Living a Stronger and Longer Life

Summary: Researchers have identified a molecule that causes the decline of motor function and increased frailty in nematodes. Targeting the molecule with paxilline helps improve motor function and longevity.

Source: University of Michigan.

Research from the University of Michigan Life Sciences Institute has uncovered a cause of declining motor function and increased frailty in tiny aging worms—and a way to slow it down.

The findings, scheduled to publish Jan. 2 in Science Advances, identify a molecule that can be targeted to improve motor function and indicate that similar pathways may be at play in aging mammals as well.

As humans and animals age, our motor functions progressively deteriorate. Millimeter-long roundworms called nematodes exhibit aging patterns remarkably similar to those of other animals, and they only live about three weeks, making them an ideal model system for studying aging.

“We previously observed that as worms age, they gradually lose physiological functions,” said Shawn Xu, professor at the LSI and senior study author. “Sometime around the middle of their adulthood, their motor function begins to decline. But what causes that decline?”

To better understand how the interactions between cells changed as worms aged, Xu and his colleagues investigated the junctions where motor neurons communicate with muscle tissue.

They identified a molecule called SLO-1 (for “slowpoke potassium channel family member 1”) that acts as a regulator for these communications. The molecule dampens neurons’ activity, slowing down the signals from neurons to muscle tissue and reducing motor function.

The researchers manipulated SLO-1, first using genetic tools and then using a drug called paxilline. In both cases, they observed two major effects in the roundworms. Not only did they maintain better motor function later in life, they also lived longer than normal roundworms.

“It’s not necessarily ideal to have a longer lifespan without improvements in health or strength,” said Xu, who is also a professor of molecular and integrative physiology at the U-M Medical School. “But we found that the interventions improved both parameters—these worms are healthier and they live longer.”

Perhaps more surprisingly, the timing of the interventions drastically changed the effects on both motor function and lifespan. When SLO-1 was manipulated early in the worms’ life, it had no effect on lifespan and in fact had a detrimental effect on motor function in young worms. But when the activity of SLO-1 was blocked in mid-adulthood, both motor function and lifespan improved.

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The researchers manipulated SLO-1, first using genetic tools and then using a drug called paxilline. In both cases, they observed two major effects in the roundworms. Not only did they maintain better motor function later in life, they also lived longer than normal roundworms. NeuroscienceNews.com image is in the public domain.

Because the SLO-1 channel is preserved across many species, Xu hopes these findings will encourage others to examine its role in aging in other model organisms.

“Studying aging in organisms with longer lifespans is a major investment,” he said. “But now we have identified a molecular target, a potential site and specific timing, which should facilitate further investigation.”

The researchers next hope to determine the importance of the SLO-1 channel in early development in the worms and also to better understand the mechanisms through which it affects lifespan.

About this neuroscience research article

Funding: The research was primarily supported by the National Institutes of Health. In addition to Xu, the study authors are: Guang Li, Jianke Gong, Jie Liu, Jinzhi Liu, Huahua Li and Ao-Lin Hsu, all of U-M; and Jianfeng Liu of the College of Life Science and Technology and Huazhong University of Science and Technology, China.

Source: Jim Erickson – University of Michigan
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Open access research for “Genetic and pharmacological interventions in the aging motor nervous system slow motor aging and extend life span in C. elegans” by Guang Li, Jianke Gong, Jie Liu, Jinzhi Liu, Huahua Li, Ao-Lin Hsu, Jianfeng Liu and X.Z. Shawn Xu in Science Advances. Published January 2 2019.
doi:10.1126/sciadv.aau5041

Cite This NeuroscienceNews.com Article
University of Michigan”Living a Stronger and Longer Life.” NeuroscienceNews. NeuroscienceNews, 3 January 2019.
<http://neurosciencenews.com/stronger-longer-life-10420/>.
University of Michigan(2019, January 3). Living a Stronger and Longer Life. NeuroscienceNews. Retrieved January 3, 2019 from http://neurosciencenews.com/stronger-longer-life-10420/
University of Michigan”Living a Stronger and Longer Life.” http://neurosciencenews.com/stronger-longer-life-10420/ (accessed January 3, 2019).

Abstract

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

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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