Lamin A蛋白结合CK2α并且抑制其酶活性，异常prelamin A堆积或CK2α过表达可引起心肌扩张/肥大，但lamin A-CK2α调控心肌衰老样改变及相关病理过程中的意义与机制亟待探讨。前期预实验发现，正常衰老小鼠心肌CK2α表达降低，p16表达增高；Zmpste24-缺陷（prelamin A）早老小鼠CK2α转基因可挽救细胞衰老和心肌扩张表型；心肌特异性CK2α敲除小鼠存在细胞衰老和心脏增大表型。因此，我们假设：lamin A功能异常可通过抑制CK2α活性抑制后者对衰老相关基因的调控作用，进而影响心肌衰老样改变及其相关的心肌扩张或肥大过程。本项目拟利用CK2α转基因、心肌特异CK2α敲除、lamin A缺失及Zmpste24-/-工具小鼠，在分子、细胞及心脏器官层次对这一假说进行验证。预期将为解析心肌衰老样改变及其相关的心肌扩张或肥大机制提供实验依据。

Lamin A inhibits the activity of CK2α by physically interacts with CK2α, prelamin A accumulation or CK2α over expression induces dilated/hypertrophic cardiomyopathy. However, the impact of lamin A-CK2α pathway in cardiac aging-like changes and related heart disorders as well as the mechanisms underlying remain to be studied. Our previous data indicated that heart tissues from aged mice exhibited reduction of CK2α protein levels, and elevation of p16 expression; Zmpste24-deficient mice with transgenic CK2α expression rescued the effect of Zmpste24 deficiency in inducing dilated cardiomyopathy phenotype and cellular senescence; and cardiomyocyte-specific conditional CK2α knockdown induced cellular aging and increased the size of heart. Based on these findings, we hypothesize that lamin A protein dysfunction represses CK2α activity and its role in regulating aging-related genes, in turn impacting on cardiac aging-like changes and related cardiac dilatation or hypertrophy. By using CK2α transgenic, cardiomyocyte- specific CK2α knockout, lamin A knockout, and Zmpste24-/- mice, we will validate this hypothesis by studies in the levels of molecule, cell, and heart organ. Our studies will highlight novel mechanisms underlying the regulation of cardiac aging-related changes and heart disorders.