This popular science article takes a look at one of the groups working on characterizing the role of FGF21 in aspects of aging. Genetic engineering to increase levels of FGF21 extends life in mice, and also improves the function of the thymus and thus the immune system, as the thymus is where some classes of immune cell mature after their creation in the bone marrow. FGF21 is also involved in the beneficial effects of calorie restriction on health and longevity, but there appear to be significant differences between mice and humans on this count - and there must be significant differences somewhere in the biochemistry of the calorie restriction response, as human life spans are nowhere near as plastic in response to circumstances and therapies as those of mice. Calorie restriction extends mouse life spans by as much as 40%, but certainly doesn't do that for people despite being very beneficial for health.
Most mice start showing signs of aging by 2 years old. These mice didn't. Instead they entered what should have been their twilight years with vigor, approaching their third birthday free of the disease and the decreased mobility expected in animals their age. In a laboratory setting, regular mice would have a life expectancy of around three years, but these mice lived much longer, almost four years. Their secret was a hormone called fibroblast growth factor-21 (FGF21) that has an extraordinary effect on the immune system. Beginning in 2007, researchers began studying the hormone and its effects on mice genetically engineered to produce more of it. In 2012, scientists published a study finding that the hormone increased the lifespan of mice by as much as 40 percent. Last January, it was shown that in addition to extending the life expectancy of mice, FGF21 protects against the loss of immune function that comes with age.
The research into FGF21 builds on previous studies showing that severely restricting food intake can extend the lifespan of several different animals. Increasing levels of FGF21, which is secreted by the liver during fasting and helps the body adapt to starvation, seems to provide the benefits of dieting without limiting food intake. FGF21 plays an important role in the thymus, a small organ located between the lungs that has an integral role in the immune system. When functioning properly, the thymus produces infection-fighting T cells, but as we age the thymus becomes fatty and stops producing T cells capable of fending off infection. As a result, the immune system is compromised, becoming more susceptible to both infection and certain forms of cancer. But increasing levels of FGF21 in the thymus fends off the organ's age-induced decline, allowing it to continue to produce T cells to battle infection.
The aging field in general has picked up over the last five to 10 years. "There's more people proposing work related to aging and definitely more funding. Normally you get a drug approved by the FDA to treat a disease. But this is different. You're not trying to slow the progression of disease. You're trying to slow the progression of aging, and aging is not a disease, so it's a different paradigm." The focus on this new paradigm comes from a growing realization in the scientific community that as we age, we become more susceptible to such a wide variety of diseases that developing effective treatments for aging itself might be something of a cure-all. "Aging is the biggest risk factor for chronic diseases. The association between aging and chronic disease is stronger than the association between smoking and lung cancer. So, if you understand what is happening during aging, how it is happening and what are the mechanisms, cellular and molecular, then we may be able to delay the onset of diseases like Alzheimer's, arthritis, diabetes, certain cancers, kidney disease, macular degeneration, you name it. All these diseases are all linked to aging. I think the question we are more interested in is not just longevity, but actually the health and lifespan. So that extension of lifespan is associated with reduction of morbidity, or a period of life where we are free of disability. That is the real goal. Nobody wants to live an additional 40 years in a bed."