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Gut function in older mice was restored to youthful levels through the use of a shark-derived compound, demonstrating that age-related changes to neurological and gut functions may not be permanent after all.

The enteric nervous system within the mammalian gut appears to be particularly vulnerable to age-related degeneration. Previous studies have shown that old age is associated with progressively higher incidences of constipation, which is thought to be linked to compromised nerve function.

Scientists from the McMaster Brain-Body Institute at St. Joseph’s Healthcare Hamilton have published the results of a study that compared gut function of young and old mice. They found that older mice, like older humans, have progressively slower gut motility and frequent constipation. Notably, the research team then demonstrated that squalamine, a synthetic version of a compound derived from sharks, can restore age-related impairment of gut motility, thereby reducing instances of constipation.

Squalamine is an aminosterol compound first discovered in the liver of the dogfish shark in 1993. It was shown to have potent activity against a range of pathological micro-organisms, and has since provided insights into the development of a new family of broad-spectrum antibiotics. A synthetic form of squalamine is currently being tested in clinical trials involving patients with Parkinson’s Disease. Its use in this study to repair age-related neural degradation in the gut is a novel concept.

The researchers also found that the firing rate of the vagus nerve, which forms an important component of gut to brain signaling, is significantly slower in older mice compared to young mice. Remarkably, squalamine was also able to improve vagus nerve firing rates in older mice to approach those seen in young animals. This may have profound applications for regulating mood and appetite in the elderly.

“Since squalamine can directly excite the enteric nervous system, we hypothesized that it could have a positive effect on gut motility and the vagus nerve, whose firing rate is strongly influenced by the enteric nervous system,” said Christine West, a PhD candidate in Biology at McMaster University and lead author of the study.

Previous studies have shown that regular constipation may be comorbid with mood disorders, such as depression. The discovery that squalamine can positively affect neural signaling between the gut and the brain may lead to new techniques to treat mood disorders in aging patients.

With life expectancy continuing to rise, researchers have focused their attention to various aging processes. Research is revealing new methods that may work to halt or even reverse age-related changes to the body that were previously considered permanent and unalterable.

“The results of this study demonstrate that age-related changes to gut motility do exist,” said Dr. Wolfgang Kunze, senior author of the study. “Notably, it also shows that these changes are not permanent, since the effects can be restored to within range of the young mice.”

Kunze is an associate professor of psychiatry and behavioural neurosciences at McMaster.

“This discovery may have profound implications for the treatment of neurodegenerative diseases in elderly individuals,” said Kunze.

The study was published in the journal Frontiers in Neuroscience, with funding provided by a grant from the Natural Sciences and Engineering Research Council of Canada (NSERC).

The McMaster Brain-Body Institute is housed within the Research Institute of St. Joe’s Hamilton.

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