越来越多的研究表明人体器官衰老与干细胞衰老密切相关，成体干细胞的功能异常和数量下降可能是人类衰老的重要原因之一。造血干细胞是一类研究比较成熟的成体干细胞，然而有关造血干细胞衰老的分子机制仍旧不清楚。蛋白泛素化在肿瘤和炎症领域被研究得较多，它与肿瘤、心血管等疾病的发病密切相关， 然而蛋白泛素化在造血干细胞衰老中的作用还有待研究。泛素化E3连接酶是调控蛋白泛素化的酶，它会影响到组蛋白H2A泛素化，以及衰老基因的表达，然而具体的调控关系还不是很清楚。Trim26是E3连接酶，它可以抑制干扰素-β的产生和抗病毒反应、影响诱导性多功能干细胞（iPSCs）的重编程以及DNA损伤反应。本项目是通过利用Trim26敲除小鼠，探索E3连接酶-Trim26、 组蛋白H2A泛素化及造血干细胞衰老之间的关系，在组蛋白泛素化层面，找到抑制造血干细胞衰老的靶点。同时可以扩展到抑制小鼠及人的成纤维细胞衰老。

More and more studies have shown that the stem cell aging is closely related to human organ aging. The abnormal function and decreased number of adult stem cells might be one of the important reasons for human aging. Hematopoietic stem cells are a relatively very studied adult stem cell, but the molecular mechanisms of hematopoietic stem cells aging remain unclear. Protein ubiquitination has been very studied in the field of tumors and inflammation. It is closely related to the pathogenesis of tumors and cardiovascular diseases. However, the role of protein ubiquitination in the aging of hematopoietic stem cells remains to be studied. Ubiquityl E3 ligases are one of the enzyme which can affect the ubiquitination of proteins. E3 ligase affects the ubiquitination of histone H2A and the expression of aging related genes. However, the exact regulatory pathway is not well understood. Trim26 is a E3 ligase that inhibits interferon-beta production and antiviral responses, affects reprogramming of induced pluripotent stem cells (iPSCs), and DNA damage responses. In this project, we want to explore the relationship between E3 ligase-Trim26, histone H2A ubiquitination and hematopoietic stem cell aging by using Trim26 knockout mice, and find a target for inhibiting hematopoietic stem cell aging at the level of histone ubiquitination. At the same time, it can be extended to inhibit mouse and human fibroblast senescence.