Perspective Chapter: The Role of Modifiable Factors, Particularly Nutritional Factors, on Age-Related Sarcopenia

Abstract

Advances in medicine result in an increase in the age of global population. The percentage of people over 60 years will approximately be duplicated up to 22 between 2015 and 2050, which is associated with a notable rise in age-related complications such as sarcopenia and frailty. The age-related sarcopenia is defined by low muscle strength, and it is considered severe if low muscle strength, low muscle mass, and low physical performance are detected.This condition is associated with poor quality of life, risk of falls, fractures, and higher healthcare costs. Despite the growing interest regarding the treatment of this phenomenon, the lack of adequate knowledge underlying the multifactorial parthenogenesis of age-related sarcopenia hinders the diagnosis of effective therapeutic approaches. In this respect, one of the major solutions would be to recognize the effect of modifiable factors on muscle health during the lifetime. Previous observations indicated that dietary and nutritional factors, beyond other environmental agents across the life course are related to muscle mass and function in the elderly. With respect to the fundamental role of nutrients with antioxidants properties in maintaining many aspects of health, this chapter aims to discuss the association between components of sarcopenia and nutritional status in older adults, and their potential effect on prevention and treatment of age-related sarcopenia.

1. Introduction

1.1 Definition of sarcopenia

The average age of populations is increasing because of numerous factors, including advances in medical care and decreasing birth rate [1, 2]. The percentage of people over 60 years will approximately be duplicated up to 22 between 2015 and 2050, which is associated with a notable rise in age-related complications such as sarcopenia and frailty [3]. Definitions of age-related sarcopenia have evolved over time in an attempt to better characterize sarcopenia. The name for this phenomenon derives from the Greek term sarx (flesh) and penia (loss) [4]. Early definitions of sarcopenia were based exclusively on an age-related reduction in muscle mass [5]. However, the two-dimensional nature of these conditions (muscle mass loss and muscle strength loss) suggests that both its quantitative and qualitative range should be evaluated [6]. Therefore, the European Working Group on Sarcopenia in Older People (EWGSOP) described sarcopenia as an age-associated decline in muscle mass and strength with functional impairment [7].

Beyond the loss of muscle tissue that occurs over a lifetime, this condition is also associated with the conversion of type II fibers to type I fibers, which results in impairment of muscle quality and muscle function [8].

Categorizing sarcopenia into pre-sarcopenia, sarcopenia, and severe sarcopenia has also been defined by the EWGSOP that suggested the pre-sarcopenia stage as low muscle mass with no impact on muscle strength or physical performance, whereas the sarcopenia stage distinguished as low muscle mass with either low muscle strength or low physical performance and severe sarcopenia as the presence of all three criteria [9]. While interest in sarcopenia has risen in recent years, contention still exists over most components of the disease, with a universally accepted definition still lacking.

1.2 Diagnosis of sarcopenia

Various approaches can be used to assess muscle mass. Current assessment tools include body imaging techniques, bioelectric impedance analysis, anthropometric parameters, and biochemical markers [10].

Computed tomography (CT) and magnetic resonance imaging are able to effectively distinguish fat from other soft tissues, which makes these presently the gold standard method for the assessment of body composition. However, limited access, the high cost, and the risk of radiation inhibit the use of these techniques in clinical practice [11]. Therefore, dual-energy X-ray absorptiometry (DXA) is the most popular method for correctly evaluating body composition and widely used to assess muscle mass in research studies due to speed of measurement and relatively low per patient scan cost with typically low radiation [12]. Though, seeking for inexpensive, easy-to-use, and derived measures methods such as phase angle causes the application of bioimpedance technology. Nevertheless, using the estimation of body composition and muscle mass through anthropometric measurements, such as mid-upper arm circumference, calf circumference, and skinfold thickness, may allow us initially assess sarcopenia in situations that imaging equipment is typically unavailable in primary care settings [13].

The defining cutoff point for the identification of muscle loss depends upon the measurement technique chosen and the availability of reference studies. Low muscle mass is usually distinguished by a skeletal muscle mass index ranging from 7.23 kg/m2 to 8.87 kg/m2 in men and 5.45 kg/m2 to 6.42 kg/m2 in women [14]. Moreover, it is generally accepted that low physical performance is defined as a gait speed of less than 0.8 m/sec [15] and low muscle strength is usually defined by handgrip strength of less than 30 kg for men and less than 20 kg for women [7]. Nevertheless, the quadriceps strength cut-off points of 18.0 kg for older men and 16.0 kg for older women proposed as a muscle strength measurement for sarcopenia diagnosis in older Asian people [16].

Because of this diversity in the cutoffs of the sarcopenia’s characterization, EWGSOP has recommended that more research is urgently needed in order to obtain accurate reference values for different nations and countries around the world [17].

1.3 Pathophysiology of and risk factors for sarcopenia

The pathophysiology of sarcopenia is multifactorial. Several underlying mechanisms have been linked to the development of sarcopenia, although not all have been fully elucidated [6]. Prevalence of sarcopenia is mostly associated with chronic inflammation, which may lead to a vicious cycle of intricate interactions among risk factors [18]. However, research on sarcopenia prevention and treatment is developing quickly because of insufficient evidence for the underlying cellular mechanisms of the progress and maintenance of sarcopenia. So, it seems that understanding the factors related to increasing sarcopenia risk may provide strategies for intervention and disease improvement.

Inflammation in aging is one of the main suggested factors of sarcopenia characterized by a chronic progressive increase in pro-inflammatory cytokines, and the reduced serum level of anti-inflammatory cytokines [17]. Decline in immune function, plays an important role in several age-related diseases, for example Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, atherosclerosis, and other complications [19, 20].

The majority of studies have demonstrated that inflammatory cytokines have an important effect on skeletal muscle wasting, leading to an imbalance between protein synthesis and catabolism [21]. It reasonably has shown that reduced rates of protein synthesis paralleled to increased protein breakdown in the skeletal muscle are associated with a variety of produced pro-inflammatory cytokines during the inflammatory response. Indeed, the effects of pro-inflammatory cytokines on muscle mass may be mediated by activating the transcription factor NF-κB in line with a production of ROS in the muscle of the elderly people [22, 23]. Additionally, we recently indicated that circulating levels of C-reactive protein (CRP) and hs-CRP are independently associated with impairment of muscle strength [24]. It is also suggested that low muscle strength is associated with the high levels of inflammatory cytokines [25] such as CRP [26]. These findings may suggest that the plasma concentration of some inflammatory molecules is related to the aspects of muscle decline and functional impairment.

Another suggested factor is Insulin resistance (IR) which is defined by reduced peripheral glucose utilization in skeletal muscle, majority of whole-body insulin-stimulated glucose disposal, that develops with age [27]. Various studies demonstrated that IR is related markedly to the different diagnostic components of sarcopenia [28]. Data on the prevalence of sarcopenia in Korean elderly men aged more than 65 years recommended that higher IR and lower vitamin D levels are independently associated with the presence of sarcopenia in community-dwelling elderly men [29]. In another study conducted by Gorshunova et al., low muscle mass and muscle strength were significantly related to increased indices of IR, probably as a result of energy homeostasis disorders and the deterioration of glucose in the skeletal muscles [30]. One of the anticipated mechanisms of insulin resistance in elderly people is a reduction in the size of type II fibers which may reduce mitochondrial activity and result in IR in muscle [31, 32].

On the other hand, recent investigations illustrated that serum level of negative regulator of muscle growth, such as myostatin could increase with advancing age [33] and may play an important role in the resistance of insulin in muscles [34]. Moreover, aging skeletal muscle inflammation through activation of the classical signaling pathway also has impact on insulin uptake [35]. Furthermore, the effect of accumulation of intramyocellular lipid has been systematically evaluated and reported a well-established association between accumulation of intramyocellular lipid and muscle IR [30]. Finally, it is understood that strategies for identifying improvements and insulin sensitivity treatments can propose possible preventive measures against sarcopenia.

Aging is also related to changes in a several hormones status, including testosterone, estrogen, growth hormone, insulin-like growth factor 1, and corticosteroids [36], and the clinical significance of these deficiencies is variable with age [37]. It is previously supposed that the age-dependent decline in GH and IGF-1 levels is related to the pathogenesis of sarcopenia [38]. Moreover, in a recent observational cohort study, low baseline serum IGF-1 levels correlated with lower handgrip strength and worse physical performance [39]. Nevertheless, the impact of long-term GH therapy in the treatment of sarcopenia in elderly individuals with low GH/IGF-1 levels is still unclear. Cortisol is also the most potent immunosuppressive agent which can be stimulated by inflammation and therefore can be related to the development of sarcopenia and its components; muscle strength, muscle mass, and physical function. We could speculate from studies that the systemic overproduction of glucocorticoids during aging is associated with an increase of sarcopenia risk. However, further longitudinal studies are required to confirm these relationships.

In terms of modifiable risk factors, the relationship between adult lifestyle and sarcopenia has been highlighted in order to provide strategies for prevention of and improvement in age-related sarcopenia. In this concern, mental state, smoking, low body mass index (BMI), nutritional status, and physical activities have been introduced as the most potential changeable factors that could be applied in future strategies to prevent or delay the progression of sarcopenia [40, 41, 42]. The strong association between alteration in body composition in lifetime, namely fat-free mass, skeletal muscle mass, and BMI with prevalence and incidence of sarcopenia has been shown [43]. In addition, various previous reviews of studies revealed the relationship between physical inactivity and losses of muscle mass and strength [40], while resistance training was reported to have a beneficial effect on the physical performance measures in most studies [44, 45]. Regarding mental health, several studies found that sarcopenia is associated with cognitive decline and depression which could be due to some of the predisposing factors underlying sarcopenia, such as oxidative stress, inflammation, and insulin resistance [46]. Among them, one of the important modifiable factors in maintaining healthy status, in helping recovery from acute conditions, and in prevention of chronic diseases across lifespan is optimal nutritional status [47]. On the other hand, poor nutritional status is associated with several adverse consequences in community-dwelling older individuals, such as inflammation, cachexia, altered gut integrity, and muscle dysfunction [48, 49]. In addition, it is shown that the quality of the diet along with the lifetime has a close relationship with the sarcopenia [50]. It has been demonstrated that individuals consuming less energy will lose more muscle tissue. Therefore, avoiding under-nutrition is required to prevent muscle loss [47, 51]. Many nutrients have also been linked with the development of sarcopenia [47]. In this regard, the Korea National Health and Nutrition Examination Survey (KNHANES) cohort has revealed a lower energy, protein, and carbohydrate intake among sarcopenic older adults [52]. Given that evaluating the role of dietary nutrient intake in the treatment and development of sarcopenia would be valuable. Following we summarized studies in which the role of various nutritional factors on age-related sarcopenia was evaluated.

2. Role of nutritional factors in prevention and treatment of sarcopenia

2.1 Role of dietary protein in prevention and treatment of sarcopenia

The scientific literature indicated that the amount of daily protein intake is related to prevention of muscle functional decline and sarcopenia treatment, as older adults have an increased need for dietary protein to stimulate their muscle protein synthesis [53, 54]. Furthermore, Sovianne et al., showed a significant difference in protein intake (gram/day) among sarcopenic and non-sarcopenic older adults [55]. It is supposed that lower energy requirements and reduced appetite decrease total energy consumption in aging, which can significantly reduce dietary intake of protein [56]. It proposed that dietary protein supplementation more than recommended dietary intake (above 0.8 g/kg/d) may have beneficial effect on sarcopenia [57, 58]. However, other recent studies have shown that muscle loss cannot be entirely stopped, even when daily protein intake is maintained at a high level [59]. So, the role of protein supplementation on age-related sarcopenia is somewhat controversial and might be affected by the nutritional status of individuals [60].

It is also worth noting that the type of protein ingested and timing of protein intake throughout the day could determine the amount of skeletal muscle mass [61]. In these regards,nutritional supplementation including 20 g whey protein and 800 IU vitamin D in previous randomized double blind research leads to further losses of intermuscular fat (p = .049) and increased normal muscle density (p = .018) after the 6-month intervention [62]. These results were also confirmed by another study [63]. However, a recent meta-analysis of eight studies (n = 557) conducted by Tieland et al., showed no significant positive effects of protein or amino acid supplementation on lean body mass, muscle strength, or handgrip. Nevertheless, it seems that there were various heterogeneities in included trials in the mentioned study, such as duration of treatment and type of supplementation, and dosage which could affect the result interpretation [64]. So, it can be concluded that this general lack of effect of protein supplements directed us to assess positive associations between protein intake and muscle mass and function through cohort studies.

The anabolic effects of some amino acids on muscle mass also have been investigated in several studies. Creatine, as one of the most important amino acids located primarily in muscle tissue, accelerates muscle ATP regeneration throughout the increased energy demand [65, 66]. In this aera, the increased muscle mass and muscle strength with exercises and an additional effect of creatine were found in clinical trials [67]. Moreover, increased physical performance with exercises and an interactive effect of creatine were observed in some studies [68]. Results of a previous meta-analyses specified that creatine supplementation combined with resistance training could have a positive effect on aging muscle mass and upper body strength compared to resistance training alone [69]. In agreement with these findings, the recent meta-analyses also showed that creatine supplementation leads to greater increases in muscle mass (SMD: 1.37 kg [95% CI = 0.97–1.76]) and leg muscle strength (SMD: 0.24 kg [95% CI = 0.05–0.43]) in participants with a mean age of 57–70 years [70]. The molecular mechanisms underlying the improved protein synthesis and muscle strength following creatine administration might be correlated with an increase in skeletal muscle phosphocreatine content and enhanced muscle glycogen storage through exercise [67]. Despite these promising results, it is worth to mention that the vast majority of these studies measured the impact of combined exercise interventions and creatine supplementation in the sarcopenic populations suffering from malnutrition [69].

2.2 Role of n-3 fatty acids in prevention and treatment of sarcopenia

Many nutrients also have anabolic effects on aging musculoskeletal health. There is growing evidence for an association between n-3 fatty acids intake alone or in combination of other nutrients and components of sarcopenia, including muscle mass, muscle strength, and physical performance [71, 72]. In this regard, the investigation of possible relationship between circulating n-3 FA levels and sarcopenia among 125 participants in Asian older adults indicated that subjects with low muscle strength had 32.4% lower serum n-3 concentrations (P = 0.030) than controls [73]. In addition, omega-3 fatty acids intake was lower in elderly sarcopenic patients than elderly subjects without sarcopenia [2.6 ± 1.0 vs. 3.0 ± 1.2 kcal/day, p = 0.046] [74].

Furthermore, the recent results of the Maastricht Sarcopenia Study also showed that sarcopenic older adults had a 10–18% lower intake of five nutrients (n-3 fatty acids, vitamin B₆, folic acid, vitamin E, magnesium) compared with non-sarcopenic older adults (P < .05) [55]. Similarly, prolonged supplementation with omega-3 fatty acids has been examined in older adults in order to improve the muscle protein synthetic response [75, 76], and importantly, the combined supplements providing high-quality proteins, leucine, vitamin D, and omega-3 fatty acids all together appear to be most favorable effects in the prevention of sarcopenia, while also being safe [77]. The positive effects of omega-3 fatty acids supplementation on muscle mass and function have also been identified by a systematic review and meta-analysis [72]. In addition, some studies specified that vitamin D supplementation combined with n-3 fatty acids, in particular EPA + DHA, may have favorable effect on physical function, muscle mass, and strength [77]. It is supposed that the anti-inflammatory effects of omega-3 fatty acids have an important role in the reduction in sarcopenia risk [78]. Nevertheless, the exact mechanisms by which n-3 fatty acids apply their beneficial effects on components of sarcopenia remain to be elucidated.

2.3 Role of vitamin D in prevention and treatment of sarcopenia

Among several nutrients, there has been increasing interest in the implications of vitamin D, either as single supplements or in combination with other supplements, for improving the physical function of older adults due to high prevalence of vitamin D deficiency [79]. A positive correlation between serum 25(OH)D concentration and muscle function has been shown [80]. The previous systematic reviews aimed at examining the benefits of vitamin D supplementation on sarcopenia in aging indicated the importance of considering baseline serum 25(OH)D concentrations in the response to supplementation [81]. While, concerning this issue, the recent meta-analysis of RCTs (2017) confirmed a slight improvement in the physical performance test following supplementation, no overall increase in handgrip strength was detected [82]. Nevertheless, this finding strengthens that vitamin D with a range of 800–1000 IU/day, but not necessarily at higher doses, has beneficial effect on muscle strength [77].

2.4 Role of gut microbiota in prevention and treatment of sarcopenia

Epidemiologic studies point out that altered gut microbiota structure according to diet, taking drugs, and other environmental factors across the lifespan result in different microbiota patterns, composition, and function in the elderly [83, 84]. The gut microbiota has the essential function maintaining some aspects of health [85]. Changing microbiota patterns are associated with significant changes in metabolic and physiologic regulation, and markers of inflammation that could result in age-related adverse health consequences [86, 87]. Recent researchers have postulated that gut microbiota composition may have a great relationship with age-related alterations in skeletal muscle function [87]. In this concern, experimental studies revealed that changes in the gut composition via probiotic/prebiotic administration could influence muscle function and inflammatory status [88, 89, 90]. Our recent meta-analysis emphasized that probiotic supplementation for more than 12 weeks has positive impact on the muscle strength. However, the clear mechanism underlying the positive effect of probiotic administration on muscle strength was not identified. The possible explanation for these findings may be related to reduced levels of IGF-1 (insulin-like growth factor 1) during lifetime [39, 91]. The beneficial probiotic effects on circulating inflammatory biomarkers could be another description [92].

2.5 Role of dietary quality in prevention of sarcopenia

Research on dietary quality and dietary patterns has recently been undertaken to better understand the effects of diet as a whole and its impact on aging health complication such as sarcopenia. Results of recent cross-sectional study in 250 menopausal women 45 years old or older found that Mediterranean dietary pattern has a favorable role in the prevention of sarcopenia [93]. Additionally, adherence to dietary pattern including “vegetables-fruits” was associated with lower odds of prevalent sarcopenia in Chinese older men [94]. Furthermore, it is shown that subjects with higher consumption of “snacks-drinks-milk products” score had lower odds of sarcopenia (OR = 0.41, 95% CI: 0.24–0.70, P_trend < 0.001) [94]. Interestingly, findings of recent cross-sectional study revealed that adherence to the Western dietary pattern, characterized by a high intake of sugar, soy, and fast foods, was not linked to sarcopenia (OR = 0.51; 95% CI: 0.21–1.24; P_trend = 0.13) [95]. The link between healthier diets and physical performance among older adults has been proposed [41]. However, there is not enough research evidence available in various communities to inform about the definitive decision on the specific food pattern for the prevention or treatment of sarcopenia.

3. Conclusion

Age-related sarcopenia is a phenomenon with significant disability among the elderly. This condition is one of the most important public health problems among the healthy community. While there are the various notable bodies of research in order to define sarcopenia, the diversity in the cutoffs of the sarcopenia’s characterization revealed the needs for more research to define accurate reference values in different nations and countries around the world. On the other hand, one of the main controversial topics in evaluating the influence of nutrition on age-related sarcopenia is related to various definitions of sarcopenia in different nations and countries. In addition, due to the lack of a valid biomarker for the detection of sarcopenia, the exact mechanism underlying beneficial effect of numerous nutritional factors on components of sarcopenia remains unknown. Furthermore, there is not enough research evidence available in various communities to inform about the definitive decision on the food for the prevention or treatment of sarcopenia. The other limitation of included studies in this review was connected to absence of information about dietary intakes and serum concentrations of many micronutrients in older adults. So, considering the biochemical levels and dietary intakes of micronutrients in future studies is recommended. Finally, further studies are needed to investigate the interaction effect of modifiable risk factors, in particularly nutrition over time based in the near future.

Overall, present findings from the scientific literature specified that the combined nutritional supplements, such as vitamin D, n-3 fatty acids, and creatine along with resistance training could have better improvement in aging muscle mass and upper body strength compared with each alone. This effect particularly was shown in subjects with low serum vitamin D concentrations. In addition, it seems that the beneficial effect of probiotic/prebiotic administration also depends on changed gut microbiota composition. It is worth to mention that adherence to healthy dietary pattern with high quality including vegetables and fruits may lead to lower odds of sarcopenia.

Conflict of interest

None.