Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose

Altered skeletal muscle fatty acid (FA) metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males)) and impaired glucose tolerance (IGT; n = 14 (7 males)) by measuring arterio-venous concentration differences across forearm muscle. [²H₂]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG) and free fatty acids (FFA), whereas [U-¹³C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG. Skeletal muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG), FFA, and phospholipid content, their fractional synthetic rate (FSR) and degree of saturation, and gene expression. Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Net skeletal muscle glucose uptake was lower (p = 0.018) and peripheral insulin sensitivity tended to be reduced (p = 0.064) in IGT as compared to IFG subjects. Furthermore, IGT showed higher skeletal muscle extraction of VLDL-TAG (p = 0.043), higher muscle TAG content (p = 0.025), higher saturation of FFA (p = 0.004), lower saturation of TAG (p = 0.017) and a tendency towards a lower TAG FSR (p = 0.073) and a lower saturation of DAG (p = 0.059) versus IFG individuals. Muscle oxidative gene expression was lower in IGT subjects. In conclusion, increased liver-derived TAG extraction and reduced lipid turnover of saturated FA, rather than DAG content, in skeletal muscle accompany the more pronounced insulin resistance in IGT versus IFG subjects.     

重复性饥饿再投喂对大鼠UCP-2、3表达影响

目的探讨幼鼠和成年大鼠重复性饥饿再投喂饲喂方式处理后,解偶联蛋白(UCPs)mRNA表达变化。方法设计重复性饥饿1 d/再投喂1 d,持续6周的饲喂方式处理幼鼠和成鼠,比较体重、Lee's指数,检测血糖、游离脂肪酸(FFA)和胆碱酯酶(CHE)含量,白色脂肪组织UCP 2 mRNA和肌肉组织UCP 3 mRNA表达水平。结果饥饿再投喂组幼鼠和成年大鼠体重分别为(243.73±17.66)、(261.12±19.51)g,明显低于对照组幼鼠(375.36±21.12)g和成年大鼠(396±18.14)g(P<0.01);与对照组比较,饥饿再投喂大鼠血清FFA升高(P<0.05),成年大鼠血糖含量降低(P<0.05);分别与幼鼠对照组与饥饿再投喂组大鼠比较,成鼠血清CHE含量明显升高(P<0.01)。与对照组比较,饥饿再投喂组大鼠白色脂肪组织UCP 2 mRNA表达升高(P<0.05);与幼鼠对照组比较,成年对照组大鼠白色脂肪组织UCP 2 mRNA表达降低(P<0.05);与饥饿再投喂幼鼠比较,饥饿再投喂组成年大鼠白色脂肪组织UCP 2 mRNA表达升高(P<0.05)。结论重复性饥饿再投喂处理能使大鼠白色脂肪组织UCP 2 mRNA的表达水平升高,提高大鼠基础能量代谢率。     

Dietary Protein Requirement Threshold and Micronutrients Profile in Healthy Older Women Based on Relative Skeletal Muscle Mass

Although multiple nutrients have shown protective effects with regard to preserving muscle function, the recommended amount of dietary protein and other nutrients profile on older adults for maintenance of high muscle mass is still debatable. The aims of this paper were to: (1) identify dietary differences between older women with low and high relative skeletal muscle mass, and (2) identify the minimal dietary protein intake associated with high relative skeletal muscle mass and test the threshold ability to determine an association with skeletal muscle phenotypes. Older women (n = 281; 70 ± 7 years, 65 ± 14 kg), with both low and high relative skeletal muscle mass groups, completed a food questionnaire. Skeletal muscle mass, fat-free mass (FFM), biceps brachii thickness, vastus lateralis anatomical cross-sectional area (VL_ACSA), handgrip strength (HGS), maximum elbow flexion torque (MVC_EF), maximum knee extension torque (MVC_KE), muscle quality (HGS/Body mass), and fat mass were measured. Older women with low relative skeletal muscle mass had a lower daily intake of protein, iodine, polyunsaturated fatty acid (PUFA), Vit E, manganese, milk, fish, nuts and seeds (p < 0.05) compared to women with high relative skeletal muscle mass. The minimum required dietary protein intake for high relative skeletal muscle mass was 1.17 g/kg body mass/day (g/kg/d) (sensitivity: 0.68; specificity: 0.62). Women consuming ≥1.17 g/kg/d had a lower BMI (B = −3.9, p < 0.001) and fat mass (B = −7.8, p < 0.001), and a higher muscle quality (B = 0.06, p < 0.001). The data indicate that to maintain muscle mass and function, older women should consume ≥1.17 g/kg/d dietary protein, through a varied diet including milk, fish and nuts that also contain polyunsaturated fatty acid (PUFA) and micronutrients such as iodine, Vit E and manganese.     

Protein Source and Muscle Health in Older Adults: A Literature Review

Research shows that higher dietary protein of up to 1.2 g/kg_bodyweight/day may help prevent sarcopenia and maintain musculoskeletal health in older individuals. Achieving higher daily dietary protein levels is challenging, particularly for older adults with declining appetites and underlying health conditions. The negative impact of these limitations on aging muscle may be circumvented through the consumption of high-quality sources of protein and/or supplementation. Currently, there is a debate regarding whether source of protein differentially affects musculoskeletal health in older adults. Whey and soy protein have been used as the most common high-quality proteins in recent literature. However, there is growing consumer demand for additional plant-sourced dietary protein options. For example, pea protein is rapidly gaining popularity among consumers, despite little to no research regarding its long-term impact on muscle health. Therefore, the objectives of this review are to: (1) review current literature from the past decade evaluating whether specific source(s) of dietary protein provide maximum benefit to muscle health in older adults; and (2) highlight the need for future research specific to underrepresented plant protein sources, such as pea protein, to then provide clearer messaging surrounding plant-sourced versus animal-sourced protein and their effects on the aging musculoskeletal system.     

Camphene Attenuates Skeletal Muscle Atrophy by Regulating Oxidative Stress and Lipid Metabolism in Rats

Sarcopenia- or cachexia-related muscle atrophy is due to imbalanced energy metabolism and oxidative stress-induced muscle dysfunction. Monoterpenes play biological and pharmacological reactive oxygen species (ROS) scavenging roles. Hence, we explored the effects of camphene, a bicyclic monoterpene, on skeletal muscle atrophy in vitro and in vivo. We treated L6 myoblast cells with camphene and then examined the ROS-related oxidative stress using Mito Tracker^TM Red FM and anti-8-oxoguanine antibody staining. To investigate lipid metabolism, we performed real-time polymerase chain reactions, holotomographic microscopy, and respiratory gas analysis. Rat muscle atrophy in in vivo models was observed using ¹⁸F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography and immunocytochemistry. Camphene reversed the aberrant cell size and muscle morphology of L6 myoblasts under starvation and in in vivo models. Camphene also attenuated E3 ubiquitin ligase muscle RING-finger protein-1, mitochondrial fission, and 8-oxoguanine nuclear expression in starved myotubes and hydrogen peroxide (H₂O₂)-treated cells. Moreover, camphene significantly regulated lipid metabolism in H₂O₂-treated cells and in vivo models. These findings suggest that camphene may potentially affect skeletal muscle atrophy by regulating oxidative stress and lipid metabolism.     

Dietary Protein and Resistance Training Effects on Muscle and Body Composition in Older Persons

The regular performance of resistance exercises and the habitual ingestion of adequate amounts of dietary protein from high-quality sources are two important ways for older persons to slow the progression of and treat sarcopenia, the age-related loss of skeletal muscle mass and function. Resistance training can help older people gain muscle strength, hypertrophy muscle, and increase whole body fat-free mass. It can also help frail elderly people improve balance and physical functioning capabilities. Inadequate protein intake will cause adverse metabolic and physiological accommodation responses that include the loss of fat-free mass and muscle strength and size. Findings from controlled feeding studies show that older persons retain the capacity to metabolically adjust to lower protein intakes by increasing the efficiency of nitrogen retention and amino acid utilization. However, they also suggest that the recommended dietary allowance of 0.8 g protein · kg^?1 · d^?1 might not be sufficient to prevent subtle accommodations and blunt desired changes in body composition and muscle size with resistance training. Most of the limited research suggests that resistance training-induced improvements in body composition, muscle strength and size, and physical functioning are not enhanced when older people who habitually consume adequate protein (modestly above the RDA) increase their protein intake by either increasing the ingestion of higher-protein foods or consuming protein-enriched nutritional supplements.     

Determining the Influence of Habitual Dietary Protein Intake on Physiological Muscle Parameters in Youth and Older Age

Protein ingestion is a potent stimulator of skeletal muscle protein synthesis (MPS). However, older adults demonstrate resistance to anabolic stimuli. Some evidence has demonstrated that a larger acute protein dose is required in older compared to younger adults to elicit the same synthetic response, suggesting that older adults should be consuming higher habitual dietary protein to optimise muscle mass. However, limited research has explored dietary habits in different age groups or the relationship between habitual dietary intake and mechanistic physiological parameters associated with muscle mass and function. This work investigated the effect of habitual dietary intake in young (n = 10, 25.9 (3.2y)) and older (n = 16, 70.2 (3.2y)) community-dwelling adults (16:10 male: female) on physiological muscle parameters. Dietary intake was assessed using four-day diet diaries. Post-absorptive MPS and MPS responses to feeding (4.25x basal metabolic rate; 16% protein) were determined in muscle biopsies of the m. vastus lateralis via stable isotope tracer ([1, 2⁻¹³C₂]-leucine) infusions with mass-spectrometric analyses. Body composition was measured by dual-energy x-ray absorptiometry. Whole body strength was assessed via 1-repetition maximum assessments. No significant differences in habitual dietary intake (protein, fat, carbohydrate and leucine as g.kgWBLM⁻¹.day⁻¹) were observed between age groups. Whole-body lean mass (61.8 ± 9.9 vs. 49.8 ± 11.9 kg, p = 0.01) and knee-extensor strength (87.7 ± 28.3 vs. 56.8 ± 16.4 kg, p = 0.002) were significantly higher in young adults. Habitual protein intake (g.kg⁻¹.day⁻¹) was not associated with whole-body lean mass, upper-leg lean mass, whole-body strength, knee-extensor strength, basal MPS or fed-state MPS across both age groups. These findings suggest that differences in muscle mass and strength parameters between youth and older age are not explained by differences in habitual dietary protein intake. Further research with a larger sample size is needed to fully explore these relationships and inform on interventions to mitigate sarcopenia development.     

Pea Proteins Have Anabolic Effects Comparable to Milk Proteins on Whole Body Protein Retention and Muscle Protein Metabolism in Old Rats

Plant proteins are attracting rising interest due to their pro-health benefits and environmental sustainability. However, little is known about the nutritional value of pea proteins when consumed by older people. Herein, we evaluated the digestibility and nutritional efficiency of pea proteins compared to casein and whey proteins in old rats. Thirty 20-month-old male Wistar rats were assigned to an isoproteic and isocaloric diet containing either casein (CAS), soluble milk protein (WHEY) or Pisane™ pea protein isolate for 16 weeks. The three proteins had a similar effect on nitrogen balance, true digestibility and net protein utilization in old rats, which means that different protein sources did not alter body composition, tissue weight, skeletal muscle protein synthesis or degradation. Muscle mitochondrial activity, inflammation status and insulin resistance were similar between the three groups. In conclusion, old rats used pea protein with the same efficiency as casein or whey proteins, due to its high digestibility and amino acid composition. Using these plant-based proteins could help older people diversify their protein sources and more easily achieve nutritional intake recommendations.     

Enhanced Glutamine Availability Exerts Different Effects on Protein and Amino Acid Metabolism in Skeletal Muscle From Healthy and Septic Rats

Background: Enhanced glutamine (GLN) intake may affect the catabolism of branched‐chain amino acids (BCAAs; valine, leucine, and isoleucine), which play a regulatory role in protein turnover. We examined the effects of enhanced GLN availability on leucine oxidation, amino acid concentrations, and protein metabolism in muscles from healthy and septic rats. Methods: Cecal ligation and puncture were used as a model of sepsis. Twenty‐four hours after surgery, the soleus (SOL, red muscle) and the extensor digitorum longus (EDL, white muscle) were incubated in medium containing 0.5 or 2.0 mM GLN. Protein breakdown, protein synthesis, and leucine oxidation were determined via 3‐methylhistidine release, muscle L‐[1‐¹⁴C]leucine radioactivity, and the radioactivity of released ¹⁴CO₂, respectively. Results: In muscles from septic animals, increased proteolysis and leucine oxidation and decreased protein synthesis were detected. These effects were more pronounced in the EDL. In septic muscles, the addition of GLN decreased leucine oxidation in both muscles and increased protein synthesis in the EDL. In muscles from untreated animals, decreased leucine oxidation after the addition of GLN to the medium was associated with decreased protein synthesis in the SOL and decreased concentrations of serine, glycine, histidine, alanine, arginine, proline, and lysine in both muscles. Conclusions: White muscle fibers are more sensitive to septic stimuli than red fibers are. In sepsis, enhanced GLN intake may ameliorate GLN deficiency, inhibit BCAA catabolism, and stimulate protein synthesis. In the healthy state, surplus of GLN may lead to severe alterations in the intramuscular concentration of several amino acids and impair protein synthesis.     

Dietary Cocoa Flavanols Enhance Mitochondrial Function in Skeletal Muscle and Modify Whole-Body Metabolism in Healthy Mice

Mitochondrial dysfunction is widely reported in various diseases and contributes to their pathogenesis. We assessed the effect of cocoa flavanols supplementation on mitochondrial function and whole metabolism, and we explored whether the mitochondrial deacetylase sirtuin-3 (Sirt3) is involved or not. We explored the effects of 15 days of CF supplementation in wild type and Sirt3^-/- mice. Whole-body metabolism was assessed by indirect calorimetry, and an oral glucose tolerance test was performed to assess glucose metabolism. Mitochondrial respiratory function was assessed in permeabilised fibres and the pyridine nucleotides content (NAD⁺ and NADH) were quantified. In the wild type, CF supplementation significantly modified whole-body metabolism by promoting carbohydrate use and improved glucose tolerance. CF supplementation induced a significant increase of mitochondrial mass, while significant qualitative adaptation occurred to maintain H₂O₂ production and cellular oxidative stress. CF supplementation induced a significant increase in NAD⁺ and NADH content. All the effects mentioned above were blunted in Sirt3^-/- mice. Collectively, CF supplementation boosted the NAD metabolism that stimulates sirtuins metabolism and improved mitochondrial function, which likely contributed to the observed whole-body metabolism adaptation, with a greater ability to use carbohydrates, at least partially through Sirt3.     

Effects of Omega-3 Supplementation Alone and Combined with Resistance Exercise on Skeletal Muscle in Older Adults: A Systematic Review and Meta-Analysis

Sarcopenia negatively affects skeletal muscle mass and function in older adults. Omega-3 (ω-3) fatty acid supplementation, with or without resistance exercise training (RET), is suggested to play a role as a therapeutic component to prevent or treat the negative effects of sarcopenia. A systematic review and meta-analysis were conducted on the impact of ω-3 fatty acid supplementation with or without RET on measures of muscle mass and function in older adults (≥55 y). The data sources included SPORTDiscus, PubMed, and Medline. All the study types involving ω-3 fatty acid supplementation on measures of muscle mass and function in older adults (without disease) were included. The mean differences (MDs) or standardized mean differences (SMDs) with 95% confidence intervals were calculated and pooled effects assessed. Sixteen studies (1660 females, 778 males) met our inclusion criteria and were included in the meta-analysis. ω-3 fatty acid supplementation did not impact lean tissue mass (SMD 0.09 [−0.10, 0.28]). Benefits were observed for lower body strength (SMD 0.54 [0.33, 0.75]), timed-up-and-go (MD 0.29 [0.23, 0.35]s), and 30-s sit-to-stand performance (MD 1.93 [1.59, 2.26] repetitions) but not walking performance (SMD −0.01 [−0.10, 0.07]) or upper body strength (SMD 0.05 [−0.04, 0.13]). Supplementing with ω-3 fatty acids may improve the lower-body strength and functionality in older adults.     

Breakfast Protein Quality and Muscle Strength in Japanese Older Adults: A Community-Based Longitudinal Study

ObjectivesThe amount of breakfast protein intake is important for maintaining muscle strength. However, the effect of breakfast protein quality (ie, bioavailability) remains unclear. We investigated the association between breakfast protein quality and the incidence of muscle weakness.DesignLongitudinal study.Setting and ParticipantsHealthy older adults age 60–83 years without stroke, arthritis, Parkinson disease, or muscle weakness at baseline (maximum follow-up period and participations were 9.2 years and 5 times, respectively).MethodsWeakness was defined by the Asian Working Group for Sarcopenia 2019 criteria, using grip strength. Breakfast protein quality was evaluated using the protein digestibility–corrected amino acid score (PDCAAS), where higher scores represent higher quality, calculated from 3-day dietary records. Participants were classified according to sex-stratified tertiles of breakfast PDCAAS (ie, low to high groups). The association between PDCAAS and incident weakness was analyzed using the generalized estimating equation, after adjusting for sex, age, follow-up time, grip strength, body mass index, physical activity, cognition, education, smoking, economics, medical history, lunch and dinner PDCAASs, and energy and protein intake during 3 regular meals at baseline.ResultsOverall, 14.4% of the initial sample was excluded owing to a diagnosis of weakness-related diseases, and 58.3% (n = 701) had at least 1 follow-up measurement for inclusion in the analysis. The mean ± SD follow-up period was 6.9 ± 2.1 years; the cumulative number of participants was 3019, and 282 developed weakness. Using the low PDCAAS group as the reference, the adjusted odds ratios (95% CIs) for incident weakness in the middle and high PDCAAS groups were 0.71 (0.43–1.18) and 0.50 (0.29–0.86), respectively.Conclusions and ImplicationsHigher breakfast protein quality was associated with a reduction in incident weakness in older adults, independent of protein intake. These findings may highlight the role of protein quality for muscle health in older adults.     

Meta-Analysis Examining the Importance of Creatine Ingestion Strategies on Lean Tissue Mass and Strength in Older Adults

Creatine supplementation in conjunction with resistance training (RT) augments gains in lean tissue mass and strength in aging adults; however, there is a large amount of heterogeneity between individual studies that may be related to creatine ingestion strategies. Therefore, the purpose of this review was to (1) perform updated meta-analyses comparing creatine vs. placebo (independent of dosage and frequency of ingestion) during a resistance training program on measures of lean tissue mass and strength, (2) perform meta-analyses examining the effects of different creatine dosing strategies (lower: ≤5 g/day and higher: >5 g/day), with and without a creatine-loading phase (≥20 g/day for 5–7 days), and (3) perform meta-analyses determining whether creatine supplementation only on resistance training days influences measures of lean tissue mass and strength. Overall, creatine (independent of dosing strategy) augments lean tissue mass and strength increase from RT vs. placebo. Subanalyses showed that creatine-loading followed by lower-dose creatine (≤5 g/day) increased chest press strength vs. placebo. Higher-dose creatine (>5 g/day), with and without a creatine-loading phase, produced significant gains in leg press strength vs. placebo. However, when studies involving a creatine-loading phase were excluded from the analyses, creatine had no greater effect on chest press or leg press strength vs. placebo. Finally, creatine supplementation only on resistance training days significantly increased measures of lean tissue mass and strength vs. placebo.     

Ultrasonography to Measure Swallowing Muscle Mass and Quality in Older Patients With Sarcopenic Dysphagia

Background

Sarcopenic dysphagia is characterized by difficulty swallowing due to a loss of whole-body skeletal and swallowing muscle mass and function. However, no study has reported on swallowing muscle mass and quality in patients with sarcopenic dysphagia.

胰岛素受体底物和酪氨酸磷酸酶在 2 型糖尿病大鼠肌肉组织中的蛋白表达及其意义

目的研究2型糖尿病对胰岛素产生抵抗的分子机制。方法用Western杂交检测2型糖尿病模型(OLETF大鼠)肌肉组织内IRS-1及SH-PTP2的蛋白表达水平,并以同种属的Wistar大鼠做比较。结果OLETF糖尿病大鼠的空腹和餐后血糖水平较对照组明显增高(P<0.05);Western杂交显示OLETF大鼠肌肉组织内IRS-1蛋白表达较对照组减少(P<0.05);而SH-PTP2的蛋白表达则较对照组增加(P<0.05)。结论IRS-1及SH-PTP2蛋白表达的异常改变,可能是引起2型糖尿病产生胰岛素抵抗的分子机制之一。     

Efficacy of Creatine Supplementation Combined with Resistance Training on Muscle Strength and Muscle Mass in Older Females: A Systematic Review and Meta-Analysis

Sarcopenia refers to the age-related loss of muscle strength and muscle mass, which is associated with a reduced quality of life, particularly in older females. Resistance training (RT) is well established to be an effective intervention to counter indices of sarcopenia. Accumulating research indicates that the addition of creatine supplementation (Cr) to RT augments gains in muscle strength and muscle mass, compared to RT alone. However, some evidence indicates that sex differences may alter the effectiveness of Cr. Therefore, we systematically reviewed randomized controlled trials (RCTs) investigating the efficacy of Cr + RT on measures of upper- and lower-body strength and muscle mass in older females. A systematic literature search was performed in nine electronic databases. Ten RCTs (N = 211 participants) were included the review. Overall, Cr significantly increased measures of upper-body strength (7 studies, n = 142, p = 0.04), with no effect on lower-body strength or measures of muscle mass. Sub-analyses revealed that both upper-body (4 studies, n = 97, p = 0.05) and lower-body strength (4 studies, n = 100, p = 0.03) were increased by Cr, compared to placebo in studies ≥ 24 weeks in duration. In conclusion, older females supplementing with Cr experience significant gains in muscle strength, especially when RT lasts for at least 24 weeks in duration. However, given the level of evidence, future high-quality studies are needed to confirm these findings.     

Cannabidiol (CBD) Dosing: Plasma Pharmacokinetics and Effects on Accumulation in Skeletal Muscle,Liver and Adipose Tissue

Oral cannabidiol (CBD) consumption is widespread in North America and Europe, as it has analgesic, neuroprotective and antitumor effects. Although oral CBD consumption in humans affords beneficial effects in epileptic and inflammatory states, its pharmacokinetics and subsequent uptake into tissue are largely unknown. This study investigated plasma pharmacokinetics and accumulation of CBD in gastrocnemius muscle, liver and adipose tissue in adult rats following oral gavage. CBD was fed relative to body mass at 0 (control), 30, 115, or 230 mg/Kg/day for 28 days; with 6 males and 6 females per dosing group. Pharmacokinetics were assessed on day 1 and day 28 in the group receiving CBD at 115 mg/Kg/day. The rise in tissue CBD was closely related to specific pharmacokinetic parameters, and adipose tissue levels were ~10 to ~100 fold greater than liver or muscle. Tissue CBD levels were moderately correlated between adipose and muscle, and adipose and liver, but were highly correlated for liver and muscle. CBD feeding resulted in several gender-specific effects, including changes in pharmacokinetics, relationships between pharmacokinetic parameters and tissue CBD and differences in tissue CBD levels. CBD accumulation in mammalian tissues has the potential to influence receptor binding and metabolism; therefore, the present findings may have relevance for developing oral dosing regimens.     

Maintenance of Skeletal Muscle to Counteract Sarcopenia in Patients with Advanced Chronic Kidney Disease and Especially Those Undergoing Hemodialysis

Life extension in modern society has introduced new concepts regarding such disorders as frailty and sarcopenia, which has been recognized in various studies. At the same time, cutting-edge technology methods, e.g., renal replacement therapy for conditions such as hemodialysis (HD), have made it possible to protect patients from advanced lethal chronic kidney disease (CKD). Loss of muscle and fat mass, termed protein energy wasting (PEW), has been recognized as prognostic factor and, along with the increasing rate of HD introduction in elderly individuals in Japan, appropriate countermeasures are necessary. Although their origins differ, frailty, sarcopenia, and PEW share common components, among which skeletal muscle plays a central role in their etiologies. The nearest concept may be sarcopenia, for which diagnosis techniques have recently been reported. The focus of this review is on maintenance of skeletal muscle against aging and CKD/HD, based on muscle physiology and pathology. Clinically relevant and topical factors related to muscle wasting including sarcopenia, such as vitamin D, myostatin, insulin (related to diabetes), insulin-like growth factor I, mitochondria, and physical inactivity, are discussed. Findings presented thus far indicate that in addition to modulation of the aforementioned factors, exercise combined with nutritional supplementation may be a useful approach to overcome muscle wasting and sarcopenia in elderly patients undergoing HD treatments.