Science's Long History of Sewing Two Animals Together

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The news stories read like Gothic tales penned by Mary Shelley or Bram Stoker. This past May, scientists from Harvard University announced that pumping the blood of young mice through the hearts of older ones rejuvenated the aged, enlarged hearts -- they grew smaller, the tissue became spry and supple, and blood flowed more readily. Dracula would be proud.

"It was quite striking how the heart responded... they were pretty much the same as in the young partner," lead researcher Amy Wagers told NewScientist.

To discern the result, the researchers didn't simply infuse the older mice with youthful blood. No, they did something much more macabre and mad science-y, an unheralded procedure that's been in science's arsenal for well over 150 years: sewing animals together.

The process, called parabiosis, is a bit more involved than a snip and a seam, of course, but not by much. Here's how to do it: Simply place two anesthetized animals (usually mice) side-by-side in the supine position and make an incision along the left side of one and the right side of the other. Next, staple the two bottom skin flaps together and flip the furry patients over. Then, make small incisions in the peritoneal cavities of both mice, just below the rib cage, and suture them together. (This provides a more intimate connection for the internal organs.) Finally, staple up the other skin flaps. The process takes between thirty and sixty minutes, and the end result has been compared to conjoined twins.

parabiosis.jpgParabiosis is not without risks. With modern methods, over 90% of joined animals recover from the procedure, but the real danger comes between one and two weeks later. In about 20-30% of cases, the immune systems of the two animals engage in brutal battle, which often results in the death of one or both animals. Scientists join together inbred strains of mice and rats to minimize the chances of this occurring.

French physician Paul Bert was the first to formerly publish an account of parabiosis back in 1864. He removed patches of skin from two rodents and stitched the two animals together, later demonstrating that fluid injected into a vein of one animal passed to a vein of the other. At the time, the work was purely exploratory, but over a century later, the procedure was adopted for a new purpose: to study aging and longevity.

For years, scientists were puzzled as to why stem cells lost their ability to regenerate tissues as mammals age. So, in 2005, Stanford researchers connected young mice with older mice to see whether the stem cells of the older mice would work better in their younger counterparts. Amazingly, they did! The results showed that stem cell functionality is tied more to the age of their surrounding environment than their actual age.

Four years later, another team sewed young and old mice together to examine the effects on cognitive function and neurogenesis -- the creation of new brain cells. The infusion of younger blood into the old mice boosted neurogenesis, while the older blood induced the opposite effect in the young mice, resulting in impaired spatial learning and memory.

Fascinatingly, what these studies appear to tell us is that individual

cells exposed to young or old environments undergo changes at the

molecular level, changes that persist even after being removed from the

environment.

"This clearly points to a kind of reprogramming,

with a certain amount of 'epigenetic memory', that occurs in vivo in

response to systemic influences," says Michael Conboy, a bioengineer at UC Berkeley.

In the coming years, Conboy plans to more closely analyze the resulting cellular changes in the wake of parabiosis, which could clue scientists in on methods to gauge cellular aging, and potentially even on ways to rejuvenate older cells and tissues.


Source: Michael J. Conboy, Irina M. Conboy and Thomas A. Rando. Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity. Aging Cell (2013) 12, pp525-530

(Image: Conboy et. al.)

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