Cholesterol metabolism in aging simultaneously altered in liver and nervous system

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 27hydroxycholesterol 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.

The NDR family of kinases: essential regulators of aging

“…Moreover, besides a systemic effect, NAFLD has been linked to reduced cognitive functions in adults (Bertolotti, 2014 ; Seo et al, 2016 ; Takahashi et al, 2017 ; Weinstein et al, 2018 , 2019 ) and in mice, HFD has been shown to impair amygdala and hippocampus-dependent memory consolidation and cause neuroinflammation during aging (Spencer et al, 2017 ). Additionally changes in cholesterol as well as TAG levels have been linked to the neuronal aging process and the etiology of various age-related diseases including Alzheimer's (AD), Parkinson's (PD) and Huntington's disease (Spitler and Davies, 2020 ; Nunes et al, 2022 ). It has been extensively demonstrated that the responsiveness of rodent AMPK to nutrient deprivation decreases during aging (Salminen and Kaarniranta, 2012 ).…”

Mechanism Explanation on Improved Cognitive Ability of D-Gal Inducing Aged Mice Model by Lactiplantibacillus plantarum MWFLp-182 via the Microbiota–Gut–Brain Axis

“…If the gut barrier is compromised, harmful metabolites can enter the liver, leading to oxidative damage and inflammatory responses, which in turn can affect the neural feedback between the liver and the brain . Elevated cholesterol levels in the liver of older individuals can lead to metabolic disturbances, which may potentially contribute to AD …”

“…15 Elevated cholesterol levels in the liver of older individuals can lead to metabolic disturbances, which may potentially contribute to AD. 16 Probiotics are defined as "live microorganisms", capable of conferring health benefits to the host when administered in adequate amounts and can regulate gut microbiota directly. 17 impairment via the regulation of the gut−brain axis.…”

The associations between peripheral inflammatory and lipid parameters, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events

“…Several studies have shown that cholesterol levels in the central nervous system are closely related to cognitive function [ 9 , 10 ]. On one hand, the close association between cholesterol and various aspects of brain function, such as cytotropic support, neuronal activity, and neural information transmission, highlights its significance as a crucial component of neurons [ 11 , 12 ].…”