Aging and GDF11: What we know

The aging process has long baffled researchers because of the complexity of system-wide changes that take place as we move through the life cycle. Different parts of our bodies decline at different rates; changes can be slow and steady, or feel like a rapid decline. What is known is that aging is related to a decrease in our ability to regenerate new tissue, causing joints, blood vessels, and other parts of our anatomy to function differently than they do when we are younger.

HSCI Executive Committee member Amy Wagers, PhD, has been studying aging since her postdoctoral days at Stanford University. She was particularly intrigued by the results of parabiosis experiments, in which the blood of younger mice seemed to have rejuvenating effects on older mice when they shared a circulatory system.

The cause of this anti-aging phenomenon remained a mystery until May 2013, when Wagers, PhD, and cardiologist Richard Lee, MD, found that a protein in the blood of young mice, called GDF11, was able to quickly reverse symptoms of heart failure in older mice. Once injected, the protein, which also exists in humans, caused the older hearts to reduce in size and thickness so they resembled the healthy hearts of younger mice.

“It’s been observed for many, many years that when aging occurs it affects multiple body systems in a semi-synchronous way,” Wagers said. “This suggests that there may be some common signal that drives the body’s response to getting older. We hypothesized that this common signal might be a substance that was traveling in the bloodstream, because the bloodstream accesses organs throughout the body.”

One year later, Wagers and Lee published another paper showing that GDF11 is not only heart specific, but is able to restore skeletal muscle stem cell function and enhance muscle repair after injury. They also explored what the protein is doing at the cellular level that makes it such a potent ‘fountain of youth.’

“We saw repair of DNA damage associated with aging,” Wagers said. “Based on other studies, we think that the accumulation of DNA damage in muscle stem cells might reflect an inability of the cells to properly differentiate to make mature muscle cells, which is needed for adequate muscle repair.”

She noted that there is still more to be learned about GDF11’s effects on DNA. “We don’t fully understand how this is happening or why,” she added.

Another 2014 paper published by Wagers’ HSCI colleague Lee Rubin, PhD, found that GDF11 also reverses aging in the brain. Older mice injected with the protein experienced an increase in neural stem cells and renewed development of blood vessels. His team also found that the older mice treated with the protein recovered function in their ability to smell odors, like mint, typically only detected by younger mice.

As Wagers and collaborators work to learn more about GDF11, aging, and stem cells, they are hopeful that the protein, or a drug developed from the protein, can be brought to clinical trials within the next three to five years.