The Search for Factors in Young Blood that Might be Used to Treat Aging
A fair number of research groups and a few startup companies are engaged in the search for factors in young blood that might explain the effects of parabiosis. Heterochronic parabiosis is a procedure in which the circulatory systems of a young and an old mouse are linked. The young mouse begins to show some early signs of aging, and the old mouse shows a reversal of some measures of aging. The evidence to date is conflicted on the topic of whether or not this effect is due to beneficial components of young blood: it is clearly the case that some signals present in young blood can be delivered on their own to old animals in order to produce benefits; yet blood and plasma transfusions don't seem to work to any meaningful degree in either mice or people; and a very compelling study provided evidence for benefits to result from a dilution of harmful factors in old blood.
Scientists initially used parabiosis to investigate how conjoined organisms, like some twins, affect each other. After a period of declining interest in the method starting in the 1970s, parabiosis returned to the scene in 2005, when scientists decided to use the approach to answer questions about tissue regeneration in older organisms. After the release of the 2005 study and other work showing that young blood could seemingly rejuvenate old mice, scientists and the public alike seized on the alluring notion of an elixir of youth.
In February, concerned about premature application in humans based on findings in mice, the US Food and Drug Administration cautioned against young plasma transfusions, noting that they have "no proven clinical benefit" for age-related or other diseases in humans. In the wake of the initial fervor surrounding young blood, researchers are taking a more measured approach. Rather than trying to reverse aging, they're identifying the molecular factors responsible for the changes seen in parabiosis experiments in hopes of targeting specific diseases associated with aging.
The relative abundance of aging and regenerative factors in our bodies shifts as we age. At birth, our blood contains more regenerative factors - like oxytocin, which has been shown to rejuvenate skeletal muscle stem cells in mice - than aging factors. But as we get older, that balance gradually tips in favor of aging factors, like the protein eotaxin, thought to play a role in age-related diseases in which systemic inflammation occurs. Aging factors lower our ability to maintain and repair tissue structure and function, while regenerative factors raise it.
Some researchers who study aging think that young blood could point us to more than just regenerative factors for treating disease. Research to slow or halt aging is more complex than searching for regenerative factors in blood. In parabiosis, animals share not only a circulatory system but also their immune and organ systems, making it difficult to rule out these systems' influence on aging or rejuvenation. Researchers developed a parabiosis-like technique that allows mice to exchange only blood. When the researchers used the technique to connect young and old mice, they found that after each mouse had equal parts old blood and young blood circulating through it, the young mouse displayed negative effects. Old blood drastically decreased hippocampal neuron generation, learning and agility, and liver regeneration in young mice.
Young blood, on the other hand, showed no significant benefits for cognition, agility, or the generation of hippocampal neurons in old mice. In other words, the secret to stalling aging may not lie in boosting rejuvenating factors but instead in blocking factors in old blood that promote aging - ones that hinder tissue maintenance and repair. Researchers have turned their focus to TGF-β, a protein that increases with age. A recent study showed that pharmacologically normalizing the activity of the TGF-β pathway, which is elevated in old age, while adding the rejuvenating factor oxytocin improves muscle regeneration, enhances hippocampal neuron growth, and boosts cognition.