Institute of Genetic Medicine, Newcastle University, The International Centre for Life, Central Parkway, Newcastle upon Tyne, United Kingdom.
Stem Cells. 2014 Sep;32(9):2291-8. doi: 10.1002/stem.1720.
Although certainly one of the most recognizable characteristics of human biology, aging remains one of the least understood. This is largely attributable to the fact that aging is both gradual and inherently complex, with almost all aspects of physiology and phenotype undergoing steady modification with advancing age. The complexity of the aging process does not allow for a single all-encompassing definition, yet decades of study using diverse systems, methodologies, and model organisms have begun to build a consensus regarding the central physiological characteristics of aging. Indeed, such studies have shown that the process of aging is invariably accompanied by a diminished capacity to adequately maintain tissue homeostasis or to repair tissues after injury. When homeostatic control diminishes to the point at which tissue/organ integrity and function are no longer sufficiently maintained, physiologic decline ensues, and aging is manifested. Inadequate organ homeostasis indicates possible dysfunction of tissue-specific stem cells. Several mechanisms have been postulated to account for age-related cellular changes; however, increasing literature evidence suggests that age-related changes to the epigenome make a major contribution to the aged phenotype. In this review, we discuss the evidence for epigenetic contributions to tissue-specific stem cell ageing.
尽管衰老无疑是人类生物学中最具特征性的现象之一，但它仍然是最不被理解的现象之一。这主要归因于以下事实：衰老是渐进的，本质上是复杂的，几乎所有生理和表型方面都随着年龄的增长而持续发生稳定的改变。衰老过程的复杂性不允许有一个单一的全面定义，但几十年来使用不同系统、方法和模式生物的研究已经开始就衰老的核心生理特征达成共识。事实上，这些研究表明，衰老过程总是伴随着组织内稳态维持能力的降低，或者在损伤后修复组织的能力降低。当体内平衡控制降低到组织/器官完整性和功能不再得到充分维持的程度时，生理功能下降就会发生，衰老就会表现出来。器官内稳态不足表明组织特异性干细胞可能出现功能障碍。已经提出了几种机制来解释与年龄相关的细胞变化；然而，越来越多的文献证据表明，表观基因组的年龄相关变化对老年表型有重大贡献。在这篇综述中，我们讨论了表观遗传对组织特异性干细胞衰老的贡献的证据。
