The nuclear sirtuin SIRT6 protects the heart from developing aging-associated myocyte senescence and cardiac hypertrophy.
The nuclear sirtuin SIRT6 protects the heart from developing aging-associated myocyte senescence and cardiac hypertrophy.
复制标题
核SIRTUIN SIRT6可保护心脏免受与衰老相关的肌细胞衰老和心脏肥大的发展。
DOI：
10.18632/aging.203027
复制
发表时间：
2021-05-02
期刊：
影响因子：
--
通讯作者：
Gupta MP
中科院分区：
文献类型：
--
作者：
Pillai VB;Samant S;Hund S;Gupta M;Gupta MP
Sirtuins已被证明可以调节衰老过程。我们之前已经证明Sirt6可以阻断小鼠压力过载引起的心脏肥厚。在这里，我们发现Sirt6也可以减轻衰老诱导的心肌细胞衰老和心脏肥大。我们发现衰老与Sirt6活性的改变以及心脏肥大和纤维化的发展有关。与年轻小鼠（4个月）相比，年老小鼠（24个月）的心脏显示出线粒体DNA损伤水平增加，端粒长度缩短，8-氧-脱氧葡萄糖加合物积累增加，这些都是衰老的标志。衰老的心脏也显示出NAD+水平的降低和线粒体融合-裂变蛋白水平的改变。在Sirt6缺陷小鼠的心脏中也观察到类似的特征。此外，我们发现阿霉素（Dox）诱导心肌细胞衰老，通过p16INK4a、p53和β-半乳糖苷酶的表达来测量，与Sirt6的丢失有关。然而，Sirt6过表达保护心肌细胞免受dox诱导的衰老。此外，与野生型小鼠相比，Sirt6的心脏。Tg小鼠显示衰老标志物表达减少，衰老相关的心脏肥大和纤维化的发展。我们的数据表明Sirt6是一种关键的抗衰老分子，它调节与衰老相关的各种细胞过程，并保护心脏免受衰老诱导的心脏肥大和纤维化。
Sirtuins have been shown to regulate the aging process. We have previously demonstrated that Sirt6 blocks the pressure overload-induced cardiac hypertrophy in mice. Here, we show that Sirt6 can also mitigate aging-induced cardiomyocyte senescence and cardiac hypertrophy. We found that aging is associated with altered Sirt6 activity along with development of cardiac hypertrophy and fibrosis. Compared to young mice (4-months), the hearts of aged mice (24-months) showed increased levels of mitochondrial DNA damage, shortened telomere length, and increased accumulation of 8-oxo-dG adducts, which are hallmarks of aging. The aged hearts also showed reduced levels of NAD+ and altered levels of mitochondrial fusion-fission proteins. Similar characteristics were observed in the hearts of Sirt6 deficient mice. Additionally, we found that doxorubicin (Dox) induced cardiomyocyte senescence, as measured by expression of p16INK4a, p53, and β-galactosidase, was associated with loss of Sirt6. However, Sirt6 overexpression protected cardiomyocytes from developing Dox-induced senescence. Further, compared to wild-type mice, the hearts of Sirt6.Tg mice showed reduced expression of aging markers, and the development of aging-associated cardiac hypertrophy and fibrosis. Our data suggest that Sirt6 is a critical anti-aging molecule that regulates various cellular processes associated with aging and protects the heart from developing aging-induced cardiac hypertrophy and fibrosis.
登录
查看更多内容
DOI：
10.1016/j.mcna.2011.11.003
发表时间：
2012-01
期刊：
The Medical clinics of North America
影响因子：
--
作者：
Dhingra R;Vasan RS
通讯作者：
Vasan RS
影响因子：
7.8
作者：
Detmer, Scott A;Chan, David C
通讯作者：
Chan, David C
影响因子：
64.5
作者：
Chen H;Vermulst M;Wang YE;Chomyn A;Prolla TA;McCaffery JM;Chan DC
通讯作者：
Chan DC
影响因子：
14.9
作者：
Cawthon RM
通讯作者：
Cawthon RM
影响因子：
20.1
作者：
Kane AE;Sinclair DA
通讯作者：
Sinclair DA