Increased production of FGF21 via genetic engineering has been shown to extend life in mice, and calorie restriction appears to also increase FGF21 levels to some degree. Here researchers link FGF21 to the thymus and the immune system in aging. The thymus is an unusual organ in that it atrophies in early adulthood. It plays a limiting role in the pace of production of new immune cells, and thus restoring its structure and activity to youthful levels is an approach to at least partially reversing the age-related decline of the immune system. That might be achieved through tissue engineering or altered levels of FOXN1, among other methods.
A hormone that extends lifespan in mice by 40% is produced by specialized cells in the thymus gland, according to a new study. The team also found that increasing the levels of this hormone, called FGF21, protects against the loss of immune function that comes with age. When functioning normally, the thymus produces new T cells for the immune system, but with age, the thymus becomes fatty and loses its ability to produce new T cells. The researchers studied transgenic mice with elevated levels of FGF21. The team knocked out the gene's function and studied the impact of decreasing levels of FGF21 on the immune system. They found that increasing the levels of FGF21 in old mice protected the thymus from age-related fatty degeneration and increased the ability of the thymus to produce new T cells, while FGF21 deficiency accelerated the degeneration of the thymus in old mice.
FGF21 is produced in the liver as an endocrine hormone. Its levels increase when calories are restricted to allow fats to be burned when glucose levels are low. FGF21 is a metabolic hormone that improves insulin sensitivity and also induces weight loss; therefore it is being studied for its therapeutic effects in type-2 diabetes and obesity. "We found that FGF21 levels in thymic epithelial cells is several fold higher than in the liver - therefore FGF21 acts within the thymus to promote T cell production. 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, and thus bolster immune function." Further studies will focus on understanding how FGF21 protects the thymus from aging, and whether elevating FGF21 pharmacologically can extend the human healthspan and lower the incidence of disease caused by age-related loss of immune function.