Deleting a single 'fat gene' may be a simple way to reduce body fat while extending lifespan, a new study suggests.
The gene appears to play a crucial role in coordinating the immune system and metabolism, and deleting the gene in mice reduces body fat and extends lifespan, according to new research by at the Jean Mayer USDA Human Nutrition Research Centre (USDA HNRCA) on Ageing at Tufts University and Yale University School of Medicine.
Based on gene expression studies of fat tissue, researchers initiated studies of the role of FAT10 in adipose tissue and metabolism.
"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 study co-author Martin S Obin.
"Turning off the FAT10 gene produces a variety of beneficial effects in the mice, including reduced body fat, which slows down ageing and extends lifespan by 20 per cent," said Obin.
Typically, mice gain fat as they age. The authors observed that activation of the FAT10 gene in normal mice increases in fat tissue with age.
Mice lacking FAT10 consume more food, but burn fat at an accelerated rate. As a result, they have less than half of the fat tissue found in normal, aged mice, researchers said.
Their skeletal muscle ramps up production of an immune molecule that increases their response to insulin, resulting in reduced circulating insulin levels, protection against type 2 diabetes and longer lifespan, they said.
The authors note that eliminating FAT10 will not fully address the dilemma of ageing and weight gain.
"Mice without the FAT10 gene might be too lean to fight infection effectively outside of the laboratory setting. More research is needed to know how to achieve that balance in mice and then hopefully, at some point, people," said Obin.
Researchers demonstrated that FAT10 impacts immune response, lipid and glucose metabolism, and mitochondrial function.
"Blocking what FAT10 does to coordinate immunity and metabolism could lead to new therapies for metabolic disease, metabolic syndrome, cancer and healthy ageing, because when we knock it out the net result is mice live longer," said co-first and corresponding author Allon Canaan.
Canaan and colleagues initially developed the FAT10-deficient mouse to study the role of FAT10 in sepsis.
In an attempt to increase sensitivity for sepsis, Canaan aged the FAT10 knockout mice and made the discovery that mice lacking the gene were lean and aged more slowly.
The mice appear younger and more robust than comparably-aged normal mice, have better muscle tone, and do not develop age-related tumours.
The study was published in the journal PNAS.
