Scientists at the Harvard Stem Cell Institute (HSCI) say they have shown that a protein they previously demonstrated can make the failing hearts in aging mice appear more like those of young healthy mice also improves brain and skeletal muscle function in aging mice.

Amy Wagers, Ph.D., and Lee Rubin, Ph.D., report that injections of 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, allowing them to detect smell as younger mice do. Two separate papers that appear early online in Science describe this work.

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, which in an earlier study by Dr. Wagers and Richard Lee, Ph.D., of Brigham and Women's Hospital was shown to be sufficient to reverse characteristics of aging in the heart.

Doug Melton, Ph.D., co-director of HSCI, noted that 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.

“From the previous work it could have seemed that GD11 was heart specific,” said Dr. Wagers, “but [these studies] show 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.”

“We show that factors found in young blood induce vascular remodeling, culminating in increased neurogenesis and improved olfactory discrimination in aging mice,” wrote the investigators in one of the Science articles entitled “Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors.” “Further, we show that GDF11 alone can improve the cerebral vasculature and enhance neurogenesis. The identification of factors that slow the age-dependent deterioration of the neurogenic niche in mice may constitute the basis for new methods of treating age-related neurodegenerative and neurovascular diseases.”

According to Dr. Wagers, while prior studies of young blood factors have shown that scientists can achieve restoration of muscle stem cell function and muscles can be better repaired, “in this study, we also saw repair of DNA damage associated with aging, we got it in association with recovery of function, and we saw improvements in unmanipulated muscle. Based on other studies, we think that the accumulation DNA damage in muscle stem cells might be reflect an inability of the cells to properly differentiate to make mature muscle cells, which is needed for adequate muscle repair.”

“We think an effect of GDF 11 is the improved vascularity and blood flow,” added Dr. Rubin. “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 GDF 11, or GDF 11 itself, could” reverse the damage of aging.

“It isn't out of question that GDF11,” or a drug developed from it, “might be worthwhile in Alzheimer's disease,” he continued.

Wagers said that the two research groups are in discussions with a venture capital group to obtain funding to “be able to do the additional preclinical work” necessary before moving GDF 11 into human trials. 

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