Parabiosis involves joining together the circulatory systems of two individuals. Joining together an old and a young mouse has proved to be very instructive now that researchers can measure quite detailed aspects of cellular biology, and in recent years it has been used to investigate age-related changes that take place in levels of various proteins in the blood. Some of those proteins can alter cellular behavior in important ways, and manipulating them in old individuals can improve degraded tissue function. This article provides a recent history of this research and hopes for the near future:
Experiments with parabiotic rodent pairs have led to breakthroughs in endocrinology, tumour biology and immunology, but most of those discoveries occurred more than 35 years ago. For reasons that are not entirely clear, the technique fell out of favour after the 1970s. In the past few years, however, a small number of labs have revived parabiosis, especially in the field of ageing research. By joining the circulatory system of an old mouse to that of a young mouse, scientists have produced some remarkable results. In the heart, brain, muscles and almost every other tissue examined, the blood of young mice seems to bring new life to ageing organs, making old mice stronger, smarter and healthier. It even makes their fur shinier. Now these labs have begun to identify the components of young blood that are responsible for these changes. And last September, a clinical trial in California became the first to start testing the benefits of young blood in older people with Alzheimer's disease.
"I think it is rejuvenation," says Tony Wyss-Coray, a neurologist at Stanford University in California who founded a company that is running the trial. "We are restarting the ageing clock." Many of his colleagues are more cautious about making such claims. "We're not de-ageing animals," says Amy Wagers, who has identified a muscle-rejuvenating factor in young mouse blood. Wagers argues that such factors are not turning old tissues into young ones, but are instead helping them to repair damage. "We're restoring function to tissues."
Six out of a planned 18 people with Alzheimer's, all aged 50 or above, have already begun to receive plasma harvested from men aged 30 or younger. In addition to monitoring disease symptoms, the researchers are looking for changes in brain scans and blood biomarkers of the disease. Wagers is eager to see the results, but she worries that a failure would be difficult to interpret and so could set the whole field back. Plasma from a 30-year-old donor may not contain factors beneficial to patients with Alzheimer's, for example. She and others would prefer to see testing for a specific blood factor or combination of known factors synthesized in the lab, for which the mechanism of action is fully understood.
There are also lingering concerns as to whether activating stem cells - which is what the young blood most often seems to do - over a long period of time would result in too much cell division. "My suspicion is that chronic treatments with anything - plasma, drugs - that rejuvenate cells in old animals is going to lead to an increase in cancer. Even if we learn how to make cells young, it's something we'll want to do judiciously."