Wagner Wolfgang, Horn Patrick, Bork Simone, Ho Anthony D
Department of Medicine V, University of Heidelberg, Heidelberg, Germany.
Exp Gerontol. 2008 Nov;43(11):974-80. doi: 10.1016/j.exger.2008.04.007. Epub 2008 Apr 22.
Adult stem cells provide the basis for regeneration of aging tissue. Their dual ability for self-renewal and multilineage differentiation is controlled by direct interaction with a specific microenvironment -- the so called "stem cell niche". Hematopoietic stem cells (HSC) reside in the bone marrow. It is still under debate if HSC can rejuvenate infinitively or if they do not possess "true" self-renewal and undergo replicative senescence such as any other somatic cell. Furthermore, the question arises to what extent age-related changes in HSC are due to intrinsic factors or regulated by external stimuli. There is growing evidence, that the stem cell niche is most important for the regulation of cellular aging in adult stem cells. It is the stem cell niche that (i) maintains HSC in a quiescent state that reduces DNA damage as well as replicative senescence, (ii) protects from radicals and toxic compounds, (iii) regulates cell intrinsic signal cascades and (iv) modulates gene expression and epigenetic modifications in HSC. Thus, the interplay with the stem cell niche controls HSC function including the aging process of the hematopoiesis.
成体干细胞为衰老组织的再生提供了基础。它们自我更新和多谱系分化的双重能力是通过与特定微环境——即所谓的“干细胞生态位”的直接相互作用来控制的。造血干细胞（HSC）存在于骨髓中。造血干细胞是否能无限期地恢复活力，或者它们是否不具备“真正的”自我更新能力，而是像其他体细胞一样经历复制性衰老，这仍存在争议。此外，造血干细胞中与年龄相关的变化在多大程度上是由内在因素引起的，或者是由外部刺激调节的，这一问题也随之而来。越来越多的证据表明，干细胞生态位对于调节成体干细胞的细胞衰老最为重要。正是干细胞生态位（i）使造血干细胞维持在静止状态，减少DNA损伤以及复制性衰老，（ii）保护细胞免受自由基和有毒化合物的侵害，（iii）调节细胞内信号级联反应，以及（iv）调节造血干细胞中的基因表达和表观遗传修饰。因此，与干细胞生态位的相互作用控制着造血干细胞的功能，包括造血的衰老过程。
