Reversing Age Related Memory Decline by Fixing Brain Cartilage?

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Most of us get “Senior Moments” as we age. You know the moments when you just can’t seem to recall that name or factoid like you used to. So what causes this and can it be completely reversed? Well, it may have something to do with “cartilage” in the brain. Let’s dive in.

The Scaffolding of the Brain

All cells in the body live in some sort of scaffolding which is also called ECM or Extra-Cellular Matrix. In the brain, this is called a “perineuronal net”. Believe it or not, this is a cartilage-like structure that surrounds brain cells and controls neuroplasticity. What’s that?

Neuroplasticity is what we have in abundance as kids. Basically, the ability to learn new things quickly by forming new neural connections in the brain. As we get older, this neuroplasticity decreases to make the brain more efficient. All of this is controlled by the mix of chemicals in the “brain cartilage” (ECM or Extracellular Matrix) surrounding these cells.

This neuroplasticity switch is controlled by the balance between two cartilage-like chemicals chondroitin-4-sulfate and chondroitin-6-sulfate. If you have more of the “4 version” of this chemical, neuroplasticity goes down and if you have more of the “6 version” it goes up. So a drug or genetic treatment that ups the amount of chondroitin-6-sulfate in an older animal should make it able to learn again like a youngster.

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Recent Research

A UK team out of Cambridge and the University of Leeds took a virus that was engineered to insert mRNA that made the protein chondroitin-6-sulfate and inserted that into the brains of older mice with memory deficits (1). Sure enough, by making more of this plasticity chemical, the mice regained their ability to learn and remember at levels similar to those seen when they were younger. They then confirmed these findings by breeding mice to produce low levels of chondroitin-6-sulfate and these mice indeed showed signs of impaired memory at a younger age. They then treated these mice with their viral vector treatment and upped the chondroitin-6-sulfate levels in the brain and the mice were able to learn again!

The team has already identified an oral drug that they believe can do the same thing. When this compound is given to mice it acts like a virus and restores memory. It also helps damaged spinal cords heal. The researchers are now investigating whether it can help an animal model of Alzheimer’s disease.

ECM and Aging

I’ve blogged before on this concept of young ECM making older cells act younger. Other research also exists showing that if we can change the stuff in which our cells are living, we may be able to help old cells function better. So while more research needs to be done, this is an exciting area.

The upshot? Can you get rid of age-related memory decline just by fixing the composition of this brain cartilage? If so, then a future where “senior moments” are a thing of the past is likely possible.

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(1) Sujeong Yang, Sylvain Gigout, Angelo Molinaro, Yuko Naito-Matsui, Sam Hilton, Simona Foscarin, Bart Nieuwenhuis, Chin Lik Tan, Joost Verhaagen, Tommaso Pizzorusso, Lisa M. Saksida, Timothy M. Bussey, Hiroshi Kitagawa, Jessica C. F. Kwok, James W. Fawcett. Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing. Molecular Psychiatry, 2021; DOI: 10.1038/s41380-021-01208-9

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Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications. View Profile

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