Edelberg Jay M, Ballard Victoria L T
GlaxoSmithKline, King of Prussia, PA 19406, USA.
Aging Cell. 2008 Aug;7(4):599-604. doi: 10.1111/j.1474-9726.2008.00404.x. Epub 2008 Jun 28.
Significant advances in the past decade have revealed that a large number of highly plastic stem cells are maintained in humans through adulthood and are present even in older adults. These findings are notable in light of the reduced capacity for repair and regeneration in older tissues. The apparent dichotomy can be reconciled through an appreciation of the age-associated changes in the microenvironmental pathways that govern adult stem cell plasticity and differentiation patterns. Specifically, the recent identification of the age-related loss of the local platelet-derived growth factor signals that promote the induction of cardiac myocytes from Oct-3/4+ bone marrow stem cells, rather than impairment in the stem cells themselves, provides a template for understanding and targeting the environmental pathways underlying the regenerative capacity of older tissues and organs. It is projected that this paradigm extends to the overall regulation of adult stem cell biology, shifting the balance from tissue generation during development and maturation to the prevention of untoward stem cell differentiation with aging.
过去十年的重大进展表明，大量具有高度可塑性的干细胞在人类成年期一直存在，甚至在老年人中也有。鉴于老年组织中修复和再生能力的下降，这些发现值得关注。通过认识到控制成体干细胞可塑性和分化模式的微环境途径中与年龄相关的变化，可以调和这一明显的二分法。具体而言，最近发现促进从Oct-3/4+骨髓干细胞诱导生成心肌细胞的局部血小板衍生生长因子信号与年龄相关的丧失，而非干细胞本身的损伤，为理解和针对老年组织和器官再生能力背后的环境途径提供了一个模板。预计这一范式扩展到成体干细胞生物学的整体调控，将平衡从发育和成熟过程中的组织生成转移到随着衰老预防干细胞的不良分化。
