Rapamycin (Gold Biotechnology, R-101) is such a remarkable drug! It’s a macrocyclic triene antibiotic, an immunosuppressant, it has anti-cancer and anti-proliferative properties and, oh, by the way, it may also help increase your life-span. That’s an awful lot of properties to keep track of for a chemical compound that looks like this:
The antibiotic was first discovered in the late 60’s by Dr. Suren Sehgal on the remote Easter Island (called Rapa Nui by its natives) from a soil sample and later isolated from the bacteria, Streptomyces hygroscopicus, in 1972. (The compound does seem to resemble this Moai a little bit.) Originally tested as an antifungal agent, it was quickly discovered that it had immunosuppressant properties, effectively killing its application as an antifungal.
Almost lost due to sudden loss of research funding, it was rediscovered in the late 1980’s by Wyeth, in which they found an analogue (CCI-779) that was broadly active against a wide range of tumor types! Even better, its mechanism was so unique, they named its molecular target TOR (Target Of Rapamycin). The drug then went on the whirlwind, cancer wonder-drug research circuit, received FDA approval in 2007, and is currently a large part of the drug program used for renal cancer.
But the journey of this humble antibiotic from the farthest corner of the planet would take another leap in public attention. In 2009, David Harrison et al. discovered that Rapamycin significantly increased the life-span of mice! Of course, there are always some side effects, such as an increased resistance to insulin…and let’s not forget that Rapamycin is still widely used as an immunosuppressant. But even more recently, there’s the prospect that treatment with Rapamycin may ameliorate age-dependent obesity and age-related cognitive decline!
So let’s tally this up. Increase life-span? Check! Weight loss drug? Check! Improve age-related mental functions? Check! And “to get all of this and more!”, all we have to do is live in a bubble without any sugar? Well…maybe. Earlier this year, Dudley Lamming et al. was able to uncouple the longevity and insulin resistance effects of Rapamycin, possibly giving us the opportunity to have our sugar-laden cake and eat it too! Of course, we’ll still be living in that bubble.
But I’m certain within another year or so, some scientist will uncouple that problem as well and we’ll all get to live healthy, double-century lives (or at least those of us with good drug coverage). As always in science, the possibilities are endless…
1. Garber, Ken. "Rapamycin’s resurrection: a new way to target the cancer cell cycle." Journal of the National Cancer Institute 93.20 (2001): 1517-1519.
2. Yong, Ed. “The two faces of rapamycin – why a life-extending drug also increases risk of diabetes.” Not Exactly Rocket Science-Blogs @ Discover Magazine. 30 March, 2012.
3. Harrison, David E., et al. "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice." nature 460.7253 (2009): 392-395.
4. Di Paolo, Salvatore, et al. "Chronic inhibition of mammalian target of rapamycin signaling downregulates insulin receptor substrates 1 and 2 and AKT activation: A crossroad between cancer and diabetes?." Journal of the American Society of Nephrology 17.8 (2006): 2236-2244.
5. Houde, Vanessa P., et al. "Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue." Diabetes 59.6 (2010): 1338-1348.
6. Yang, Shi-Bing, et al. "Rapamycin Ameliorates Age-Dependent Obesity Associated with Increased mTOR Signaling in Hypothalamic POMC Neurons." Neuron 75.3 (2012): 425-436.
7. Majumder, Smita, et al. "Lifelong rapamycin administration ameliorates age‐dependent cognitive deficits by reducing IL‐1β and enhancing NMDA signaling." Aging cell (2012).
8. Lamming, Dudley W., et al. "Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity." Science Signaling 335.6076 (2012): 1638.
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