**1. Introduction**

Frailty refers to a state of increased vulnerability and reduced resilience to stressful events. Sarcopenia, on the other hand, is a syndrome characterized by progressive and generalized loss of musculoskeletal mass and function (muscle strength or physical performance), with an increased risk of adverse outcomes (falls, fractures, hospitalization, worse quality of life, and mortality). These two conditions actually present large overlaps. The sarcopenia, in fact, constitutes an essential component within the physical model of frailty proposed by Fried (involuntary weight loss, muscle weakness, slowed walking speed, reduced physical activity, exhaustion) [1]. This physical phenotype can be in turn inserted, as suggested by Rockwood, in a larger multidimensional model of frailty, comprising psychological and social aspects, multi-morbidity, and disability [2, 3].

Currently, sarcopenia is considered a true and own biological substrate of physical frailty. Loss of muscle mass typically begins in the fifth decade of life and proceeds with a falling speed of 0.8% per year [4]. Epidemiological data suggest wide prevalence variability, depending on population type study, gender, age, setting, and diagnostic criteria used. According to a recent review, comprising 5 European clinical trials, the prevalence of sarcopenia is 7.5% (elderly subjects in community) to 77.6% (patients in rehabilitation/convalescence) [5].

Sarcopenia can occur in sedentary subjects as a result of a long period of physical inactivity [6] or it can be accentuated simply by the onset of old age [7–9]. According to current studies, sarcopenia is not an inevitable consequence of age but occurs under conditions of oxidative stress, increasing over time with the formation of free radicals.

Regarding sarcopenia linked to the third age in the male sex, is related to the decrease in the production of testosterone that has anabolic effects, in particular on protein metabolism.

In sarcopenia, the loss of muscle mass and the consequent loss of strength are also accompanied by reduced muscle function. In general, sarcopenia produces a deterioration of physical functions and also means:


With the passing of the years of life of a standard subject (considered as an examination sample) the loss of muscle mass advances in step with the loss of muscle strength that can be of the same or even greater proportions. At 50 years of age, many people have already lost about 10% of their muscle mass and at 70 years of age, they will have lost about 70% [10].

The effects of sarcopenia contribute to the functional decline of the musculoskeletal system, responsible for impaired gait and balance and a high risk of falls and consequent serious fractures [11]. The disease thus becomes an integral part of everyday life and the elderly feel even weaker, less efficient, and of great weight for the family.

The highly negative impact of multidimensional compromise on the risk of isolation and mortality confirms that frailty is the most common condition associated with mortality in the elderly. Low levels of activity and decreased protein and micronutrient intake in the diet can trigger and accelerate it. For these reasons in clinical practice, it becomes crucial to identify, measure and treat frailty.

Primary objective of care is the preservation of maximum autonomy personal and social. Proper nutrition characterized by a sufficient energy intake and associated with the implementation of protein intake and targeted and constant exercise can encourage the health conditions and autonomy of the subject elderly and prevent serious complications.

## **2. Classification and pathophysiology of sarcopenia**

Sarcopenia is a frequent condition in the elderly but can also be observed in younger individuals. Sarcopenia can be considered "primitive" (or age-related) when no cause is highlighted if not aging, while it is considered "Secondary" when one or more causes are identifiable [8].

Muscle trophism is a consequence of a balance between anabolic stimuli (insulin, exercise, amino acids, testosterone, adrenaline, growth hormone) and catabolic stimuli (cortisol, catecholamines, glucagon, cytokines, intense exercise) [12]. It has been seen in the elderly how it tends to be there, associated with the normal aging process, a prevalence of the catabolic state which becomes predominant if there are particular conditions such as comorbidity [12]. In these cases also muscle mass suffers effects of the general catabolic state in which the organism is found [12].

From a pathophysiological point of view, they are several factors that can contribute to the development of sarcopenia [13]. Among the main ones recognized causes include:


Medicines can also play a role in a protective or causative sense in the development of sarcopenia. Recently Campins et al. have highlighted such as statins, sulfonylureas and glinides have potential detrimental effects on muscle metabolism while Angiotensin-converting enzyme (ACE) inhibitors, incretins, allopurinol, formoterol, and vitamin D can play a protective role on muscle function [14].

Muscle is made up of several types of fibers muscle, such as slow fibers (type I) and fast fibers (type IIa and IIb). With aging and in particular, in sarcopenic patients, there is a reduction in the diameter of the muscle fibers as well as a progressive loss of rapid fibers which translates, clinically, in a reduction of the strength, the coordination of movements, and speed of the way. This happens because the fibers lost in rapid muscles are replaced by slow fibers by motor neurons adjacent [15]. However, given the dynamic nature of the neuromuscular remodeling, it has been seen as well as the muscle of the elderly subject, under certain stimuli, maintains the ability to respond and adapt to the new state required [16]. So much so that it is proved as even just the lifestyle can greatly affect the development muscle mass [17].

It is precisely from the reversibility of the processes that lead to sarcopenia which derives the possibility of a therapeutic intervention (and still more preventive) is effective.

## **3. Sarcopenia and frailty**

Sarcopenia is considered a key component of frailty since, by acting on the reduction of mass and power muscle, causes a reduced physical performance with a consequent reduction in walking speed up to hypo-immobility [18].

Frailty is the most problematic expression of characterized aging from a state of vulnerability to any stressful event. It is due to the reduced homeostatic reserve of the body which follows the functional decline of different physiological systems over the course of life.

These changes mean that the fragile person is exposed to disproportionate responses to the triggering event leading to important repercussions on the plan socio-sanitary.

In fact, it is demonstrated how frailty is associated with an increased risk of negative outcomes such as falls, delirium, disability, institutionalization, hospitalization, and death [19].

## **4. Prevention and treatment**

Given the multifactorial pathogenesis of sarcopenia and the lack of knowledge of the interactions between the various causal factors, a global and standardized approach to the prevention and treatment of this condition does not exist.

It is now universally accepted and recognized that following a diet balanced and complete (Mediterranean diet) and practicing regular physical activity have a fundamental role in the prevention of sarcopenia [20]. In particular, in the elderly, scientific evidence suggests that the protein requirement in the diet has increased compared to the 0.8 g/kg required for adults [21]. On the other hand, it is very

frequent to note a progressive reduction in protein intake with increasing age [22]. These cases can be considered protein integration through the administration of whole proteins or amino acids essential. Several studies have shown how important not only the quantity administered but also the modality of administration and subdivision in the day. Amino acids have a greater ability to stimulate the synthesis of protein after taking orally or intravenously compared to integration in the whole protein diet. They are also directly usable by the body without the need for additional metabolic steps. However, their effects depend on the moment of administration: if administered before physical activity they are used mainly as energy substrates while if taken after exercise they mainly contribute to the repair muscular [23]. There are several on the market both oral formulations, such as tablets, sachets, or jellies for dysphagia patients than for intravenous use. The systemic effect of administering essential amino acids has been shown to be much more ample being able because it affects metabolism glycidic and insulin resistance [24]. Also supplementation with vitamin D is considered important. More controversial is resorting to hormonal therapies, for example with estrogen and Dehydroepiandrosterone (DHEA) [25].

Exercise plays a key role in the prevention and treatment of sarcopenia and, a today, it turns out to be the most effective approach. Through the stimulus given by physical activity, numerous are activated at the muscular level pathways that converge towards anabolic pathways with positive consequences on trophism and on muscle quality. In particular, moderate resistance exercises intensity produces the greatest results in elderly and/or sarcopenic subjects [26]. Particularly intense exercise is not beneficial further benefits if not actually harmful.

Due to the multifaceted nature of sarcopenia, the best therapeutic approach can only be multidisciplinary, requiring collaboration between different figures specialists such as the geriatrician, the internist, the physiatrist, the general practitioner, the nutritionist, and physiotherapist.

In addition, the nutritional aspect is important and not only intended as a protein supplement. In fact, elderly patients often have unbalanced diet, and a nutritional assessment with the advice of a specific diet is essential [21, 27]. Once you have all the information from anamnestic and necessary clinics comes a personalized rehabilitation plan is recommended, which also takes into account any clinical conditions that may limit or contraindicate certain exercises. Like this, depending on the individual patient, they come recommended exercises to be performed in the gym either at home or cycles are prescribed rehabilitation to be performed on an outpatient basis through a specific machine. The follow-up includes a control outpatient periodical with a re-evaluation of physical performance to monitor the progress and make any changes to rehabilitation plans.
