The vampires have it right. Well, almost right. According to new research from Amy Wagers, factors circulating in the blood of the young revitalize the blood of the old.
Blood is constantly replenished by blood stem cells in the bone marrow that produce millions of new blood cells each second. Within four months, every blood cell in a human body will die and be replaced. With age, however, the stem cells that rejuvenate the blood change. As a result, the blood also changes. The immune system becomes less vigorous. Blood-related cancers increase.
“But is this a permanent change?” asked Wagers, HMS assistant professor of stem cell and regenerative biology.
She investigated by surgically joining mice in parabiotic pairs so the animals shared a common blood circulation. Pairing young mice with old set the clocks back for the older mice. Something in the blood of the young mice influenced the blood stem cells in the older mice to restore their youthful functions.
The molecular picture is not complete yet, said Wagers, “but we’re beginning to identify the components of what is probably a very large and complicated signaling cascade.” The study, by Wagers and her colleagues, appeared in the Jan. 28 Nature.
By looking at bone marrow, where blood stem cells live, Wagers identified two important signals in that cascade. Cells called osteoblasts, which make bone and live at the intersection of the bone and bone marrow, also change with age. Elderly osteoblasts produce insulin-like growth factor-1 (IGF-1) and may become more sensitive to it, creating a feedback loop that changes the signals these cells send to blood stem cells. This altered signaling, in turn, triggers blood stem cells to malfunction. By blocking aged osteoblasts from responding to IGF-1, Wagers could shut down this cascade and restore more youthful interactions between osteoblasts and blood stem cells.
These findings point to the possibility that this natural youthful essence could be turned into drugs that could be delivered therapeutically into elderly bloodstreams (not drunk from young necks) to maintain improved health later in life. More broadly, said Wagers, the reversibility of age-related changes to blood stem cells indicates that it is possible to use blood-borne signals to stimulate improved functioning of the body’s own blood stem cells. Drugs that target those blood-borne signals might also be useful as an alternative or complement to stem cell replacement therapies.
For more information, students may contact Amy Wagers at amy.wagers@joslin.harvard.edu.
Conflict Disclosure: The authors declare no conflicts.
Funding Sources: The Burroughs Welcome Fund, the W.M. Keck Foundation, the Glenn Foundation, the National Institutes of Health, and the Iacocca Foundation; the authors are solely responsible for the content of this work.
