Whenever an important new discovery is made that extends life- and health-span, we ask how can we apply it? A great example is the recent discovery that the fasting hormone fibroblast growth factor 21 extends life in mice.
But, so what? The study used genetically altered mice that overproduce the hormone. That’s not going to happen in humans.
So we need to know how the hormone works, and Dr. Cynthia Kenyon provides guidance in this – in this excellent review of the discovery:
[F]ibroblast growth factor-21 (FGF-21), can extend lifespan in mice (Zhang et al., 2012). When food is withheld from an animal for 12 hours or longer, liver cells produce this hormone, which then mobilizes fat stores in the liver, and promotes the synthesis of glucose and ketones. FGF-21 also reduces basal insulin levels and increases insulin sensitivity. In addition, it suppresses further growth of the mice by preventing growth hormone from triggering the production of IGF-1 (insulin-like growth factor-1) in the liver.
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Because FGF-21 is a hormone, it should be possible to increase its level in humans. It is possible that this will extend lifespan, because there are already hints that inhibiting the growth hormone/IGF-1 pathway promotes human longevity. First, genetic mutations that prevent cells from responding to IGF-1 are over-represented in centenarians (Suh et al., 2008), as are other rare DNA variants that reduce the activities of other components of this pathway, including the receptor for growth hormone (Y. Suh, personal communication). Second, DNA variants in the FOXO3A gene have been linked to exceptional longevity in at least eight studies across the world. FOXO proteins switch on genes that extend lifespan when insulin/IGF-1 signalling is inhibited in animals, although we do not know how these human DNA variants affect gene function. Third, genome-wide association studies for longevity highlight this pathway (Deelen et al., 2011).
References
- Deelen J, Uh HW, Monajemi R, van Heemst D, Thijssen PE, Böhringer S, et al. 2011. Gene set analysis of GWAS data for human longevity highlights the relevance of the insulin/IGF-1 signaling and telomere maintenance pathways. Age (Dordr). doi: 10.1007/s11357-011-9340-3.
- Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ, et al. 2008. Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci USA 105:3438–42 doi: 10.1073/pnas.0705467105. [PMC free article] [PubMed]
- Zhang Y, Xie Y, Berglund ED, Coate KC, He TT, Katafuchi T, et al. 2012. The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. eLife 1:e00065 doi: 10.7554/eLife.00065.
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Could a hormone point the way to life extension?
elife. 2012;1:e00286. doi: 10.7554/eLife.00286. Epub 2012 Oct 15.
Kenyon C.
University of California, San Francisco, United States, Cynthia.kenyon@ucsf.edu.
PMID: 23071903. NIH, NLM, PubMed access to Medline biomedical citations
Teleconference on Sunday!!
Reading Dr. Kenyon’s review as well as the research report itself made it clear that LivingTheCRWay members would benefit from talking with the researchers. We are delighted to announce that Drs. Steven Kliewer and David Mangelsdorf, (UT Southwestern Medical Center, Dallas) will appear as Guest Hosts at the CR Way full-member teleconference this Sunday at 5:00 P.M.(ET).
We will discuss how FGF-21 extends life, its role in weight loss and weight gain, and using ideas from the research to protect against cancer.
You can read more by becoming a Healthy Start member, which will give you access to the following blog and forum post, as well as a host of free information.
- LivingTheCRWay blog post: “Hunger Hormone Extends Life up to 40%.”
And
- LivingTheCRWay forum post: “FGF21 limits growth and extends life”
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