Can we rejuvenate aging brains?

Summary: Researchers discuss current studies on cognitive rejuvenation and discuss steps we can take to help protect our brains as we age.

Source: Stanford

Neuroscientist Tony Wyss-Coray, Ph.D., has spent 20 years unearthing and examining various molecules with neuroprotective and neurodegenerative properties. These molecules are found in or on different types of cells in the brain and on the blood vessels adjoining it, or floating in the blood and the cerebrospinal fluid that bathes it. And they become more and more important as we get older.

Wyss-Coray and his colleagues have discovered substances in the blood that can speed up or slow down the brain’s aging clock. They have identified proteins on the surface of blood vessels through which some of these molecules can act on the brain, despite the existence of the blood-brain barrier. He even showed that older mice given cerebrospinal fluid from young mice look and act younger.

I asked Wyss-Coray, DH Chen Professor Emeritus of Neurology and Neurological Sciences and director of the Phil and Penny Knight Initiative for Brain Resilience, to relate his findings in the field of cognitive rejuvenation.

Tell us about cognitive loss related to aging.

The problems of aging begin to become tangible for most people beyond the age of 50 or 60, when one realizes that finding a person’s name or a word on the tip of one’s tongue is not just the result of a bad day, but a manifestation of aging, such as wrinkles or graying hair. These memory lapses become more frequent and we begin to speak more slowly so that we can replace the missing words with others.

Although it is not clear how this normal age-related decline is linked to more severe cognitive impairment and dementia, one-third of Americans over the age of 85 have symptoms of Alzheimer’s disease, and this number doubles over the next 10 years of life. Unfortunately, we have no tools to predict who will go from oblivion to dementia.

However, not everyone is destined to experience this downward trajectory. One in three centenarians appears to be resilient to cognitive decline. This provides hope and a springboard for studying brain aging and cognitive decline.

How did you come to research “youthful fluids” as a means of cognitive rejuvenation?

Brain tissue is rarely available in living subjects, so we focused our research on cerebrospinal fluid and blood. Those early studies, now more than 15 years ago, of fluids from older people with normal cognition and patients with Alzheimer’s disease were hampered by unreliable tests, but they showed us one thing: Global age-related changes in blood protein composition were profound.

We confirmed that the levels of a large number of proteins changed significantly between the 20th and 90th year of life. Because age is, by far, the most important risk factor for Alzheimer’s disease and other neurodegenerative diseases, the question arose whether the changes we observed were a cause of aging. cerebral or a consequence.

To find out, we resorted to a method that former Stanford Medicine neurology professor Tom Rando, MD, Ph.D. (now at UCLA), whose lab was right next to mine, used to study the aging of muscle stem cells: by surgically joining the circulatory systems of a young and an old mouse, so that the animals share their blood.

What we observed is striking: aged mice exposed to the blood of their young partner showed multiple signs of rejuvenation, including an increase in the number of certain types of neurons, an increase in neuronal activity and a reduction in cerebral inflammation.

When we treated old mice with repeated intravenous infusions of young plasma (the liquid fraction of blood), these mice became more intelligent, behaving more like young mice on several cognitive tests. Conversely, young mice exposed to aged blood or treated with aged plasma experienced accelerated brain aging and loss of cognitive function.

Are these discoveries applicable to humans?

The results have, in part, been transposed to humans. In clinical trials, young plasma infusions have produced significant benefits in patients with Alzheimer’s disease. In a double-blind, placebo-controlled clinical trial (conducted by others), removal of plasma and replacement with albumin-rich plasma from young donors resulted in significant functional improvements in patients with Alzheimer’s disease .

This implies that blood exchange experiments in mice may be relevant to humans and that blood plasma may hold the secret to rejuvenation.

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You and your colleagues have identified many substances and proteins found in various body fluids and tissues, all acting in different places to enhance the youthfulness of different types of brain cells. Can you explain how so many different substances, cell types, and processes seem to produce similar results?

Biology is a complex web of interconnected systems. There are several hundred thousand nodes in this network that we call a biological organism, comprising proteins, sugars, lipids and metabolites. Each of these components performs a function fine-tuned by evolution; it is sometimes essential and irreplaceable, but often it is redundant.

Imagine a flight map over the United States including all carriers and made up of hundreds of connection points, some larger than others. The network helps run the economy by moving goods and people from one place to another. Removing some nodes can cause the system to crash, while others can be taken out of service with little impact.

This shows a brain in a light bulb
Brain tissue is rarely available in living subjects, so we focused our research on cerebrospinal fluid and blood. Image is in public domain

Some of the most effective drugs, such as the go-to anti-inflammatory aspirin, have been shown to target multiple biological pathways across many different cell types and tissues. Young plasma or cerebrospinal fluid – nature’s cocktails – seems to contain dozens of beneficial proteins and probably other types of molecules, and may well remain the most potent elixir.

In mice, at least, it seems possible to obtain therapeutic benefits using the individual protein factors we have identified. One protein may be particularly helpful in delaying muscle loss, while another may boost brain function.

What can we all do here and now to keep our brains in shape?

Stress seems to be the greatest source of damage we can inflict on our bodies. This not only leads to physical symptoms such as high blood pressure, chest pain, digestive issues, and trouble sleeping; it also weakens the immune system and contributes to inflammation, possibly accelerating the aging process. Chronic stress is a key source of psychiatric manifestations and unhappiness.

A recent large study suggests that up to 40% of dementia cases in the United States are due to modifiable risk factors, including hypertension, obesity, and physical inactivity. Currently, there are no good pharmacological treatments for cognitive decline and neurodegeneration. In their absence, some of the most scientifically documented benefits to brain function come from exercise.

About this aging and neuroscience research news

Author: Bruce Goldman
Source: Stanford
Contact: Bruce Goldman–Stanford
Image: Image is in public domain

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