Schumacher Björn, Garinis George A, Hoeijmakers Jan H J
MGC Department of Cell Biology and Genetics, Center for Biomedical Genetics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands.
Trends Genet. 2008 Feb;24(2):77-85. doi: 10.1016/j.tig.2007.11.004. Epub 2008 Jan 14.
Aging represents the progressive functional decline and increased mortality risk common to nearly all metazoans. Recent findings experimentally link DNA damage and organismal aging: longevity-regulating genetic pathways respond to the accumulation of DNA damage and other stress conditions and conversely influence the rate of damage accumulation and its impact for cancer and aging. This novel insight has emerged from studies on human progeroid diseases and mouse models that have deficient DNA repair pathways. Here we discuss a unified concept of an evolutionarily conserved 'survival' response that shifts the organism's resources from growth to maintenance as an adaptation to stresses, such as starvation and DNA damage. This shift protects the organism from cancer and promotes healthy aging.
衰老代表了几乎所有后生动物共有的渐进性功能衰退和死亡风险增加。最近的研究结果通过实验将DNA损伤与机体衰老联系起来:调节寿命的遗传途径对DNA损伤和其他应激条件的积累做出反应,反之又会影响损伤积累的速率及其对癌症和衰老的影响。这一新颖的见解来自对患有早衰症的人类疾病和DNA修复途径缺陷的小鼠模型的研究。在这里,我们讨论一个进化上保守的“生存”反应的统一概念,即作为对饥饿和DNA损伤等应激的适应,将生物体的资源从生长转移到维持。这种转变保护生物体免受癌症侵害并促进健康衰老。