LONGECITY

OK, so what would stimulate FGF21???

Fibroblast growth factor-21 (FGF21) is a hormone secreted by the liver during fasting that elicits diverse aspects of the adaptive starvation response. Among its effects, FGF21 induces hepatic fatty acid oxidation and ketogenesis, increases insulin sensitivity, blocks somatic growth and causes bone loss. Here we show that transgenic overexpression of FGF21 markedly extends lifespan in mice without reducing food intake or affecting markers of NAD+ metabolism or AMP kinase and mTOR signaling. Transcriptomic analysis suggests that FGF21 acts primarily by blunting the growth hormone/insulin-like growth factor-1 signaling pathway in liver. These findings raise the possibility that FGF21 can be used to extend lifespan in other species.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466591/

I don't know what (if anything, other than not eating) would stimulate FGF21, but wouldn't the blocking of somatic growth and the bone loss be potential problems?

Perhaps, or maybe not if it's boosted after growth is basically complete. As in adults. The article does state that:

We conclude that FGF21 could potentially be used as a hormone therapy to extend lifespan in mammals.

Actually I'd be interested to know if smaller individuals have more FGF21 than taller ones, and what the effect on lifespan is. In dogs, at least, smaller animals have less IGF-1 and live a lot longer. We do see in this table that the top 3 countries in terms of life expectancy are all ones which are populated mainly by short people: Japan, Hong Kong and Macau. One would guess that Mainland China and other countries with short people might be on the list as well, but aren't due to poverty, working conditions, etc.

http://en.wikipedia....life_expectancy

One would guess that Mainland China and other countries with short people might be on the list as well, but aren't due to poverty, working conditions, etc.

I dunno. Yao Ming comes to mind... There's a lot of tall people in China. If there's a lot of short stature there, it's probably due to diet during development. However, if that's sufficient to provoke or suppress the various growth factors, then maybe that would do it.

I don't know what (if anything, other than not eating) would stimulate FGF21, but wouldn't the blocking of somatic growth and the bone loss be potential problems?

These (and others) would be potential problems, but as usual, it would be a matter of modulation i.e. finding the exact ideal dose in order to exert a physical benefit.

As for stimulating FGF21, I don't know any substance that could do it, but I am sure that an analogue (natural or synthetic) would be available in the near future. It is an interesting study though.

This article is interesting and to the point:
Height, body size, and longevity: is smaller better for the human body?
http://www.ncbi.nlm....les/PMC1071721/

They don't mention FGF21, focusing on other factors, but their data do support something like FGF21 extending lifespan in humans.

From the paper: a graph of the lifespan of professional baseball players vs their heights:

Edited by smithx, 21 October 2012 - 07:47 PM.

Fasting, exercise and cold induce FGF21. Also, ketogenic diet and fibrate drugs.

In fasting mice, FGF21 is doubled after 24h. In man, 7 DAYS of fasting will finally up it by 75% (which once again underscores the old and largely ignored on this board fact that, metabolically, a day of fasting in mice equals to a 7-day fast in a man).

http://www.ncbi.nlm....pubmed/18680716 The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARalpha activation in man.

http://www.pnas.org/...6/26/10853.full
"...in humans, circulating glucagon concentrations spike after 3-5 days of fasting and then decline, whereas plasma FGF21 levels increase only after a 7-day fast."

http://genesdev.cshl...t/26/4/312.full
FGF21 expression is induced in various tissues in response to fasting, feeding, and cold.

FGF21 is also strongly induced in the mouse liver by a high-fat, low-carbohydrate ketogenic diet... and conditions that mimic starvation in forcing the body to burn fatty acids rather than carbohydrates.

FGF21 is induced by cold in BAT.

Consistent with this activation of BAT and 'browning' of WAT, FGF21 administration causes weight loss in obese rodents and monkeys, with more striking weight loss in rodents, which have more BAT.

http://www.plosone.o...al.pone.0038022
Exercise Increases Serum FGF21 Levels (2012)

http://www.ncbi.nlm....les/PMC2793111/
We subsequently showed that FGF21 reduces circulating concentrations of IGF-I by ~50% without causing a corresponding decrease in GH concentrations. Thus, FGF21 causes GH resistance.

A comination of ppar activators such as resveratrol/stillbenes, cinnamon, olive leaf extract, all star supplements, may upregulate it significantly.

Also brings to mind this study:
Tocotrienol-Rich Fraction Prevents Cell Cycle Arrest and Elongates Telomere Length in Senescent Human Diploid Fibroblasts
http://www.hindawi.c...bb/2011/506171/

Tocotrienols also activate PPAR and improve insulin sensitivity:
http://www.ncbi.nlm....pubmed/19866471