细胞衰老是由多种内外因素引发的一种细胞增殖停滞的生理过程，是导致个体衰老及衰老相关疾病发生发展的潜在重要原因。内源性逆转录病毒（ERVs）属于逆转录转座子，约占人类基因组的8%。多项研究表明ERVs与衰老及衰老相关疾病密切相关，但具体作用和机制目前仍不清楚。我们前期研究发现由ERV编码的一种包膜蛋白HEMO在衰老细胞及年老人群的脑组织和皮肤成纤维细胞中表达上调，并且HEMO在细胞中过表达后DNA损伤增加、细胞增殖减缓、促进细胞衰老。这些前期数据提示HEMO在细胞衰老过程中发挥重要作用。本项目拟研究HEMO在细胞衰老过程中的表达模式及调控机制，揭示HEMO蛋白在细胞衰老中的生物学作用，阐明HEMO蛋白调控细胞衰老的分子机制，为衰老相关疾病的预防和治疗、药物靶点及抗衰老药物的研发等临床应用提供科学依据。

Cell senescence is a process that imposes permanent proliferative arrest on cells in response to various stressors, emerged as a potentially important contributor to aging and age-related disease. Endogenous retroviruses (ERVs) are retrotransposons in genome, accounting for ~8% of human genome. Although ERVs involved in aging and age-related disease has been reported, the underlying mechanisms of ERVs function in cell senescence remain elusive. In our preliminary study, we found that expression of the ERV-encoding envelope protein HEMO significantly increased in senescent cells, and in brain tissues and skin fibroblasts of aged individuals. Furthermore, we showed that overexpression of HEMO resulted in increased DNA damage, restrained cell proliferation and promoted cell senescence in human fibroblasts. Together, these data suggest that HEMO plays an important role in cell senescence. This project aims to understand the mechanistic function of HEMO in cell senescence and to provide insights for senescence marker, drug target and therapy of age-related disease.