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Sci Adv. 2019 Jan 2;5(1):eaau5041. doi: 10.1126/sciadv.aau5041. eCollection 2019 Jan.

Genetic and pharmacological interventions in the aging motor nervous system slow motor aging and extend life span in C. elegans.

Li G1,2, Gong J1,2, Liu J2,3, Liu J1,2, Li H2, Hsu AL4,5,6, Liu J1, Xu XZS2,4.

Author information

1
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.
2
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
3
Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia.
4
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
5
Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
6
Research Center for Healthy Aging, China Medical University, Taichung 404, Taiwan.

Abstract

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 Caenorhabditis elegans 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.

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