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Investigating cholesterol metabolism and ageing using a systems biology approach

A E Morgan1, K M Mooney2, S J Wilkinson1

  • 1Department of Chemical Engineering,University of Chester,Thornton Science Park,Chester CH2 4NU,UK.

The Proceedings of the Nutrition Society
|November 3, 2016
PubMed

Insights

Cardiovascular disease (CVD) is a major cause of death, increasing with age. Systems biology offers integrated approaches to study cholesterol metabolism and aging, vital for developing new hypercholesterolemia therapies.

Area of Science:

  • Gerontology
  • Metabolic Diseases
  • Systems Biology

Background:

  • Cardiovascular disease (CVD) is a leading cause of death in the UK, with prevalence increasing significantly in individuals over 75.
  • Age-related dysregulation of cholesterol metabolism, particularly elevated LDL-cholesterol, is linked to CVD pathogenesis.
  • Growing global aging population and statin intolerance necessitate novel hypercholesterolemia and CVD prevention strategies.

Purpose of the Study:

  • To review cholesterol metabolism, its modulation by diet and aging, and current therapeutic strategies for hypercholesterolemia.
  • To explore the application of systems biology in understanding the complex interplay between aging and cholesterol metabolism.
  • To highlight the need for interdisciplinary collaboration between nutritionists and systems biologists for innovative research.

Main Methods:

  • Literature review focusing on cholesterol metabolism, aging, and cardiovascular disease.
  • Discussion of existing and potential therapeutic interventions for hypercholesterolemia.
  • Exploration of systems biology as a methodology for studying complex biological systems.

Main Results:

  • Cholesterol metabolism is significantly influenced by diet and the aging process.
  • Current hypercholesterolemia treatments face challenges due to increasing drug resistance and intolerance.
  • Systems biology provides a framework for a holistic investigation of aging's impact on metabolic pathways.

Conclusions:

  • Integrated approaches, particularly systems biology, are crucial for understanding the complex relationship between aging and cholesterol metabolism.
  • Novel therapeutic strategies for hypercholesterolemia and CVD prevention are urgently needed.
  • Collaboration between nutrition science and systems biology is essential for advancing research in this field.

Keywords:
ABC ATP-binding cassetteBSH bile salt hydrolaseCETP cholesteryl ester transfer proteinCYP7A1 cholesterol 7α-hydroxylaseHMG 3-hydroxy-3-methylglutarylLDLr LDL receptorsNPC1L1 Niemann–Pick C1-like 1 proteinTC total cholesterolAgeingCholesterolComputational modellingSystems biology

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