On the Cholesterol Theory of Aging–2022

The author’s point of view is presented, according to which the cholesterol theory of aging and death, which was formulated back in the 1980s by Yu.M. Lopukhin et al., is now often misunderstood by many biologists and physicians. It is emphasized that this theory prioritized the structural role of cholesterol in the plasma membrane of the cell rather than the well-known role of cholesterol in metabolic processes. It was assumed that an increase in the microviscosity of the cell membrane due to the accumulation of cholesterol in it leads to a deterioration in the transfer of external signals and nutrients to the cell as well as to a decrease in the activity of membrane enzymes. This, according to the authors, triggers the occurrence of “senile” changes in cells, tissues, and organs and then in the entire multicellular organism, which ultimately leads to an increase in the probability of its death, that is, to aging. At the same time, the content of cholesterol (mainly cholesterol of low-density lipoproteins, which is considered especially “bad”) in serum was assigned only a minor role, because, according to the authors of the concept, its increase does not necessary lead to adverse changes in the body. This article briefly discusses the evolution of ideas about the possible role of cholesterol in aging and the development of various age-related pathologies, mainly cardiovascular diseases and mental disorders. Experimental data on the effect of liposomes containing both normal and oxidized cholesterol on the proliferative activity of cultured cells are analyzed. The data of longitudinal studies are considered, suggesting that, paradoxically, it is people with elevated levels of cholesterol in the blood plasma who live to an advanced age. At the same time, the consumption of large amounts of cholesterol-rich food may not affect the health of some patients. It is noted that a number of studies indicate the absence of a causal relationship between the level of cholesterol in serum and the occurrence of atherosclerotic changes. It is emphasized that cholesterol is a very important compound for our body, without which cell proliferation and, as a result, normal regeneration are impossible. It is noted that there is a continuously increasing amount of data on the negative role of statins in the formation of age-related pathologies, especially in people of older age groups. It is concluded that, at present, it becomes obvious that there is a need for a significant reappraisal (using the systems approach) of ideas about the possible role of cholesterol in aging and in the development of atherosclerosis and other age-related diseases as well as dementias caused by various factors, including Alzheimer’s disease.