Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Trends Genet. 2013 Sep;29(9):506-12. doi: 10.1016/j.tig.2013.05.004. Epub 2013 Jun 13.
Physicochemical properties preclude ideal biomolecules and perfect biological functions. This inherent imperfectness leads to the generation of damage by every biological process, at all levels, from small molecules to cells. The damage is too numerous to be repaired, is partially invisible to natural selection, and manifests as aging. I propose that the inherent imperfectness of biological systems is the true root of the aging process. Because each biomolecule generates specific forms of damage, the cumulative damage is largely non-random and is indirectly encoded in the genome. I consider this concept in light of other proposed theories of aging and integrate these disparate ideas into a single model. I also discuss the evolutionary significance of damage accumulation and strategies for reducing damage. Finally, I suggest ways to test this integrated model of aging.
物理化学性质使理想的生物分子和完美的生物功能无法实现。这种内在的不完美性导致了每个生物过程在从小分子到细胞的各个层面上产生损伤。损伤太多以至于无法修复,并且部分损伤对自然选择是不可见的,表现为衰老。我提出,生物系统的内在不完美性是衰老过程的真正根源。由于每个生物分子都会产生特定形式的损伤,因此累积损伤在很大程度上是非随机的,并以间接的方式编码在基因组中。我根据其他提出的衰老理论来考虑这个概念,并将这些不同的想法整合到一个单一的模型中。我还讨论了损伤积累的进化意义和减少损伤的策略。最后,我提出了测试这个综合衰老模型的方法。