It is fair to say that everything changes with age, every aspect of cellular biochemistry. That doesn't mean that researchers can point to any specific change and say that it is important, however. It could be far downstream from underlying causes. It could be hard to fix in comparison to those causes. It may be shown to detrimentally affect a range of vital cellular processes, but those mechanisms could turn out to be minor and unimportant in comparison to others. The major challenge in aging research is exactly that everything changes. It is thus very hard to determine the importance of any given change, given that it takes place in this complex environment of interacting dysfunction, chains of cause and consequence, a network falling into failure.
Lipid rafts are assemblies that constantly form and break down in and around the cell membrane, a complex little world in and of itself. The cell membrane influences everything to do with cell signaling, uptake of materials from the environment, export of materials from the cell, and a good many other things besides. Thus any changed aspect of the cell membrane, such as altered behavior of lipid rafts, will also influence these line items. But is it important?
That is a hard and expensive question to answer. Theorizing costs little, however, and thus we see a great deal of theorizing. Today's open access paper is good example of a fairly aggressive joining of dots with little to no support for the importance of the proposed mechanisms as a target for intervention. Which is, sadly, business as usual in the matter of aging: the only practical way to prove that any given approach is a good approach is to try it. Unfortunately, building the means to try it in the context of something as complex as lipid raft behavior gets us right back to hard and expensive again.
Lipid rafts (LRs) are microdomains (10-200 nm) with a short life, and their components, such as sphingolipids, cholesterol, and proteins, are assembled to function and disassemble quickly afterward. The components and sizes of LRs are not constant, and they can merge with each other to become larger when necessary. As hubs for signal transduction, LRs contain various signal proteins. Because signal transduction is essential for aging processes, the relationship between LRs and aging has attracted increasing attention. Aging drastically affects the components and functions of LRs. Further, considering the evidence, the influences of LRs on the hallmarks of aging are apparent. Many of these hallmarks contribute to the development of sustained inflammatory stage and aging. Hence, attempts to "cure" aging should involve amelioration of inflammaging (chronic, sterile, low-grade inflammation during aging), which can be achieved by regulating LRs.
Modulation of cholesterol is one way to regulate LRs, as cholesterol is a critical constituent of LRs. Most cellular cholesterol exists in the membrane and is enriched in LRs. Depleting cholesterol can disrupt the form of LRs and reduce the content of LRs, suggesting that cholesterol-lowering drugs such as statins, can alleviate inflammaging to anti-aging by inhibiting the formation of LRs. As expected, clinical results have demonstrated that new statin use is associated with a decreased death rate among American veterans (75 years and older).
However, one of the frequently reported adverse reactions of statins is memory impairment and cognitive decline. Coincidentally, Alzheimer's disease, which is characterized by cognitive and memory deterioration, is associated with reduced levels of cholesterol and LRs in the frontal cortex. Based on these results, we speculate that the adverse effects of statins on memory and cognitive alterations may partly be due to their cholesterol-lowering effects and hindered formation of LRs. Therefore, when using statins to delay aging, it is recommended to adopt some pharmaceutical modifications to increase the polarity of the statins or to choose hydrophilic statins instead of lipophilic statins for making them selective and inaccessible to the central nervous system, thus reducing their side effects.
Overall, aging has been proven modifiable, and some drugs for slow aging have been discovered. For example, rapamycin inhibits mTOR activation to delay aging; senolytics can target and eliminate senescent cells; sirtuin activators, which enhance sirtuin activity; Nicotinamide adenine dinucleotide (NAD) precursors that can supply cellular NAD levels; antidiabetic drugs such as metformin and acarbose; and non-steroidal anti-inflammatory drugs, can also be used. However, none of drugs target LRs to delay aging, making it a future objective. Overall, targeting LRs will be a novel strategy for prolonging life, and statins might be promising candidates for new anti-aging agents.