Overexpression of FGF21 Extends Life in Mice

An enormously complex web of genes and protein machinery controls the operation of metabolism, a layered nest of interactions and feedback loops. It is thus possible for many different genetic alterations to extend life by working through the same basic mechanism. The example here involving fibroblast growth factor 21 is a newly discovered change that seems to work through a known life extension method involving suppression of growth hormone, used in the past to extend life by 60-70% in mice.

Restricting food intake has been shown to extend lifespan in several different kinds of animals. In our study, we found transgenic mice that produced more of the hormone fibroblast growth factor-21 (FGF21) got the benefits of dieting without having to limit their food intake. Male mice that overproduced the hormone had about a 30 percent increase in average life span and female mice had about a 40 percent increase in average life span.

FGF21 seems to provide its health benefits by increasing insulin sensitivity and blocking the growth hormone/insulin-like growth factor-1 signaling pathway. FGF21 is a hormone secreted by the liver during fasting that helps the body adapt to starvation. It is one of three growth factors that are considered atypical because they behave like hormones. ... Previous research has found that FGF21 can reduce weight in obese mice. The mice that overproduced FGF21 in this latest study were lean throughout their lives and remained lean even while eating slightly more than the wild-type mice.

The hormone does have some downsides: FGF21 overproducers tended to be smaller than wild-type mice and the female mice were infertile. While FGF21 overproducers had significantly lower bone density than wild-type mice, the FGF21-abundant mice exhibited no ill effects from the reduced bone density.

Link: http://www.utsouthwestern.edu/newsroom/news-releases/year-2012/october/starvation-hormone-mangelsdorf-kliewer.html

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