Young Blood: Chasing the Fountain of Youth
Learn new information quickly. Repair and grow new muscle and bone tissue. Fend off infection. These physiological superpowers are hallmarks of the youthful, however as we age these diminish and we are subject to a multitude of diseases and ailments. Can we slow or even rejuvenate age-related decline? A number of papers published in the last decade suggest that substances circulating in the blood, known as factors, may act as agents of rejuvenation. The activity and regulation of these youth-promoting factors remains a hot area of research.
Researchers who investigate blood rejuvenation factors often employ a somewhat curious, if not creepy, experimental technique which involves transplanting a circulatory system from a mouse to another of a different age. The technique, known as heterochronic parabiosis, allows researchers to examine the effects of young blood on the elderly mouse, and vice versa. Parabiosis (from the Greek roots para "besides," and bios "life") is done by, essentially, attaching two animals (normally rodents) together by their sides. Blood vessels grow after the stitches heal, so that the blood of one rodent flows into the other, and vice versa. Heterochronic (from hetero "different" and chron "time") parabiosis refers to the circulatory pairing of two animals at opposing ends of the age spectrum. This procedure allows scientists to ask the questions: what effect does young blood have on an old animal? And, conversely, what does blood from an old animal do to a young animal?
Diagram showing the process of heterochronic parabiosis in mice
So far, young blood has been shown to elicit numerous effects on aged tissue. Older mice that receive young blood grow new liver cells, regenerate muscle tissue, and repair bone fractures like a growing pup. Even the brain seems to benefit from an influx of young blood. Older mice exposed to young blood show marked improvement in structural and functional brain tissue hallmarks of age-related impairment, and perform better in assays that test learning and memory than their older counterparts who didn't get a dose of young blood. These effects came at a cost to the younger mouse, who exhibited decreased brain functioning in an age-dependent fashion.
So how does young blood rejuvenation work? Could it be that stem cells from the young blood, which have the potential to turn into any kind of cell, are spreading in the older animal, replacing dying cells and revitalising tissues? Nope. It turns out that aging tissues aren't missing their stem cells. Rather, the stem cells are there, but they're not very active. Researchers found that it was the environment around the stem cells that made the difference. Aged stem cells are revitalised by steeping them in the proteins, or factors found in young blood. Bathing young stem cells in old blood has just the opposite effect: stem cells don't proliferate into new cells as quickly, and tissues decline accordingly.
So what are these rejuvenation factors in young blood that bring aged stem cells back to life? And conversely, what factors in old blood are responsible for the decline of young tissues? Hunting down these circulating regenerative and degenerative agents is an active area of study, with various research groups presenting different signalling molecules at play. So far, the growth factor GDF11, the chemokine CCL11, the transcriptional modulator CREB, and the cell adhesion and developmental fate regulator β-catenin have all been shown to mediate the effects of young and/or old blood. These signalling molecules reside in complex networks replete with similar members of protein families and many regulatory influences. This means that isolating and understanding these mysterious blood-borne agents of youthful physiology will likely be no small task, with much debate and discussion.
Recently, David Glass from Novartis challenged Harvard's Amy Wagers assertion of GDF11's rejuvenating powers, while Wagers claims that "there is a very compelling biological explanation for the apparent discrepancies," an explanation that she says will be revealed in upcoming publications.
It's clear there is a lot to sort out with respect to how various molecules circulating around in our blood create an environment that tips our physiology toward youthful or aged constitutions. The potential applications of this bloodborne fountain of youth are numerous. One day, we could boost our aging blood with factors derived from young blood and prevent or even reverse ailments ranging from heart attacks to bone loss to senility. First, though, we'll have to find those factors--and prove that they work. Isolating the factors in old blood that impart ill health could also prove useful, since inhibiting those substances could reverse age-related maladies. Until the youth and age-promoting agents in our blood are tracked down and isolated, practical applications for human health will have to wait, lest we conjure up horrific notions of vampires.