随着人口老龄化，衰老相关疾病慢性粒-单核细胞白血病（CMML）逐渐增加，老年群体易患CMML的具体机制不明，深入研究其分子病理基础，有利于针对性的治疗。最新研究表明，衰老微环境可以促进肿瘤的发生发展。我们发现CMML（NrasG12D诱导）在Terc-/-小鼠（端粒功能障碍衰老小鼠模型）中发病更快。Terc-/-小鼠中存在炎症因子的上调和转座子LINE1（L1）的激活；通过抑制L1的激活能够降低炎症，延迟CMML在Terc-/-小鼠中的发生。进一步研究发现Terc-/-小鼠存在L1 DNA胞质积累和cGAS表达上调，提示cGAS-STING通路可能参与其中。本项目拟通过cGAS-/-Terc-/-小鼠阐明cGAS介导的炎症在衰老微环境促进肿瘤发展的分子机制，并寻找激活L1的上游分子靶点，结合人类生存数据和测序结果评估L1与CMML早期诊断和预后的相关性，为衰老相关疾病的研究提供新思路。

With population aging, aging-related diseases such as Chronic myelomonocytic leukemia (CMML) are gradually increased. The exact mechanism of susceptibility to CMML in the elderly is unknown. Further study on the molecular basis of pathology is helpful for targeted therapy. Recent research shows that the aging microenvironment can promote the development of tumors. We found that CMML (NrasG12D-induced) developed more rapidly in Terc-/- mice (telomere dysfunctional aging mouse model). Upregulation of inflammatory cytokines and activation of transposon LINE1 (L1) were observed in Terc-/- mice. Inhibition of L1 activation reduced the expression of inflammatory cytokines and delayed the occurrence of CMML in Terc-/- mice. Further study found that Terc-/- mice exist L1 DNA cytoplasmic accumulation and cGAS upregulation, suggesting that cGAS-STING pathway may be involved. This project aims to elucidate the molecular mechanism by which cGAS-mediated inflammation promotes the development of tumors in senescent microenvironment using cGAS-/-Terc-/- mice and to look for upstream molecular targets involved in L1 activation, combined with human survival data and sequencing results to evaluate the correlation between L1 and CMML in early diagnosis and prognosis，providing new ideas for the study of aging-related diseases.