Grimes Kelly M, Reddy Anilkumar K, Lindsey Merry L, Buffenstein Rochelle
Department of Physiology and the Sam and Ann Barshop Institute for Aging and Longevity Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas;
Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas; Indus Instruments, Webster, Texas;
Am J Physiol Heart Circ Physiol. 2014 Aug 1;307(3):H284-91. doi: 10.1152/ajpheart.00305.2014. Epub 2014 Jun 6.
The naked mole-rat (NMR) is the longest-lived rodent known, with a maximum lifespan potential (MLSP) of >31 years. Despite such extreme longevity, these animals display attenuation of many age-associated diseases and functional changes until the last quartile of their MLSP. We questioned if such abilities would extend to cardiovascular function and structure in this species. To test this, we assessed cardiac functional reserve, ventricular morphology, and arterial stiffening in NMRs ranging from 2 to 24 years of age. Dobutamine echocardiography (3 μg/g ip) revealed no age-associated changes in left ventricular (LV) function either at baseline or with exercise-like stress. Baseline and dobutamine-induced LV pressure parameters also did not change. Thus the NMR, unlike other mammals, maintains cardiac reserve with age. NMRs showed no cardiac hypertrophy, evidenced by no increase in cardiomyocyte cross-sectional area or LV dimensions with age. Age-associated arterial stiffening does not occur since there are no changes in aortic blood pressures or pulse-wave velocity. Only LV interstitial collagen deposition increased 2.5-fold from young to old NMRs (P < 0.01). However, its effect on LV diastolic function is likely minor since NMRs experience attenuated age-related increases in diastolic dysfunction in comparison with other species. Overall, these findings conform to the negligible senescence phenotype, as NMRs largely stave off cardiovascular changes for at least 75% of their MLSP. This suggests that using a comparative strategy to find factors that change with age in other mammals but not NMRs could provide novel targets to slow or prevent cardiovascular aging in humans.
裸鼹鼠是已知寿命最长的啮齿动物，其最大寿命潜能（MLSP）超过31年。尽管寿命极长，但这些动物在其MLSP的最后四分之一阶段之前，许多与年龄相关的疾病和功能变化都有所减轻。我们质疑这种能力是否会延伸到该物种的心血管功能和结构。为了验证这一点，我们评估了2至24岁裸鼹鼠的心脏功能储备、心室形态和动脉僵硬度。多巴酚丁胺超声心动图（3μg/g腹腔注射）显示，无论是在基线状态还是在类似运动应激的情况下，左心室（LV）功能均未出现与年龄相关的变化。基线和多巴酚丁胺诱导的LV压力参数也没有改变。因此，与其他哺乳动物不同，裸鼹鼠随着年龄增长仍能维持心脏储备功能。裸鼹鼠未出现心脏肥大，这可通过心肌细胞横截面积或LV尺寸未随年龄增加得到证明。由于主动脉血压或脉搏波速度没有变化，因此未发生与年龄相关的动脉僵硬化。只有LV间质胶原沉积从幼年到老年裸鼹鼠增加了2.5倍（P<0.01）。然而，其对LV舒张功能的影响可能较小，因为与其他物种相比，裸鼹鼠与年龄相关的舒张功能障碍增加有所减轻。总体而言，这些发现符合可忽略衰老表型，因为裸鼹鼠在其MLSP的至少75%时间内基本避免了心血管变化。这表明，采用比较策略来寻找在其他哺乳动物中随年龄变化而在裸鼹鼠中不变化的因素，可能为延缓或预防人类心血管衰老提供新的靶点。
