原创力文档a whole-body mathematical model of cholesterol metabolism and its age-associated dysregulation一个全身胆固醇代谢的数学模型及其与年龄有关的失调.pdfVIP
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a whole-body mathematical model of cholesterol metabolism and its age-associated dysregulation一个全身胆固醇代谢的数学模型及其与年龄有关的失调
Mc Auley et al. BMC Systems Biology 2012, 6:130
/1752-0509/6/130
RESEARCH ARTICLE Open Access
A whole-body mathematical model of cholesterol
metabolism and its age-associated dysregulation
Mark T Mc Auley1*†, Darren J Wilkinson2†, Janette JL Jones3† and Thomas BL Kirkwood1†
Abstract
Background: Global demographic changes have stimulated marked interest in the process of aging. There has
been, and will continue to be, an unrelenting rise in the number of the oldest old ( 85 years of age). Together
with an ageing population there comes an increase in the prevalence of age related disease. Of the diseases of
ageing, cardiovascular disease (CVD) has by far the highest prevalence. It is regarded that a finely tuned lipid profile
may help to prevent CVD as there is a long established relationship between alterations to lipid metabolism and
CVD risk. In fact elevated plasma cholesterol, particularly Low Density Lipoprotein Cholesterol (LDL-C) has
consistently stood out as a risk factor for having a cardiovascular event. Moreover it is widely acknowledged that
LDL-C may rise with age in both sexes in a wide variety of groups. The aim of this work was to use a whole-body
mathematical model to investigate why LDL-C rises with age, and to test the hypothesis that mechanistic changes
to cholesterol absorption and LDL-C removal from the plasma are responsible for the rise. The whole-body
mechanistic nature of the model differs from previous models of cholesterol metabolism which have either focused
on intracellular cholesterol homeostasis or have concentrated on an isolated area of lipoprotein dynamics. The
model integrates both current and previously published data relating to molecular biology, physiology, ageing and
nutrition in an integrated fashion.
Results: The model was used to test the hypothesis that alterations
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