There is a trend towards examining drugs that treat cardiovascular and metabolic disease in search of modest effects on aging. This is most obvious in the attempted repurposing of antidiabetic drugs such as metformin, acarbose, and canagliflozin, but this also extends to lipid-lowering drugs such as atorvastatin. Now that SGLT2 inhibitors are popular as weight loss drugs for the control of obesity, rather than just antidiabetics, that portfolio is also under consideration. One might consider that a possible common thread here is manipulation of lipid metabolism to reduce localized excesses of free cholesterol and other lipids that become toxic when present in too large an amount. One might also argue that reduction in blood glucose is also a common thread, but it is worth noting that statins can increase this measure.
The effect on life span in mice resulting from treatment by some these drugs (e.g. arcabose and canagliflozin) is smaller than that produced by mTOR inhibitors such as rapamycin, but large enough to think that there is something real going on under the hood. That said, others such as metformin come with a panoply of very poor animal data and questionable human data for effects on aging, despite their popularity. It may be that these drugs only help in the context of a sedentary, overweight population and are of little use to physically fit individuals. It may also be that effects on aging in long-lived species such as our own are too small to spend much time on - certainly one can already argue that to be the case for calorie restriction mimetics, which as a class have a larger effect on life span in mice than antidiabetics.
Cardiovascular and metabolic drugs are frequently repurposed due to their diverse molecular mechanism in many diseases. With various molecular mechanisms found in the aging process, cardiometabolic drugs possess the potential to delay aging. For instance, aspirin and statins are potentially beneficial for cancer, or the pleiotropic effect of metformin in cancer, cardiovascular disease, and dementia in diabetic patients. Of note, aspirin and metformin could extend the lifespan of rodents. Our systematic review primarily focused on animal studies, with additional consideration given to clinical trials and their protocols.
Dramatic growth in the variety of longevity medicines that are being identified from animal studies is not always successfully translated to clinical applications. Aspirin treatment failed to prevent mortality and morbidity in healthy older adult people and potentially increased the hemorrhagic risk in those people. In parallel, metformin could not prolong the lifespan in drosophila and rather increased the mortality in female mice. Moreover, the clinical trials of metformin, such as MILES (Metformin In Longevity Study), showed the enhancement of longevity-related gene expressions, but the valid molecular mechanisms by which metformin facilitates this activity remain unknown.
Analysis of 49 animal trials and 10 clinical trial registries show that various cardiovascular and metabolic drugs have the potential to target lifespan. Metformin, acarbose, and aspirin are the three most studied drugs in animal trials. Aspirin and acarbose are the promising ones, whereas metformin exhibits various results. In clinical trial registries, metformin, omega-3 fatty acid, acarbose, and atorvastatin are currently cardiometabolic drugs that are repurposed to target aging. Published clinical trial results show great potential for omega-3 and metformin in healthspan.
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