A group of Yale researchers investigating the potentially life-extending capacity of a hormone was recently jointly awarded $10.5 million in research funding by the National Institute of Aging.
The research group, which was led by medical school professor Vishwa Dixit, worked in collaboration with researchers at Yale and the University of Texas Southwestern. In September, it was awarded the funding to continue to study the implications of the hormone fibroblast growth factor 21, or FGF21, on extending the human lifespan.
This grant supports four new projects that will further investigate the anti-aging effects of FGF21 and the protein’s impact on age-related chronic illnesses. Dixit will focus on how FGF21 interacts with the immune response. In particular, he will attempt to elucidate how the protein can reverse the effects of aging by preventing immune cells from losing the ability to fight cancer cells and viruses.
Dixit’s research group discovered that FGF21 serves an important function in the thymus, a lymphoid organ in the immune system. It helps to produce new T cells, a type of white blood cell vital for immune response, and prevents age-related fat degeneration. According to the study, this hormone extends the lifespan of mice by 40 percent. This study was published in the Proceedings of the National Academy of Sciences on Jan. 11.
As humans grow older, the deterioration of the thymus is one of the main factors causing the immune system to fail. The thymus is essential for the production of T cells, so finding a way to slow down the fatty degeneration of the thymus that comes with age would help curb this age-related immune system collapse, according to the researchers.
Dixit added that the research group found that elevating the levels of FGF21 in the elderly or in cancer patients who undergo bone marrow transplantation may be an additional strategy to increase T cell production, thus bolstering immune function.
Led by Dixit, the researchers first sought to understand when and how much of this hormone is expressed in the thymus. They found that FGF21 expression steadily drops with age.
Furthermore, only 1 percent of cells in the thymus produce this hormone: thymic epithelial cells (TECs), which are important for the development of T cells. Dixit said that the fact that FGF21 was being produced and was acting on such a central cell type in the thymus suggested its importance as a hormone.
The researchers next decided to investigate the functions of FGF21 by studying the effect of elevated and decreased levels of this hormone in mice. They found that increasing levels of FGF21 raised T cell function in the thymus, while FGF21 deficiency increased the rate of thymus degeneration in the mice.
“The overexpression of FGF21 prevents thymic lipoatrophy, which protects the mice from age-induced loss of T cells,” according to the study.
Dixit added that FGF21 serves as an endocrine hormone in the liver, increasing when glucose levels are low to allow fats to be burned. Thus, the researchers will also investigate the protein’s therapeutic promise as a treatment against obesity and type-2 diabetes. They will try to develop a way to mimic calorie restriction to enhance immune function without actually reducing caloric intake.
Medical school professor Tamas Horvath, whose research group will also receive funding from the grant, will look specifically at the protein’s impact on the nervous system and the brain, according to a Sept. 23 press release from the Yale Office of Public Affairs & Communications.
FGF21 was first cloned in 2000 as a novel secretory protein in the liver with an unknown function.