Shared and Divergent Epigenetic Mechanisms in Cachexia and Sarcopenia

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.

Extracellular vesicles and Duchenne muscular dystrophy pathology: Modulators of disease progression

“…Frontiers in Physiology frontiersin.org derived from healthy sources (Aminzadeh et al, 2018) (Yedigaryan et al, 2022a or custom-cargo-engineered EVs that can efficiently deliver molecules to recipient cells (Matsuzaka et al, 2022). The inhibition of EV release represents a paradigm shift in the manner of treatment for diseases (Gartz et al, 2020) (Catalano & O'Driscoll, 2019) (Figure 3).…”

“…There is an abundant amount of evidence suggesting that DMD EVs induce deleterious effects, so it may be beneficial to understand which molecules are responsible for the adverse effects and to explore the possibility of counteracting the release of these molecules from EVs. Nowadays, the focus of EV-related potential therapies lies with the delivery of either EVs derived from healthy sources ( Aminzadeh et al, 2018 ) ( Yedigaryan et al, 2022a ) or custom-cargo-engineered EVs that can efficiently deliver molecules to recipient cells ( Matsuzaka et al, 2022 ). The inhibition of EV release represents a paradigm shift in the manner of treatment for diseases ( Gartz et al, 2020 ) ( Catalano & O'Driscoll, 2019 ) ( Figure 3 ).…”

Targeting Epigenetic Regulators with HDAC and BET Inhibitors to Modulate Muscle Wasting

“…However, little focus has been afforded to investigate their role in mediating metabolic reactions. Although miRNAs have been suggested to function as biomarkers and potential therapeutic targets for cachexia and sarcopenia [145], to date, the only therapeutic study targeting skeletal muscle has been miR-23a/27a delivery, which preserved muscle mass in mice with diabetes-induced cachexia [146].…”

“…Overall, the importance of muscle metabolism in controlling muscle mass and function is growing and the specific pathways associated with the epigenetic status (Figure 4) are being elucidates; these factors could lead to the identification of prospective epigenetic drugs to counteract the metabolic dysfunction underlying sarcopenia and cachexia. cachexia and sarcopenia [145], to date, the only therapeutic study targeting skeletal muscle has been miR-23a/27a delivery, which preserved muscle mass in mice with diabetesinduced cachexia [146].…”

The efficacy of nutritional support and its role in the treatment of persons with sarcopenia

“…Распространённость саркопении широко варьируется в зависимости от региона и страны проживания, методов и критериев оценки (биоимпедансометрия, МРТ, КТ, ДРА, калиперометрия) [5,10], а также уровня финансирования конкретным государством программ, направленных на профилактику и лечение заболеваний у людей пожилого и старческого возраста [11]. В частности, число людей с саркопенией в Бразилии составляет 4,5 % [12], Турции 5,2 % [13], Китае 10 % (мужчин 12,3 %; женщин 7,6 %), Российской Федерации до 22,1 % [9,14].…”