Aiming to double cats' lifespan The circulating protein "AIM" improves kidney function

Nearly 10 million cats are kept in Japan, and many of them die of kidney disease. Since discovering 20 years ago the "AIM" protein which is found in the blood, Professor Miyazaki has been devoted to the research of this particular protein. Over the course of his research, it became apparent that AIM improves kidney function. He is now working on developing medication that may substantially extend the lifespan of cats.

Cats and medicine

Structure of AIM

AIM is a blood protein of approximately 40 kDa, with three domains called SRCR which consist of large amounts of cysteine (a type of amino acid). Normally it is bound together with a large IgM (immunoglobulin M) pentamer in the blood, and it is not carried into the urine.

Professor Miyazaki, who graduated from the UTokyo Faculty of Medicine in 1986, was working at a hospital in Kodaira, Tokyo as a medical intern when he happened to pick up a specialist magazine. In it, there was an article about Professor Kenichi Yamamura of Kumamoto University, who was one of the first in Japan to create a transgenic and knockout (genetically modified) mouse. Seeing this, Miyazaki immediately thought, "I must go and study with this professor." Thereafter, he went to France and Switzerland to further deepen his research on immunology, and in Switzerland he discovered a new molecule at the renowned Basel Institute for Immunology. Upon verifying in vitro that this molecule has the function to impede the death of macrophages, a type of white blood cell, he himself named it AIM, which is an acronym for "apoptosis inhibitor of macrophage."

A chance exchange served as the key

AIM exists abundantly in blood and has a complex structure, with three domains in the shape of little balls connected to one another. It was during Miyazaki’s time as an associate professor at the University of Texas Southwestern Medical Center at Dallas that he ascertained its function inside the body. Until then, however much Miyazaki examined AIM in mice, nothing happened. He had been laboring away for six whole years with no data being produced, until one day he bumped into a man on university grounds and engaged in a conversation with him that nudged Miyazaki in the right direction. That man was Professor Joseph Goldstein, an authority on cholesterol metabolism and winner of the Nobel Prize in Physiology or Medicine in 1985 for his research in the field. Professor Goldstein’s words inspired Miyazaki to treat mice without AIM with a high-fat diet to fatten them up, by which he discovered that compared to fat mice with AIM, obesity and fatty liver were likely to worsen for those without the gene. "(Fattening the mice up) is something that wouldn’t even cross the mind of an immunology researcher, and I thought it sounded ridiculous. But I wasn’t finding anything otherwise, so I did it out of desperation. That led to the elucidation of the function of AIM." He says that at that time, he fully realized the need to tear down the walls separating academic disciplines in order to learn about illnesses.

"As someone who had been on the fast track to a successful career in immunology, I was so shocked when I learned that we cannot determine even one of the functions of a protein produced by cells of the immune system based on the knowledge of immunology alone."