title: Cholesterol metabolism: A review of how ageing disrupts the biological mechanisms responsible for its regulation.
abstract: Cholesterol plays a vital role in the human body as a precursor of steroid hormones and bile acids, in addition to providing structure to cell membranes. Whole body cholesterol metabolism is maintained by a highly coordinated balancing act between cholesterol ingestion, synthesis, absorption, and excretion. The aim of this review is to discuss how ageing interacts with these processes. Firstly, we will present an overview of cholesterol metabolism. Following this, we discuss how the biological mechanisms which underpin cholesterol metabolism are effected by ageing. Included in this discussion are lipoprotein dynamics, cholesterol absorption/synthesis and the enterohepatic circulation/synthesis of bile acids. Moreover, we discuss the role of oxidative stress in the pathological progression of atherosclerosis and also discuss how cholesterol biosynthesis is effected by both the mammalian target of rapamycin and sirtuin pathways. Next, we examine how diet and alterations to the gut microbiome can be used to mitigate the impact ageing has on cholesterol metabolism. We conclude by discussing how mathematical models of cholesterol metabolism can be used to identify therapeutic interventions.
authors.affiliation: Department of Chemical Engineering, University of Chester, Thornton Science Park, Chester CH2 4NU, United Kingdom.
authors.forename: A E
authors.initials: AE
authors.lastname: Morgan
authors.affiliation: Faculty of Health and Social Care, Edge Hill University, Ormskirk, Lancashire L39 4QP, United Kingdom.
authors.forename: K M
authors.initials: KM
authors.lastname: Mooney
authors.affiliation: Department of Chemical Engineering, University of Chester, Thornton Science Park, Chester CH2 4NU, United Kingdom.
authors.forename: S J
authors.initials: SJ
authors.lastname: Wilkinson
authors.affiliation: Department of Biological Sciences, University of Chester, Parkgate Road, Chester CH1 4BJ, United Kingdom.
authors.forename: N A
authors.initials: NA
authors.lastname: Pickles
authors.affiliation: Department of Chemical Engineering, University of Chester, Thornton Science Park, Chester CH2 4NU, United Kingdom. Electronic address: m.mcauley@chester.ac.uk.
authors.forename: M T
authors.initials: MT
authors.lastname: Mc Auley
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000517:prevention & control; D002784:Cholesterol / Q000378:metabolism*; D004032:Diet; D006801:Humans; D050356:Lipid Metabolism; D008962:Models, Theoretical; D018384:Oxidative Stress
chemical_list: D002784:Cholesterol
keywords: Ageing; Cholesterol; High density lipoprotein cholesterol (HDL-C); Longevity; Low density lipoprotein cholesterol (LDL-C); Microbiome