• Effects of obesity on cholesterol metabolism and its implications for healthy ageing.

      Mc Auley, Mark Tomás; University of Chester (Cambridge University Press, 2020-01-27)
      The last few decades have witnessed a global rise in the number of older people. Despite this demographic shift, morbidity within this population group is high. Many factors influence healthspan; however an obesity pandemic is emerging as a significant determinant of older peoples’ health. It is well established obesity adversely effects several metabolic systems. However, due to its close association with overall cardiometabolic health, the impact obesity has on cholesterol metabolism needs to be recognised. The aim of this review is to critically discuss the effects obesity has on cholesterol metabolism and to reveal its significance for healthy ageing.
    • Investigating Cholesterol Metabolism and Ageing Using a Systems Biology Approach

      Morgan, Amy; Mooney, Kathleen M.; Wilkinson, Stephen J.; Pickles, Neil; Mc Auley, Mark T.; University of Chester (Cambridge University Press, 2016-11-02)
      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.
    • The role of DNA methylation in ageing and cancer

      Morgan, Amy; Davies, Trevor J.; Mc Auley, Mark T.; University of Chester (Cambridge University Press, 2018-04-30)
      The aim of the present review paper is to survey the literature related to DNA methylation, and its association with cancer and ageing. The review will outline the key factors, including diet, which modulate DNA methylation. Our rationale for conducting this review is that ageing and diseases, including cancer, are often accompanied by aberrant DNA methylation, a key epigenetic process, which is crucial to the regulation of gene expression. Significantly, it has been observed that with age and certain disease states, DNA methylation status can become disrupted. For instance, a broad array of cancers are associated with promoter-specific hypermethylation and concomitant gene silencing. This review highlights that hypermethylation, and gene silencing, of the EN1 gene promoter, a crucial homeobox gene, has been detected in various forms of cancer. This has led to this region being proposed as a potential biomarker for diseases such as cancer. We conclude the review by describing a recently developed novel electrochemical method that can be used to quantify the level of methylation within the EN1 promoter and emphasise the growing trend in the use of electrochemical techniques for the detection of aberrant DNA methylation.