FGF21 is not required for CR-mediated IGF-1 reduction or cell proliferation inhibition


Calorie restriction (CR) is a regimen based on low daily caloric intake without malnutrition. It can decelerate biological aging process, resulting in a delay of many age-related disease and an increase of lifespan. One possible mechanism, related to CR-induced lifespan extension, is down-regulation of insulin-like growth factor-1 (IGF-1) leads to a reduction of cell proliferation rate, then inhibits tumor formation. In addition, it is possible that nutritional deprivation induces up-regulation of fibroblast growth factor 21 (FGF21), leads to a decrease of IGF-1 expression. Thompson et al. design a series of experiments to investigate the changes of growth hormone (GH)-regulated IGF-1 production and the role of FGF21 under CR condition. The article was published on Plos One, recently.


In response to moderate CR (25%CR) in adult mice, phosphorylation levels of hepatic signal transducer and activator of transcription 5 (STAT5) were reduced, however, circulating GH and JAK2 levels were unchanged . This result indicates phosphorylated STAT5 may act as a key molecule in the process of CR. On the other hand, FGF21 was not required for the down-regulation of IGF-1 expression level or cell proliferation rates in FGF-knockout mice during moderate CR, although it showed anti-mitotic effects in ad libitum (AL)-fed mice. Due to the well-known glucose-lowering and insulin-sensitizing effects of FGF21, researchers suspect that FGF21 may play other roles in the effects of CR, instead of reducing IGF-1 production and cell proliferation rates.


Plos One. 2014 Nov 4;9(11):e111418.

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