Paul Bert, who died in 1886 in Hanoi at the age of 53, was a Frenchman who wore many hats, varying from politician to scientist. He is best known for his understanding of life at both high pressure—he understood the malady that beset a person returning too quickly from the depths of the sea, the bends—and low pressure, the latter awarding him the title, according to Wikipedia, of “Father of Aviation Medicine.” Here we are interested in a lesser-known accomplishment. Bert, in a technique known in modern terms as parabiosis, wrote a doctoral thesis entitled “LaGreffe Animale,” for the Faculty of Medicine in Paris in 1863( https://archive.org/stream/delagreffeanimal00bert#page/n7/mode/2up ) in which he described experiments sewing two rats together so that on healing they would share the same circulatory system—like conjoined twins in humans.
Our story jumps ahead to 1956 when a Cornell professor, Colin McCay, published an article in the Bulletin of the New York Academy of Sciences entitled “Experimental Prolongation of the Life Span.” McCay took a broad view of the subject, even taking note of a claim “that woman lived longer because they worried less than men,” and quoting the belief “that an old man regains some youth by acquiring a young woman.” I’m not aware of his experiments along these lines but McCay is credited with experimental work, begun in the 1930s, demonstrating that so-called caloric restriction, subjecting rats to a lifetime of hunger, prolonged the rat’s life. There is a great deal of work in the modern literature trying to figure out the biochemical source of this reproduced observation. He is reported to also have experimented with Bert’s technique of parabiosis. McCay’s interest in prolonging life caused him to sew old and young rats together to see if the older rat showed signs of reverse aging. He did see this effect, but at that time in the 1950s there was not the necessary biochemical knowledge to understand what was happening.
Parabiosis has been valuable in understanding life. Research reported in 1969 demonstrated that sewing together obese mice with slim mice, with the expectation that the slim mice would become obese and the obese mice become slim, led to the opposite result. The obese mouse kept eating while the slim mouse stopped eating. The researchers concluded that the obese mouse was circulating, in its bloodstream, something to tell it to stop eating but was incapable of responding to it. A factor in the blood was hypothesized to be transferred to the linked slim mouse that responded and stopped eating. Many years later the hypothesized factor, named Leptin, was discovered to be a protein that is at work also in human beings.
It was not until the beginning of this century that scientists took up sewing together young and old mice with the scientific underpinning to understand the resulting biochemistry. The results have been amazing. In two papers in the May 9, 2014 issue “Science” and in a review in the September 12 issue of “Science,” one could almost conclude that we are upon the Fountain of Youth.
The scientific work centered at Stanford and Harvard demonstrates that stem cells lay dormant in their ability to regenerate cells in our bodies necessary for functions as varied as brain cognition, nerve function, and regeneration of heart muscle, among others. Dormant, that is, until activated by a factor found in the blood, by a protein called GDF 11 (Growth Differentiation Factor). After many experiments with sewing together old and young mice and seeing what is summed up in a Science headline as: ““Rejuvenation Factor” in Blood Turns Back the Clock in Old Mice,” scientists discovered that GDF 11 is present in both blood streams but is greatly diminished as the mice grow older. Indeed, simply injecting the GDF 11 protein into elderly mice shows generally the same effect as found from sewing the elderly and young mice together. Scientists at Stanford have found that injection of blood serum from young mice into elderly mice suffering from a form of dementia or Alzheimer’s disease brings back some lost memory function.
There may be a paradigm shift in the way medical science treats diseases associated with aging, not by focusing on the particular age related malady, but rather by a systemic approach that activates the stem cells necessary for rejuvenation.
But don’t get excited too soon. Activating stem cells can bring on various forms of cancer, and there is no evidence yet that mice that get the protein live longer. Also GDF 11 cannot easily be added to the blood, which has resistance to the addition of large proteins. Nevertheless, at least two commercial ventures are being formed to find a variation on GDF 11. There is hope that something really new is on the horizon concerned with aging and regeneration of damaged tissue.