儿童早老症（HGPS）和限制性皮肤病（RD）是两种由于基因突变所致核纤层蛋白A(lamin A)缺陷性疾病，导致全长或缩短的核纤层蛋白A前体（prelamin A/progerin）在细胞核堆积，引起核形态异常、异染色质结构紊乱、基因组不稳定性和成熟前衰老。我们前期研究发现异染色质蛋白HP1αThr50位点磷酸化水平降低介导了异染色质DNA损伤应答障碍和细胞早老表型。由于蛋白激酶CK2（casine kinase）催化HP1该特异位点磷酸化，本项目以Zmpste24-缺陷小鼠胚胎成纤维细胞（MEFs）及HEK293转染细胞为模拟RD和HGPS的早老模型，拟围绕CK2在早老细胞中稳态和活性改变为中心内容，对CK2引发的异染色质DNA损伤修复障碍与早老表型通路进行探讨，并通过调节CK2活性研究其抗早老的可能性。本项目有利于加深对早老发生机制的认识，为临床治疗早老症和延缓正常衰老提供策略和依据。

Hutchinson-Gilford progeria syndrome (HGPS) and Restrictive dermopathy (RD)are two laminopathies caused by mutations leading to celluar accumulation of prelamin A or one of its truncated forms, progerin, which induces misshapen nuclei, heterochromatin disorganization, genomic instability and premature aging. Our previous study showed that the compromised HP1α phosphorylation at Thr50 site mediates the defective heterochromatin DNA damage response and accelerated senescence in progeriod cells. Based on CK2 (casine kinase 2) is specially phosphorylation of HP1α at Thr50 site, the aim of this study is to investigate the effects of prelamin A/progerin on CK2 homeostasis and enzyme activity in mouse embryonic fibroblasts (MEFs) derived from Zmpste24-dificient mice as well as HEK293 cells, further to explore the functional alternation of CK2 triggers defective heterochromatin DNA damage responses and their contribution to accelerated senescence，evaluating the possibility of reverse early senescence through regulating CK2 activity. These studies will extend the understanding of HGPS, suggesting a potential therapeutic strategy for laminopathy-based premature aging via the intervention of CK2, and also providing evidences for anti- aging.