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

Guang Li, Jianke Gong, Jie Liu, Jinzhi Liu, Huahua Li, Ao Lin Hsu, Jianfeng Liu, X. Z. Shawn Xu

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Article numbereaau5041
Number of pages12
JournalScience Advances
Volume5
Issue number1
DOIs
Publication statusPublished - 2 Jan 2019

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