Cholesterol metabolism: A review of how ageing disrupts the biological mechanisms responsible for its regulation

Morgan, Amy; Mooney, Kathleen M.; Wilkinson, Stephen J.; Pickles, Neil A.; Auley, Mark T. Mc

doi:10.1016/j.arr.2016.03.008

Cited by 112 publications

(86 citation statements)

References 243 publications

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“…The modifications of cholesterol metabolism associated with ongoing age are still ill‐defined, partly because of the paucity of direct experimental data on lipid pathophysiology. Such alterations have been recently reviewed …”

Section: Age‐associated Changes In Cholesterol Homeostasismentioning

confidence: 99%

“…Such alterations have been recently reviewed. 9 Epidemiological studies have shown a trend towards an increase in plasma total and low-density lipoprotein (LDL) cholesterol with aging; [10][11][12] this is particularly evident from middle age to the seventh decade. In the very old, cholesterol levels tend to plateau or even decrease.…”

Section: Age-associated Changes In Cholesterol Homeostasismentioning

confidence: 99%

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Management of high cholesterol levels in older people

Bertolotti

Lancellotti

Mussi

2019

Geriatrics Gerontology Int

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The management of hypercholesterolemia in older adults still represents a challenge in clinical medicine. The pathophysiological alterations of cholesterol metabolism associated with aging are still incompletely understood, even if epidemiological evidence suggests that serum cholesterol levels increase with ongoing age, possibly with a plateau after the age of 80 years. Age is also one of the main determinants of cardiovascular disease, according to all cardiovascular risk estimate tools. Cholesterol‐lowering treatment, therefore, would be expected to bring significant protection, even in these patients. Unfortunately, direct experimental evidence is extremely limited, particularly in the very old age strata of the population; a clinical benefit still seems to be present, but the risk for drug‐related adverse events is clearly higher. At any rate, at the present time, definite guidelines for the correct management of hypercholesterolemia in older patients are not available. Therefore, the decision whether or not a pharmacological treatment should be set up, and the choice of the drug, need to be tailored to the individual patient, and requires accurate clinical judgment. The specific aspects of frailty and disability, along with the actual age of the patients, have to be considered together, with a comprehensive assessment approach. The present review summarizes the evidence regarding the modifications of cholesterol metabolism in older patients, the impact of lipid‐lowering drugs on cardiovascular outcomes and focuses on the considerations that can help to define the most appropriate treatment strategy, in view of the individual functional profile. Geriatr Gerontol Int 2019; 19: 375–383.

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Section: Age‐associated Changes In Cholesterol Homeostasismentioning

confidence: 99%

Section: Age-associated Changes In Cholesterol Homeostasismentioning

confidence: 99%

Management of high cholesterol levels in older people

Bertolotti

Lancellotti

Mussi

2019

Geriatrics Gerontology Int

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“…In total, 126 GWAS have been performed on CHL related phenotypes in humans and animal model species (https://www.ebi.ac.uk/gwas/search?query=cholesterol, accessed on 09 th January, 2018). Although mechanisms regulating CHL have been intensively studied in humans 15–18 , few studies have been devoted to the genetics of CHL in livestock species. In cows, several gene expression/proteomics studies have reported genes with potential involvement in milk CHL concentration/metabolism 19–27 but their actual roles and associated SNPs with CHL content in milk have not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Genome wide association study identifies novel potential candidate genes for bovine milk cholesterol content

Ngoc

Schenkel

Miglior

et al. 2018

Sci Rep

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This study aimed to identify single nucleotide polymorphisms (SNPs) associated with milk cholesterol (CHL) content via a genome wide association study (GWAS). Milk CHL content was determined by gas chromatography and expressed as mg of CHL in 100 g of fat (CHL_fat) or in 100 mg of milk (CHL_milk). GWAS was performed with 1,183 cows and 40,196 SNPs using a univariate linear mixed model. Two and 20 SNPs were significantly associated with CHL_fat and CHL_milk, respectively. The important regions for CHL_fat and CHL_milk were at 41.9 Mb on chromosome (BTA) 17 and 1.6–3.2 Mb on BTA 14, respectively. DGAT1, PTPN1, INSIG1, HEXIM1, SDS, and HTR5A genes, also known to be associated with human plasma CHL phenotypes, were identified as potential candidate genes for bovine milk CHL. Additional new potential candidate genes for milk CHL were RXFP1, FAM198B, TMEM144, CXXC4, MAML2 and CDH13. Enrichment analyses suggested that identified candidate genes participated in cell-cell signaling processes and are key members in tight junction, focal adhesion, Notch signaling and glycerolipid metabolism pathways. Furthermore, identified transcription factors such as PPARD, LXR, and NOTCH1 might be important in the regulation of bovine milk CHL content. The expression of several positional candidate genes (such as DGAT1, INSIG1 and FAM198B) and their correlation with milk CHL content were further confirmed with RNA sequence data from mammary gland tissues. This is the first GWAS on bovine milk CHL. The identified markers and candidate genes need further validation in a larger cohort for use in the selection of cows with desired milk CHL content.

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“…Of the diseases associated with advancing age, CVD is the leading cause of morbidity in individuals over 60 years of age (3) . The dysregulation of cholesterol metabolism is intimately associated with the pathogenesis of CVD (4) , and age-related alterations in the metabolism of cholesterol are implicated in the disturbance of this system (5) . These include, a decrease in LDL-cholesterol clearance; a potential increase in cholesterol absorption; a decrease in bile acid synthesis; a decrease in bacterial bile acid modification (6)(7)(8) .…”

mentioning

confidence: 99%

Investigating cholesterol metabolism and ageing using a systems biology approach

et al. 2016

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CVD accounted for 27 % of all deaths in the UK in 2014, and was responsible for 1·7 million hospital admissions in 2013/2014. This condition becomes increasingly prevalent with age, affecting 34·1 and 29·8 % of males and females over 75 years of age respectively in 2011. The dysregulation of cholesterol metabolism with age, often observed as a rise in LDL-cholesterol, has been associated with the pathogenesis of CVD. To compound this problem, it is estimated by 2050, 22 % of the world's population will be over 60 years of age, in culmination with a growing resistance and intolerance to pre-existing cholesterol regulating drugs such as statins. Therefore, it is apparent research into additional therapies for hypercholesterolaemia and CVD prevention is a growing necessity. However, it is also imperative to recognise this complex biological system cannot be studied using a reductionist approach; rather its biological uniqueness necessitates a more integrated methodology, such as that offered by systems biology. In this review, we firstly discuss cholesterol metabolism and how it is affected by diet and the ageing process. Next, we describe therapeutic strategies for hypercholesterolaemia, and finally how the systems biology paradigm can be utilised to investigate how ageing interacts with complex systems such as cholesterol metabolism. We conclude by emphasising the need for nutritionists to work in parallel with the systems biology community, to develop novel approaches to studying cholesterol metabolism and its interaction with ageing.

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Cholesterol metabolism: A review of how ageing disrupts the biological mechanisms responsible for its regulation

Cited by 112 publications

References 243 publications

Management of high cholesterol levels in older people

Management of high cholesterol levels in older people

Genome wide association study identifies novel potential candidate genes for bovine milk cholesterol content

Investigating cholesterol metabolism and ageing using a systems biology approach

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