Nutritional frailty refers to the disability that occurs in old age owing to Sarcopenia, a loss of muscle mass and strength, contributes to .. is inﬂuenced by age-related alterations in a number of complex and . mass,therelationship betweengrowthhormoneand Figure 1 Dimensions of nutritional frailty. Nutrition, sarcopenia and frailty: a complex relationship. Juergen M. Bauer The stages of frailty can be arrayed on a continuum (Figure 2). In its early stages. effects of complex interactions between food constituents. A recent systematic review on the relationship between diet quality and . Figure 1 shows how studies were identified and selected for inclusion in the review. DQ: diet quality; FICSIT, Frailty and Injuries: Cooperative Studies of Intervention.
Moreover, they could inhibit a protein phosphatase ie, protein phosphatase 2A or interact with proteins associated with mTOR ie, raptor. An increased exposure to corticosteroids — together with the reduction of the lipolytic effects of declining GH levels — may contribute to the age-dependent increase of visceral fat and decreased LBM and bone mineral density.
In fact, an interesting study has shown higher glucose clearance in the arm than in the leg muscles and higher insulin resistance in the lower limb muscles of patients with type 2 diabetes T2D. In particular, RONS contributes to sarcopenia by increasing proteolysis and decreasing muscle protein synthesis, leading to a reduction in the muscle mass.
Because simple, reproducible, and cost-effective techniques are needed for the early diagnosis of sarcopenia in older patients in everyday clinical practice, further investigations are needed to standardize this diagnostic technique before its use can be recommended in clinical practice although M-US has requisite characteristics to become a reference method for this evaluation. Figure 1 Sarcopenia assessment flowchart. Thus, we can distinguish: The lack of a univocal definition for sarcopenia and its complex underlying pathophysiology make the development of biomarkers for this condition extremely challenging.
Markers of NMJ degeneration such as C-terminal again fragment CAFderiving from the inactivation of the agrin — a protein synthesized by motoneurons — with a consequent destabilization of the receptor for acetylcholine. Moreover, these biomarkers are only able to capture single aspects of this condition and are weakly associated with clinically meaningful aspects.
[Full text] Sarcopenia: assessment of disease burden and strategies to improve out | CIA
In fact, many of the adverse outcomes of frailty are probably mediated by sarcopenia, which may be considered the biological substrate for the development of PF and related negative health outcomes Figure 2. Although PF encompasses only a part of the frailty spectrum, the identification of a definite biological basis ie, sarcopenia opens new views for the development of interventions to slow or reverse the progression of this condition.
Therapeutic approaches Sarcopenia is an important geriatric syndrome which increases the risk of negative consequences such as physical disability, poor quality of life, and death, especially in institutionalized elderly residents of nursing homes. Exercise As mentioned earlier, physical inactivity and disease — both highly prevalent in the elderly — are the main contributors to the decline of muscle mass and function.
So far, no other treatment proposed and investigated for the prevention and improvement of sarcopenia has shown better results than PRT. Nevertheless, the implementation of PRT in community-dwelling elderly patients is still underused because it requires trained therapists and special equipment that are not routinely available.
Increased protein intake An increase in protein intake above 0. In fact, as mentioned earlier, essential amino acids are the primary stimulus for protein synthesis. Thus, elderly patients should be recommended to consume protein sources containing a relatively high proportion of amino acids — the so-called high-quality proteins.
Caloric restriction CR and regular physical exercise exert beneficial effects on overall health and muscle homeostasis in advanced age.
Selective androgen receptor modulators Dose-dependent adverse effects related to testosterone supplementation have driven the development of therapeutic agents with anabolic effects specific for skeletal muscle and bone tissues. In one study enrolling women aged 65 or older with sarcopenia and frailty, the treatment with MK produced statistically significant increases in LBM compared to placebo, but no significant improvement in strength or function.
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- Sarcopenia: assessment of disease burden and strategies to improve outcomes
Angiotensin-converting enzyme inhibitor Some drugs, involved in the treatment of congestive heart failure to improve functional performance and prognosis, are under investigation for skeletal muscle preservation — in particular, angiotensin-converting enzyme inhibitors ACE-Is.
However the exact effective and safe dosage is still unclear, but current suggestions include: Therefore, supplementation with high quality protein in its elemental form of AA especially BCAA may be a more effective way for optimum MPS stimulation as it by-passes digestive step that appears to be problematic for older adults.
Furthermore, on a cautionary note, although higher protein consumption is recommended to attenuate muscle mass loss in sarcopenia, potential adverse effects associated with higher than 0.
Nutritional supplementations and administration considerations for sarcopenia in older adults
For instance, bone disorders and imbalance in calcium homeostasis, renal dysfunction, predisposition to cancer and coronary artery disease are some of the adverse effects mentioned in the literature as consequences of higher than RDA protein consumption [ 56 ]. Future studies looking more in depth in the proper dose and timing of administration of protein and AA are required to establish a practical guideline for prevention and management of sarcopenia in the elderly.
It is important to mention both muscle and bone diseases as they appear to be linked in both direct function and tissue cross-talk Fig. One of these mutual regulators appears to be vitamin D. Research findings showed that vitamin D-responsive hormones that are produced by bone tissue are activated in the presence of vitamin D and in return have positive effects on MPS.
Similar association is seen with vitamin D-responsive factors produced by muscle cells, resulting in positive effect on bone tissue [ 59 ]. Therefore, both muscle and bone strengths have to be considered in order to provide optimum treatment and preventative measures for older adults with sarcopenia.
Following the discovery of vitamin D receptors in human muscle cells, it has been identified that vitamin D may induce MPS through direct initiation of transcription and indirect muscle-bone cross talk mechanism [ 59 ]. In addition to anabolic effects on muscles, vitamin D may also have a role in moderating inflammation in skeletal muscles. For instance, Mastaglia et al. Indeed, lower vitamin D level in the blood was found to be associated with frailty in older adults [ 62 ].
A meta-analysis by Bischoff-Ferrari et al. In fact, sarcopenia in older Koreans was inversely associated with serum vitamin D concentrations [ 64 ]. However, further gender-specific analysis of the KNHANES IV data revealed that blood vitamin D levels tended to have a negative association with sarcopenia only in women 50 years of age or older [ 65 ].
In contrast, Dupuy et al. Although in this study low muscle mass revealed a significant, positive correlation with obesity, malnutrition and decreased handgrip strength, no association was observed between muscle mass and dietary vitamin D intake [ 66 ]. In addition to vitamin D status and intake, the effect of calcium intake on body composition in older adults has been reported in the literature.
Furthermore, calcium status is influenced by blood vitamin D levels, since 1,dihydroxyvitamin D, the active form of vitamin D in the body, binds to vitamin D receptors in the gut and stimulates production of proteins involved in the transluminal transport of calcium in the intestine [ 68 ]. In summary, although, the mechanism of muscle-bone cross-talk is poorly understood, its existence has been prior suspected. Unfortunately, to date there has been no clear randomized clinical trials showing the benefits of vitamin D for sarcopenia.
Nevertheless, supplementation might be effective for protection against loss of musculoskeletal unit and the subsequent complications, such as falls, which lead to immobility and further decrease in lean muscles mass i. Since natural vitamin D requires sun exposure for activation, which may not be feasible in many situations, thus pharmacological supplementation with its active form may be the most efficient way to achieve optimum vitamin D status for most elders.
Since free radicals are unstable and have high chemical reactivity, they can wreak havoc on a wide spectrum of biomolecules including DNA, lipids and proteins. Amongst the various free radicals, reactive oxygen species ROSwhich are derived from oxygen, are of utmost importance in biological systems because of their major production site in the cells, i.How to Prevent Sarcopenia (Age-Related Muscle Loss)
For more information on the generation of ROS and counteraction of cells to oxidative stress during aging the readers are referred to comprehensive literature review such as by Finkel et al. Among various proposed mechanisms in sarcopenia, impairment in mitochondria and increased oxidative stress are strongly supported by the literature [ 76—79 ]. Aging results in reduced content and bioenergetics of mitochondria within skeletal muscle and consequently, oxidative phosphorylation capacity will be diminished in myocytes [ 76, 78 ].
Decreased functionality of mitochondria, not only leads to less adenosine triphosphate ATP production, but also contributes to greater production and release of ROS from mitochondria [ 76 ]. In addition, skeletal muscle mass loss or sarcopenia was observed at 18 months of age. These mice also showed an increase in ROS levels and a decrease in antioxidant enzymes levels in skeletal muscle, indicating a possible role of oxidative damage in sarcopenia [ 80 ].
Cross sectional studies in human subjects also demonstrated that older adults with sarcopenia consume below the RDA for antioxidant nutrients compared to those without sarcopenia [ 81 ]. Hence, strategies aiming at reduction of ROS production or detoxifying them may contribute to reversing the devastating consequences of these compounds. Some researches in the field of sarcopenia have been focused on oxidative stress and treatment strategies using antioxidants. After 7 weeks, fast-twitch epitrochlearis muscles were dissected and further incubated in incremental concentrations of leuicne.
In Aox- groups, addition of leucine increased protein synthesis in adult rats and to a lesser extent in old rats. No significant alteration was observed in adult rats supplemented with the antioxidants; however, MPS response to leucine was enhanced as a result of antioxidant supplementation in old rats. Although, the effect of antioxidants on MPS activation of elements of protein synthesis pathway and inflammatory biomarkers were assessed in this study, the exact mechanism by which antioxidants induce their impacts on the muscle cells was not investigated.
Animal and human bodies possess endogenous antioxidant compounds and enzymes, e. The ability of antioxidants to scavenge ROS prevents further damage to the cell structures notably mitochondria [ 90 ]. Carotenoids; organic pigments abundantly found in plants and vegetables, are supposed to have an inverse association with muscle dysfunction and disability in older adults [ 92 ]. Follow-up study of elderly men and women aged 65 and older for 6 years revealed that lower plasma concentrations of carotenoids were accompanied by greater risk of poor hip, knee and grip muscle strength [ 92 ].
Similar results regarding the relationship between plasma carotenoid levels and hip, knee and grip strengths were also attained from elderly women who participated in a cross-sectional study; in fact, higher carotenoids levels were correlated with better strength measures [ 93 ]. These observational studies suggest that carotenoids may have protective effect against aging-associated muscle function loss. However, further clinical controlled studies are required to demonstrate the beneficial roles of carotenoids in attenuating sarcopenia in older adults.
In addition to carotenoids, vitamins C and E, the antioxidant effect of other dietary nutrients such as resveratrol, has been investigated in the literature. Resveratrol is a member of the polyphenolic compounds, which are known for their antioxidative and anti-inflammatory properties.
Skin of red grapes is the major natural source of resveratrol, but it can also be found in peanuts and berries [ 94 ]. Resveratrol is present in plants and fruits in a small amount, therefore in order to reach the pharmacological doses effective for health related conditions, resveratrol is extracted from Polygonum cuspidatum knotweed as a nutritional supplement [ 95 ].
Nevertheless, there are some discrepancies in the literature regarding antioxidative effect of resveratrol. When Barger et al. Although the duration of this study was long enough to give rise to any beneficial effects of resveratrol, the provided dosage might not be sufficient to initiate the antioxidative impacts of resveratrol. Ingestion of higher doses, Although Jackson et al. However, the resveratrol supplementation regimen did not have any impact on oxidative stress markers and muscle mass [ ].
To assess the effect of resveratrol in aging-associated muscle mass loss, Bennett et al. Although resveratrol was not effective in preventing the plantaris muscle mass loss during loading period, it improved type II, fast-twitch muscle fiber size and muscle mass during the recovery period. This mouse model exhibit chronic inflammation, accelerated muscle mass loss and frailty.
Supplementing these animals with resveratrol for 12 weeks ameliorated tibialis anterior muscle mass loss, reduced protein degradation and rectified the inhibition of anabolic signaling pathway [ ]. Although resveratrol revealed a protective effect against oxidative damage by reducing autophagy and apoptosis, some researchers claim that it was not able to attenuate muscle mass loss in sarcopenia [ ].
In fact month resveratrol supplementation of middle-aged mice was effective in preserving the fast-twitch muscle fiber function and age related oxidative stress, however it could not prevent muscle mass loss in these animals [ ].
Although the result of this study in regard to the effect of resveratrol on muscle mass was in agreement with Joseph et al. Therefore, it is not clear whether the effect of resveratrol is fiber-specific and if so, which fiber types are more responsive to this treatment. More research is required to elucidate the mechanism and role of resveratrol in attenuating muscle mass and function loss in elderly.
Overall, antioxidants provide a promising venue for combating muscle mass loss in sarcopenia, since increased oxidative stress is an inseparable part of this disorder and many other aging-associated conditions. Antioxidants are found in plenty of foods, primarily in vegetables and fruits. It is well known that the bioavailability of antioxidants from vegetable and fruit sources is optimum to maintain defenses against oxidative stress in healthy young people.
As stated earlier in this review, a number of digestive misalignments prevent older adults from optimal nutrient utilization. However, in the case of antioxidants, it appears that older adults benefit from dietary vegetable and fruit consumptions as much as do younger adults.
For instance, Kim, et al. The results of the study showed that after adjustment for all covariates, higher frequency of vegetables, fruits and combined fruits and vegetables consumption was accompanied by lower risk of sarcopenia among older men.
For women, the risk of sarcopenia decreased as the number of servings of fruit per day increased. Although, without a doubt, dietary antioxidant intake is superior to synthetic antioxidants, some older adults might be forced to resort to synthetic supplementation.
A number of studies indicated that there is a difference in bioavailability between different synthetic antioxidants. For instance, pharmacokinetic studies indicate that carotenoids are less bioavailable in the form of a supplement, while synthetic and food-derived vitamin C is relatively comparable . Therefore, unless indicated otherwise, it appears prudent to use dietary therapy rich in vegetables and fruits in efforts to combat sarcopenia-induced oxidative stress.
However, given the anorexia of aging, more research is needed to identify if some older adults might be experiencing significant difficulty consuming sufficient amounts of vegetables and fruits to obtain their beneficial health effects.
Furthermore, more research is required to determine if supplementation with antioxidants could be beneficial adjuvant therapy to AA and proteins for enhancing or maintaining muscle mass and function in aging populations.
One of these possible mechanisms is the increased circulating cytokines and pro-inflammatory markers Fig. In younger muscles, anabolic stimuli affects MPS, outpacing it from MPD and subsequently resulting in increased muscle mass [ ]. Nevertheless, anabolic resistance in aged muscle deranges this equilibrium between MPS and MPD, which leads to gradual loss of muscle mass [ ].
It has been shown that the presence of even low-grade inflammation in aged rats results in irresponsiveness of post-prandial MPS to nutritional stimuli, whereas control non-inflamed counterpart rats have increased MPS after food intake [ ]. In addition, long-term prevention of inflammation with a non-steroidal anti-inflammatory drug e.
Omega-3 fatty acids are polyunsaturated fatty acids PUFA that are essential nutrients with anti-inflammatory properties. Oily fish like salmon is a common source of omega-3 fatty acids, while plant oils such as canola and flaxseed oil also contain omega-3 fatty acids [ ]. A large body of evidence supports the beneficial effects of these omega-3 fatty acids in various clinical conditions including cancers, cardiovascular diseases, inflammatory disorders and cognitive impairments [ ]. Omega-3 fatty acids exert their anti-inflammatory activity through several mechanisms including reduced leukocyte chemotaxis, decreased production of eicosanoids from arachidonic acid, and reduced T-cell reactivity [ ].
Therefore, it has been speculated that older adults with sarcopenia would also benefit from more omega-3 fatty acids consumption, since inflammation is one of the underlying pathophysiological events during the disease process [ 15, ].
Furthermore, it has been shown that the anabolic response of skeletal muscle to AA administration may be enhanced by combining with omega-3 fatty acids supplementation [ 15, ]. In this randomized controlled trial, subjects were assigned to either omega-3 fatty acid or corn oil control group.
The measurements were done at basal, post-absorptive conditions and after administration of hyperaminoacidemic-hyperinsulinemic clamp, before and after supplementation with omega-3 fatty acids and corn oil. Overall, the data from this trial suggested a possible role of omega-3 fatty acids in overcoming the metabolic resistance in skeletal muscle and attenuating muscle mass loss in older adults [ 15 ].
The effect of omega-3 fatty acids on muscles has also been studied beyond the scope of increasing MPS and muscle mass. In fact, consumptions of omega-3 fatty acids have been shown to improve muscle function by enhancing muscle strength and performance [ — ]. Another study by Smith et al. Similarly, dietary assessments of nearly elderly men and women have shown positive associations between fatty fish consumption and grip strength in both genders [ ].
As discussed earlier, one of the hypothesis behind the beneficial effects of omega-3 fatty acids on improvement of muscle mass size and function is primarily thought to be due to reduced inflammatory processes and its associated biomarkers [ ]. To test this theory Cornish et al. At the same time, both groups were completing a resistance-training program. However, male subjects in the placebo group and women in both ALA and placebo group did not show any significant changes in IL-6 concentrations.
The researchers speculated that the lack or minimum effect of omega-3 fatty acid in this study in enhancing muscle mass may be due to the supplemented form, i. That is, flax seed fatty acids Nevertheless, the potential influence of ALA in lowering plasma IL-6 level in older men is promising for future directions toward the treatment of sarcopenia.
Although consumption of fatty fish and plant-based rich sources appears to be reasonable strategies to achieve adequate omega-3 fatty acids supplementation, research shows that dietary intake of omega-3 fatty acids in older adults might be insufficient [ ].
Therefore, more research is needed to identify barriers preventing older adults from consuming substantial amounts of omega-3 fatty acids from natural sources. Sarcopenia is a severe debilitating condition with a progressive, frequently irreversible nature.
A broad range of investigations is required to understand the pathophysiology of this condition in order to find feasible treatment approaches to combat this age-related disorder.
Without a doubt, nutrition plays a central role in attenuating muscle mass loss in aging population, with some research to date highlighting the roles of proteins and AA, vitamin D and calcium, antioxidants and omega-3 fatty acids as some of the most promising nutritional strategies to manage sarcopenia.
Looking in depth into the mechanism of action of each nutrient can assist researchers in perceiving the cellular targets, possible interactions, synergistic or antagonistic effects of these nutritious elements.
To optimize these nutritional strategies, one should also consider the physiological impairments that seemed to accompany aging such as as early onset of satiety in combination with prolonged chewing might significantly diminish the amount of dietary nutrients consumed by an elderly person. Therefore, in efforts to prevent the onset of the sarcopenia or attenuate its progression, early continued nutritional therapies should be considered for older adults in forms of both pharmacological and dietary interventions with reflection of both mechanistic and physiologic aspect of each and all nutrients.
Overall, more research is needed to establish exact age of supplementation initiation, exact amounts for the nutrients of interest, combinations of nutrients, and optimum form and schedule of administration.
Conflict of interest The authors declare no conflicts of interest. The American Journal of Clinical Nutrition. Current opinion in clinical nutrition and metabolic care. Association of vegetables and fruits consumption with sarcopenia in older adults: Sarcopenia in older adults.
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