Find Your Inner Superhero to Boost Metabolism and Longevity: Fight the Evil mTOR

How can you find your inner superhero to boost metabolism and longevity and fight evil mTOR? Most of us are interested in the ability to being able to fight the effects of aging. Whether it’s to increase longevity or improve quality of life, it’s important to understand what controls and influences aging so that you can unleash your superhero efforts.

Well, exactly what is mTOR, is it destructive, and how does it affect aging? Target of rapamycin (TOR) is a highly conserved serine/threonine kinase (enzyme) that controls cell growth and metabolism in response to nutrients, growth factors, cellular energy, and stress.[i] Research evidence suggests that mTOR signaling influences longevity and aging. TOR is what regulates cell growth which plays a key role in aging. It is a nutrient-sensitive regulator of growth and as such, is involved in the development of diseases such as cancer, cardiovascular disease, obesity, and diabetes. 

Specifically, mTOR consists of two protein complexes, mTORC1 and mTOR2 in response to nutrient and nutrient-induced signals such as insulin. These two complexes stabilize mTOR. mTOR is involved not only involved in aging (cellular senescence), it is also involved in the immune response. This means that regulating mTOR is vital for health. Defects or dysregulation of TOR can lead to abnormal cell growth and diseases such as cancer and epilepsy. MTOR is also associated with glucose intolerance and insulin resistance and may even activate type II diabetes.[ii]

A review of what has been learned in the past quarter-century about mTORC1 is that inhibiting it increases lifespan in multiple organism studies which suggests that it may offer increasing health and life span in humans. [iii] As activation of mTOR promotes tumor growth and metastasis, many mTOR inhibitors have been used in treating cancer.[iv] While many other studies have used pharmacologic mTOR inhibitors in animals demonstrating the ability to promote longevity, side effect profiles were a major cause of concern.[v] However, studies continue to find that magic pill to increase your longevity. This doesn’t mean, however, that there aren’t some ways we can naturally influence our longevity.

So, where does that leave you in terms of tapping into your inner superhero to boost your metabolism and longevity to fight the evil effects of an mTOR gone awry? Here are some natural ways to keep your mTOR in balance to promote a stable metabolism and decrease risk of aging, cancer[vi], and other diseases:

• Limit intake of added sugar to reduce the risk of developing diabetes and insulin resistance.
• Maintain cholesterol levels below 200.
• Calorie restriction without promoting malnutrition may potentially be helpful as it is thought to be at least partially mediated by TOR. What is particularly important is to not overeat and avoid obesity.  
• Consider natural products derived from foods that may reduce mTOR signaling including: [vii]
  • Curcumin-Inhibits both mTOR pathways and is found in multiple studies to be effective against cancer. [viii]
  • Green tea (epigallocatechin gallate or EGCG)- EGCG is able to reduce proliferation and induce the apoptosis of pancreatic cancer cells and other cancers as well as inhibit mTOR.[ix]^,[x]
  • Genistein- Genistein is an isoflavone that may be found in soybean, chickpeas, and other soy-based food that is protective against certain cancers. Genistein also modulates metabolic pathways such as gluconeogenesis via the mTOR pathway.[xi]
  • 3, 3-diindolylmethane (DIM) found in foods such as broccoli, kale, brussel sprouts, and cabbage. This has also been found to be effective as a supplement to decrease fibroglandular tissue as well as decrease estrogen and testosterone in women at risk for breast cancer who carry the BRCA mutation. [xii]
  • Apigenin, a flavonoid, is abundant in fruits (oranges, apples, cherries, grapes), vegetables (onions, parsley, broccoli, sweet green pepper, celery, barley, tomatoes) and beverages (tea, wine) inhibits mTOR.[xiii]
  • Fisetin, a flavonoid, occurs in fruits and vegetables, such as strawberries, apples, persimmons, and onions. Fisetin can modulate the activity of two key signaling pathways associated with the growth and progression of cancer.[xiv]
  • Quercetin, a polyphenolic compound, is mainly from the consumption of tea, onions, red grapes, and apples. Quercetin is known to decrease inflammation, decrease atherosclerosis, and can inhibit mTOR in cancer cells. [xv]
  • Resveratrol- a natural polyphenol found in a variety of daily food including grapes and red wine, has long been suspected to have multifaceted health beneficial properties, including anti-inflammation, anti-oxidant, and anticancer activities, and targets mTOR pathways making it a potentially viable cancer treatment.[xvi]
  • Caffeine-Caffeine inhibits mTOR function by targeting its kinase activity [xvii]
  • Tocotrienols-members of the vitamin E family, exhibit strong antioxidant properties and potent anticancer activity.[xviii]
  • Capsaicin such as found in red chili peppers activates AMPK leading to mTOR inhibition, and apoptosis (cancer cell death). [xix]^,[xx]

Zap, bam, boom, shazaam, and find your inner superhero to eat improve your metabolism, fight against an evil mTOR enemy, and potentially improve your longevity.

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[i] Hall MN. mTOR-what does it do?. Transplant Proc. 2008;40(10 Suppl):S5-S8. doi:10.1016/j.transproceed.2008.10.009

[ii] Kezic A , Popovic L, Lalic K. mTOR Inhibitor Therapy and Metabolic Consequences: Where Do

We Stand? Oxidative Medicine and Cellular Longevity Volume 2018, Article ID 2640342, https://doi.org/10.1155/2018/2640342

[iii] Sabatini, DM. Twenty-five years obsessing over mTOR. Proceedings of the National Academy of Sciences Nov 2017, 114 (45) 11818-11825; DOI: 10.1073/pnas.1716173114

[iv] Hua, H., Kong, Q., Zhang, H. et al. Targeting mTOR for cancer therapy. J Hematol Oncol 12, 71 (2019). https://doi.org/10.1186/s13045-019-0754-1

[v] Weichhart T. mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review. Gerontology. 2018;64(2):127-134. doi:10.1159/000484629

[vi] Sun H, Wang Z, Yakisich JS. Natural products targeting autophagy via the PI3K/Akt/mTOR pathway as anticancer agents. Anticancer Agents Med Chem. 2013;13(7):1048-1056. doi:10.2174/18715206113139990130

[vii] Zhou H, Luo Y, Huang S. Updates of mTOR inhibitors. Anticancer Agents Med Chem. 2010;10(7):571-581. doi:10.2174/187152010793498663

[viii] Beevers CS, Zhou H, Huang S. Hitting the golden TORget: curcumin’s effects on mTOR signaling. Anticancer Agents Med Chem. 2013;13(7):988-994. doi:10.2174/1871520611313070004

[ix] Liu S, Xu ZL, Sun L, Liu Y, Li CC, Li HM, Zhang W, Li CJ and Qin W: (‑)‑Epigallocatechin‑3‑gallate induces apoptosis in human pancreatic cancer cells via PTEN. Mol Med Rep 14: 599-605, 2016

[x] Van Aller, Glenn & Carson, Jeff & Tang, Wei & Peng, Hao & Zhao, Lin & Copeland, Robert & Tummino, Peter & Luo, Lusong. (2011). Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor. Biochemical and biophysical research communications. 406. 194-9. 10.1016/j.bbrc.2011.02.010.

[xi] Javed, Z., Khan, K., Herrera-Bravo, J. et al. Genistein as a regulator of signaling pathways and microRNAs in different types of cancers. Cancer Cell Int 21, 388 (2021). https://doi.org/10.1186/s12935-021-02091-8

[xii] Yerushalmi R, Bargil S, Ber Y, Ozlavo R, Sivan T, Rapson Y, Pomerantz A, Tsoref D, Sharon E, Caspi O, Grubsrein A, Margel D. 3,3-Diindolylmethane (DIM): a nutritional intervention and its impact on breast density in healthy BRCA carriers. A prospective clinical trial, Carcinogenesis, Volume 41, Issue 10, October 2020, Pages 1395–1401, https://doi.org/10.1093/carcin/bgaa050

[xiii] Huang S. Inhibition of PI3K/Akt/mTOR signaling by natural products. Anticancer Agents Med Chem. 2013;13(7):967-970. doi:10.2174/1871520611313070001

[xiv] Syed DN, Adhami VM, Khan MI, Mukhtar H. Inhibition of Akt/mTOR signaling by the dietary flavonoid fisetin. Anticancer Agents Med Chem. 2013;13(7):995-1001. doi:10.2174/18715206113139990129

[xv] Bruning A. Inhibition of mTOR signaling by quercetin in cancer treatment and prevention. Anticancer Agents Med Chem. 2013;13(7):1025-1031. doi:10.2174/18715206113139990114

[xvi] Wu Y, Liu F. Targeting mTOR: evaluating the therapeutic potential of resveratrol for cancer treatment. Anticancer Agents Med Chem. 2013;13(7):1032-1038. doi:10.2174/18715206113139990113

[xvii] Gibbs B. F., Gonçalves Silva I., Prokhorov A., Abooali M., Yasinska I., Casely-Hayford M. A., Berger S. M., Fasler-Kan E., Sumbayev V. Caffeine affects the biological responses of human hematopoietic cells of myeloid lineage via downregulation of the mTOR pathway and xanthine oxidase activity. Oncotarget. 2015; 6: 28678-28692. Retrieved from https://www.oncotarget.com/article/5212/text/

[xviii] Sylvester PW, Ayoub NM. Tocotrienols target PI3K/Akt signaling in anti-breast cancer therapy. Anticancer Agents Med Chem. 2013;13(7):1039-1047. doi:10.2174/18715206113139990116

[xix] Maiese K. Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin. Curr Neurovasc Res. 2017;14(2):184-189. doi:10.2174/1567202614666170313105337

[xx] Bort A, Sánchez BG, Spínola E, Mateos-Gómez PA, Rodríguez-Henche N, Díaz-Laviada I (2019) The red pepper’s spicy ingredient capsaicin activates AMPK in HepG2 cells through CaMKKβ. PLoS ONE 14(1): e0211420. https://doi.org/10.1371/journal.pone.0211420