Yokomizo Takako, Oshima Motohiko, Iwama Atsushi
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Curr Opin Hematol. 2024 Jul 1;31(4):207-216. doi: 10.1097/MOH.0000000000000818. Epub 2024 Apr 12.
The development of new antiaging medicines is of great interest to the current elderly and aging population. Aging of the hematopoietic system is attributed to the aging of hematopoietic stem cells (HSCs), and epigenetic alterations are the key effectors driving HSC aging. Understanding the epigenetics of HSC aging holds promise of providing new insights for combating HSC aging and age-related hematological malignancies.
Aging is characterized by the progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. During aging, the HSCs undergo both quantitative and qualitative changes. These functional changes in HSCs cause dysregulated hematopoiesis, resulting in anemia, immune dysfunction, and an increased risk of hematological malignancies. Various cell-intrinsic and cell-extrinsic effectors influencing HSC aging have also been identified. Epigenetic alterations are one such mechanism.
Cumulative epigenetic alterations in aged HSCs affect their fate, leading to aberrant self-renewal, differentiation, and function of aged HSCs. In turn, these factors provide an opportunity for aged HSCs to expand by modulating their self-renewal and differentiation balance, thereby contributing to the development of hematological malignancies.
新型抗衰老药物的研发对当前老年及老龄化人群具有重大意义。造血系统的衰老归因于造血干细胞(HSC)的老化,而表观遗传改变是驱动HSC老化的关键因素。了解HSC老化的表观遗传学有望为对抗HSC老化及与年龄相关的血液系统恶性肿瘤提供新的见解。
衰老的特征是生理完整性逐渐丧失,导致功能受损和死亡易感性增加。在衰老过程中,HSC会发生数量和质量上的变化。HSC的这些功能变化会导致造血失调,进而引发贫血、免疫功能障碍以及血液系统恶性肿瘤风险增加。还发现了各种影响HSC老化的细胞内在和外在因素。表观遗传改变就是其中一种机制。
老年HSC中累积的表观遗传改变会影响其命运,导致老年HSC出现异常的自我更新、分化和功能。反过来,这些因素通过调节老年HSC的自我更新和分化平衡,为其扩增提供了机会,从而促进血液系统恶性肿瘤的发展。