CHICAGO - Researchers from the University of Michigan (UM) Life Sciences Institute have uncovered a cause of declining motor function and increased frailty in tiny aging worms, and identified a molecule that can be targeted to improve motor function.

As humans and animals age, their 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.

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

They identified a molecule called SLO-1, namely 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 Shawn Xu, a professor of molecular and integrative physiology at the UM Medical School. "But we found that the interventions improved both parameters-these worms are healthier and they live longer."

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.

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

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

The findings were published on Wednesday in Science Advances.