FGF21 as Calorie Restriction Mimetic

Boosting levels of fibroblast growth factor 21 (FGF21) has been shown to extend life in mice. Here, researchers classify it as a calorie restriction mimetic treatment:

Dietary or caloric restriction (DR or CR), typically a 30-40% reduction in ad libitum or "normal" nutritional energy levels, has been reported to extend lifespan and healthspan in diverse organisms, including mammals. Although the lifespan benefit of DR in primates and humans is unproven, preliminary evidence suggests that DR confers healthspan benefits.

A serious effort is underway to discover or engineer DR mimetics. The most straightforward path to a DR mimetic requires a detailed understanding of the molecular mechanisms that underlie DR and related lifespan-enhancing protocols. Increased expression of FGF21, a putative mammalian starvation master regulator, promotes many of the same beneficial physiological changes seen in DR animals, including decreased glucose levels, increased insulin sensitivity, and improved fatty acid/lipid profiles. Ectopic over-expression of FGF21 in transgenic mice (FGF21-Tg) extends lifespan to a similar extent as DR in a recent study.

FGF21 may achieve these effects by attenuating GH/IGF1 signaling. Although FGF21 expression does not increase during DR, and therefore is unlikely to mediate DR, it does increase during short-term starvation in rodents which is a critical component of alternate day fasting, a DR-like protocol that also increases lifespan and healthspan in mammals. Various drugs have been reported to induce FGF21 [but] of these, only metformin has been reported to extend lifespan in mammals, and the extent of benefit is less than that seen with ectopic FGF21 expression.

Perhaps the most parsimonious explanation is that high, possibly unphysiological, levels of FGF21 are needed to achieve maximum life- and healthspan benefits and that sufficiently high levels are not achieved by the identified FGF21 inducers. More in-depth studies of the effects of FGF21 and its inducers on longevity and healthspan are warranted.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23173578

Comments

Since watching a very good Horrizon programme on TV which recorded the benefits of fasting, my husband and I have decided that on 2 days a week we only eat a piece of fruit for both breakfast and lunch and so 'fast' between one evening meal and the next.

From the information on the TV programme fasting for one, two or three days a week can be very beneficial to the internal organs and the fast gives your body a chance to dispose of toxins and do other good healing things rather than put its energy into digesting food.

It makes such good sense and we are benefiting from having more energy. We have been doing this seriously now for 3 months.

Posted by: Jean Purcell at December 4th, 2012 10:25 AM

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