Scientists gain insight into the earliest changes that impair motor function during aging

A team of biomedical scientists led by Gregorio Valdez, an assistant professor at the Virginia Tech Carilion Research Institute, has found that the motor neurons responsible for controlling muscle movement do not age. Rather, it’s the synaptic inputs connected to the motor neurons that age and cause bodily decay.

The study was published in Aging Cell.

“Motor function progressively erodes as individuals transition from adulthood into old age. Aging compromises gait speed, balance, and the command of fine motor skills, increasing the risk of injury due to falls and age-associated diseases,” said Valdez, who is also an assistant professor of biological sciences in Virginia Tech’s College of Science. “While it is well established that skeletal muscles and neuromuscular junctions degenerate with increasing age, the effect of aging on motor neurons and their inputs remains largely unknown.”

Valdez and his team analyzed two lines of motor neurons in an animal model. They examined the size of the neuron’s soma — the cell body of the neuron that can shrink with age — using a light microscope at different age points. They also measured levels of lipofuscin, the biological equivalent of rust. It’s a residual pigment that appears in aging organs.

“We found that the motor neurons retain their soma size despite an accumulation of large amounts of cellular waste or lipofuscin,” Valdez said.

The researchers also saw that while the neurons seemed unaffected by aging, they had fewer synaptic connective inputs. According to Valdez, this provides evidence that aging causes the motor neurons to shed these inputs.

Synaptic inputs from the brain and other spinal neurons to the motor neurons direct movement control. It appears the coordination of this movement control depends on the number of synaptic inputs – fewer inputs leads to less coordination. 

“These findings broaden our understanding of the degeneration of the somatic motor system that precipitates motor dysfunction with advancing age,” Valdez said.

Other authors include Nicholas Maxwell, who was a research associate in the Valdez lab; Ryan Castro, a doctoral student in the translational biology, medicine, and health graduate program; Natalia Sutherland, a research associate in the Valdez lab; Kelli Vaughn and Mark Szarowicz, both from the Translational Gerontology Branch of the National Institute on Aging and SoBran Inc.; and Rafael de Cabo and Julie Mattison, from the Translational Gerontology Branch of the National Institute on Aging.

This work was supported by National Institute of Neurological Disorder and Stroke, the National Institute on Aging, and VTCRI.