, 44:6 | Cite as

Sarcopenia: an overview and analysis of molecular mechanisms

  • Adriana BottoniEmail author
  • Sérgio dos Anjos Garnes
  • Fernanda Lasakosvitsch
  • Andrea Bottoni
Open Access


Healthy aging is the individual’s possibility of maintaining the functional ability that enables well-being in older age, along with the maintenance of independence, a crucial factor for ensuring health and quality of life in older people. Loss of muscle mass, strength, and function are relevant threats to independent living and progressively occur with senescence and aging, worsening physical performance, and thus characterizing sarcopenia. Identifying sarcopenia in clinical practice is essential for the early onset of treatment minimizing its impacts and thus improving the patient’s quality of life. The purpose of this work was to conduct a literature review of the pathophysiological and molecular mechanisms underlying muscle changes during aging, highlighting the role of oxidative stress, cytokines, and inflammation, as well as strategies to prevent and treat age-related muscle alterations.


Molecular signaling Sarcopenia Aging Muscle mass Anorexia Nutrition 


Healthy aging is defined by the World Health Organization as “the process of developing and maintaining the functional ability that enables well-being in older age.” Functional ability is understood as the sum of the physical and mental capacities and comprises the health-related attributes that enable people to be and to do what they have reason to value. The determinants in its maintenance are lifelong behaviors related to the health of the individual, such as the involvement in physical activities and the balanced and adequate feeding for nutrition maintenance [1]. Maintaining independence is a crucial factor for ensuring health and quality of life in older people. During the aging process, there is a progressive loss of muscle mass which can be followed by loss of strength and function with impairment in physical performance, characterizing sarcopenia, and representing a threat to independent living. Sarcopenia is a progressive and generalized disorder of skeletal muscle associated with an increased likelihood of adverse outcomes including falls, fractures, physical disability, and mortality. It is the largest cause of frailty and disability in the elderly around the world. In recent years, the concept of muscle strength has emerged as a defining factor for sarcopenia, since strength is better than muscle mass in predicting adverse outcomes. Muscle quality is impaired in sarcopenia and this term has been used to describe micro- and macroscopic aspects of muscle architecture and composition [2].

The loss of muscle mass, strength, and function that progressively occurs with aging is a major threat to independent living [3, 4]. This condition also impairs the ability to perform activities of daily living and increases the risk of falls [5]. Thus, sarcopenia is a geriatric syndrome that has a significant clinical impact and involves a multiplicity of underlying etiological mechanisms and phenotype described in the literature. Sarcopenia as a muscular disease was formally recognized in 2016, and thereafter, a unique international code of disease for sarcopenia was established (ICD-10 CM-M62.84). This establishment is a crucial factor for stimulating its recognition as a disease, increasing the number of diagnoses with better epidemiological data, and for the development of effective treatments [6].

There is considerable variation in epidemiological data on the prevalence of sarcopenia in the international literature, and this is due to the difficult definition of diagnostic criteria in previous studies and to the variation of the subjects’ age. Studies conducted by Baumgartner et al. and Iannuzzi-Sucich et al. [7, 8] showed a high prevalence of sarcopenia in individuals aged between 65 and 70 years and over 80 years, ranging between 10 and 24% and 30–50%, respectively. More recent studies have reported prevalence rates of 25.3% among hospitalized older adults, with an average age of 80 years [9], and 14.4–16.6% in older persons aged over 65 years, living in Brazil [10].

In a meta-analysis performed by Zhang X et al. [11], a correlation was observed between elderly patients with sarcopenia and an increased risk of hospitalization as a consequence of the greater influence of sarcopenia as a determinant of unfavorable prognosis. This association by itself demonstrates the importance of identifying and defining preventive strategies against this functional disorder to improve clinical outcomes in the elderly.

Specialists have come together to develop diagnostic criteria and measures for the treatment of this disease in the last decade, and work groups have emerged. In Europe, the European Working Group on Sarcopenia in Older People (EWGSOP) [12] was created along with the International Working Group on Sarcopenia (IWGS) and the Asian Working Group on Sarcopenia (AWGS) all with the aim of defining sarcopenia based on the appendicular muscle mass adjusted by the height squared, handgrip strength, and/or gait speed. In addition, an initiative from the Foundation for the National Institutes of Health (FNIH) proposed that sarcopenia should be defined based on muscle mass adjusted by the body mass index (BMI), with cutoff values of (< 0.789 kg/m2 for men and < 0.512 kg/m 2 for women) and grip strength (< 26 kg for men and < 16 kg for women) [13]. In early 2018, the European Working Group on Sarcopenia in Older People met again (EWGSOP2) to update the original definition of the term with the aim of reflecting scientific and clinical evidence that was built over the last decade and to delineate clear criteria and tools that define and characterize sarcopenia in clinical practice and in research populations. The EWGSOP2 has updated its algorithm for sarcopenia case-finding, diagnosis, and severity determination, and a “Find-Assess-Confirm-Severity” (FACS) pathway was recommended for use in clinical practice and in research studies (Fig. 1). In clinical practice, EWGSOP2 advises the use of the SARC-F questionnaire to detect people with a probability of sarcopenia [14]. The SARC-F questionnaire was developed as a quick and easy-to-perform test for the diagnosis of sarcopenia. There are 5 components of SARC-F: strength, walking assistance, elevating a chair, climbing stairs, and falls. Scores vary from 0 to 10, with 0 to 2 points for each component (Fig. 2). A score equal to or greater than 4 is predictive of sarcopenia and if there is no effective intervention, it may lead to a negative clinical outcome [15].
Fig. 1

Algorithm suggested by EWGSOP2 to detect sarcopenia cases, perform diagnosis, and quantify severity in clinical practice. Path steps are represented as Find-Assess-Confirm-Severity or FACS. It is necessary to consider other reasons for muscle strength decrease (e.g., depression, balance disorders, peripheral vascular disorders) [14]

Fig. 2

SARC-F screen for sarcopenia [15]

A meta-analysis based on the accuracy of SARC-F was performed from the bivariate random effects model the summary estimates of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (RLN), and diagnostic odds ratio (DOR) using EWGSOP, IWGS, AWGS, or FNIH as the reference standard (Fig. 3). The high PLR value and positive test results reflect a higher probability of a definitive diagnosis for sarcopenia. On the other hand, the lower PLR and negative test results reflect a higher probability of diagnosis of disease exclusion. The DOR represents the screening ability of one indicator, the higher its value, the greater its accuracy. Although the meta-analysis showed low sensitivity, patients with positive results for SARC-F were highly prone to sarcopenia [16].
Fig. 3

The pooled results of sensitivity, specificity, PLR, NLR, and DOR with EWGSOP as the reference standard using the bivariate random effects model [17]

Low sensitivity indicates the poor ability of a screening tool to detect individuals with sarcopenia. On the other hand, SARC-F exhibited excellent specificity (> 80% for all definitions used to diagnose sarcopenia). The high specificity indicates that this questionnaire is able to determine with great precision the absence of sarcopenia [17].

The diagnosis of sarcopenia is often accompanied by challenges as it requires time and specific equipment to measure muscle mass and perform an evaluation of grip strength and physical function. SARC-F is a viable tool, since it is inexpensive and easy to apply. When selecting the individuals most likely to have sarcopenia using SARC-F, the time and cost for assessing muscle mass, grip strength, and physical performance required for final definitive diagnosis may be reduced. Thus, despite its low sensitivity, its high specificity makes SARC-F a useful screening tool for the selection of individuals who must undergo additional tests to confirm the diagnosis of sarcopenia [16].

Diagnosis of sarcopenia

Diagnosis based on muscle mass quantification

Some of the earliest discoveries about the composition of the human body were based on chemical analysis carried out on specific organs. The body is composed of two parts: body fat and fat-free mass. The latter includes tissues and skeletal muscle [18]. Skeletal muscle is the largest body compartment among adults within the healthy weight range. There are more than 600 skeletal muscles, each of which has a variety of mechanical and structural functions and play a vital role in the body’s metabolic functions. Skeletal muscles grow in size from birth, reaching peak mass in the third decade of life [19]. Many factors determine an individual’s skeletal muscle mass, including height [20], adiposity [21], ethnicity [19], genetic factors [22], physical activity [23], hormone levels [24], and diet [25].

Several techniques can be used to assess muscle mass [26]. Several factors must be considered when choosing the best technique to use for research and clinical practice, including cost, availability, and ease of. Imaging techniques used to measure muscle mass include computed tomography (CT), magnetic resonance imaging (MRI), and dual-energy X-ray absorptiometry (DXA). CT and MRI are gold standard research methods; however, factors such as high cost, shortages of equipment, and the health risks of radiation exposure limit the use of these methods in routine clinical practice. DXA is a non-invasive method for both research and clinical practice, since it is able to distinguish between body fat mass, bone mass, and lean mass; however, DXA equipment is not portable. DXA takes into account the rationale that muscle mass is correlated with body size, which means that individuals with a larger body size will usually have larger muscle mass [27].

Bioelectrical impedance analysis (BIA) estimates fat and lean body mass. The test is cheap, easy to use, reproducible, suitable for both outpatients and bedridden patients, and may be a useful alternative to DXA [28]. Anthropometry is the simplest and cheapest method and its results have been shown to have a high correlation with those of MRI [29] and DXA [30].

It is important to assess muscular strength and physical performance as a complement to muscle mass measurement. The measurement of palmar grip strength using a handheld dynamometer is the most widely used indicator of muscle strength.

Muscle strength does not depend only on muscle mass and the relationship between strength and mass is not linear [31, 32].

In clinical practice, EWGSOP2 indicates the use of the SARC-F questionnaire to detect the probability of sarcopenia. The use of palmar grip strength along with the chair stand test is a parameter to identify a decrease in muscle strength. When evidence confirms low muscle quantity or quality, muscle assessment using DXA and BIA methods is recommended in routine clinical management and the use of DXA, MRI, or CT in research and special care for individuals at high risk of adverse outcomes. Physical performance measurements are also used (Short Physical Performance Battery, Time Up and Go battery, and 400 m walk test) to assess sarcopenia severity. It is worth noting that it is not always possible to use physical performance measurements, since the patient’s performance can be impaired by gait disorder, balance disorder, and dementia [14].

According to EWGSOP2, the sarcopenia cutoff points for low strength are for grip strength < 27 kg for men and < 16 kg for women and chair stand > 15 s for five rises. Sarcopenia cutoff points for low muscle quantity assessment are appendicular skeletal muscle mass (ASM) < 20 kg for men and < 15 kg for women and appendicular skeletal muscle mass adjusted using height squared (ASM/height2) < 7.0 kg/m2 for men and < 6.0 kg/m2 for women. Sarcopenia cutoff points for low performance are Gait speed, ≤ 0.8 m/s; SPPB, ≤ 8 point score; TUG, ≥ 20 s; and 400 m walk test, non-completion of the test or time ≥ 6 min for test completion [14].

Sarcopenia can be grouped into two general categories: primary sarcopenia, which refers to age-related alterations, and secondary sarcopenia, when causes other than aging are identified, such as underlying disease or malnutrition. Age-related baseline factors for primary sarcopenia include decreasing amounts of satellite cells and motor neurons, decreased hormone secretion (growth hormone, testosterone, ghrelin, etc.), increased production of inflammatory cytokines, a decline in mitochondrial function, an abnormally high production of miocines, and weight loss due to a decrease in appetite. These changes lead to a decrease in the capacity for muscle protein synthesis and increase the protein degradation rate, thus contributing to sarcopenia [33].

With regard to secondary sarcopenia, lack of physical activity leads to a decrease in skeletal muscle mass, while physical training may lead to muscular hypertrophy. Increased amounts of nitrogen and potassium in skeletal muscle tissue, as well as decreased skeletal muscle mass, were observed in patients who had been bedridden for 6 to 7 weeks. A study conducted by Deitrick et al. showed a marked decrease in muscle strength (approximately 20%), particularly in the lower extremity [34]. The underlying conditions that lead to secondary sarcopenia include organ failure, inflammatory diseases, malignant cancers, and endocrine disorders. Nutrition-related causes of secondary sarcopenia include inadequate intake of branched-chain amino acids and foods rich in antioxidants such as n-3 long-chain polyunsaturated fatty acids, vitamins, and carotenoids [33].

Torres-de Araújo JR et al. [35] carried out a systematic review on the prevalence and incidence of mobility limitations in the elderly and their associated factors. Low weight and obesity are both associated with a high risk of developing mobility impairments in the elderly. Low weight and malnutrition in the elderly are associated with significant levels of movement limitations. On the other hand, the increase in intermuscular adipose tissue is positively associated with mobility limitation among the elderly of both genders. Therefore, nutritional status is a factor independently and positively associated with functional impairment of mobility.

Acute and chronic sarcopenia

EWGSOP2 identified sarcopenia as acute and chronic. Acute sarcopenia is related to an acute disease or injury and has lasted less than 6 months. Chronic sarcopenia is associated with chronic and progressive conditions and increases the risk of mortality, and is a condition lasting more than 6 months. With this categorization, the need for periodic sarcopenia assessments in susceptible individuals is evident in order to facilitate early intervention by preventing or delaying sarcopenia progression [14].

Sarcopenic obesity

The sarcopenic condition may be exacerbated by obesity, leading to higher rates of disability, frailty, and morbidity and mortality. In this condition, the adipocytes undergo hypertrophy and hyperplasia, and an inflammatory response is activated with deregulated production of several adipokines. In addition, lipids that accumulate ectopically in skeletal muscle induce mitochondrial dysfunction characterized by impaired β-oxidation capacity and increased reactive oxygen species formation, providing a lipotoxic environment and insulin resistance, as well as increased secretion of some pro-inflammatory myokines capable of inducing muscular dysfunction. In this scenario, adipose tissue inflammation is predominant over skeletal muscle inflammation, and therefore, there is a redirection of the vector of processes from “sarcopenia → obesity” to “obesity → sarcopenia” [36].

Molecular mechanisms of sarcopenia

Skeletal muscle tissue is affected by progressive changes inherent to aging that compromise muscle structure and functional organization [37]. Although sarcopenia has several causes, it mainly occurs when protein degradation (catabolism) is much greater than synthesis (anabolism), which may occur due to sedentary lifestyle [5]. Over time, skeletal muscle is replaced by fat and fibrous tissue and there is a decrease of muscle reinnervation, aggravating sarcopenia during aging [38]. Aging seems to be a predisposing factor for increased oxidative stress in skeletal muscles, both at rest and in disuse atrophy, thus suggesting a correlation between oxidative stress and sarcopenia [39, 40]. Redox imbalance, common during the aging process, appears to be the primary cause of chronic inflammation and redox-sensitive transcription factors such as Nuclear factor-kappa B (NF-κB) are directly involved in the inflammatory process.

NF-κB is a pleiotropic transcription factor that modulates immune and inflammatory response, survival, and cell proliferation [41]. During aging, the upregulation of key molecules such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) is mediated by NF-κB [42, 43]. Furthermore, reactive oxygen species (ROS) act as a second messenger to TNF-α in skeletal muscle, directly or indirectly activating NF-κB.

Several recent studies suggest that constitutive activation of NF-κB leads to muscle loss, while inhibition avoids such muscle loss due to various catabolic stimuli, including TNF-α [44, 45, 46, 47, 48].

The stages of myogenesis are associated with the expression of specific proteins involved mainly in the organization of the muscle contractile apparatus. Those proteins are called transcription factors or MRF (myogenic regulatory factors) and belong to the bHLH (basic helix-loop-helix) transcription factors superfamily. The MRF family includes MyoD (Myf-3), Myf-5, myogenin (Myf-1), and MRF4. MyoD and Myf-5 are primary factors, which act in the early stages of myogenesis by acting on muscle cell proliferation, while myogenin and MRF4 act later, denominated as differentiation factors, playing a crucial role in processes of plasticity, adaptation, and rehabilitation in adult muscle [49, 50, 51]. The inhibitory effect of TNF-α on myogenesis is mediated by the activation of NF-κB, which negatively regulates MyoD myogenic transcription factor levels in myoblasts. One of the known mechanisms is the delayed cell cycle exit of the myoblast caused by TNF-α. Study findings suggest that TNF-α inhibits myogenic differentiation through destabilizing of the MyoD protein in a NF-kappaB-dependent manner, which affects skeletal muscle regeneration and may contribute to muscle catabolism [52].

The literature shows that at least four proteolytic pathways are activated in skeletal muscle and may be altered during aging, thus contributing to sarcopenia: the caspase-dependent, the lysosomal, the calcium-dependent, and the ubiquitin/proteasome-dependent pathways [53]. Caspases belong to a family of cysteine proteases and play a role in the initiation and execution of apoptosis, a highly regulated type of cell death characterized by specific morphological, biochemical, and molecular events. Studies have shown that aging is associated with increased DNA fragmentation leading to caspase-3 activation in rat skeletal muscles, and consequently, apoptosis [54, 55]. In addition, other caspases such as caspase-2 can be activated by both calcium release and oxidative stress, also triggering apoptosis in muscle cells [56].

In aging skeletal muscles, stimuli such as calcium [57], oxidative stress [58, 59], and TNF-α [60, 61] can trigger apoptosis. Oxidative stress can occur due to a mitochondrial dysfunction, which in turn can trigger early events in the apoptotic process through the release of pro-apoptotic proteins into the cytosol [62]. The literature shows that mitochondrial turnover is fundamental for recycling defective organelles and is altered with muscular aging, resulting in homeostatic imbalance in the myocytes [63].

The calcium-dependent system comprises several cysteines, called calpains, and a physiological inhibitor called calpastatin. Calpains perform limited proteolysis on their substrates, resulting in irreversible modifications that lead to changes in activity or degradation via other proteolytic pathways. In addition, there is evidence that cytosolic calcium levels increase with age [57], providing a favorable environment for the activation of the apoptotic pathway mediated by the endoplasmic reticulum.

The ubiquitin-proteasome system, initially described as playing an important role in regulatory or damaged protein catabolism, is also involved in massive protein degradation in skeletal muscles [64]. The endosome-lysosome system is relatively non-selective and mainly involved in the degradation of long-lasting proteins [65]. Lysosomal autophagic degradation was induced in skeletal muscle in a 6-h fasting model [66]. Autophagins, a class of cysteine proteases involved in the formation of autophagosomes, are particularly abundant in skeletal muscles [67]. Recently, it has been shown that there was overexpression of autophagy-related genes during fasting or denervation-induced muscle atrophy [68, 69, 70].

Cell death and inflammation processes are directly involved in aging-related decreased muscle strength and mass [71, 72]. Inflammation can negatively influence skeletal muscle through direct catabolic effects or indirect mechanisms. Interleukin-6 and other cytokines can function through direct catabolic effects by causing reduced dietary energy intake (aging anorexia), inducing insulin resistance, or lowering concentrations of growth factor (GH) and insulin-like growth factor 1 (IGF-1). The association between apoptosis and sarcopenia suggests that an inflammatory signal could trigger the loss of muscle cells in older persons even in the absence of evident inflammatory disease [73].

IGF-1 and insulin, along with exercise and testosterone, are able to upregulate the anabolic pathway inducing protein synthesis, which involves the activation of phosphatidylinositol 3-kinase (PI3K)/serine threonine kinase (Akt), which in turn stimulates the mTOR (mammalian target of rapamycin) pathway [74]. Testosterone is also capable of stimulating myoblasts and satellite cells, while IGF-1, besides inhibiting proteolysis, stimulates the proliferation of satellite cells. Aging is associated with lower testosterone and IGF-1 levels, and insulin resistance, leading to decreased muscle protein synthesis [75] and thus resulting in a vicious cycle where muscle loss impairs physical capacity causing immobility, further shrinking muscle mass.

The following figure (Fig. 4) presents a schematic summary of the molecular pathways activated in sarcopenia genesis.
Fig. 4

Schematic representation of the molecular pathways activated against endogenous and exogenous factors in sarcopenia genesis. Modified from Sandri M. (2008) [74]

Aging and nutrition

Calorie intake decreases significantly with age due to a decline in protein and energy needs [76]. Intake can drop up to 25% between the ages of 40 and 70 [77], and older persons tend to eat more slowly, eat smaller, and only meals, unlike younger adults [78]. The “anorexia of aging” is multifactorial and involves derangements of both peripheral and central regulatory systems. Several factors, including age-related gradual decrease in smell and taste perception, hormonal changes in gut mediators, and altered secretion pattern of ghrelin after nutrient intake, affect satiety and dietary behaviors [79]. In addition, the elderly may present dysphagia caused by a compromised central nervous system function, with impairments of the cortex, basal nucleus, or brainstem; efferent/afferent peripheral nerves (motor and sensory); or muscle function [80].

Anorexia of aging contributes to the loss of weight, muscle mass, strength, and physical functioning. There is a growing body of research investigating the effects of diet on muscle mass and physical functioning, Malnutrition, overweight, obesity, decreased micronutrients amount, re-feeding syndrome, sarcopenia, and frailty are nutritional disorders [81]. The sarcopenia phenotype is associated with malnutrition, regardless of whether malnutrition is caused by low food intake (anorexia or motor changes), reduced bioavailability of nutrients (due to repeated events of vomiting or diarrhea), or a high energy requirement [81, 82].

Observational studies showed that the nutrients that had the greatest impact on sarcopenia and frailty in were proteins, vitamin D, antioxidant nutrients (which include carotenoids, selenium, and vitamins E and C), and long-chain polyunsaturated fatty acids [83].


Current recommended daily intake for dietary protein in adults (0.8 to 1.2 g/kg of body weight/d) is based predominantly on short-term nitrogen balance, not on maintenance of physical function [84]. Coelho-Júnior et al. [85] conducted a systematic review and meta-analysis of observational studies in order to investigate the association of protein intake and physical function in the elderly. The findings of this study indicate that a very high (≥ 1.2 g/kg/day) and a high protein intake (≥ 1.0 g/kg/day) are associated with better lower-limb performance, when compared with low protein intake (< 0.80 g/kg/day) in the elderly.

The intake of amino acids stimulates protein synthesis and/or suppresses muscle proteolysis [86]. The supply of essential amino acids (EAA), especially branched-chain amino acids such as leucine, may favor muscle mass gain through the activation of the mTOR pathway. Favorable conditions, such as nutrient and oxygen availability, induce cell growth by activating this pathway. Cellular growth occurs through anabolic processes such as protein synthesis and the synthesis of many classes of lipids (unsaturated and saturated fatty acids, phosphatidylcholine, phosphatidylglycerol, and sphingolipids) required for membrane biosynthesis and energy storage, and by limiting catabolic processes, such as autophagy, thus leading to muscle mass gain [87].

Age-related muscle mass loss involves a diminished response to essential amino acids due to a decrease in mTOR phosphorylation [88]. The expression of protein-encoding genes associated with muscle protein synthesis and satellite cell function in response to exercise and supplementation with EAA is different for younger and older adults [89]. These findings suggest changes in mTOR sensitivity and factors related to the anabolic response and anabolic resistance in older persons. This explains why an injury or long stay in the hospital leads to a rapid decline in skeletal muscle function in older patients [90]. Despite this change in mTOR sensitivity, it has recently been shown that the intake of low-dose leucine-rich essential amino acids can stimulate muscle anabolism to the same extent as whey protein in older women at rest and after exercise [91].

Vitamin D

There is a progressive decline in vitamin D blood levels with aging. This decrease may be caused by inadequate vitamin intake, decreased sun exposure, a reduction in the ability of the skin to synthesize vitamin D from UV light, and decreased renal conversion of calcidiol to its active form [92]. Low levels of vitamin D seem to be associated with osteoporosis, diabetes mellitus, rheumatoid arthritis, various cancers, cardiovascular disease, cognitive decline, multiple sclerosis, and infectious diseases [93]. Research conducted with older persons also reported an association between low vitamin D levels and high parathyroid hormone (PTH) concentrations and a decrease in muscle mass and strength [94].

Vitamin D binds to the vitamin D receptor (VDR) present in both the plasma membrane and the cell nucleus. When the nuclear receptor is activated, transcription of the genes involved in calcium uptake takes place, together with the transport of phosphate across the cell membrane, phospholipid metabolism, production of inflammatory cytokines, and proliferation and terminal differentiation of satellite cells. The binding of vitamin D to the membrane-bound VDR activates a nongenomic pathway that regulates the release of calcium into the cytosol, which is crucial for muscle contraction and stimulates protein synthesis [95].

Despite the molecular activation triggered, the literature does not show solid evidence on the use of vitamin D and the effective improvement in muscle mass gain and performance. A systematic review by Beaudart et al. [96] evaluated the effect of combined exercise and nutritional intervention on muscle mass and muscle function in the elderly. Regarding the use of vitamin D, a study by Bunout et al. [97] reported effects of combined exercise and vitamin D3 supplementation on muscle strength and physical performance. The dose of vitamin D3 used was 400 IU/day for 9 months, and resulted in an improvement in mass gain and muscle strength, but there was no difference between the training-only group and the group that combined training and vitamin D supplementation.

A prospective cohort study showed an association between mobility limitation and low levels of 25-hydroxy vitamin D [25 (OH) D] in the elderly. Older people with 25 (OH) D < 50 and 50 to < 75 nmol/L were at greater risk of developing mobility limitation, showing that an inefficient intake represents a factor that induces mobility limitations. In this scenario, prevention or treatment of low vitamin D levels may reduce the impact of mobility limitation in older people [98].

Magnesium, selenium, iron, and zinc

A systematic review conducted by Dronkelaar et al. [99] showed that magnesium intake was significantly associated with sarcopenia, and its supplementation significantly improved muscle performance in older people. The administration of 300 mg/d magnesium oxide for 12 weeks led to a significant increase of serum concentrations, improving physical performance in sarcopenic individuals with a dietary magnesium intake below the recommended daily intake at baseline. Another potential nutrient that may affect sarcopenic patients is selenium, which presented a positive impact on muscle mass and physical performance of treated individuals. Still in this systematic review, evidence indicates that zinc and iron may be important in the prevention and treatment of sarcopenia, since they are associated with oxidative stress. Aging is caused by the accumulation of ROS, which leads to changes in the plasma membrane and in DNA molecule. Oxidative stress, through the accumulation of ROS, can cause muscle degeneration and reduced muscle strength in the elderly, but divergent studies have not been able to find an association with positive clinical outcomes in sarcopenic patients. Therefore, the role of iron and zinc on sarcopenia remains unclear.

Anabolic hormones

Sex hormones (testosterone, estrogens, and dehydroepiandrosterone sulfate (DHEAS)) play an important role in the development of age-related onset of sarcopenia. Skeletal muscle is able to convert DHEA into active androgens and estrogens, and stimulates insulin-like growth factor-1 (IGF-1), which is important for cell proliferation. On muscle, testosterone has an anabolic effect and a potentially anti-inflammatory effect, as it leads to satellite cell activation, proliferation, survival, and differentiation. Sex hormones can stimulate muscle protein synthesis and improve recycling of intracellular amino acids, the breakdown rate, and promote the activity of motor neurons. Testosterone is also capable of promoting the differentiation of pluripotent stem cells into the myogenic lineage but inhibits their differentiation into adipocytes via androgen receptor, an effect that may justify its effects on the reduction in body fat mass and the increase in fat-free mass and insulin sensitivity [100].

Evidences on the benefits of hormone therapy for the treatment of sarcopenia are currently inconsistent. According to the International Clinical Practice Guidelines for Sarcopenia (ICFSR), there is no recommendation for the use of anabolic hormones for the management of sarcopenia. Evidence to date offers only a very low level of certainty and does not guarantee that a testosterone supplementation regimen would be effective in older people with sarcopenia [101].

Physical exercise and sarcopenia

Physical exercise can influence both catabolic and anabolic pathways. Physical exercise increases IGF-1 levels, which leads to the activation of mTOR and, consequently, protein synthesis. MTOR can also be activated by mechanical overload of the muscle [102, 103]. In addition, exercise increases the amount of myofibrillar protein by activating satellite cells and decreases fat infiltration in the muscle [103]. Besides stimulating muscle anabolism, physical exercise inhibits protein degradation, an effect probably mediated by lower levels of oxidative stress after training [102].

Cruz-Jentoft et al. [104] systematically evaluated the effects of physical exercise on body composition and functional outcomes in older persons with sarcopenia. Their results suggested that the combination of several types of exercises into one program can improve both muscle strength and physical performance.


Age-related sarcopenia is a slow, progressive process, and the associated underlying pathophysiological disorders are closely linked to the frailty phenotype. This condition directly affects functioning and quality of life in older people and has serious impacts on social, economic, and health aspects, resulting in extreme vulnerability to endogenous and exogenous stressors. In recent years, significant progress has been made not only in defining clinically relevant characteristics of sarcopenia but also in elucidating altered molecular pathways. Sarcopenia syndrome appears to result in part from a chronically activated catabolic state mediated by pro-inflammatory cytokines and altered mitochondrial energy status associated with a decreased ability to survive critical illness. The elucidation of the molecular mechanisms and the genesis of sarcopenia opens new perspectives on the interventions needed to improve the quality of life of patients.



This article was translated by Vanina Monique TUCCI-VIEGAS, Ph.D., Biologist & Translator/Reviewer of Scientific, Medical, and Technical Texts. E-mail address:

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Beard JR, Officer A, de Carvalho IA, et al. The World report on ageing and health: a policy framework for healthy ageing. Lancet. 2016;387(10033):2145–154. Scholar
  2. 2.
    Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Consensus definition of sarcopenia, cachexia and pre-cachexia: Joint document elaborated by Special Interest Groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics.”. Age Ageing. 2018;29:1–16.Google Scholar
  3. 3.
    Goisser S, Kemmler W, Porzel S, Volkert D, Sieber CC, Bollheimer LC, et al. Sarcopenic obesity and complex interventions with nutrition and exercise in community-dwelling older persons--a narrative review. Clin Interv Aging. 2015;10:1267–82.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Wolfe RR. The role of dietary protein in optimizing muscle mass, function and health outcomes in older individuals. Br J Nutr. 2012;108(S2):S88–93.PubMedCrossRefGoogle Scholar
  5. 5.
    Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing. 2010;39(4):412–23.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Vellas B, Fielding R, Bens C, Bernabei R, Cawthon P, Cederholm T, et al. Implications of ICD-10 for sarcopenia clinical practice and clinical trials: report by the International Conference on Frailty and Sarcopenia Research Task Force. J Frailty Aging. 2018;7(1):2–9.PubMedGoogle Scholar
  7. 7.
    Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol. 1998;147(8):755–63.PubMedCrossRefGoogle Scholar
  8. 8.
    Iannuzzi-Sucich M, Prestwood KM, Kenny AM. Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J Gerontol A Biol Sci Med Sci. 2002;57(12):M772–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Smoliner C, Sieber CC, Wirth R. Prevalence of sarcopenia in geriatric hospitalized patients. J Am Med Dir Assoc. 2014;15(4):267–72.PubMedCrossRefGoogle Scholar
  10. 10.
    Alexandre TDS, Duarte YADO, Santos JLF, Wong R, Lebrão ML. Prevalence and associated factors of sarcopenia among elderly in Brazil: findings from the sabe study. J Nutr Health Aging. 2014;18(3):284–90.CrossRefGoogle Scholar
  11. 11.
    Zhang X, Zhang W, Wang C, Tao W, Dou Q, Yang Y. Sarcopenia as a predictor of hospitalization among older people: a systematic review and meta-analysis. BMC Geriatr. 2018;18(1):188.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Cruz-Jentoft AJ, Landi F, Topinková E, Michel JP. Understanding sarcopenia as a geriatric syndrome. Curr Opin Clin Nutr Metab Care. 2010;13(1):1–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Carvalho do Nascimento PR, Poitras S, Bilodeau M. How do we define and measure sarcopenia? Protocol for a systematic review. Syst Rev. 2018;7(1):51.
  14. 14.
    Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16–31.CrossRefGoogle Scholar
  15. 15.
    Malmstrom TK, Morley JE. SARC-F: a simple questionnaire to rapidly diagnose sarcopenia. J Am Med Dir Assoc. 2013;14(8):531–2.PubMedCrossRefGoogle Scholar
  16. 16.
    Ida S, Kaneko R, Murata K. SARC-F for screening of sarcopenia among older adults: a meta-analysis of screening test accuracy. J Am Med Dir Assoc. 2018;19(8):685–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Bahat G, Yilmaz O, Kiliç C, Oren MM, Karan MA. Performance of SARC-F in regard to sarcopenia definitions, muscle mass and functional measures. J Nutr Health Aging. 2018;22(8):898–903.PubMedCrossRefGoogle Scholar
  18. 18.
    Ellis KJ. Human body composition: in vivo methods. Physiol Rev. 2000;80(2):649–80.PubMedCrossRefGoogle Scholar
  19. 19.
    Silva AM, Shen W, Heo M, Gallagher D, Wang Z, Sardinha LB, et al. Ethnicity-related skeletal muscle differences across the lifespan. Am J Hum Biol. 2010;22(1):76–82.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Heymsfield SB, Peterson CM, Thomas DM, Heo M, Schuna JM, Hong S, et al. Scaling of adult body weight to height across sex and race/ethnic groups: relevance to BMI. Am J Clin Nutr. 2014;100(6):1455–61.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Thomas D, Das SK, Levine JA, Martin CK, Mayer L, McDougall A, et al. New fat free mass - fat mass model for use in physiological energy balance equations. Nutr Metab (Lond). 2010;7:39.CrossRefGoogle Scholar
  22. 22.
    McNally EM. Powerful genes — myostatin regulation of human muscle mass. N Engl J Med. 2004;350(26):2642–4.PubMedCrossRefGoogle Scholar
  23. 23.
    Heymsfield SB, Scherzer R, Pietrobelli A, Lewis CE, Grunfeld C. Body mass index as a phenotypic expression of adiposity: quantitative contribution of muscularity in a population-based sample. Int J Obes. 2009;33(12):1363–73.CrossRefGoogle Scholar
  24. 24.
    Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in adult men with androgen deficiency syndromes : an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536–59.PubMedCrossRefGoogle Scholar
  25. 25.
    Houston DK, Nicklas BJ, Ding J, Harris TB, Tylavsky FA, Newman AB, et al. Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) Study. Am J Clin Nutr. 2008;87(1):150–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Lee SY, Gallagher D. Assessment methods in human body composition. Curr Opin Clin Nutr Metab Care. 2008;11(5):566–72. Scholar
  27. 27.
    Kim KM, Jang HC, Lim S. Differences among skeletal muscle mass indices derived from height-, weight-, and body mass index-adjusted models in assessing sarcopenia. Korean J Intern Med. 2016;31(4):643–50. Scholar
  28. 28.
    Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis. Age Ageing. 2010;39(4):412–23.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Valensise H, Andreoli A, Lello S, Magnani F, Romanini C, De Lorenzo A. Total-body skeletal muscle mass: development and cross-validation of anthropometric prediction models. Am J Clin Nutr. 2000;72(3):796–803.CrossRefGoogle Scholar
  30. 30.
    Rech CR, Dellagrana RA, Marucci M d FN, Petroski EL. Validade de equações antropométricas para estimar a massa muscular em idosos. Rev Bras Cineantropometria e Desempenho Hum. 2012;14(1):23–31. Scholar
  31. 31.
    Goodpaster BH, Park SW, Harris TB, Kritchevsky SB, Nevitt M, Schwartz AV, et al. The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J Gerontol A Biol Sci Med Sci. 2006;61(10):1059–64.PubMedCrossRefGoogle Scholar
  32. 32.
    Janssen I, Baumgartner RN, Ross R, Rosenberg IH, Roubenoff R. Skeletal muscle cutpoints associated with elevated physical disability risk in older men and women. Am J Epidemiol. 2004;159:413–21.PubMedCrossRefGoogle Scholar
  33. 33.
    Morley JE, Anker SD, von Haehling S. Prevalence, incidence, and clinical impact of sarcopenia: facts, numbers, and epidemiology-update 2014. J Cachexia Sarcopenia Muscle. 2014;5(4):253–9.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Deitrick JE, Whedon GD, Shorr E. Effects of immobilization upon various metabolic and physiologic functions of normal men. Am J Med. 1948;4(1):3–36.PubMedCrossRefGoogle Scholar
  35. 35.
    Torres-de Araújo JR, Tomaz-de Lima RR, Ferreira-Bendassolli IM, Costa-de LK. Functional, nutritional and social factors associated with mobility limitations in the elderly: a systematic review. Salud Publica Mex. 2018;60(5):579–85.PubMedCrossRefGoogle Scholar
  36. 36.
    Kalinkovich A, Livshits G. Sarcopenic obesity or obese sarcopenia: a cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis. Ageing Res Rev. 2017;35:200–21.PubMedCrossRefGoogle Scholar
  37. 37.
    Matsudo SM, Matsudo VKR, Neto TLDB. Impacto do envelhecimento nas variáveis antropométricas, neuromotoras e metabólicas da aptidão física. Rev Bras Ciênc Mov. 2000;8(4):21–32.Google Scholar
  38. 38.
    Visser M, Kritchevsky S, Goodpaster B, Newman AB, Nevitt MC, Stamm E, et al. Leg muscle mass and composition in relation to lower extremity performance in men and women aged 70 to 79: the health, aging and body composition study. J Am Geriatr Soc. 2002;50(5):897–904.PubMedCrossRefGoogle Scholar
  39. 39.
    Siu PM, Pistilli EE, Alway SE. Age-dependent increase in oxidative stress in gastrocnemius muscle with unloading. J Appl Physiol. 2008;105(6):1695–705.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Cannavino J, Brocca L, Sandri M, Grassi B, Bottinelli R, Pellegrino MA. The role of alterations in mitochondrial dynamics and PGC-1α over-expression in fast muscle atrophy following hindlimb unloading. J Physiol. 2015;593(8):1981–95.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Piette J, Piret B, Bonizzi G, Schoonbroodt S, Merville MP, Legrand-Poels S, et al. Multiple redox regulation in NF-kappaB transcription factor activation. Biol Chem. 1997;378(11):1237–45.PubMedGoogle Scholar
  42. 42.
    Chung HY, Cesari M, Anton S, Marzetti E, Giovannini S, Seo AY, et al. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev. 2009;8:18–30.PubMedCrossRefGoogle Scholar
  43. 43.
    Davalli P, Mitic T, Caporali A, Lauriola A, D’Arca D. ROS, cell senescence, and novel molecular mechanisms in aging and age-related diseases. Vol. 2016, Oxidative Med Cell Longev 2016.Google Scholar
  44. 44.
    Li H, Malhotra S, Kumar A. Nuclear factor-kappa B signaling in skeletal muscle atrophy. J Mol Med (Berl). 2008;86(10):1113–26. Scholar
  45. 45.
    Rodriguez J, Vernus B, Chelh I, Cassar-Malek I, Gabillard JC, Hadj Sassi A, et al. Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways. Cell Mol Life Sci. 2014;71:4361–71.PubMedCrossRefGoogle Scholar
  46. 46.
    Cai D, Frantz J, Tawa NEJ, Melendez PA, Oh BC, Lidov HG, et al. IKKβ/NF-κB activation causes severe muscle wasting in mice. Cell. 2017;119(2):285–98. Available from:. Scholar
  47. 47.
    Li YP, Schwartz RJ, Waddell ID, Holloway BR, Reid MB. Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-kappaB activation in response to tumor necrosis factor alpha. FASEB J. 1998;12(10):871–80.PubMedCrossRefGoogle Scholar
  48. 48.
    Dogra C, Changotra H, Wedhas N, Qin X, Wergedal JE, Kumar A. TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine. FASEB J. 2007;21(8):1857–69 Available from: Scholar
  49. 49.
    Frontera WR, Ochala J. Skeletal muscle: a brief review of structure and function. Calcif Tissue Int. 2015;96(3):183–95 Available from: Scholar
  50. 50.
    Schiaffino S, Reggiani C. Fiber types in mammalian skeletal muscles. Physiol Rev. 2011;91(4):1447–531 Available from: Scholar
  51. 51.
    Mastroyiannopoulos NP, Nicolaou P, Anayasa M, Uney JB, Phylactou LA. Down-regulation of myogenin can reverse terminal muscle cell differentiation. PLoS One. 2012;7(1).PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Bhatnagar S, Panguluri SK, Gupta SK, Dahiya S, Lundy RF, Kumar A. Tumor necrosis factor-α regulates distinct molecular pathways and gene networks in cultured skeletal muscle cells. PLoS One. 2010;5(10).PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Sakuma K, Yamaguchi A. Sarcopenia and cachexia: the adaptations of negative regulators of skeletal muscle mass Cachexia Sarcopenia Muscle. 2012;3(2):77–94. Scholar
  54. 54.
    López-Lluch G, Irusta PM, Navas P, de Cabo R. Mitochondrial biogenesis and healthy aging. Exp Gerontol. 2008;43:813–9.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Baker BM, Haynes CM. Mitochondrial protein quality control during biogenesis and aging. Trends Biochem Sci. 2011;36:254–61.PubMedCrossRefGoogle Scholar
  56. 56.
    Braga M, Sinha Hikim AP, Datta S, Ferrini MG, Brown D, Kovacheva EL, et al. Involvement of oxidative stress and caspase 2-mediated intrinsic pathway signaling in age-related increase in muscle cell apoptosis in mice. Apoptosis. 2008;13(6):822–32.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Nitahara JA, Cheng W, Liu Y, Li B, Leri A, Li P, et al. Intracellular calcium, DNase activity and myocyte apoptosis in aging Fischer 344 rats. J Mol Cell Cardiol. 1998;30(3):519–35.PubMedCrossRefGoogle Scholar
  58. 58.
    Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med. 2000;29(3–4):222–30.PubMedCrossRefGoogle Scholar
  59. 59.
    Dai D-F, Chiao YA, Marcinek DJ, Szeto HH, Rabinovitch PS. Mitochondrial oxidative stress in aging and healthspan. Longev Healthspan 2014;3(1):6. Scholar
  60. 60.
    Phillips T, Leeuwenburgh C. Muscle fiber specific apoptosis and TNF-alpha signaling in sarcopenia are attenuated by life-long calorie restriction. FASEB J. 2005;19(6):668–70 Available from: Scholar
  61. 61.
    Sakuma K, Aoi W, Yamaguchi A. Current understanding of sarcopenia: possible candidates modulating muscle mass. Pflugers Arch Eur J Physiol. 2014;467:213–29.Google Scholar
  62. 62.
    Chabi B, Ljubicic V, Menzies KJ, Huang JH, Saleem A, Hood DA. Mitochondrial function and apoptotic susceptibility in aging skeletal muscle. Aging Cell. 2008;7(1):2–12.PubMedCrossRefGoogle Scholar
  63. 63.
    Calvani R, Joseph AM, Adhihetty PJ, Miccheli A, Bossola M, Leeuwenburgh C, et al. Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy. Biol Chem. 2013;394:393–414.Google Scholar
  64. 64.
    Bodine SC, Baehr LM. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am J Physiol Endocrinol Metab. 2014;307(6):E469–84.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Endo F, Tanaka Y, Tomoeda K, Tanoue A, Tsujimoto G, Nakamura K. Amino acids as regulators of proteolysis. Nutrition. 2003;133(4):2068–72.Google Scholar
  66. 66.
    Grumati P, Coletto L, Sabatelli P, Cescon M, Angelin A, Bertaggia E, et al. Autophagy is defective in collagen VI muscular dystrophies, and its reactivation rescues myofiber degeneration. Nat Med. 2010;16(11):1313–20.PubMedCrossRefGoogle Scholar
  67. 67.
    Mariño G, Uría J, Puente X, Quesada V, Bordallo J, López-Otín C. Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy. J Biol Chem. 2003;278(6):3671–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, et al. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab. 2007;6(6):458–71.PubMedCrossRefGoogle Scholar
  69. 69.
    O’Leary MFN, Hood DA. Denervation-induced oxidative stress and autophagy signaling in muscle. Autophagy. 2009;5(2):230–1.PubMedCrossRefGoogle Scholar
  70. 70.
    Vainshtein A, Desjardins EM, Armani A, Sandri M, Hood DA. PGC-1α modulates denervation-induced mitophagy in skeletal muscle. Skelet Muscle. 2015:5–9 Available from:
  71. 71.
    Carter CS, Hofer T, Seo AY, Leeuwenburgh C. Molecular mechanisms of life- and health-span extension: role of calorie restriction and exercise intervention. Appl Physiol Nutr Metab. 2007;32(5):954–66.PubMedCrossRefGoogle Scholar
  72. 72.
    Minor RK, Allard JS, Younts CM, Ward TM, De Cabo R. Dietary interventions to extend life span and health span based on calorie restriction. J Gerontol Ser A Biol Sci Med Sci. 2010;65A:695–703.CrossRefGoogle Scholar
  73. 73.
    Roubenoff R. Catabolism of aging: is it an inflammatory process? Curr Opin Clin Nutr Metab Care [Internet]. 2003;6(3):295–9 Available from: Scholar
  74. 74.
    Sandri M. Signaling in muscle atrophy and hypertrophy. Physiology. 2008;23(3):160–70.PubMedCrossRefGoogle Scholar
  75. 75.
    Ali S, Garcia JM. Sarcopenia, cachexia and aging: diagnosis, mechanisms and therapeutic options - a mini-review. Gerontology. 2014;60:294–305.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Wakimoto P, Block G. Dietary intake, dietary patterns, and changes with age: an epidemiological perspective. J Gerontol A Biol Sci Med Sci. 2001;56 Spec No(Ii):65–80.CrossRefGoogle Scholar
  77. 77.
    Nieuwenhuizen WF, Weenen H, Rigby P, Hetherington MM. Older adults and patients in need of nutritional support: review of current treatment options and factors influencing nutritional intake. Clin Nutr. 2010;29:160–9.PubMedCrossRefGoogle Scholar
  78. 78.
    Otsuka R, Kato Y, Nishita Y, Tange C, Tomida M, Nakamoto M, et al. Age-related changes in energy intake and weight in community-dwelling middle-aged and elderly Japanese. J Nutr Health Aging. 2016;20(4):383–90.PubMedCrossRefGoogle Scholar
  79. 79.
    Landi F, Picca A, Calvani R, Marzetti E. Anorexia of aging. Clin Geriatr Med. 2017;33(3):315–23.PubMedCrossRefGoogle Scholar
  80. 80.
    Maeda K, Takaki M, Akagi J. Decreased skeletal muscle mass and risk factors of sarcopenic dysphagia: a prospective observational cohort study. J Gerontol A Biol Sci Med Sci. 2017;72(9):1290–4.PubMedGoogle Scholar
  81. 81.
    Cederholm T, Barazzoni R, Austin P, Ballmer P, Biolo G, Bischoff SC, et al. ESPEN guidelines on definitions and terminology of clinical nutrition. Clin Nutr. 2017;36(1):49–64.CrossRefGoogle Scholar
  82. 82.
    Muscaritoli M, Anker SD, Argilés J, Aversa Z, Bauer JM, Biolo G, et al. Consensus definition of sarcopenia, cachexia and pre-cachexia: Joint document elaborated by Special Interest Groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics.”. Clin Nutr. 2010;29(2):154–9.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Robinson SM, Reginster JY, Rizzoli R, Shaw SC, Kanis JA, Bautmans I, et al. Does nutrition play a role in the prevention and management of sarcopenia? Clin Nutr. 2017;Google Scholar
  84. 84.
    Zello GA. Dietary reference intakes for the macronutrients and energy: considerations for physical activity. Appl Physiol Nutr Metab. 2006;31(1):74–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Coelho-Júnior HJ, Milano-Teixeira L, Rodrigues B, Bacurau R, Marzetti E, Uchida M. Relative protein intake and physical function in older adults: a systematic review and meta-analysis of observational studies. Nutrients. 2018;10(9).PubMedCentralCrossRefPubMedGoogle Scholar
  86. 86.
    Wolfe RR. Regulation of muscle protein by amino acids. J Nutr. 2002;132(10):3219S–24S.PubMedCrossRefGoogle Scholar
  87. 87.
    Laplante M, Sabatini DM. An emerging role of mTOR in lipid biosynthesis. Vol. 19, Curr Biol. 2009.Google Scholar
  88. 88.
    Cuthbertson D, Smith K, Babraj J, Leese G, Waddell T, Atherton P, et al. Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J. 2005;19(3):422–4.PubMedCrossRefGoogle Scholar
  89. 89.
    Drummond MJ, Miyazaki M, Dreyer HC, Pennings B, Dhanani S, Volpi E, et al. Expression of growth-related genes in young and older human skeletal muscle following an acute stimulation of protein synthesis. J Appl Physiol. 2009;106(4):1403–11.PubMedCrossRefGoogle Scholar
  90. 90.
    Baum JI, Kim IY, Wolfe RR. Protein consumption and the elderly: what is the optimal level of intake? Vol. 8, Nutrients. 2016.Google Scholar
  91. 91.
    Bukhari SSI, Phillips BE, Wilkinson DJ, Limb MC, Rankin D, Mitchell WK, et al. Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after 1. Am J Physiol Endocrinol Metab. 2015;308(12):E1056–65.PubMedCrossRefGoogle Scholar
  92. 92.
    Johnson MA, Kimlin MG. Vitamin D, aging, and the 2005 dietary guidelines for Americans. Nutr Rev. 2006;64(9):410–21.PubMedCrossRefGoogle Scholar
  93. 93.
    Visser M, Deeg DJH, Lips P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the longitudinal aging study Amsterdam. J Clin Endocrinol Metab. 2003;88(12):5766–72.PubMedCrossRefGoogle Scholar
  94. 94.
    Scott D, Blizzard L, Fell J, Ding C, Winzenberg T, Jones G. A prospective study of the associations between 25-hydroxy-vitamin D, sarcopenia progression and physical activity in older adults. Clin Endocrinol. 2010;73(5):581–7.CrossRefGoogle Scholar
  95. 95.
    Ceglia L, Harris SS. Vitamin D and its role in skeletal muscle. Calcif Tissue Int. 2013;92:151–62.PubMedCrossRefGoogle Scholar
  96. 96.
    Beaudart C, Dawson A, Shaw SC, Harvey NC, Kanis JA, Binkley N, et al. Nutrition and physical activity in the prevention and treatment of sarcopenia: systematic review. Osteoporos Int. 2017;28(6):1817–33.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Bunout D, Barrera G, Leiva L, Gattas V, de la Maza MP, Avendaño M, et al. Effects of vitamin D supplementation and exercise training on physical performance in Chilean vitamin D deficient elderly subjects. Exp Gerontol. 2006;41(8):746–52.PubMedCrossRefGoogle Scholar
  98. 98.
    Houston DK, Neiberg RH, Tooze JA, Hausman DB, Johnson MA, Cauley JA, et al. Low 25-hydroxyvitamin D predicts the onset of mobility limitation and disability in community-dwelling older adults: the health ABC study. J Gerontol A Biol Sci Med Sci. 2013;68(2):181–7.PubMedCrossRefGoogle Scholar
  99. 99.
    van Dronkelaar C, van Velzen A, Abdelrazek M, van der Steen A, Weijs PJM, Tieland M. Minerals and sarcopenia; the role of calcium, iron, magnesium, phosphorus, potassium, selenium, sodium, and zinc on muscle mass, muscle strength, and physical performance in older adults: a systematic review. J Am Med Dir Assoc. 2017; Available from:. Scholar
  100. 100.
    Maggio M, Lauretani F, Ceda GP. Sex hormones and sarcopenia in older persons. Curr Opin Clin Nutr Metab Care. 2013;16(1):3–13.PubMedGoogle Scholar
  101. 101.
    Dent E, Morley JE, Cruz-Jentoft AJ, Arai H, Kritchevsky SB, Guralnik J, et al. International clinical practice guidelines for sarcopenia (ICFSR): screening, diagnosis and management. J Nutr Health Aging. 2018;22(10):1148–61.PubMedCrossRefGoogle Scholar
  102. 102.
    Lenk K, Schuler G, Adams V. Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. J Cachexia Sarcopenia Muscle. 2010;1:9–21.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Phu S, Boersma D, Duque G. Exercise and sarcopenia. J Clin Densitom. 2015;18(4):488–92.PubMedCrossRefGoogle Scholar
  104. 104.
    Cruz-Jentoft AJ, Landi F, Schneider SM, Zúñiga C, Arai H, Boirie Y, et al. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing. 2014;43(6):748–59.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Adriana Bottoni
    • 1
    Email author
  • Sérgio dos Anjos Garnes
    • 1
  • Fernanda Lasakosvitsch
    • 1
  • Andrea Bottoni
    • 1
  1. 1.Funzionali Serviços Médicos LtdaSão PauloBrazil

Personalised recommendations