Data from: Sustained high levels of neuregulin-1 in the longest-lived rodents; a key determinant of rodent longevity

Naked mole-rats (Heterocephalus glaber), the longest-lived rodents, live 7-10 times longer than similarly–sized mice and exhibit normal activities for ∼75% of their lives. Little is known about the mechanisms that allow them to delay the aging process and live so long. Neuregulin-1 (NRG-1) signaling is critical for normal brain function during both development and adulthood. We hypothesized that long-lived species will maintain higher levels of NRG-1 and that this contributes to their sustained brain function and concomitant maintenance of normal activity. We monitored the levels of NRG-1 and its receptor ErbB4 in H. glaber at different ages ranging from 1 day to 26 years and found that levels for NRG-1 and ErbB4 were sustained throughout development and adulthood. In addition, we compared seven rodent species with widely divergent (4-32y) maximum lifespan potential (MLSP) and found that at a physiologically-equivalent age, the longer-lived rodents had higher levels of NRG-1 and ErbB4. Moreover, phylogenetic independent contrast analyses revealed that this significant strong correlation between MLSP and NRG-1 levels was independent of phylogeny. These results suggest that NRG-1 is an important factor contributing to divergent species MLSP through its role in maintaining neuronal integrity.

裸鼹鼠（Naked mole-rats，学名*Heterocephalus glaber*）是寿命最长的啮齿类动物，其寿命为同等体型小鼠的7至10倍，且一生中约75%的时间均可维持正常活动。目前学界对其延缓衰老进程、实现超长寿命的具体机制仍知之甚少。神经调节蛋白-1（Neuregulin-1，NRG-1）信号通路在发育与成年阶段的正常脑功能中均发挥关键调控作用。我们提出假说：长寿物种会维持更高水平的NRG-1，该因素有助于其持续维持脑功能，并伴随正常活动能力的稳定维持。我们检测了不同年龄段（从1日龄至26年）的裸鼹鼠体内NRG-1及其受体ErbB4的表达水平，发现二者的蛋白水平在发育及成年阶段均保持稳定。此外，我们对比了7种最大寿命潜力（Maximum Lifespan Potential，MLSP）差异显著（4至32年）的啮齿类动物，发现在生理等效年龄下，寿命更长的啮齿类动物体内NRG-1与ErbB4的水平更高。进一步的系统发育独立对比分析显示，MLSP与NRG-1水平之间的显著强相关性不受系统发育关系的影响。上述结果表明，NRG-1通过维持神经元完整性的作用机制，是影响不同物种最大寿命潜力的重要因素之一。