A few years ago, scientists from Stanford discovered that it's possible to reverse cognitive decline in old mice by injecting them with the blood of the young. Now, researchers have isolated the mechanism responsible for this rejuvenation — and it's a protein that's found in humans as well.
Back in 2012, when Stanford University scientist Saul Villeda showed that young blood has rejuvenating qualities, he wasn't entirely sure how it reversed the effects of cognitive decline — but he suspected that it has something to do with the limited production of stem cells as we get older.
And now, two new studies suggest he was on the right track.
The independent research papers, one from Harvard and one from Stanford, are reporting that injections of a protein, or growth factor, known as GDF11 is capable of rejuvenating a number of seemingly unrelated physiological aspects.
Above: Reconstructions of blood vessels in an old mouse's brain (left) and in an old mouse that received young mouse blood. Lida Katsimpardi.
The Harvard study, which now appears in Science, used the protein to improve the exercise capability and skeletal muscle function of mice (tests showed improvements in recovery from muscle injury, along with improved performance on running and grip strength tasks). The Stanford researchers showed that the transfusions encouraged the growth of new blood vessels and improved the function of the olfactory region of the brains of older mice, allowing them to detect smells just as well as younger mice. The injected mice were also shown to perform better on memory tests than mice of the same age that hadn't received the youthful blood plasma.
Previously, GDF11 was shown to make the failing hearts in aging mice appear more like those of young healthy mice.
As noted, humans have this protein, too. According to Amy Wagers and Lee Rubin of Harvard's Department of Stem Cell and Regenerative Biology (HSCRB), barring unexpected developments, they expect to have GDF11 in human clinical trials within three to five years. The goal is to develop interventions that treat neurodegnerative disorders such as Parkinson's and Alzheimer's.
In a prepared statement, HSCRB co-chair Doug Melton said that he couldn't
recall a more exciting finding to come from stem cell science and clever experiments. This should give us all hope for a healthier future. We all wonder why we were stronger and mentally more agile when young, and these two unusually exciting papers actually point to a possible answer: the higher levels of the protein GDF11 we have when young. There seems to be little question that, at least in animals, GDF11 has an amazing capacity to restore aging muscle and brain function.
It's definitely an amazing discovery — and the first example of a rejuvenation factor that's naturally produced by our own bodies, one that's capable of reversing (or slowing) aging in multiple tissues.
Both research teams examined the effect of GDF11 in two ways. First, they created a parabiotic system in which two mice were surgically joined, so that the blood of the younger mouse could circulate through the older mouse. The second method involved direct injections of the protein into the older mice. Subsequent tests, along with comparisons to control groups, revealed the therapeutic effects of the procedure.
Previous studies have shown that GDF11 works by regulating and restoring stem cell activity. This protein is abundant in young organisms, but drops off as animals age. After the experiments, 3D reconstructions of the brain and fMRI scans showed more new blood vessels and more blood flow, both of which are normally associated with younger, healthier brain tissue.
The researchers speculate that GDF11 improves vascularity and blood flow, which is associated with increased brain re-growth.
"However, the increased blood flow should have more widespread effects on brain function," noted Rubin. "We do think that, at least in principle, there will be a way to reverse some of the cognitive decline that takes place during aging, perhaps even with a single protein. It could be that a molecule like GDF11, or GDF11 itself, could [reverse the damage of aging]."
Rubin says that a potential drug is not "out of the question."
To date, the only other interventions known to reverse or slow aging have been caloric restriction, rapamycin, and the administration of nicotinamide mono nucleotide (NMN). But one of the primary advantages of GDF11 is that it's found naturally in the blood.
Writing in ScienceNews, Jocelyn Kaiser discusses the potential for human applications:
Harvard has filed for patents on GDF11, and Wagers says she and her colleagues are "in the process of talking with people" about commercializing it to treat diseases such as Alzheimer's and heart disease. Giving GDF11 itself "would require huge amounts of protein," Wagers says, so it may be better to use a modified form or to target the GDF11 pathway with a different molecule. "These are tractable problems," Wagers says. "The most important hurdle was figuring out a pathway to go after."
Temple agrees that GDF11 has therapeutic promise, but she says she will remain cautious until more is known about GDF11's mechanism. She also notes that some of the "old" mice in the Harvard brain studies were only middle-aged, and whether the effects would hold up in elderly people is unclear. "It's a matter of where you can step in," she says. Nor have any studies yet shown that the treated mice live longer.
Top image: The Moth Diaries.