Fight Aging!

If only all popular science articles were this good. The author here manages to accurately capture the state and uncertainties of heterochronic parabiosis research, which involves the transfer of blood between animals of different ages in search of factors that might be impacting tissue functions, either positively in youth or negatively in old age. From the results to date, I'd say that parabiosis is somewhat analogous in scope and likely impact to, say, research surrounding a class of drugs that modestly slow aging in mice. I'd not expect to see significantly better or worse advances in the treatment of aging resulting from this part of the field than from the development of mTOR inhibitors such as rapamycin. From my point of view it is an interesting area of science, but not the path ahead to rejuvenation.

Research into parabiosis can be technically challenging, and had more or less died out by the late 1970s. These days, though, it is back in the news - for a string of recent discoveries have suggested that previous generations of researchers were on to something. The blood of young animals, it seems, may be able to ameliorate at least some of the effects of ageing. In 2005, research joined the circulatory systems of mice aged between two and three months with members of the same strain that were 19-26 months old. That is roughly equivalent to hooking a 20-year-old human up to a septuagenarian. After five weeks, the researchers deliberately injured the older mice's muscles. Usually, old animals heal far less effectively from such injuries than young ones do. But these mice healed almost as well as a set of young control animals. The young blood had a similar effect on liver cells, too, doubling or tripling their proliferation rate in older animals.

Since then, a torrent of papers have shown matching improvements elsewhere in the body. No one has yet replicated the finding that young blood makes superannuated mice live longer. But it can help repair damaged spinal cords. It can encourage the formation of new neurons in mouse brains. It can help rejuvenate their pancreases. The walls of mouse hearts get thicker as the animals age; young blood can reverse that process as well. The effects work backwards, too. Old blood can impair neuron growth in young brains and decrepify youthful muscles. Finding out exactly what is happening is tricky. The working theory is that chemical signals in young blood are doing something to stem cells in older animals. Stem cells are special cells kept in reserve as means to repair and regrow damaged tissue. Like every other part of the body, they wear out as an animal ages. But something in the youngsters' blood seems to restore their ability to proliferate and encourages them to repair damage with the same vigour as those belonging to a younger animal would. In all probability, it is not one thing at all, but dozens or hundreds of hormones, signalling proteins and the like, working together. Researchers have been comparing the chemical composition of old and young blood, searching for those chemicals that show the biggest changes in level between the two.

Even with a list of targets, working out what is going on is hard. Blood is complicated stuff, and the tools available to analyse it are far from perfect. In 2014 a group suggested GDF-11 as a possible rejuvenating factor. The following year another team said that they were unable to replicate those results. They claimed the original test was sensitive to proteins besides GDF-11, messing up the results. The original team replied within months that, no, it was in fact the new test that was flawed, because it was itself picking up extra proteins. And there, at the moment, the matter stands. There are further possible explanations for parabiotic rejuvenation besides blood chemistry. One is that older animals may also benefit from having their blood scrubbed by young kidneys and livers, which mere blood transfusion would not offer. A 2016 paper described blood exchanges that were done in short bursts (thus eliminating the possibility of such scrubbing) and reported rejuvenating effects, but ones that were not as widespread as those obtained by full-on parabiosis. Another idea is that cells from the young animal, rather than chemicals in its blood, could be doing some of the work. The mechanisms by which parabiosis operates, then, are foggy.

Link: https://www.economist.com/news/science-and-technology/21724967-might-be-true-people-too