Division of Cardiology and Clinical Gerontology, Department of Internal Medicine, Beppu Hospital, Kyushu University, 4546 Tsurumihara, Beppu, 874-0838, Japan.
Mol Cell Biochem. 2021 Jan;476(1):221-229. doi: 10.1007/s11010-020-03899-0. Epub 2020 Sep 12.
The aims of this study were to investigate the impact of caloric restriction (CR) on cardiac senescence in an animal model of diabetes and examine the signal transduction mechanisms for changes in cell survival as well as cardiac function. Male 8-week-old Otsuka Long-Evans Tokushima fatty (OLETF) diabetic rats were divided into 2 groups: a group fed ad libitum (AL), and a group fed with CR (30% energy reduction). Long-Evans Tokushima Otsuka (LETO) non-diabetic rats were used as controls. LETO rats were divided into 3 groups: a high fat diet (HFD) group with a 22% increase in caloric intake, a CR group, and a group fed AL. At 40 weeks of age, the telomere length was significantly shorter in the heart tissue of HFD rats but was not altered by CR in experimental rats with or without CR, however, telomerase activity in both strains of CR rats was significantly elevated. Protein expression of IGF-1, Sirt 1 and phospho-FoxO1 was increased in both CR groups. Echocardiography showed that CR preserved LV diastolic function with a significantly shorter E-wave deceleration time and a greater E/A ratio compared with the AL groups. These findings suggest that CR protocol increased telomerase activity without changing of telomere length, enhanced autophagy and improved LV diastolic function in animal model of diabetes rats. It is finally suggested that those impacts may be important for the maintenance of normal cardiac function and for delayed cardiac aging.
本研究旨在探讨热量限制(CR)对糖尿病动物模型中心脏衰老的影响,并研究细胞存活和心脏功能变化的信号转导机制。将 8 周龄雄性 Otsuka Long-Evans Tokushima 肥胖(OLETF)糖尿病大鼠分为 2 组:自由进食组(AL)和热量限制组(CR,能量减少 30%)。将 Long-Evans Tokushima Otsuka(LETO)非糖尿病大鼠作为对照。LETO 大鼠分为 3 组:高卡路里饮食(HFD)组,热量摄入增加 22%;CR 组;AL 组。40 周龄时,HFD 大鼠心脏组织中端粒长度明显缩短,但 CR 对有或没有 CR 的实验大鼠没有改变,然而,两种 CR 大鼠的端粒酶活性均显著升高。IGF-1、Sirt 1 和磷酸化 FoxO1 的蛋白表达在两种 CR 组中均增加。超声心动图显示,与 AL 组相比,CR 组左室舒张功能得到改善,E 波减速时间缩短,E/A 比值增大。这些发现表明,CR 方案在不改变端粒长度的情况下增加端粒酶活性,增强自噬并改善糖尿病大鼠的左室舒张功能。最后,这些影响可能对维持正常心脏功能和延缓心脏衰老很重要。