Adventures of Medicine from Easter Island
The former antibiotic has turned into a promising cure for old age
Polina Loseva, "The Attic"
A group of scientists from New Zealand and several research units of the pharmaceutical giant Novartis has found that the drug rapamycin helps strengthen the immunity of older people. This remedy is considered the main candidate for "old age pills". It is not yet known how much the detected effect will prolong the life of the subjects, but the new work has shown the safety of rapamycin for completely healthy people and the fundamental possibility of its use in anti-aging therapy.
Panacea of the South Seas
When scientists collected soil samples on Easter Island in 1965, hardly anyone could have imagined that a commemorative plaque would be hung on this very place in 35 years. Together with the soil, bacteria got into the sample, one of which in 1972 gave people a new antibiotic – rapamycin (in honor of Rapa Nui - the name of the island in the local dialect). At first, only its antibacterial and antifungal properties were known, but later it turned out that it most effectively suppresses our own immunity.
As medicine develops, it becomes increasingly necessary to "fix" something in the body bypassing the immune system. For example, if we want to transplant into the body a foreign organ or tissue against which the immune system will deploy protection. It was the use of rapamycin in kidney transplants that provided him with a path to clinics where it is still used. This antibiotic is also effective in the development of autoimmune diseases (rapamycin is actively being investigated as a remedy against systemic lupus erythematosus).
Research on the miracle drug did not stop there, and it soon became clear that it could also be used against cancer. Now the American Food and Drug Administration (FDA) recommends the use of rapamycin–based drugs for renal carcinomas and neuroendocrine tumors, as well as for tuberous sclerosis - a rather rare genetic disease in which benign tumors appear throughout the body in different tissues.
But rapamycin's abilities have not exhausted themselves. It turned out that it prolongs the life of a variety of organisms, including mice. And not only cancer patients, but also absolutely healthy. There is a contradiction: this multifunctional antibiotic suppresses the work of the immune system, but at the same time fights tumors. It prevents cells from dividing and simultaneously prolongs the life of the whole body. How does he do it?
TORa Hammer
Rapamycin owes all its properties to a single molecular complex. It was so called – the target of rapamycine (abbreviated TOR). This complex reacts to external stimuli (for example, nutrients or signaling molecules of other cells) and makes the cell "work". At the same time, the specific "work" of each cell depends on the specialization: the adipose tissue cell must store energy, the immune cell must attack the target, well, and the cancer cell must multiply and take food from its neighbors. Rapamycin binds to the TOR complex and blocks its activity, while the level of metabolism in tumor cells decreases (initially higher than in all other cells), and they die, and immune cells cease to activate when they encounter an antigen.
The TOR complex is a double–edged sword. On the one hand, it is certainly useful for the development of the body. In the presence of food and growth hormones, cells divide, build their macromolecules and store excess energy. But the excessive activity of cells from some point begins to harm them. Too intensive metabolism leads to breakdowns in proteins and whole organelles, as well as mutations in DNA. But if you block the extra signals from the outside, then the cells have a chance to live longer. That is why calorie restriction turned out to be beneficial for prolonging life: no food – no signal. And that's why rapamycin is also effective: by blocking TOR, it simulates the absence of food.
But no success story is complete without falls. In the case of rapamycin, serious side effects became a failure. Suppression of immunity is fraught with the development of both infections and tumors, which for some reason escaped the action of the drug. Despite the fact that modern medicines do not use rapamycin itself, but its more effective and harmless derivatives (everolimus, temsirolimus), the danger does not completely disappear. And if you can put up with this in a critical situation when a transplant is needed, then putting healthy people at such risk for the sake of a possible prolongation of life seems inhumane. Therefore, research in the field of animal aging continues, but rapamycin is still contraindicated for humans.
A new hope
Nevertheless, the results of the latest clinical studies published on July 11 in the journal Science Translational Medicine (Mannick et al., TORC1 inhibition enhances immune function and reduces infections in the elderly) have added optimism to gerontologists. Of the 264 volunteers over the age of 65, 200 people received rapamycin analogues for six weeks. After that, they were injected with a seasonal flu vaccine, and then the number of antibodies to the virus was measured as an indicator of immune activity.
One of the groups of subjects received not only an analogue of rapamycin, but also another TOR blocker. And although rapamycin analogues work as immunosuppressors in high concentrations (i.e. they suppress immunity), in small doses (up to 100 times less than they are used in transplants), on the contrary, they have shown themselves to be effective immune stimulants. In the case of a double blockade of the TOR complex, patients had 30 percent more antibodies than those who received a placebo. At the same time, side effects occurred infrequently – only 10 percent of people (however, it should be borne in mind that all participants in the experiment were elderly), and none seriously threatened their life and health. After vaccination, the subjects who received rapamycin analogues also turned out to be stronger: in the next season, their incidence of colds decreased by half (those who took a placebo were ill two or three times a season, and those who received the most "successful" combination of drugs - on average 1.5).
Scientists have not only managed to find a way to strengthen the immunity of older people, but also to prove two fundamental things. Firstly, until now, all proposals to use rapamycin and its analogues to prolong life have caused great doubts and controversy. Now for the first time there is convincing evidence that they can be safe for health, which means that the field for research has opened up. Secondly, the development of "old age pills" for humans is associated with unavoidable obstacles: the subjects live too long (not every scientist himself will live to the end of his experiment, and not every company will want to invest in such a long-term perspective) and are not ready to take risks to decide to participate in such a study. But now we know for sure: the medicine that claims to be the "elixir of eternal youth" has specific short-term positive effects. This means that it can be studied, it can be applied and it is hoped that new experiments with rapamycin will show what it is really capable of.
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