Print“There seems to be little question that, at least in animals, GDF11 has an amazing capacity to restore aging muscle and brain function, says Doug Melton, co-director of Harvard Stem Cell Institute.”
Two teams of Harvard Stem Cell Institute researchers have shown that a protein abundant in the blood of young mice, can improve brain and skeletal muscle function in aging mice.
In two separate papers to be published in the journal Science, Amy Wagers and Lee Rubin, professors in Harvard’s Department of Stem Cell and Regenerative Biology, report that injections of a protein known as GDF11, which is found in humans as well as mice, improved the exercise capability of mice equivalent in age to that of about a 70-year-old human, and also improved the function of the olfactory region of the brains of the older mice where they could detect smell as well as younger mice.
The researchers hope to test GDF11 in initial human clinical trials within three to five years.
Both studies examined the effect of GDF11 in two ways: first, by using what is called a parabiotic system in which two mice are surgically joined and the blood of the younger mouse circulates through the older mouse; and second, by injecting the older mice with GDF11. In an earlier study, Wagers and Richard Lee, of Brigham and Women’s Hospital and also an author on the two current papers, showed that injection of GDF11 in mice was sufficient to reverse characteristics of aging in the heart.
“This should give us all hope for a healthier future,” says Doug Melton, co-chair of Harvard’s Department of Stem Cell and Regenerative Biology and co-director of the Harvard Stem Cell Institute. “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.”
GDF11 is naturally found in much higher concentration in young mice than in older mice, and raising its levels in the older mice has improved the function of every organ system thus far studied.
Wagers first began using the parabiotic system in mice 14 years ago as a post doctoral fellow at Stanford University, when she and colleagues observed that the blood of young mice circulating in old mice seemed to have some rejuvenating effects on muscle repair after injury.
In 2013 she and Richard Lee published a paper in which they reported that when exposed to the blood of young mice, the enlarged, weakened hearts of older mice returned to a more youthful size, and their function improved. Working with a Colorado firm, the pair reported that GDF11 was the factor in the blood apparently responsible for the rejuvenating effect. That finding has raised hopes that GDF11 may prove, in some form, to be a possible treatment for diastolic heart failure, a fatal condition in the elderly that now is irreversible, and fatal.
“From the previous work it could have seemed that GD11 was heart specific,” says Wagers, “but this shows that it is active in multiple organs and cell types. Prior studies of skeletal muscle and the parabiotic effect really focused on regenerative biology. Muscle was damaged and assayed on how well it could recover.”
While prior studies of young blood factors have shown that we achieve restoration of muscle stem cell function and they repair the muscle better, in this study, we also saw repair of DNA damage associated with aging, and we got it in association with recovery of function, and we saw improvements in unmanipulated muscle” Wagers says.
Based on other studies, the researchers 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.
Rubin’s primary focus is developing treatments for neurodegenerative diseases, particularly in children. His group, working independently of Wagers’ group, used the same techniques to look at changes in the brain where they saw an increase in neural stem cells and increased development of blood vessels in the brain, both of which are normally associated with younger, healthier brain tissue.
Younger mice have a keen sense of olfactory discrimination and can sense fine differences in odor. Young mice avoid the smell of mint while old mice don’t. But the old mice exposed to the blood of the young mice, and those treated with GDF11 avoided the smell of mint.
“We think an effect of GDF11 is the improved vascularity and blood flow, associated with increased neurogenesis,” Rubin says. “This should have other more widespread effect on other areas of the brain. We do think that, at least in principal, there will be a way to reverse some of the decline of aging with a single protein. It could be that a molecule like GDF11, or GDF11 itself, could” reverse the damage of aging.
GDF11, or a drug developed from it, might be worthwhile in Alzheimer's Disease, says Rubin. “You might be able to separate out the issues of treating the plaque and tangles associated with the disease, and the decline in cognition, and perhaps improve cognition,” he says.
Wagers says that the two research groups are in discussions with a venture capital group to obtain funding to do additional preclinical work necessary before moving GDF 11 into human trials.
“I would wager that the results of this work, together with the other work, will translate into a clinical trial and a treatment,” says Wagers, “but of course that's just a wager.”
May 05, 2014
http://www.burrillreport.com/article-scientists_find_potential_key_to_reverse_aging.html
