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Study shows starvation hormone increases lifespan in mice

Published On: Tue, Oct 16th, 2012 | Biochemistry | By BioNews

A team of researchers at UT Southwestern Medical Center, showed that a secreting hormone involved in response to starvation – fibroblast growth factor-21 (FGF21) – dramatically increased the lifespan of mice in which it was overexpressed. The transgenic mice had a longer median survival time than wild-type mice (38 months vs. 28 months) and transgenic female mice on average lived four months longer than their male counterparts. The study represents an important advance in aging research, and raises the prospect of hormone-based therapy to extend lifespan without the need for a low-calorie diet, although much further research is needed in mice to understand and mitigate the effects of FGF21 on growth and fertility.

Venn diagrams showing overlap of genes significantly regulated in liver, muscle and adipose tissue of FGF21-transgenic (Tg) vs wild-type (WT) mice. Image credit – eLife.

In 1934, in a famous experiment at Cornell University, it was discovered that laboratory mice could live twice as long as expected if they were fed a low-calorie diet that included enough nutrients to avoid malnutrition. This phenomenon has since been observed in species ranging from worms to primates, but not in humans. Reducing calorie intake leads to longer lives by modifying a number of the biochemical pathways that sense nutrients, including pathways that involve insulin and various other biomolecules. Chemical and genetic methods can also increase longevity by modifying these pathways, which suggests that it might be possible to develop drugs that can increase lifespan without the reducing calorie intake.

Mice, humans and other creatures respond to prolonged fasting through a number of adaptive changes that include mobilizing and burning fatty acids. The liver has an important role in this response, secreting a hormone called fibroblast growth factor-21 (FGF21) that coordinates these processes among tissues. Previous experiments on transgenic mice with high levels of this hormone have shown that it suppresses the activity of growth hormone and reduces the production of insulin-like growth factor, which prevents growth and can lead to hibernation-like behavior.

Zhang et al. compare groups of wild-type mice and transgenic mice with high levels of FGF21. They find that the transgenic mice have a longer median survival time than wild-type mice (38 months vs. 28 months), and that the transgenic female mice on average live for four months longer than their male counterparts. However, unlike in other examples of increased longevity, they find that decreased food intake is not required. Instead, they find that transgenic mice eat more food than wild-type mice, yet remain profoundly insulin-sensitive. The results suggest that the longer survival times are caused by a reduction in the production of insulin-like growth factor, but they also suggest that the mechanism responsible for the increased longevity is independent of the three pathways that are usually associated with such increases. Further research is needed to understand this mechanism in greater detail and could, perhaps, pave the way for the use of FGF21-based hormone therapy to extend lifespan without the need for a low-calorie diet.

Reference :

Zhang Y, Xie Y, Berglund ED, Coate KC, He TT, Katafuchi T, Xiao G, Potthoff MJ, Wei W, Wan Y, Yu RT, Evans RM, Kliewer SA, Mangelsdorf DJ. The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. elife. 2012;1:e00065. doi: 10.7554/eLife.00065. Epub 2012 Oct 15.

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