Molecular basis of ageing in chronic metabolic diseases

J Endocrinol Invest. 2020 Oct;43(10):1373-1389. doi: 10.1007/s40618-020-01255-z. Epub 2020 May 1.

Abstract

Aim: Over the last decades, the shift in age distribution towards older ages and the progressive ageing which has occurred in most populations have been paralleled by a global epidemic of obesity and its related metabolic disorders, primarily, type 2 diabetes (T2D). Dysfunction of the adipose tissue (AT) is widely recognized as a significant hallmark of the ageing process that, in turn, results in systemic metabolic alterations. These include insulin resistance, accumulation of ectopic lipids and chronic inflammation, which are responsible for an elevated risk of obesity and T2D onset associated to ageing. On the other hand, obesity and T2D, the paradigms of AT dysfunction, share many physiological characteristics with the ageing process, such as an increased burden of senescent cells and epigenetic alterations. Thus, these chronic metabolic disorders may represent a state of accelerated ageing.

Materials and methods: A more precise explanation of the fundamental ageing mechanisms that occur in AT and a deeper understanding of their role in the interplay between accelerated ageing and AT dysfunction can be a fundamental leap towards novel therapies that address the causes, not just the symptoms, of obesity and T2D, utilizing strategies that target either senescent cells or DNA methylation.

Results: In this review, we summarize the current knowledge of the pathways that lead to AT dysfunction in the chronological ageing process as well as the pathophysiology of obesity and T2D, emphasizing the critical role of cellular senescence and DNA methylation.

Conclusion: Finally, we highlight the need for further research focused on targeting these mechanisms.

Keywords: Adipose tissue; Ageing; Cellular senescence; DNA methylation; Obesity; Type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Adipose Tissue / physiopathology*
  • Aged
  • Aged, 80 and over
  • Aging / genetics
  • Aging / pathology
  • Aging / physiology*
  • Cellular Senescence / genetics
  • Chronic Disease
  • DNA Methylation / physiology
  • Humans
  • Metabolic Diseases* / etiology
  • Metabolic Diseases* / genetics
  • Metabolic Diseases* / metabolism
  • Metabolic Diseases* / pathology
  • Middle Aged
  • Signal Transduction / genetics
  • Signal Transduction / physiology