The author of this paper is one of the more outspoken advocates in the research community when it comes to mTOR and rapamycin as a path to slowing the progression of aging. He keeps up quite the output of position papers, such as this one, which calls for immediate human trials of polypills made up of rapamycin and a brace of other drugs broadly used in treatment of age-related conditions, such as statins and metformin. I have to think that the evidence to date suggests this will be less effective than hoped, while still very plausibly being better than doing nothing, even considering the side-effects of the drugs involved. Effects in animal studies usually tend to be much more pronounced than effects in humans when it comes to slowing or preventing specific age-related diseases through pharmaceuticals.
If it was the only game in town, I'd be all for it, but there are far more effective ways forward towards the effective treatment of aging as a medical condition - approaches that aim at rejuvenation, not a mere slowing of aging. Still, I think the author here has the right general idea, in that the research community should move faster, the sooner plausible approaches are trialed the better, and that we should all pitch in to help, it is just that he is advocating a poor approach with a limited upside in comparison to other methodologies.
Inhibitors of mTOR, including clinically available rapalogs such as rapamycin (Sirolimus) and Everolimus, are gerosuppressants, which suppress cellular senescence. Rapamycin slows aging and extends life span in a variety of species from worm to mammals. Rapalogs can prevent age-related diseases, including cancer, atherosclerosis, obesity, neurodegeneration and retinopathy and potentially rejuvenate stem cells, immunity and metabolism. Here, I suggest how rapamycin can be combined with metformin, inhibitors of angiotensin II signaling (Losartan, Lisinopril), statins, propranolol, aspirin and a PDE5 inhibitor. Rational combinations of these drugs can maximize their anti-aging effects and decrease side effects.
At first, the discovery of anti-aging properties of rapamycin was met with skepticism because it challenged the dogma that aging is a decline driven by molecular damage caused by free radicals. By now, rapamycin has been proven to be an anti-aging drug. In contrast, anti-oxidants failed in clinical trials and the dogma was shattered. In the last decade, anti-aging effects of rapamycin have been confirmed. Anti-aging doses and schedules can be extrapolated from animal studies. Well-tolerated doses with minimal side effects can be deducted based on clinical use of rapalogs. So optimal anti-aging doses/schedules can be suggested. Given that rapamycin consistently extends maximal lifespan in mice, rapamycin will likely allow mankind to beat the current record of human longevity, which is 122 years. Yet, rapamycin will not extend life span as much as we might wish to. Now is the time for anti-aging drug combinations. For example, metformin is currently undergoing re-purposing as an anti-aging agent. Several other existing drugs can be re-purposed. Now we can design an anti-aging formula, using drugs available for human use.
Rapamycin (or another rapalog) should be a cornerstone of anti-aging combinations, given its universal anti-aging effect and the ability to delay almost all diseases of aging. Rapamycin and metformin: Both drugs extend lifespan in animals and have non- overlapping effects. In addition, they may, in theory, cancel possible metabolic side-effects of each other. Rapamycin and statins: Rapamycin promotes lipolysis increasing blood levels of fatty acids. This, in turn, increases levels of lipoproteins produced by the liver. Rapamycin-induced hyperlipidemia is benevolent and reversible. Still, statins are already used to prevent rapamycin-induced hyperlipidemia.
The 7-drug combination can be tested in mice, especially in mice on high fat diet and in cancer-prone mice. If started late in life, the experiments will take just several months to evaluate the effect on lifespan and cancer incidence as well as weight, blood pressure, glucose, insulin, triglycerides and leptin. In humans, the treatment program can be initiated regardless of any pre-clinical studies, because all 7 drugs are approved for human use and some of them such as aspirin and statin are widely used for disease prevention anyway. The only what is needed is to watch for side effects. Especially, heart rate, blood pressure, and glucose levels should be monitored.
The anti-aging formula is ready for human use. If one will wait until the life-extending effect will be shown in others, this individual will not be alive by the time of the result. Human clinical trials are needed to optimize the doses and schedules. However, unless we participate in clinical trials ourselves, we will not know how long participants will live because they are expected to outlive non-participants. If we want to live longer we should be participants in clinical trials. In the best scenario, this might allow us to live long enough to benefit from future discoveries of anti-aging remedies.