Brain Science

The “Zombie” That’s Threatening Your Memory

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The “Zombie” That’s Threatening Your Memory about undefined
You probably think zombies are only made up for scary television, movies, and books. However, that’s not entirely true… There’s a real-life zombie that can weaken your memory and lead you down the road to Alzheimer’s disease. Here’s what you need to know… As cells age, their health can be compromised by a process called cellular senescence. Although the cells remain functional, they undergo multiple changes that disrupt normal tissue repair and regeneration, thereby contributing to aging. Senescence is also thought to play a role in cellular stress, molecular damage, and cancer. However, researchers believed senescence primarily occurs in dividing cells, not in brain cells, or neurons, which don’t divide. Turns out, they knew very little about the senescence-like state of aging human neurons. Recently, scientists at the Salk Institute carried out some brand-new research. What they found was shocking…

Aging Brain Cells Turn Into Zombie Cells 

The Salk team began by taking samples of skin from people with Alzheimer’s. Then, they converted the skin cells into neurons and tested them to see if they undergo senescence, examining the mechanisms involved in the process. They also tested brain samples from twenty post-mortem victims of Alzheimer’s and the same number of matched controls from the bodies of people who did not have Alzheimer’s disease to explore senescence markers and gene expression. After completing their analysis, the scientists found senescent neurons are like zombie cells. Instead of being swept away and disposed of by the body, these senescent zombie cells hang around and accumulate in the aging brain to secrete a cocktail of toxins that damage healthy cells.

Trigger Brain Inflammation Found In Alzheimer’s Disease 

The researchers found these zombie cells are a source of the late-life brain inflammation observed in Alzheimer’s disease. As the neurons deteriorate, they release inflammatory factors that trigger a cascade of brain inflammation and cause other brain cells to go haywire and not function correctly. This can result in memory loss, dementia, and even Alzheimer’s disease. The team also found that a gene called KRAS, which is commonly involved in cancer, can activate the senescent response.

Senescent “Zombie” Brain Cells Can Damage Memory, Cognition 

Rusty Gage, senior author of the new study published in the journal Cell in December, said, “Our study clearly demonstrates that these non-replicating cells are going through the deterioration process of senescence and that it is directly related to neuroinflammation and Alzheimer’s disease.” First author Joseph Herdy added, “Scientists typically do not validate their lab results in human brain tissue. The fact that our findings were consistent across both settings supports our results that these senescent neurons are truly having a robust inflammatory response that is significantly affecting the brain.” The authors note that the consequences of even a small number of senescent neurons in the aging brain could have a significant impact on brain function. This is because a single neuron can make more than a thousand connections with other neurons, affecting the brain’s communication system. The researchers achieved a lot, but they weren’t finished yet. The next step was to see if these zombie cells could be cleared away from the brain.

Good News: Zombies Can Be Mopped Up 

Drugs to clear senescent cells, called senolytics, are hot topics in anti-aging research. But a breakthrough study suggests senolytics should be a key ingredient of treatment in the neurology field, too. Especially when it comes to Alzheimer’s disease. For example, DQ, the senolytic used by the Salk team, contained two strange bedfellows. It combined the leukemia drug dasatinib with quercetin, a plant pigment and potent antioxidant found in many nutritious fruits and vegetables. Earlier research had already shown DQ is effective at clearing zombie cells from the body in conditions such as osteoarthritis. When they added DQ to neurons of Alzheimer’s patients in a petri dish, the drug cocktail reduced the number of senescent neurons to normal levels. The scientists therefore believe targeting senescent cells could be a useful approach for slowing neuroinflammation and neurodegeneration in Alzheimer’s disease and preserving memory. Although under normal circumstances DQ cannot enter the brain, other drugs can, and the scientists believe they should have a similar effect and could be used as a treatment option in the future. The Salk team will continue to pursue how senescent neurons lead to Alzheimer’s disease as well as the consequences of removing these neurons from the brain. They also plan to test senolytic drugs that can cross the blood brain barrier. I’ll keep you posted on any new developments in this exciting research.
  1. https://www.salk.edu/news-release/deteriorating-neurons-are-source-of-human-brain- inflammation-in-alzheimers-disease/
  2. https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00457-X 

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