging. Yet the biological processes upon which these pathways act to control life span remain unclear. A long-standing guiding assumption about aging is that it is caused by wear and tear, particularly damage at the molecular level. One view is that reactive oxygen species (ROS), including free radicals, generated as by-products of cellular metabolism, are a major contributor to this damage. Yet many recent tests of the oxidative damage theory have come up negative. Such tests have opened an exciting new phase in biogerontology in which fundamental assumptions about aging are being reexamined and revolutionary concepts are emerging. Among these concepts is the hyperfunction theory, which postulates that processes contributing to growth and reproduction run on in later life, leading to hypertrophic and hyperplastic pathologies. Here we reexamine central concepts about the nature of aging.
探索衰老的生物学基础是科学面临的最大挑战之一。衰老生物学的研究已经发现了一系列可以控制衰老速度的干预措施和途径。目前已经出现了一幅信号网络的图景，该网络对营养状况敏感，并控制着生长、抗应激和衰老。这个网络包括胰岛素/IGF-1 和雷帕霉素靶蛋白 (TOR) 途径，可能介导了饮食限制对衰老的影响。然而，这些途径控制寿命的生物学过程仍不清楚。关于衰老的一个长期存在的指导假设是，衰老是由磨损引起的，特别是在分子水平上的损伤。一种观点认为，活性氧物种 (ROS)，包括自由基，作为细胞代谢的副产物产生，是造成这种损伤的主要因素。然而，最近对氧化损伤理论的许多测试结果都是否定的。这些测试为生物老年学开辟了一个令人兴奋的新阶段，在这个阶段中，关于衰老的基本假设正在被重新检验，新的革命性概念正在出现。其中一个概念是功能亢进理论，该理论假设促进生长和繁殖的过程在生命后期仍在继续，导致肥大和增生性病变。在这里，我们重新审视了衰老本质的核心概念。
