A scientist at the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF may have discovered an unlikely source of the fountain of youth.
“I thought of aging as wear and tear,” said Saul Villeda, an assistant professor of anatomy at UC San Francisco and a member of the Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. “But that’s not what it is. There are genes that control how long you live. There are interventions that can extend the lifespan. There are reasons a tortoise lives hundreds of years and a mouse lives three.”
Answering the centuries-old question of how to stay young, Villeda found that the blood of young mice can help rejuvenate old mice.
After injecting elderly mice with plasma from the blood of young mice, Villeda put the old mice through a series of tests: they had to find their way through an underwater maze to a platform above the water line. It was an easy task for a 3-month-old mouse but a challenging one for a rodent of the ripe old age of 18 months. Villeda likened it to trying to find a car in a parking lot—a young person will remember the location with clues from the environment without giving it any thought, while an older person might struggle.
Villeda observed that old mice with blood plasma from their younger peers could find their way around the maze as if they were only 6 months old thanks to improved stem cell functioning. When put into a threatening environment, the old mice reacted like 3-month-olds—suggesting that survival instincts improved even more dramatically than memory.
The study, published in Nature Medicine magazine in 2014, cannot be applied to humans yet, even if it holds promise for Alzheimer’s disease and heart disease. In a follow-up study, published in the same journal in 2015, Villeda identified a protein in blood plasma that causes memory loss in older mice—when the protein was blocked, the older mice had improved memory function. And when the protein was introduced in younger mice, their memory suffered.
“We started out studying the good factors of young blood,” Villeda said. “But now we also know that old blood is bad.”
The study was not Villeda’s first foray into what he calls “rejuvenation research.” As a graduate student at Stanford University, Villeda surgically attached young mice to old mice to circulate blood between both. He discovered that the older mice developed healthier connections between cells in the hippocampus, the area of the brain that helps create memories and that degenerates in Alzheimer’s patients. (The younger mice did not fare so well in Villeda’s experiment—they grew old prematurely.) Similar studies also found that young blood helped older mice grow stronger and faster, leading to a small clinical trial that is in progress to test the impact of young blood on Alzheimer’s patients.
Villeda continues to study the impacts of aging and possible treatments for the physical and mental degeneration that can come with it.
“I don’t want to live forever,” Villeda said. “I want to live my 85 years. But I’d love to be able to read a book as I go to sleep, and think about it, and then peace out. I want my faculties there. I want my ‘healthspan’ to be as improved as I can have it.”