Sounds like the perfect test run for a eugenics experiment: Find and delete a single gene as a way to reduce body fat while extending lifespan. Sadly or happily (depending on your point of view), science is not there yet, but many would still call the current research promising. Medical researchers from Tufts University and Yale University have observed the crucial role a familiar gene appears to play in metabolism as well as the immune system of mice. One day they hope to translate their understanding of the FAT10 gene — and how it might best be manipulated — to a human population.
"No one really knew what the FAT10 gene did, other than it was 'turned on' by inflammation and that it seemed to be increased in gynecological and gastrointestinal cancers," said Dr. Martin S. Obin, an adjunct scientist in the Functional Genomics Core Unit at Tufts University. However, the FAT10 gene is present in all mammals and past research has indeed proved that certain cancerous tumors show an increased proportion of the FAT 10 gene, while more recent studies have reported how FAT10 interacts with hundreds of different proteins in cells. To observe the ways in which FAT10 might influence metabolism and fat tissue, the team of researchers decided to use a FAT10-deficient mouse from a previous study. Initially, the team (and colleagues) had engineered these so-called FAT10 knockout mice to investigate whether a relationship existed between the FAT10 gene and sepsis; for that experiment, they had aged the engineered mice in an effort to increase sensitivity for sepsis.
Basing their current study on an understanding that mice typically gain fat with age, the researchers established two separate colonies — mice engineered to lack FAT10 and normal mice — and then watched them grow old. Surprisingly, the engineered mice aged more slowly than the normal mice and they also gained less weight. In fact, those lacking the FAT10 gene appeared younger and more robust, with better muscle tone and no age-related tumors.
Upon analysis, the FAT10-deleted mice, despite eating more food than the normal mice, showed 50 percent less fat tissue than their counterparts. It was clear they were burning fat at an accelerated rate. Plus, their skeletal muscles had ramped up production of an immune molecule that increased their response to insulin, and this resulted in reduced circulating insulin levels, added protection against type 2 diabetes, and a longer lifespan. "Turning off the FAT10 gene produces a variety of beneficial effects in the mice, including reduced body fat, which slows down aging and extends lifespan by 20 percent," said Obin in a press release.
Is this just too good to be true? Eliminating FAT10, the researchers warned, cannot fully address the dilemma of aging and weight gain. "Laboratory mice live in a lab under ideal, germ-free conditions," Obin explained. "Fighting infection requires energy, which can be provided by stored fat. Mice without the FAT10 gene might be too lean to fight infection effectively outside of the laboratory setting."
Although much more study is needed to understand the full effects of FAT10 gene deletion in mice (and eventually, some would hope, people), the many possibilities for future research are exciting. "Now there is a dramatic road map for researchers looking at all of the proteins that FAT10 gets involved with," said Dr. Allon Canaan, an associate scientist in the Department of Genetics at Yale. "Blocking what FAT10 does to coordinate immunity and metabolism could lead to new therapies for metabolic disease, metabolic syndrome, cancer and healthy aging, because when we knock it out the net result is mice live longer." Let the experiments commence!
Source: Canaan A, Defuria J, Perelman E, et al. Extended Lifespan and Reduced Adiposity in Mice Lacking the FAT10 Gene. Proceedings of the National Academy of Sciences. 2014.