Blavatnik Institute, Department of Genetics, Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School, Boston, MA, US.
Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
Sci Rep. 2020 Jun 22;10(1):10052. doi: 10.1038/s41598-020-66903-z.
We investigated effects of age, sex and frailty on contractions, calcium transients and myofilament proteins to determine if maladaptive changes associated with aging were sex-specific and modified by frailty. Ventricular myocytes and myofilaments were isolated from middle-aged (12 mos) and older (24 mos) mice. Frailty was assessed with a non-invasive frailty index. Calcium transients declined and slowed with age in both sexes, but contractions were largely unaffected. Actomyosin Mg-ATPase activity increased with age in females but not males; this could maintain contractions with smaller calcium transients in females. Phosphorylation of myosin-binding protein C (MyBP-C), desmin, tropomyosin and myosin light chain-1 (MLC-1) increased with age in males, but only MyBP-C and troponin-T increased in females. Enhanced phosphorylation of MyBP-C and MLC-1 could preserve contractions in aging. Interestingly, the age-related decline in Hill coefficients (r = -0.816; p = 0.002) and increase in phosphorylation of desmin (r = 0.735; p = 0.010), tropomyosin (r = 0.779; p = 0.005) and MLC-1 (r = 0.817; p = 0.022) were graded by the level of frailty in males but not females. In these ways, cardiac remodeling at cellular and subcellular levels is graded by overall health in aging males. Such changes may contribute to heart diseases in frail older males, whereas females may be resistant to these effects of frailty.
我们研究了年龄、性别和虚弱对收缩、钙瞬变和肌丝蛋白的影响，以确定与衰老相关的适应性变化是否具有性别特异性，并受虚弱影响。从中年（12 个月）和老年（24 个月）小鼠中分离心室肌细胞和肌丝。使用非侵入性虚弱指数评估虚弱。钙瞬变在两性中都随年龄增长而下降和减慢，但收缩基本不受影响。肌球蛋白结合蛋白 C（MyBP-C）、结蛋白、原肌球蛋白和肌球蛋白轻链-1（MLC-1）在雌性中的磷酸化随年龄增长而增加，但仅在雌性中肌球蛋白结合蛋白 C 和肌钙蛋白-T 增加。MyBP-C 和 MLC-1 的增强磷酸化可维持衰老时的收缩。有趣的是，Hill 系数（r=-0.816;p=0.002）与年龄相关的下降和结蛋白（r=0.735;p=0.010）、原肌球蛋白（r=0.779;p=0.005）和 MLC-1（r=0.817;p=0.022）的磷酸化增加与男性的虚弱程度呈等级相关，但与女性无关。以这种方式，衰老过程中心脏细胞和亚细胞水平的重塑是根据男性整体健康状况分级的。这些变化可能导致虚弱的老年男性心脏病，而女性可能对这些虚弱影响具有抗性。
