Abstract
In humans, aging, triggers increased plasma concentrations of triglycerides, cholesterol, low-density lipoproteins and lower capacity of high-density lipoproteins to remove cellular cholesterol. Studies in rodents showed that aging led to cholesterol accumulation in the liver and decrease in the brain with reduced cholesterol synthesis and increased levels of cholesterol 24-hydroxylase, an enzyme responsible for removing cholesterol from the brain. Liver diseases are also related to brain aging, inducing changes in cholesterol metabolism in the brain and liver of rats. It has been suggested that late onset Alzheimer’s disease is associated with metabolic syndrome. Non-alcoholic fatty liver is associated with lower total brain volume in the Framingham Heart Study offspring cohort study. Furthermore, disorders of cholesterol homeostasis in the adult brain are associated with neurological diseases such as Niemann-Pick, Alzheimer, Parkinson, Huntington and epilepsy. Apolipoprotein E (apoE) is important in transporting cholesterol from astrocytes to neurons in the etiology of sporadic Alzheimer’s disease, an aging-related dementia. Desmosterol and 24S-hydroxycholesterol are reduced in ApoE KO hypercholesterolemic mice. ApoE KO mice have synaptic loss, cognitive dysfunction, and elevated plasma lipid levels that can affect brain function. In contrast to cholesterol itself, there is a continuous uptake of 27- hydroxycholesterol in the brain as it crosses the blood-brain barrier and this flow can be an important link between intra- and extracerebral cholesterol homeostasis. Not surprisingly, changes in cholesterol metabolism occur simultaneously in the liver and nervous tissues and may be considered possible biomarkers of the liver and nervous system aging.
Highlights
Over the last few decades, there has been an increase in the elderly population
non-alcoholic fatty liver disease (NAFLD) patients present cholesterol metabolism alterations characterized by increased synthesis and decreased intestinal absorption of cholesterol [39] associated with liver fat content, regardless of body weight [39]
Desmosterol, campesterol and 24S-HC are significantly lower in ApoE KO mice compared to wild-type controls. These results demonstrate that brain cholesterol content, rate of synthesis and 24S-HC export are reduced in ApoE KO hypercholesterolemic mice [78]
Summary
Over the last few decades, there has been an increase in the elderly population. Between 2015 and 2050 the number of people aged 60 and over is expected to double worldwide (https://www.who.int/news-room/ fact-sheets/detail/ageing-and-health). Cholesterol is one of the main components of the cell plasma membrane, giving it its physicochemical properties, such as fluidity and stability, cholesterol is not evenly distributed in the membranes It www.aging-us.com focuses on specialized sphingolipid-rich domains called lipid rafts and caveolae, which are involved in important cellular functions such as signaling across membranes [4, 5], regulation of membrane traffic, and signal transduction pathways that initiate in the membrane by stimulation or dimerization of receptors [6]. When the cellular cholesterol content decreases, the sterol leaves its binding site to SCAP and the SREBP-SCAP complex moves to the Golgi, where two proteases (S1P and S2P) release the amino terminal domain of the transcription factor This amino terminal peptide enters the nucleus and binds the SREs. When the cytoplasmic concentration of cholesterol increases, the sterol molecules bind to SCAP and prevent the complex’s translocation to the Golgi, leading to a reduction in HMGCoAR transcription [8, 11]. Cholesterol metabolites may be more relevant than cholesterol itself in these pathologies [14,15,16]
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