Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA, USA.
Graduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Blacksburg, VA, USA.
Aging Cell. 2018 Apr;17(2). doi: 10.1111/acel.12726. Epub 2018 Feb 4.
Motor function deteriorates with advancing age, increasing the risk of adverse health outcomes. While it is well established that skeletal muscles and neuromuscular junctions (NMJs) degenerate with increasing age, the effect of aging on α-motor neurons and their innervating synaptic inputs remains largely unknown. In this study, we examined the soma of α-motor neurons and innervating synaptic inputs in the spinal cord of aged rhesus monkeys and mice, two species with vastly different lifespans. We found that, in both species, α-motor neurons retain their soma size despite an accumulation of large amounts of cellular waste or lipofuscin. Interestingly, the lipofuscin profile varied considerably, indicating that α-motor neurons age at different rates. Although the rate of aging varies, α-motor neurons do not atrophy in old age. In fact, there is no difference in the number of motor axons populating ventral roots in old mice compared to adult mice. Moreover, the transcripts and proteins associated with α-motor neurons do not decrease in the spinal cord of old mice. However, in aged rhesus monkeys and mice, there were fewer cholinergic and glutamatergic synaptic inputs directly abutting α-motor neurons, evidence that aging causes α-motor neurons to shed synaptic inputs. Thus, the loss of synaptic inputs may contribute to age-related dysfunction of α-motor neurons. These findings broaden our understanding of the degeneration of the somatic motor system that precipitates motor dysfunction with advancing age.
随着年龄的增长，运动功能会逐渐恶化，增加不良健康后果的风险。虽然骨骼肌肉和神经肌肉接头 (NMJs) 随着年龄的增长而退化已经得到充分证实，但年龄对α-运动神经元及其支配的突触输入的影响在很大程度上仍然未知。在这项研究中，我们检查了衰老恒河猴和小鼠脊髓中α-运动神经元的体和支配的突触输入，这两种物种的寿命差异很大。我们发现，在这两种物种中，尽管积累了大量的细胞废物或脂褐素，α-运动神经元仍然保持其体大小。有趣的是，脂褐素的分布差异很大，表明α-运动神经元以不同的速度衰老。尽管衰老的速度不同，但α-运动神经元在老年时不会萎缩。事实上，与成年小鼠相比，老年小鼠的腹根中支配运动神经元的运动轴突数量没有差异。此外，与α-运动神经元相关的转录物和蛋白质在老年小鼠的脊髓中没有减少。然而，在衰老的恒河猴和小鼠中，直接毗邻α-运动神经元的胆碱能和谷氨酸能突触输入较少，这表明衰老导致α-运动神经元失去突触输入。因此，突触输入的丧失可能导致与年龄相关的α-运动神经元功能障碍。这些发现拓宽了我们对引发运动功能随着年龄增长而恶化的躯体运动系统退化的理解。
