International Research Center for Sensory Biology and Technology of MOST, Key Laboratory of Molecular Biophysics of MOE, and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Sci Adv. 2019 Jan 2;5(1):eaau5041. doi: 10.1126/sciadv.aau5041. eCollection 2019 Jan.
As animals and humans age, the motor system undergoes a progressive functional decline, leading to frailty. Age-dependent functional deteriorations at neuromuscular junctions (NMJs) contribute to this motor aging. However, it is unclear whether one can intervene in this process to slow motor aging. The BK channel SLO-1 dampens synaptic transmission at NMJs by repressing synaptic release from motor neurons. Here, we show that genetic ablation of SLO-1 not only reduces the rate of age-dependent motor activity decline to slow motor aging but also surprisingly extends life span. SLO-1 acts in motor neurons to mediate both functions. Genetic knockdown or pharmacological inhibition of SLO-1 in aged, but not young, worms can slow motor aging and prolong longevity. Our results demonstrate that genetic and pharmacological interventions in the aging motor nervous system can promote both health span and life span.
随着动物和人类年龄的增长，运动系统会逐渐出现功能衰退，导致虚弱。神经肌肉接点 (NMJ) 的年龄依赖性功能恶化是导致这种运动衰老的原因之一。然而，目前尚不清楚是否可以干预这一过程以减缓运动衰老。BK 通道 SLO-1 通过抑制运动神经元的突触释放来调节 NMJ 的突触传递。在这里，我们发现 SLO-1 的基因缺失不仅可以降低与年龄相关的运动活动下降的速度，从而减缓运动衰老，而且还可以出人意料地延长寿命。SLO-1 在运动神经元中发挥作用，介导这两种功能。在年老的而非年轻的蠕虫中，SLO-1 的基因敲低或药理学抑制可以减缓运动衰老并延长寿命。我们的研究结果表明，对衰老运动神经系统的遗传和药理学干预可以促进健康寿命和寿命的延长。
