The starvation hormone increases lifespan

In the last post, I discussed the growth-longevity trade-off in the context of intermittent fasting. In this post, I’ll discuss some further evidence for the connection between growth and lifespan.

A very neat paper shows that transgenic mice made to overexpress a certain hormone live much longer than wild type mice: The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. First of all, I’ll just emphasize something from the title of the paper, namely that fibroblast growth factor, or FGF-21, is the starvation hormone.

In mice, FGF21 is strongly induced in liver in response to prolonged fasts… FGF21 in turn elicits diverse aspects of the adaptive starvation response. Among these, FGF21 increases insulin sensitivity and causes a corresponding decrease in basal insulin concentrations; FGF21 increases hepatic fatty acid oxidation, ketogenesis and gluconeogenesis; and, FGF21 sensitizes mice to torpor, a hibernation-like state of reduced body temperature and physical activity. FGF21 also blocks somatic growth by causing GH resistance, a phenomenon associated with starvation. Transgenic (Tg) mice overexpressing FGF21 are markedly smaller than wild-type mice and have a corresponding decrease in circulating IGF-1 concentrations despite having elevated growth hormone (GH) levels…. In liver, FGF21 inhibits the GH signaling pathway… Thus, FGF21-mediated repression of the GH/IGF-1 axis provides a mechanism for blocking growth and conserving energy under starvation conditions. [my emphases]

So, it can be seen from this passage how growth and lifespan are opposed. FGF-21 causes better insulin sensitivity and increased fat burning, both known to be associated with better health and longevity, and it interferes with the growth hormone signaling pathway.

Here are the survival curves for the mice, transgenic vs. wild type:


Median survival time in the mice was increased by 36%, and maximum survival was even longer, as around 30% of the transgenic mice were still alive at the time the paper was written.

According to an accompanying article written by one of the most prominent aging researchers around, Cynthia Kenyon, FGF-21 is produced by the liver after 12 hours of fasting.

All in all, we see that a hormone produced by fasting inhibits growth pathways and extends lifespan. Worth noting also is that FGF-21 also increases insulin sensitivity and promotes the production of ketones. Low-carbohydrate diets do this also, suggesting that they may promote longevity as well. And exercise, especially resistance exercise, strongly increases insulin sensitivity.

Could regular use of intermittent fasting increase longevity in humans? In my opinion, very likely it will. What is needed now are studies to see how and to what extent FGF-21 is increased in humans in response to fasting.

Finally, as further evidence of the growth-longevity trade-off, we should note that, in humans, growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes. Also in humans, functionally significant mutations in the insulin-like growth factor receptor are more common in centenarians.


Leave a Comment:

Tokyo Joe says November 27, 2014


Another solid post. This blog has rapidly grown into an indispensable source of intelligence on men’s health. Hat’s off to you!

Let me ask you a question. Perhaps this could become fodder for a future post, or if you haven’t the time maybe you could briefly comment here. To be sure I did search the blog once again and turned up some interesting posts from early 2013 in relation to Celiac’s disease and allergies, but I would be curious to hear your considered opinion on gluten in general, in the absence of any allergic indications. Big Mike at Danger & Play as well as Jay at FabFitover40 — two men I have great respect for — swear up and down that gluten is evil and should be avoided at all costs. Frankly I am not so sure.

The reason I ask: I have found through personal experimentation that taking a hefty dose of carbohydrates about 70 minutes before hitting the gym results in markedly more productive lifting sessions. I simply have more energy and stamina than I do if I go in on an empty stomach. I take these carbs in one of three forms: plain steel-cut Irish oatmeal; plain brown rice; or plain DeCecco pasta; I haven’t been able to discern any real difference in performance among the three. Of course, the variety is welcome. Apart from this pre-workout carbo loading, I generally avoid carbohydrates, consistent with my paleo diet.

It would be grand to hear your take on the raging Gluten Debate.

Keep up the great work–in the gym and on the blogs. Best wishes for a Happy Thanksgiving.

–Tokyo Joe

    P. D. Mangan says November 28, 2014

    TJ, thanks very much. As for carbs in general, if they work well for you and you don’t need to lose weight, I’d say go for it. My personal experience is that I don’t see a lot of performance difference whether I eat carbs or not. As for gluten in particular, I believe that there’s great validity to avoiding it, but maybe not everyone needs to. For example, I’ve tested positive for anti-gluten antibodies in the blood; these antibodies are not supposed to be there. There’s one theory that these are the antibodies that cross-react with thyroid tissue, causing hypothyroidism, a very common autoimmune disease.

Sam says December 6, 2014

Thanks. Excellent info.

George Ironthumb says December 13, 2014

Another great post, Mangan!

By the way I have updated the RSS aggregator and removed the one for Breviary and replaced it for the one for RH&F.

To be honest I was away from the interwebz for quite a while , I didn’t know that you have already established a .com until recently. Keep up the great job bro!

Your site is a service to humanity!

    P. D. Mangan says December 13, 2014

    Thanks, George!

The starvation hormone increases lifespan | says January 20, 2015

[…] Read the whole thing. […]

John McLeod says September 29, 2016

More studies and science need to happen before humans understand the evidence at hand

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