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.