Molecular basis of ageing in chronic metabolic diseases
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REVIEW
Molecular basis of ageing in chronic metabolic diseases R. Spinelli1,2 · L. Parrillo1,2 · M. Longo1,2 · P. Florese1,2 · A. Desiderio1,2 · F. Zatterale1,2 · C. Miele1,2 · G. Alexander Raciti1,2 · F. Beguinot1,2 Received: 21 February 2020 / Accepted: 10 April 2020 © The Author(s) 2020
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 Ageing · Cellular senescence · Adipose tissue · Obesity · Type 2 diabetes · DNA methylation
Introduction Human life expectancy has increased at a very rapid rate. Over the past 200 years, the mean age to death for countries with the most extended lifespans has steadily risen by 2.5 years per decade [1]. Nevertheless, the quality of life for elderly individuals did not proportionately increase. Indeed, although ageing may occur even in the absence of diseases (e.g., centenarians), ageing is also the major risk factor for most disorders with a significant public health impact [1–3]. * F. Beguinot [email protected] 1
Department of Translation Medicine, Federico II University of Naples, 80131 Naples, Italy
URT Genomic of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, 80131 Naples, Italy
2
These are known as age-related diseases (ARDs) and include chronic metabolic disorders such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), as well as cancer, neurodegenerative diseases and kidney diseases [1
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