Shared and Divergent Epigenetic Mechanisms in Cachexia and Sarcopenia

Cells. 2022 Jul 25;11(15):2293. doi: 10.3390/cells11152293.

Abstract

Significant loss of muscle mass may occur in cachexia and sarcopenia, which are major causes of mortality and disability. Cachexia represents a complex multi-organ syndrome associated with cancer and chronic diseases. It is often characterized by body weight loss, inflammation, and muscle and adipose wasting. Progressive muscle loss is also a hallmark of healthy aging, which is emerging worldwide as a main demographic trend. A great challenge for the health care systems is the age-related decline in functionality which threatens the independence and quality of life of elderly people. This biological decline can also be associated with functional muscle loss, known as sarcopenia. Previous studies have shown that microRNAs (miRNAs) play pivotal roles in the development and progression of muscle wasting in both cachexia and sarcopenia. These small non-coding RNAs, often carried in extracellular vesicles, inhibit translation by targeting messenger RNAs, therefore representing potent epigenetic modulators. The molecular mechanisms behind cachexia and sarcopenia, including the expression of specific miRNAs, share common and distinctive trends. The aim of the present review is to compile recent evidence about shared and divergent epigenetic mechanisms, particularly focusing on miRNAs, between cachexia and sarcopenia to understand a facet in the underlying muscle wasting associated with these morbidities and disclose potential therapeutic interventions.

Keywords: cachexia; epigenetics; extracellular vesicles; miRNAs; sarcopenia; skeletal muscle.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cachexia / etiology
  • Epigenesis, Genetic
  • Humans
  • MicroRNAs* / genetics
  • Muscular Atrophy / metabolism
  • Quality of Life
  • Sarcopenia* / genetics

Substances

  • MicroRNAs

Grants and funding

This work was supported by The Research Foundation—Flanders (FWO) (#G066821N), INTERREG—Euregio Meuse-Rhine (GYM—Generate your muscle 2020-EMR116), and Italian Ministry of Health, Ricerca Finalizzata (RF-2019-12369703). L.Y. was supported by KU Leuven Ron- doufonds voor Duchenne Onderzoek (EQQ-FODUCH-O2010).