In the paper referenced here researchers dig more deeply into the effects of statins on cellular metabolism, and in particular its effects on stem cell activities. Statins act to reduce cholesterol levels in the blood and are widely used to attempt to slow the onset of cardiovascular diseases, particularly atherosclerosis. The consensus view of the evidence suggests that overall the outcome of statin use is modestly positive, but there are always outlier studies, such as those suggesting statin use causes more harm than it prevents to the cardiovascular system. Like all drugs in widespread use today statins have very broad effects on the operation of cellular metabolism, and far from all of these effects are completely understood.
Still, statins were selected to be one of the components of a proposed polypill program aiming to slightly slow the later stages of aging. Trials have been carried out or are underway, but the proponents of polypills are still a fair way distant from implementing the original vision of blanket prescription of low doses of statins and a range of other drugs for everyone over the age of fifty. If we're lucky, this and all other similar programs will be overtaken by circumstances, rendered irrelevant by progress in rejuvenation therapies. Tinkering with metabolism and mining the world for drugs that might slightly slow aging isn't the path forward, but it is certainly expensive and time-consuming.
That both beneficial and harmful actions result from the interaction of drugs with tissues is well illustrated in this examination of statins, but the actual biochemistry involved is an unusually constrained case. A single type of change, a reduction in the ability of stem cells to deliver a supply of new cells into tissues, spirals out to bring both benefits and harms. These occur on different timescales and for different aspects of the integrity of the cardiovascular system. A drug can be seen as beneficial if slows a rapid cause of death but speeds up a slower cause of death, as might be argued is happening in the case of statins. Much of the downside will be masked because many people will die due to other causes along the way. With the advance of biotechnology and greater knowledge of cellular biochemistry some drugs will no doubt be altered to successfully split apart beneficial and harmful actions. This is underway for rapamycin, to pick one example, but I think it less likely to happen here.
This is also a good illustration of the point that altering the operation of metabolism away from its present evolved state always comes with trade-offs. Our biology is too complex for any other outcome: every system is connected in some way to every other system. Nothing can be altered in isolation, nothing can be easily switched around. The only approach to medicine free from considerations of benefit versus harm is to aim at repair of the root cause damage that causes age-related system failures in cells and tissues. Strive to maintain the metabolism we have when we are young through periodic repair, in other words, don't try to build a new system that can slightly better cope with being damaged. The former is the easier path, with much larger potential gains in health and longevity, while the latter is far harder and cannot produce anything more than a modest slowing of aging. Yet most research follows the latter path. It is a crazy world we live in.
Atherosclerosis develops when plaques build up inside blood vessels, which can lead to heart attack, stroke and death. Statins lower the risk by blocking cholesterol production in the liver, reducing a person's "bad" cholesterol. The immune cells macrophages play a major role in plaque formation and rupture in atherosclerosis. Macrophages ingest fat deposits along the blood vessel wall and attract more macrophages, other cells and inflammation-related proteins to the injury site. The enhanced inflammation builds up the plaque within the vessel wall and further narrows the artery. Macrophages also release enzymes that weaken the fibrous cap that separates the plaque from the blood flow, increasing the likelihood that the plaque breaks open. Plaque ruptures lead to blood clots that result in strokes and heart attacks.
Macrophages primarily develop from stem cells that reside in the bone marrow, but can also develop from mesenchymal stem cells (MSCs), which are found throughout the body. While bone marrow stem cells mainly become blood cells, MSCs can become all cell types, including bone, cartilage, muscle cells and macrophages. In this study, the research team found that long-term statin use prevented MSCs from turning into macrophages, which could decrease inflammation and improve plaque stability in patients with cardiovascular disease. However, statins also prevented MSCs from becoming bone and cartilage cells. Statins increased aging and death rate of MSCs and reduced DNA repair abilities of MSCs. "While the effect on macrophage differentiation explains the beneficial side of statins, their impact on other biologic properties of stem cells provides a novel explanation for their adverse clinical effects."
Statins reduce atherosclerotic events and cardiovascular mortality. Their side effects include memory loss, myopathy, cataract formation, and increased risk of diabetes. As cardiovascular mortality relates to plaque instability, which depends on the integrity of the fibrous cap, we hypothesize that the inhibition of the potential of Mesenchymal Stem Cells (MSCs) to differentiate into macrophages would help to explain the long known, but less understood "Non Lipid Associated" or pleiotropic benefit of statins on cardiovascular mortality. While the effect on macrophage differentiation explain the beneficial side of statins, their impact on other biologic properties of stem cells provides a novel explanation for their adverse clinical effects.