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Study discovers link between fatal childhood disease and age-related muscle deterioration

by Pragati Singh
mental

According to new study, adopting some of the tactics used to successfully treat the juvenile condition spinal muscular atrophy may enable the creation of medicines to slow the muscle degeneration that occurs with age. The study poster was exhibited at Neuroscience 2022, the Society for Neuroscience’s annual meeting. The survival motor neuron protein, which is distributed throughout the body and is necessary for keeping motor neuron cells alive and transmitting correct signals from the central nervous system to muscles, lies at the core of both illnesses.

Spinal muscular atrophy (SMA) is caused by a gene mutation that results in lower quantities of this protein, and gene therapy is one of three clinically accessible SMA treatments. The initial gene therapy recipients are already six years old.
Based on years of SMA research demonstrating the relevance of survival motor neuron protein to neuromuscular integrity, Ohio State University researchers are investigating linkages between the protein and sarcopenia, or the age-related loss of skeletal muscle mass and strength.

Their recent mouse study reveals a definite function for survival motor neuron (SMN) protein in muscle ageing: The protein levels in the spinal cords and motor neurons of advanced-age mice were 22% and 55% lower, respectively, than in middle-aged animals, and these protein decreases were followed by decreased muscle function.

“We found that SMN protein and aging are related – there is a decline in the protein with age and it correlates with a decline in neuromuscular function,” said first author Maria Balch, a postdoctoral scholar in neuroscience at Ohio State’s College of Medicine. “Based on what we know about SMA and therapeutics, we have a background in targeting SMN protein – and it’s possible that could be something down the line that could be applied to age-induced neuromuscular decline.”

The survival motor neuron protein is produced by two genes, SMN1 and SMN2. SMN1 is essential for motor neuron survival and function because it conducts the majority of the effort in producing the full-length protein. SMN2, which largely produces a shortened version, contributes slightly to full-length protein synthesis and may be regarded of as a helper – having more copies of the SMN2 gene is related with milder types of SMA.

The Ohio State researchers discovered that mice modified to express higher-than-normal quantities of the SMN protein had greater overall neuromuscular resilience and recovered from nerve damage faster. “That raised some questions,” said senior Ohio State author Arthur Burghes, a professor of biological chemistry and pharmacology and molecular genetics who developed the mouse model that advanced SMA research. “Different people get different amounts of weakness with age. Why are some people completely resistant to it, and other people are more susceptible?

“With aging and sarcopenia, there is an increased chance of injury due to falling. So it’s an important problem.” Though the researchers assume that a mix of genetics and behaviour is at work, there is a potential that the problem may be solved by enticing the ageing body to generate more SMN protein based on what they’ve discovered so far. This new study assessed a variety of parameters in mice divided into three age groups: 6-10 months, 21 months, and 27 months, which correspond roughly in human years to 35-50, 55, and above 70.

Researchers discovered other trends in older mice, in addition to the natural decrease in protein levels in the spinal cord and motor neurons with age: reductions in the number of motor units, or motor neurons plus the muscle cells they stimulate, as well as a decline in the function of muscles responding to nerve stimulation.
In terms of prospective therapeutic options, the viral-mediated gene therapy now in the clinic for newborns with SMA is unlikely to be effective for adults due to the enormous amount of virus required. The team is looking at different ways to boost SMN output.

“We know in the field of SMA that targeting an increase in SMN protein can be approached from different directions.
If we can determine that this is a viable therapeutic target in aging, there’s a lot of research we can lean on to help drive the direction of age-related therapeutics,” Balch said.

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