Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France.
LabEx Ion Channels Science and Therapeutics (ICST), Sophia Antipolis, France.
Sci Rep. 2023 Feb 21;13(1):3054. doi: 10.1038/s41598-023-29723-5.
Microcebus murinus, or gray mouse lemur (GML), is one of the smallest primates known, with a size in between mice and rats. The small size, genetic proximity to humans and prolonged senescence, make this lemur an emerging model for neurodegenerative diseases. For the same reasons, it could help understand how aging affects cardiac activity. Here, we provide the first characterization of sinoatrial (SAN) pacemaker activity and of the effect of aging on GML heart rate (HR). According to GML size, its heartbeat and intrinsic pacemaker frequencies lie in between those of mice and rats. To sustain this fast automaticity the GML SAN expresses funny and Ca currents (I, I and I) at densities similar to that of small rodents. SAN automaticity was also responsive to β-adrenergic and cholinergic pharmacological stimulation, showing a consequent shift in the localization of the origin of pacemaker activity. We found that aging causes decrease of basal HR and atrial remodeling in GML. We also estimated that, over 12 years of a lifetime, GML generates about 3 billion heartbeats, thus, as many as humans and three times more than rodents of equivalent size. In addition, we estimated that the high number of heartbeats per lifetime is a characteristic that distinguishes primates from rodents or other eutherian mammals, independently from body size. Thus, cardiac endurance could contribute to the exceptional longevity of GML and other primates, suggesting that GML's heart sustains a workload comparable to that of humans in a lifetime. In conclusion, despite the fast HR, GML replicates some of the cardiac deficiencies reported in old people, providing a suitable model to study heart rhythm impairment in aging. Moreover, we estimated that, along with humans and other primates, GML presents a remarkable cardiac longevity, enabling longer life span than other mammals of equivalent size.
灰鼠狐猴（GML），又名小褐鼠狐猴，是已知最小的灵长类动物之一，体型介於老鼠和大鼠之间。其体型小、与人类的遗传关系密切以及衰老过程延长，使这种狐猴成为神经退行性疾病的新兴模型。同样，它也可以帮助了解衰老如何影响心脏活动。在这里，我们首次描述了窦房结（SAN）起搏活动，并研究了衰老对 GML 心率（HR）的影响。根据 GML 的体型，其心跳和固有起搏频率介於老鼠和大鼠之间。为了维持这种快速的自动性，GML 的 SAN 表达有趣和 Ca 电流（I、I 和 I）的密度与小型啮齿动物相似。SAN 的自动性也对β-肾上腺素能和胆碱能的药理学刺激有反应，从而导致起搏活动起源的位置发生相应变化。我们发现衰老会导致 GML 的基础 HR 和心房重构减少。我们还估计，在 12 年的寿命中，GML 大约会产生 30 亿次心跳，因此，与人类一样多，是同等体型的啮齿动物的三倍。此外，我们估计，一生中的心跳次数多是灵长类动物与啮齿动物或其他真兽类哺乳动物的区别特征，与体型无关。因此，心脏耐力可能有助于 GML 和其他灵长类动物的异常长寿，这表明 GML 的心脏可以承受与人类一生中相当的工作量。总之，尽管 GML 的心率很快，但它复制了一些在老年人中报告的心脏缺陷，为研究衰老中心律失常提供了合适的模型。此外，我们估计，与人类和其他灵长类动物一样，GML 具有显著的心脏长寿性，使其寿命比同等体型的其他哺乳动物更长。
