Rapamycin and TOR

Of all the known chemical substances in the universe, a single drug has emerged as the most robust in extending lifespan. That drug has extended the lifespan of every living thing tested in the laboratory: yeast, worms, flies, and even middle-aged mice. That drug is Rapamycin. In a recent 2014 paper, it was reported rapamycin extended the median lifespan 23% in male mice and 26% in female mice.

It has been known since the 1930s that caloric restriction extends lifespan and slows aging. Rapamycin could be characterized as caloric restriction in a pill. In a mouse study discussed in the “Cardiomyopathy” section, rapamycin had similar effect in aged mice as 40% caloric restriction in restoring the dysfunction of old hearts to normal function of young hearts. The effect of caloric restriction is to decrease TOR indirectly, the effect of rapamycin is to  decrease TOR directly.

Aging is defined as an increase in the probability of death. If a drug extends lifespan, that drug is slowing aging. Aging is the main risk factor for age-related disease: heart disease, cancer, Alzheimer’s disease, blindness, etc.  Slowing down aging, staying young, is the goal of Rapamycin Medicine.

Rapamycin has only one action; it targets or binds to TOR and thereby lowers TOR activity. TOR stands for Target-Of-Rapamycin. TOR and rapamycin are related as a key to a lock. TOR has been conserved through 2 billion years of evolution. TOR functions as the central hub of the cell signaling system, the command and control center of the cell.

Rapamycin was approved in 1999 as a prescription medicine to be used in high daily dose as an immunosuppressant in transplant medicine. Used in this manner, Rapamycin has very limited benefits aside from use in transplant medicine as it has too many side effects to be of general interest.  Miraculously, when used as a non-immunosupressant, low dose, weekly medication, rapamycin is transformed into a silver bullet, with minimal side effects and extraordinary benefits. For rapamycin, less is more.

Rapamycin, like penicillin, was the product of biologic warfare between bacteria and yeast. Like a mirror image,  penicillin, discovered in 1928, was made by yeast to target bacteria, while Rapamycin, found in the soil of Easter Island in 1965, was made by bacteria to target yeast. The bacteria of Easter Island targeted TOR, the command and control center of the yeast cell. However, TOR, the substance targeted in this never ending war between yeast and bacteria, is the command and control center of not just yeast; but every living thing on planet earth. TOR is in essence, the secret of how life is organized within the cell.

Rapamycin has another similarity to thediscovery of penicillin. In the “Cancer” section (Ref 7), Mikhail Blagosklonny stated, “Rapamycin could be used for extension of healthy lifespan and prevention of age-related diseases by slowing down the aging process. This may become one of the major breakthroughs in medicine since the discovery of antibiotics.”

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