Calico Life Sciences LLC, 1170 Veterans Blvd, South San Francisco, CA, 94080, USA.
Department of Medical Biology, Amsterdam University Medical Centers, University of Amsterdam, 1105, AZ, Amsterdam, The Netherlands.
Geroscience. 2022 Apr;44(2):731-746. doi: 10.1007/s11357-022-00522-6. Epub 2022 Feb 2.
The prevalence of cardiovascular disease increases exponentially with age, highlighting the contribution of aging mechanisms to cardiac diseases. Although model organisms which share human disease pathologies can elucidate mechanisms driving disease, they do not provide us with innate examples how cardiac aging might be slowed or attenuated. The identification of animal models that preserve cardiac function throughout most of life offers an alternative approach to study mechanisms which might slow cardiac aging. One such species may be the naked mole-rat (NMR), a mouse-sized (40 g) rodent with extraordinary longevity (> 37 years), and constant mortality hazard over its four decades of life. We used a cross-sectional study design to measure a range of physiological parameters in NMRs between 2 and 34 years of age and compared these findings with those of mice aged between 3 months and 2.5 years. We observed a rapid decline in body fat content and bone mineral density in old mice, but no changes in NMRs. Similarly, rhythm disorders (premature atrial and ventricular complexes) occurred in aged mice but not in NMRs. Magnetic resonance and ultrasound imaging showed age-dependent increases in cardiac hypertrophy and diastolic dysfunction in mice which were absent in NMRs. Finally, cardiac stress tests showed an age-dependent decline in normalized cardiac output in mice, which was absent in NMRs. Unlike mice, that manifest several aspects of human cardiac aging, NMRs maintain cardiac function and reserve capacity throughout their long lives and may offer insights on how to delay or prevent cardiac aging.
心血管疾病的患病率随年龄呈指数级增长，这突出了衰老机制对心脏疾病的贡献。虽然具有人类疾病病理的模式生物可以阐明导致疾病的机制，但它们不能为我们提供固有示例，说明如何减缓或减弱心脏衰老。鉴定在大多数生命中保持心脏功能的动物模型为研究可能减缓心脏衰老的机制提供了一种替代方法。裸鼹鼠（NMR）可能是一种这样的物种，它是一种老鼠大小（40 克）的啮齿动物，具有非凡的长寿（>37 年），并且在其四十年的生命中始终存在死亡危险。我们使用横断面研究设计来测量 NMR 中 2 至 34 岁之间的一系列生理参数，并将这些发现与 3 个月至 2.5 岁之间的小鼠进行了比较。我们观察到老年小鼠的体脂肪含量和骨矿物质密度迅速下降，但 NMR 没有变化。同样，节律障碍（房性和室性早搏）发生在老年小鼠中，但不在 NMR 中。磁共振和超声成像显示，小鼠的心脏肥大和舒张功能随年龄增长而增加，而 NMR 中则没有。最后，心脏压力测试显示，小鼠的正常化心输出量随年龄增长而下降，而 NMR 中则没有。与表现出多种人类心脏衰老特征的小鼠不同，NMR 在其漫长的一生中保持心脏功能和储备能力，并可能为如何延缓或预防心脏衰老提供见解。
