It is used in medicine to prevent organ transplant rejection. It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It inhibits activation of T cells and B cells by reducing the production of interleukin-2 (IL-2). Sirolimus is also used as a coating for coronary stents.
Effects on longevity[change | change source]
In a 2009 study, the lifespans of mice fed rapamycin were increased between 28 and 38% from the beginning of treatment. That is a 9 to 14% increased maximum lifespan. The treatment began in mice aged 20 months, the equivalent of 60 human years.
Later, rapamycin has been shown to extend mouse lifespan in several separate experiments. It is now being tested for this purpose on nonhuman primates (the marmoset monkey). A study on dogs is also planned.
It is thought that some dietary regimes, like restricting calories and methionine, cause lifespan extension by decreasing mTOR activity. It is believed that this is achieved by limiting the essential amino acid leucine, a potent activator of mTOR. The administration of leucine into the rat brain has been shown to decrease food intake and body weight via activation of the mTOR pathway.
According to the free radical theory of aging, reactive oxygen causes damage to mitochondrial proteins, and decreases ATP production. Then, the mTOR pathway is inhibited and ATP consuming protein synthesis is downregulated. This means the proportion of damaged proteins grows. Moreover, disruption of mTORC1 directly inhibits mitochondrial respiration.
These positive feedbacks on the aging process are counteracted by protective mechanisms: decreased mTOR activity (among other factors) upregulates glycolysis, and removal of dysfunctional cellular components by autophagy.
References[change | change source]
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