Kosan Christian, Heidel Florian H, Godmann Maren, Bierhoff Holger
Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine (CMB), Friedrich Schiller University Jena, Hans-Knöll-Str. 2, 07745 Jena, Germany.
Leibniz-Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07745 Jena, Germany.
Cells. 2018 Nov 29;7(12):237. doi: 10.3390/cells7120237.
In complex organisms, stem cells are key for tissue maintenance and regeneration. Adult stem cells replenish continuously dividing tissues of the epithelial and connective types, whereas in non-growing muscle and nervous tissues, they are mainly activated upon injury or stress. In addition to replacing deteriorated cells, adult stem cells have to prevent their exhaustion by self-renewal. There is mounting evidence that both differentiation and self-renewal are impaired upon aging, leading to tissue degeneration and functional decline. Understanding the molecular pathways that become deregulate in old stem cells is crucial to counteract aging-associated tissue impairment. In this review, we focus on the epigenetic mechanisms governing the transition between quiescent and active states, as well as the decision between self-renewal and differentiation in three different stem cell types, i.e., spermatogonial stem cells, hematopoietic stem cells, and muscle stem cells. We discuss the epigenetic events that channel stem cell fate decisions, how this epigenetic regulation is altered with age, and how this can lead to tissue dysfunction and disease. Finally, we provide short prospects of strategies to preserve stem cell function and thus promote healthy aging.
在复杂生物体中，干细胞是组织维持和再生的关键。成体干细胞补充上皮和结缔组织中持续分裂的组织，而在不生长的肌肉和神经组织中，它们主要在损伤或应激时被激活。除了替换退化细胞外，成体干细胞还必须通过自我更新来防止自身耗竭。越来越多的证据表明，衰老会损害分化和自我更新，导致组织退化和功能衰退。了解老年干细胞中失调的分子途径对于对抗与衰老相关的组织损伤至关重要。在本综述中，我们重点关注调控静止和活跃状态之间转变以及三种不同干细胞类型（即精原干细胞、造血干细胞和肌肉干细胞）自我更新与分化决定的表观遗传机制。我们讨论引导干细胞命运决定的表观遗传事件、这种表观遗传调控如何随年龄改变以及这如何导致组织功能障碍和疾病。最后，我们简要展望了维持干细胞功能从而促进健康衰老的策略。
