Can we rejuvenate the aging brain?

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

A source: Stanford

Neuroscientist Tony Wiss-Corey, Ph.D., has spent 20 years digging and researching various molecules with neuroprotective and neurodegenerative properties. These molecules float in or on the various cell types of the brain and in the blood vessels that connect to it or in the blood and cerebrospinal fluid that washes it. And they become more important as we age.

Wyss-Coray and her colleagues found substances in the blood that speed up or slow down the brain’s aging clock. They identified proteins on blood vessel surfaces where some of these molecules can affect the brain despite the presence of the blood-brain barrier. He even showed that older mice with younger cerebrospinal fluid looked younger and acted younger.

I asked Wyss-Coray, Distinguished Professor of Neurology and Neuroscience and Director of the Phil and Penny Knight Brain Resilience Initiative, to synthesize his findings in the field of cognitive rejuvenation.

Tell us about cognitive loss associated with aging.

For most people in their 50s or 60s, the problems of aging begin to appear, and repeating a person’s name or a word on the tip of the tongue isn’t just the result of a bad day, but the opposite of aging—like wrinkles or gray hair. This memory loss is frequent and we start speaking more slowly to replace the missing words with other words.

Although it is unclear how this normal age-related decline relates to greater cognitive impairment and dementia, one-third of Americans over 85 have symptoms of Alzheimer’s disease, and that number is expected to double in the next 10 years. Unfortunately, we have no means of predicting who will progress from forgetfulness to dementia.

Not everyone is destined to experience this downward trajectory. One in every three centenarians appears to have sustained cognitive decline. This provides hope and a springboard for research into brain aging and cognitive decline.

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

Cerebral tissue is rarely found in living subjects, so we focused our study on cerebrospinal fluid and blood. These early studies, now more than 15 years ago, of fluids from cognitively normal elderly people and Alzheimer’s patients were hampered by unreliable analyses, but they did show us one thing: the general age-related changes in blood protein content were profound.

We have confirmed that levels of a large number of proteins change significantly between people’s 20s and 90s. Because age is the most important driver of risk for Alzheimer’s disease and other neurodegenerative diseases, the question is whether the changes we observed are a cause or a consequence of brain aging.

To find out, we asked Tom Rando, MD, Ph.D., a former professor of neurology at Stanford Medicine. (now at UCLA), whose lab was near mine, was using muscle stem cells to study aging: surgically connecting the circulatory system of a young mouse to an old mouse, and the animals shared their blood.

What we observed was surprising: old mice exposed to their young partner’s blood showed several signs of rejuvenation, including an increase in the number of certain types of neurons, increased neuronal activity, and reduced brain inflammation.

When we treated old mice with repeated intravenous infusions of young plasma (the liquid part of blood), these mice became smarter and performed as well as young mice on several cognitive tests. Conversely, young mice exposed to aged blood or treated with aged plasma showed accelerated brain aging and loss of cognitive function.

Do these findings apply to humans?

The findings, in part, have been translated to humans. In clinical trials, infusions of young plasma have shown significant benefits in Alzheimer’s patients. In a placebo-controlled, double-blind clinical trial (performed by others), its removal and replacement with albumin-rich plasma from young plasma donors led to significant improvements in Alzheimer’s disease patients.

This means that the blood transplant mouse experiments may be applicable to humans and that blood plasma may hold the secret to rejuvenation.

See also

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

Biology is a complex web of interconnected systems. This network contains several hundred thousand nodes, which we call a biological organism, including proteins, sugars, lipids, and metabolites. Each of these components fulfills a function honored by evolution; sometimes it is essential and indispensable, but often it is superfluous.

Imagine a flight map over the US that includes all the carriers and has hundreds of points of contact, some more important than others. Networks help run economies by moving goods and people from one place to another. Removing some nodes may cause the system to crash, while others may fail with little impact.

This shows the brain inside the bulb
Cerebral tissue is rarely found in living subjects, so we focused our study on cerebrospinal fluid and blood. Image is in the public domain

Some of the most successful drugs—for example, this powerful anti-inflammatory, aspirin—target multiple biological pathways across many different cell types and tissues. Young plasma or spinal fluid—nature’s cocktail—seems to contain dozens of beneficial proteins and other types of molecules, and may be the most potent elixir.

In mice, at least, it seems possible to achieve therapeutic benefit using the individual protein factors we have identified. One protein may be particularly useful for delaying muscle loss, while another may enhance brain function.

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

Stress seems to be the biggest source of damage we can do to our bodies. Not only does it cause physical symptoms such as high blood pressure, chest pain, digestive problems and sleep disturbances; it also weakens the immune system and promotes inflammation, possibly accelerating the aging process. Chronic stress is a major source of psychiatric symptoms and unhappiness.

A recent large study found that up to 40% of dementia in the US is caused by modifiable risk factors such as hypertension, obesity and physical inactivity. Currently, there are no good pharmacological treatments for cognitive decline and neurodegeneration. In their absence, the strongest scientifically proven benefits for brain function come from physical exercise.

About it aging and neuroscience research news

Author: Bruce Goldman
A source: Stanford
The connection: Bruce Goldman – Stanford
Photo: Image is in the public domain

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