Brain aging could soon be reversible


Last week I asked my brother Bill, a molecular biologist and founder of the field of regenerative medicine, if a radical life extension, up to 120 years or beyond, was possible.

Bill responded that extrapolations from current regenerative medicine techniques (e.g., stem cell therapies, tissue engineering, and molecular signals to slow or reverse cell aging and death) could one day enable many between us to reach 120 – the current upper limit of human lifespan – but going beyond that limit would be a great challenge due to the extreme difficulty of getting our brains to reverse the inexorable neural deterioration that accompanies aging.

In other words, stem cell implants could rejuvenate old hearts, or lab-grown organs or host animals such as pigs could replace worn out lungs, livers, and kidneys, but many scientists believe rejuvenating or replacing the brain (or parts of it) may never be possible, due to the brain’s unique complexity and inability to repair itself like, say, damaged skin.

But a few daring neuroscientists are exploring ways to not only slow but also reverse brain aging, which suggests some of us might be celebrating our 120th birthday with all of our mental faculties intact.

This exciting work falls into roughly three categories: preventing aging brains from self-destruction, reactivating neuron growth, and injecting new cells to replace lost neurons.

Prevent the brain from suppressing itself

Dr. Peter Walter’s lab at UC San Francisco found that brain tissue routinely senses when certain neurons are in trouble, such as viral infections, and through a mechanism called the integrative stress response (ISR), actively suppresses it. activity (protein synthesis) of diseased neurons to prevent them from further disrupting brain function. As we age and the neurons in the brain deteriorate, for example with inflammation, ISR activity increases, increasingly suppressing neuronal function. Walter and his collaborator, Dr Susanna Rosi, recently discovered that inhibiting SRI activity (which itself inhibits brain function) can reverse cognitive decline in old mice at an astonishing rate. For example, old mice have a much harder time learning to navigate mazes than young mice, but when the UC San Francisco team treated older mice with an ISR inhibitor, within days only, the old mice performed just as well as the young mice on a maze task.

This almost immediate improvement in cognitive abilities implies that the age-related mental decline is not entirely due to neural death or other permanent losses, but in part to active and reversible metabolic processes. Teams at UC San Francisco believe that treatments such as ISR inhibitors could one day restore functions lost not only with aging, but also with strokes and trauma.

Reactivate the growth and development of neurons

Dr. Saul Villeda (also at the University of California at San Francisco) recently built on the discovery that even older adult brains regularly produce new neurons (a process called neurogenesis) in a few parts of the brain, such as the hippocampus. By exploring why some parts of the brain regenerate but not others, Dr Villeda’s team have discovered a range of signaling molecules, such as compounds found in the blood of young people that can ‘trick’ old neurons into them. spawn new ones, even in areas of the brain that normally lack them. adult neurogenesis. These molecules also help the newly formed adult cells to develop dendrites and axons. Older animals treated with such rejuvenating molecules have indeed shown improvements in cognitive function.

Inject new cells to restore or replace lost brain neurons

Research conducted in Dr. Walter’s lab suggests that brain aging may be slowed down or reversed by causing brain tissue to perform unnatural acts of rejuvenation. But in case the magic of molecular signaling couldn’t repair or replace all of the brain tissue damaged by age, some researchers are looking at ways to restore or replace lost brain tissue with new tissue from outside the brain. brain. Much of this work, for example at the Mayo Clinic Center for Regenerative Medicine, focuses on injecting stem cells (embryonic-like cells that can divide and differentiate into several types of cells) that cause new ones to grow. blood vessels in the brain, nourishing and invigorating old neurons and possibly helping to grow new ones.

Scientists at Zhejiang University School of Medicine in China are also making progress by injecting stem cells and migrating those cells to damaged regions and starting to differentiate into neurons that replace those lost as a result of a traumatic brain injury. It’s not yet clear how much lost function this new technique can restore, but neuroscientists hope it may one day help reduce cognitive and motor deficits in neurodegenerative diseases such as dementia and Parkinson’s disease.

Towards longer lifespans

While it is not clear when each of the three strategies for slowing or reversing brain aging will begin to repair and rejuvenate the human brain, I believe that at least some of you who will read this article will, thanks to these techniques and other advances in regenerative medicine, will be able to re-read the article, and fully appreciate it, in a hundred years or so.

And when you look back on my predictions in the next century, your sharp mind will clearly remember… I told you!

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