What can we do to boost the longevity hormone FGF21?
Life Extension with FGF21
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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
In the year 2000, a new human hormone was discovered. It was the 21st documented fibroblast growth factor; so, they called it FGF21. Since its discovery, FGF21 has emerged as a key agent for promotion of metabolic and artery health, leanness, and longevity. Inject it into fat monkeys, and they lose body weight without reducing food intake, and not just a little—a 27 percent drop in body fat eating the same amount. In mice, it increases their lifespan 30 to 40 percent, comparable to lifelong caloric restriction, but again was achieved without decreasing food intake. The researchers conclude that FGF21 could potentially be used as a hormone therapy to extend lifespan in mammals, which has gotten big pharma salivating, raising the question “Can aging be ‘drugged’?”
And that’s not all it can do. The idea that one drug can treat obesity, diabetes, dyslipidemia (like high cholesterol), and hypertension all at once might have seemed impossible a few years ago, but is now a tantalizing and exciting prospect. The reason you can’t just give people straight FGF21 is that it gets rapidly broken down in the body; so, you’d have to get injections like every hour or two around the clock. So, drug companies are trying to patent a variety of longer-acting FGF21 look-alikes. And indeed, give people a little PF-05231023, and they can lose about 10 pounds in 25 days, along with dramatic drops in triglycerides and cholesterol.
But then, the side effects of these new-fangled drugs started cropping up. Okay, so what about this: we package the FGF21 gene into a virus, and then inject the virus and have it stitch extra FGF21 genes into our DNA. Or you can just lace on your running shoes. Exercise boosts FGF21 levels, which may in fact be one of the reasons exercise is so good for us.
Which works better, though, aerobic exercise—eight weeks of running training—or resistance exercise—eight weeks of weights? The answer is both, but the resistance exercise edged out the running, a 42 percent increase in FGF21 versus a 25 percent increase in the aerobic exercise group.
Okay, but what can we do with food? Yeah, you could try engineering and injecting it, but wouldn’t it be easier to just stimulate our own endogenous, natural production through diet? One way is through no diet at all. You may have noticed it’s been dubbed the starvation hormone. That’s because fasting induces FGF21, but not just a day or two.
Physiologically, FGF21 expression is markedly increased in response to fasting/starvation. But, unlike mice, which show an increase after just six hours of fasting, humans don’t get a notable surge in FGF21 until after a week. Fasting can quadruple FGF21, but it takes 10 days of fasting, which is the very poster child of an unsustainable eating pattern.
So, how do you get the benefits without the starvation? Might a ketogenic diet be able to mimic the fast? Nope. Keto diets don’t work. In fact, keep it up for a few months, and you can actually get a significant decline in levels. High-fat diets may even interfere with the boost you get from exercise, seen here in a study of high intensity interval training.
What kind of diet does work, then? We’ll find out next.
Please consider volunteering to help out on the site.
- Nishimura T, Nakatake Y, Konishi M, Itoh N. Identification of a novel FGF, FGF-21, preferentially expressed in the liver. Biochim Biophys Acta. 2000;1492(1):203-6.
- McCarty MF. Practical prospects for boosting hepatic production of the “pro-longevity” hormone FGF21. Horm Mol Biol Clin Investig. 2017;30(2).
- Zhang Y, Xie Y, Berglund ED, et al. The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. Elife. 2012;1:e00065.
- Huang Z, Xu A, Cheung BMY. The Potential Role of Fibroblast Growth Factor 21 in Lipid Metabolism and Hypertension. Curr Hypertens Rep. 2017;19(4):28.
- Pérez-Martí A, Sandoval V, Marrero PF, Haro D, Relat J. Nutritional regulation of fibroblast growth factor 21: from macronutrients to bioactive dietary compounds. Horm Mol Biol Clin Investig. 2017;30(1).
- Sonoda J, Chen MZ, Baruch A. FGF21-receptor agonists: an emerging therapeutic class for obesity-related diseases. Horm Mol Biol Clin Investig. 2017;30(2).
- Talukdar S, Zhou Y, Li D, et al. A Long-Acting FGF21 Molecule, PF-05231023, Decreases Body Weight and Improves Lipid Profile in Non-human Primates and Type 2 Diabetic Subjects. Cell Metab. 2016;23(3):427-40.
- Jimenez V, Jambrina C, Casana E, et al. FGF21 gene therapy as treatment for obesity and insulin resistance. EMBO Mol Med. 2018;10(8):e8791.
- Cuevas-Ramos D, Almeda-Valdés P, Meza-Arana CE, et al. Exercise Increases Serum Fibroblast Growth Factor 21 (FGF21) Levels. Atkin SL, ed. PLoS ONE. 2012;7(5):e38022.
- Keihanian A, Arazi H, Kargarfard M. Effects of aerobic versus resistance training on serum fetuin-A, fetuin-B, and fibroblast growth factor-21 levels in male diabetic patients. Physiol Int. 2019;106(1):70-80.
- Erickson A, Moreau R. The regulation of FGF21 gene expression by metabolic factors and nutrients. Horm Mol Biol Clin Investig. 2017;30(1):1-14.
- Holmes D. Fasting induces FGF21 in humans. Nat Rev Endocrinol. 2016;12(1):3.
- Jin L, Lin Z, Xu A. Fibroblast growth factor 21 protects against atherosclerosis via fine-tuning the multiorgan crosstalk. Diabetes Metab J. 2016;40(1):22-31.
- Fazeli PK, Lun M, Kim SM, et al. FGF21 and the late adaptive response to starvation in humans. J Clin Invest. 2015;125(12):4601-11.
- Gälman C, Lundåsen T, Kharitonenkov A, et al. The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARalpha activation in man. Cell Metab. 2008;8(2):169-74.
- Christodoulides C, Dyson P, Sprecher D, Tsintzas K, Karpe F. Circulating fibroblast growth factor 21 is induced by peroxisome proliferator-activated receptor agonists but not ketosis in man. J Clin Endocrinol Metab. 2009;94(9):3594-601.
- Johnstone AM. Fasting - The ultimate diet? Obes Rev. 2007;8(3):211-22.
- Andersen B, Straarup EM, Heppner KM, et al. FGF21 decreases body weight without reducing food intake or bone mineral density in high-fat fed obese rhesus macaque monkeys. Int J Obes (Lond). 2018;42(6):1151-60.
- Riera CE, Dillin A. Can aging be 'drugged'?. Nat Med. 2015;21(12):1400-5.
- Kim AM, Somayaji VR, Dong JQ, et al. Once-weekly administration of a long-acting fibroblast growth factor 21 analogue modulates lipids, bone turnover markers, blood pressure and body weight differently in obese people with hypertriglyceridaemia and in non-human primates. Diabetes Obes Metab. 2017;19(12):1762-72.
- Asle mohammadi zadeh M, Kargarfard M, Marandi SM, Habibi A. Diets along with interval training regimes improves inflammatory & anti-inflammatory condition in obesity with type 2 diabetes subjects. J Diabetes Metab Disord. 2018;17(2):253-67.
Motion graphics by Avo Media
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
In the year 2000, a new human hormone was discovered. It was the 21st documented fibroblast growth factor; so, they called it FGF21. Since its discovery, FGF21 has emerged as a key agent for promotion of metabolic and artery health, leanness, and longevity. Inject it into fat monkeys, and they lose body weight without reducing food intake, and not just a little—a 27 percent drop in body fat eating the same amount. In mice, it increases their lifespan 30 to 40 percent, comparable to lifelong caloric restriction, but again was achieved without decreasing food intake. The researchers conclude that FGF21 could potentially be used as a hormone therapy to extend lifespan in mammals, which has gotten big pharma salivating, raising the question “Can aging be ‘drugged’?”
And that’s not all it can do. The idea that one drug can treat obesity, diabetes, dyslipidemia (like high cholesterol), and hypertension all at once might have seemed impossible a few years ago, but is now a tantalizing and exciting prospect. The reason you can’t just give people straight FGF21 is that it gets rapidly broken down in the body; so, you’d have to get injections like every hour or two around the clock. So, drug companies are trying to patent a variety of longer-acting FGF21 look-alikes. And indeed, give people a little PF-05231023, and they can lose about 10 pounds in 25 days, along with dramatic drops in triglycerides and cholesterol.
But then, the side effects of these new-fangled drugs started cropping up. Okay, so what about this: we package the FGF21 gene into a virus, and then inject the virus and have it stitch extra FGF21 genes into our DNA. Or you can just lace on your running shoes. Exercise boosts FGF21 levels, which may in fact be one of the reasons exercise is so good for us.
Which works better, though, aerobic exercise—eight weeks of running training—or resistance exercise—eight weeks of weights? The answer is both, but the resistance exercise edged out the running, a 42 percent increase in FGF21 versus a 25 percent increase in the aerobic exercise group.
Okay, but what can we do with food? Yeah, you could try engineering and injecting it, but wouldn’t it be easier to just stimulate our own endogenous, natural production through diet? One way is through no diet at all. You may have noticed it’s been dubbed the starvation hormone. That’s because fasting induces FGF21, but not just a day or two.
Physiologically, FGF21 expression is markedly increased in response to fasting/starvation. But, unlike mice, which show an increase after just six hours of fasting, humans don’t get a notable surge in FGF21 until after a week. Fasting can quadruple FGF21, but it takes 10 days of fasting, which is the very poster child of an unsustainable eating pattern.
So, how do you get the benefits without the starvation? Might a ketogenic diet be able to mimic the fast? Nope. Keto diets don’t work. In fact, keep it up for a few months, and you can actually get a significant decline in levels. High-fat diets may even interfere with the boost you get from exercise, seen here in a study of high intensity interval training.
What kind of diet does work, then? We’ll find out next.
Please consider volunteering to help out on the site.
- Nishimura T, Nakatake Y, Konishi M, Itoh N. Identification of a novel FGF, FGF-21, preferentially expressed in the liver. Biochim Biophys Acta. 2000;1492(1):203-6.
- McCarty MF. Practical prospects for boosting hepatic production of the “pro-longevity” hormone FGF21. Horm Mol Biol Clin Investig. 2017;30(2).
- Zhang Y, Xie Y, Berglund ED, et al. The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. Elife. 2012;1:e00065.
- Huang Z, Xu A, Cheung BMY. The Potential Role of Fibroblast Growth Factor 21 in Lipid Metabolism and Hypertension. Curr Hypertens Rep. 2017;19(4):28.
- Pérez-Martí A, Sandoval V, Marrero PF, Haro D, Relat J. Nutritional regulation of fibroblast growth factor 21: from macronutrients to bioactive dietary compounds. Horm Mol Biol Clin Investig. 2017;30(1).
- Sonoda J, Chen MZ, Baruch A. FGF21-receptor agonists: an emerging therapeutic class for obesity-related diseases. Horm Mol Biol Clin Investig. 2017;30(2).
- Talukdar S, Zhou Y, Li D, et al. A Long-Acting FGF21 Molecule, PF-05231023, Decreases Body Weight and Improves Lipid Profile in Non-human Primates and Type 2 Diabetic Subjects. Cell Metab. 2016;23(3):427-40.
- Jimenez V, Jambrina C, Casana E, et al. FGF21 gene therapy as treatment for obesity and insulin resistance. EMBO Mol Med. 2018;10(8):e8791.
- Cuevas-Ramos D, Almeda-Valdés P, Meza-Arana CE, et al. Exercise Increases Serum Fibroblast Growth Factor 21 (FGF21) Levels. Atkin SL, ed. PLoS ONE. 2012;7(5):e38022.
- Keihanian A, Arazi H, Kargarfard M. Effects of aerobic versus resistance training on serum fetuin-A, fetuin-B, and fibroblast growth factor-21 levels in male diabetic patients. Physiol Int. 2019;106(1):70-80.
- Erickson A, Moreau R. The regulation of FGF21 gene expression by metabolic factors and nutrients. Horm Mol Biol Clin Investig. 2017;30(1):1-14.
- Holmes D. Fasting induces FGF21 in humans. Nat Rev Endocrinol. 2016;12(1):3.
- Jin L, Lin Z, Xu A. Fibroblast growth factor 21 protects against atherosclerosis via fine-tuning the multiorgan crosstalk. Diabetes Metab J. 2016;40(1):22-31.
- Fazeli PK, Lun M, Kim SM, et al. FGF21 and the late adaptive response to starvation in humans. J Clin Invest. 2015;125(12):4601-11.
- Gälman C, Lundåsen T, Kharitonenkov A, et al. The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARalpha activation in man. Cell Metab. 2008;8(2):169-74.
- Christodoulides C, Dyson P, Sprecher D, Tsintzas K, Karpe F. Circulating fibroblast growth factor 21 is induced by peroxisome proliferator-activated receptor agonists but not ketosis in man. J Clin Endocrinol Metab. 2009;94(9):3594-601.
- Johnstone AM. Fasting - The ultimate diet? Obes Rev. 2007;8(3):211-22.
- Andersen B, Straarup EM, Heppner KM, et al. FGF21 decreases body weight without reducing food intake or bone mineral density in high-fat fed obese rhesus macaque monkeys. Int J Obes (Lond). 2018;42(6):1151-60.
- Riera CE, Dillin A. Can aging be 'drugged'?. Nat Med. 2015;21(12):1400-5.
- Kim AM, Somayaji VR, Dong JQ, et al. Once-weekly administration of a long-acting fibroblast growth factor 21 analogue modulates lipids, bone turnover markers, blood pressure and body weight differently in obese people with hypertriglyceridaemia and in non-human primates. Diabetes Obes Metab. 2017;19(12):1762-72.
- Asle mohammadi zadeh M, Kargarfard M, Marandi SM, Habibi A. Diets along with interval training regimes improves inflammatory & anti-inflammatory condition in obesity with type 2 diabetes subjects. J Diabetes Metab Disord. 2018;17(2):253-67.
Motion graphics by Avo Media
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Title
Life Extension with FGF21
LicenseCreative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Content URLDoctor's Note
Stay tuned for part two: How to Boost FGF21 with Diet for Longevity.
How Much Should You Exercise? Check out the video to find out.
For more on longevity, see How to Increase Your Life Expectancy 12 to 14 Years.
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