**Abstract**

Sarcopenia has been defined as the loss of skeletal muscle mass and strength that occurs with advancing age and has also been related to many metabolic diseases. In late stages, sarcopenia precedes cachexia, defined as a multifactorial syndrome characterized by an ongoing skeletal muscle wasting, with or without loss of fat mass, associated with poor prognosis in diseases, worsening quality of life and survival. Heart failure and cancer-associated cachexia represents a progressive involuntary weight loss and is mainly the result of an imbalance in the muscle protein synthesis and degradation, inflammation, and oxidative stress, causing muscle wasting. Importantly, both diseases are still the main causes of death worldwide and the molecular basis of cachexia is still poorly understood. Recently, non-coding RNAs have been described to regulate the cardiac and cancer-associated cachexia. On the other hand, exercise training is a promising ally in slowing down cachexia and improving the quality of life of patients. New studies demonstrate that exercise training, acting through non-coding RNAs, may be able to mitigate muscle wasting, as protein turnover, mitochondrial biogenesis, and antioxidant capacity improvement. This review will therefore discuss the molecular mechanisms associated with the muscle wasting in both cardiac and cancer cachexia, as well as highlighting the effects of exercise training in attenuating the loss of muscle mass in these specific conditions.

**Keywords:** cancer, cardiovascular diseases, exercise, muscle wasting, non-coding RNAs

## **1. Introduction**

Cardiovascular diseases (CVD) and cancer (CA) are the two leading causes of death worldwide, representing about 28 million deaths per year [1–4]. Only CVDs affected 523 million cases worldwide, representing the main cause with 18 million deaths each year [4]. Currently, CA is the second disease in the number of deaths in the world, but its prevalence has been increasing in recent years and, in some countries, it is the main cause of death [5]. GLOBOCAN data show that in 2021,

19.3 million new cases and 10 million deaths from the CA disease were reported [6]. Considering the worldwide increase in the prevalence of CA and the high mortality from CVD, both diseases represent a serious public health problem.

The heart failure (HF) is the final common pathway of most cardiac and circulatory diseases [7]. The American Heart Association (AHA) defined HF as clinical syndrome characterized by typical symptoms such as edema, dyspnea, and fatigue; caused by changes in cardiac function and structure, with reduced cardiac contraction and/or increased intraventricular pressure at rest and physical stress [7–9]. In addition to central cardiac alterations, HF promotes changes in peripheral structure and function, impairing oxidative metabolism accompanied by microvascular rarefaction and skeletal muscle wasting [8, 10–12]. These changes in skeletal muscles contribute to reduced quality of life and increased mortality. Worldwide, HF affects more than 23 million people [7, 9], and just in the United States, around 6 million American citizens are affected, leading to more than 1 million hospitalizations/year and a mortality rate of 1 in every 9 patients hospitalized [2]. Furthermore, worsen projections are expected for the next 10 years, with an increase of 46% in cases, generating an estimated annual expenditure of 70 billion dollars, making a health epidemic [2, 13, 14].

In CA, studies have been shown that is a group of diseases characterized by uncontrolled cell growth, spreading and progressing to other cells beyond physiological limits, affecting any organ and tissue in the human body [1]. In 2021, 2.2 million new cases of breast CA have been reported worldwide, thus being the most prevalent, followed by lung CA (2.1 million), colon and rectum (1.8 million), and prostate (1.3 million). Regarding mortality, lung CA is the most lethal in the world followed by breast CA [15, 16].

Even with new drugs and therapies, there is still an increase in the prevalence of both diseases [6, 17]. Furthermore, the progression of HF and CA is related to muscle wasting and loss of body weight as well as consequent weakness toward to important clinical consequences in these diseases [18, 19]. Numerous studies demonstrate that involuntary body weight reduction, with increased muscle wasting, is the main sign of cachexia, represented by a multifactorial syndrome related to pre-established chronic diseases [18, 20]. Currently, in the world, 12 million patients have cachexia, which is responsible for worsting prognoses on established diseases, reduced quality of life, impaired therapeutic effectiveness, and increased mortality [21, 22].

To date, there are no effective pharmacological treatments for cachexia for both HF and CA [17, 23]. On the other hand, exercise training (ET) is a non-pharmacological treatment, relatively cheap and safe. In addition, ET promotes anabolic stimuli, which may preserve the muscle wasting, and at the same time enhance the quality of life and reduce mortality in cachexia patient [18, 24, 25]. During the last decades, the class of non-coding RNAs (ncRNAs): microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) have been demonstrating important associations with CVD, CA [26, 27], and with the muscle wasting promoted by cachexia [28, 29], becoming a promising mechanism to the understanding cardiac and CA cachexia.

Although great advances have been made to understand HF and CA, the mechanisms involved in skeletal muscle abnormalities, still poorly understood [3, 12, 15, 30, 31]. Therefore, understanding the mechanisms and pathways involved in skeletal muscle structure and function may help to develop new therapeutic strategies against cachexia, resulting in improved treatment and quality of life for patients [20, 32]. Consequently, this review aims to discuss the molecular mechanisms, involving ncRNAs in cardiac and CA cachexia. In addition, to known the implication of ET and ncRNAs in the treatment of cachexia.

*Cardiac and Cancer-Associated Cachexia: Role of Exercise Training, Non-coding RNAs, and… DOI: http://dx.doi.org/10.5772/intechopen.100625*
