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

doi:10.1126/sciadv.aau5041

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

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

Authors

Guang Li^{1

2}, Jianke Gong^{1

2}, Jie Liu^{2

3}, Jinzhi Liu^{1

2}, Huahua Li², Ao-Lin Hsu^{4

5

6}, Jianfeng Liu¹, X Z Shawn Xu^{2

4}

Affiliations

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging / metabolism*
Animals
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / antagonists & inhibitors*
Caenorhabditis elegans Proteins / genetics*
Forkhead Transcription Factors / genetics
Gene Knockdown Techniques
Indoles / pharmacology
Large-Conductance Calcium-Activated Potassium Channels / antagonists & inhibitors*
Large-Conductance Calcium-Activated Potassium Channels / genetics*
Locomotion / drug effects
Locomotion / genetics
Longevity*
Motor Activity / drug effects*
Motor Activity / genetics*
Motor Neurons / metabolism*
Neuromuscular Junction / metabolism
Synaptic Transmission

Substances

Caenorhabditis elegans Proteins
Forkhead Transcription Factors
Indoles
Large-Conductance Calcium-Activated Potassium Channels
daf-16 protein, C elegans
slo-1 protein, C elegans
paxilline

Abstract

Publication types

MeSH terms

Substances

Grants and funding