Finding Secrets of Youth in the Blood

Amy Wagers, Ph.D.

For years, biologists have known that infusing aged lab mice with the blood of young mice can reverse some aspects of aging in the older mice, and they have steadily worked to understand the mechanisms that drive this process.

Joslin principal investigator Amy Wagers, Ph.D., Brigham and Women’s Hospital researcher Richard Lee, M.D., and their colleagues at the Harvard Stem Cell Institute and Joslin took a major step forward last November by demonstrating that infusing large amounts of a blood protein called GDF11 can help to rejuvenate the weakened hearts of aging mice.

In a related study published this month in Science, the Wagers lab showed that aged mice given high levels of GDF11 also gain greater skeletal muscle strength and exercise endurance, and a study led by their coworkers in Harvard professor Lee Rubin’s lab at the Stem Cell Institute demonstrated that the treatment increases blood flow and blood vessel production in the brains of older mice.

Humans also have GDF11 in the blood, and the levels of the molecule appear to drop as we age much as they do in mice, notes Dr. Wagers, who is also a Harvard professor and a member of the Stem Cell Institute.

“We’ve identified a single molecule that is beneficial for the function of multiple tissues: the skeletal muscle, the brain and the heart,” she emphasizes. “It’s actually quite surprising, since these are not tissues that are very similar.”

The ability to help rejuvenate multiple organs that has been suggested by the pre-clinical studies offers promise for developing therapies to enhance health during aging, Dr. Wagers says.

“However, we don’t know yet what the first clinical trials might be, because we need to understand more about the biology of GDF11 and more about the most optimal ways to target its molecular pathway,” she says.

“We also want to know why it is that GDF11 goes away with age,” she adds. “If it has such a healthful effects, then why do we lose it? Is there any downside to having high levels of GDF11 in older individuals?”

The research is also likely to be relevant to people with diabetes, who are particularly vulnerable to certain complications similar to those experienced in aging, such as deficient wound-healing, Dr. Wagers points out.

Much of her research on blood factors and aging is based on examining the effects of connecting the blood systems of two different types of mice—in the most recent studies, between young and old mice.

In a 2009 study, however, her lab studied wound-healing in diabetes by connecting normal mice with mice that were genetically altered to model type 2 diabetes. The Joslin scientists found that this exposure to normal blood circulation in the diabetic mice improved their wound-healing, and that the improvement was not driven by lower blood glucose levels.

“The experiment says there’s the potential to improve wound-healing responses in people with diabetes without having perfect control over blood sugar,” Dr Wagers points out. She speculates that the GDF11 pathway may be involved, although that possibility hasn’t yet been tested yet.

Among plans for follow-up research, she’s interested in finding out whether higher GDF11 levels can successfully target other organs that become dysfunctional with age, including organs that are particularly prone to complications in diabetes such as the kidney.

Additionally, “we could look to see whether GDF11 levels are different in older mice with or without diabetes, and we could add GDF11 back to older animals who are diabetic and see what difference that makes,” Wagers notes.

Contributors to her latest Science paper include Joslin principal investigators Laurie Goodyear, Ph.D., who helped in examining muscle function and physiology in the mice, and Thomas Serwold, Ph.D., who aided in measuring levels of GDF11 in the blood.

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