Polygonatum sibiricum polysaccharide ameliorates skeletal muscle aging via mitochondria-associated membrane-mediated calcium homeostasis regulation.

BACKGROUND: Sarcopenia, an age-related disease, is characterized by a gradual loss of muscle mass, strength, and function. It has been linked to abnormal organelle function in myotubes, including the mitochondria and endoplasmic reticulum (ER). Recent studies revealed that mitochondria-associated membranes (MAM), the sites connecting mitochondria and the ER, may be implicated in skeletal muscle aging. In this arena, the potential of Polygonatum sibiricum polysaccharide (PSP) emerges as a beacon of hope. PSP, with its remarkable antioxidant and anti-senescence properties, is on the cusp of a therapeutic revolution, offering a promising strategy to mitigate the impacts of sarcopenia. PURPOSE: The objective of this research is to explore the effects of PSP on age-related muscle dysfunction and the underlying mechanisms involved both in vivo and in vitro. METHODS: In this investigation, we used in vitro experiments using D-galactose (D-gal)-induced aging in C2C12 myotubes and in vivo experiments on aged mice. Key indices were assessed, including reactive oxygen species (ROS) levels, mitochondrial function, the expression of aging-related markers, and the key proteins of mitochondria and MAM fraction. Differentially expressed genes (DEGs) related to mitochondria and ER were identified, and bioinformatic analyses were performed to explore underlying mechanisms. Muscle mass and function were determined to evaluate the quantity and quality of skeletal muscle in vivo. RESULTS: PSP treatment effectively mitigated oxidative stress and mitochondrial malfunction caused by D-gal in C2C12 myotubes, preserving mitochondrial fitness and reducing MAM formation. Besides, PSP attenuated D-gal-induced increases in Ca2+ concentrations intracellularly by modulating the calcium-related proteins, which were also confirmed by gene ontology (GO) analysis of DEGs. In aged mice, PSP increased muscle mass and improved grip strength, hanging time, and other parameters while reducing ROS levels and increasing antioxidant enzyme activities in skeletal muscle tissue. CONCLUSION: PSP offers protection against age-associated muscle impairments. The proposed mechanism suggests that modulation of calcium homeostasis via regulation of the MAM results in a favorable functional outcome during skeletal muscle aging. The results of this study highlight the prospect of PSP as a curative intervention for sarcopenia and affiliated pathological conditions, warranting further investigation.

Active vitamin D treatment in the prevention of sarcopenia in adults with prediabetes (DPVD ancillary study): a randomised controlled trial.

BACKGROUND: Observational studies show inverse associations between serum 25-hydroxyvitamin D concentrations and sarcopenia incidence; however, it remains unclear whether treatment with vitamin D prevents its development. We aimed to assess whether treatment with active vitamin D (eldecalcitol [0·75 µg per day]) can reduce the development of sarcopenia among adults with prediabetes. METHODS: This randomised, double-blind, placebo-controlled, multicenter trial as an ancillary study was conducted at 32 clinics and hospital sites in Japan. Participants were assigned (1:1) by using a central randomisation method in which a randomisation list was made for each hospital separately using a stratified permuted block procedure. The primary endpoint was sarcopenia incidence during 3 years in the intention-to-treat population defined as weak handgrip strength (<28 kg for men and <18 kg for women) and low appendicular skeletal muscle index (<7·0 kg/m2 for men and <5·7 kg/m2 for women in bioelectrical impedance analysis). Although the usual criterion of hypercalcaemia was 10·4 mg/dL (2·6 mmol/L) or higher, hypercalcaemia that was enough to discontinue the study was defined as 11·0 mg/dL or higher. This study is registered with the UMIN clinical trials registry, UMIN000005394. FINDINGS: A total of 1094 participants (548 in the eldecalcitol group and 546 in the placebo group; 44·2% [484 of 1094] women; mean age 60·8 [SD 9·2] years) were followed up for a median of 2·9 (IQR 2·8-3·0) years. Eldecalcitol treatment as compared with placebo showed statistically significant preventive effect on sarcopenia incidence (25 [4·6%] of 548 participants in the eldecalcitol group and 48 [8·8%] of 546 participants in the placebo group; hazard ratio 0·51; 95% CI 0·31 to 0·83; p=0·0065). The incidence of adverse events did not differ between the two groups. INTERPRETATION: We found that treatment with eldecalcitol has the potential to prevent the onset of sarcopenia among people with prediabetes via increasing skeletal muscle volume and strength, which might lead to a substantial risk reduction of falls. FUNDING: Kitakyushu Medical Association. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

Systematic review and meta-analysis of nutrient supplements for treating sarcopenia in people with chronic obstructive pulmonary disease.

Individuals with chronic obstructive pulmonary disease (COPD) are prone to malnutrition and sarcopenia as a result of nutritional deficiencies and increased energy metabolism. However, the effects of nutrient supplements (NS) on treating sarcopenia in patients with COPD are not well established from systematic evidence. This meta-analysis examined the effect of NS on sarcopenia in patients with COPD. A systematic search of multiple databases was conducted, and 29 randomized controlled trials involving 1625 participants (age, mean [SD] = 67.9 [7.8] years) were analyzed. NS demonstrated significant improvements in body weight (MD,1.33 kg; 95% CI, 0.60, 2.05 kg; P = 0.0003; I2 = 87%), fat-free mass index (MD, 0.74 kg/m2; 95% CI, 0.21, 1.27 kg/m2; P = 0.007; I2 = 75%), and 6-min walk test (MD, 19.43 m; 95% CI, 4.91, 33.94 m; P = 0.009; I2 = 81%) compared with control. However, NS had nonsignificant effects on handgrip strength (SMD, 0.36; 95% CI, - 0.15, 0.88; P = 0.16; I2 = 87%) and quadriceps muscle strength (SMD, 0.11; 95% CI, -  0.06, 0.27; P = 0.20; I2 = 25%) compared with the control. In conclusion, NS may be an effective treatment for improving body composition and physical performance in COPD. Future studies should explore the effects of intervention durations, specific NS types, or combined training in patients with COPD and sarcopenia.

Pathophysiological-Based Nutritional Interventions in Cirrhotic Patients with Sarcopenic Obesity: A State-of-the-Art Narrative Review.

In recent decades, following the spread of obesity, metabolic dysfunction has come to represent the leading cause of liver disease. The classical clinical presentation of the cirrhotic patient has, therefore, greatly changed, with a dramatic increase in subjects who appear overweight or obese. Due to an obesogenic lifestyle (lack of physical activity and overall malnutrition, with an excess of caloric intake together with a deficit of proteins and micronutrients), these patients frequently develop a complex clinical condition defined as sarcopenic obesity (SO). The interplay between cirrhosis and SO lies in the sharing of multiple pathogenetic mechanisms, including malnutrition/malabsorption, chronic inflammation, hyperammonemia and insulin resistance. The presence of SO worsens the outcome of cirrhotic patients, affecting overall morbidity and mortality. International nutrition and liver diseases societies strongly agree on recommending the use of food as an integral part of the healing process in the comprehensive management of these patients, including a reduction in caloric intake, protein and micronutrient supplementation and sodium restriction. Based on the pathophysiological paths shared by cirrhosis and SO, this narrative review aims to highlight the nutritional interventions currently advocated by international guidelines, as well as to provide hints on the possible role of micronutrients and nutraceuticals in the treatment of this multifaceted clinical condition.

Impact of Chinese herbal medicine on sarcopenia in enhancing muscle mass, strength, and function: A systematic review and meta-analysis of randomized controlled trials.

Sarcopenia has become important to the public health with the increase in the aging population in society. However, the therapeutic effects of conventional approaches, including pharmacotherapy, exercise, and nutritional intervention, are far from satisfactory. Chinese herbal medicine is a new treatment format with interesting possibilities in sarcopenia has been widely practiced. The study aims to explore the effectiveness of Chinese herbal medicine in sarcopenia. We comprehensively searched the following electronic databases: Medline, EMBASE, APA PsycInfo, Cochrane Library, Web of Science, PubMed, and Chinese database from the establishment of the database to December 2022 (no language restrictions). Randomized controlled clinical studies on the use of Chinese herbal medicine in sarcopenia were selected in compliance with PRISMA guidelines. Review Manager and Stata were used for statistical analysis and the mean difference and standardized mean difference were adopted. Of 277 identified studies, 17 were eligible and included in our analysis (N = 1440 participants). The results showed that Chinese herbal medicine can improve total efficiency (RR = 1.29, 95% CI [1.21, 1.36], p < 0.00001) in sarcopenia and enhance muscle mass (SMD = 1.02, 95% CI [0.55, 1.50], p < 0.0001), and muscle strength measured by grip strength (SMD = 0.66, 95% CI [0.36, 0.96], p < 0.0001), measured by 60°/s knee extension peak TQ (MD = 5.63, 95% CI [-0.30, 11.57], p = 0.06) and muscle function measured by 6-meter walking speed (SMD = 1.34, 95% CI [0.60, 2.08], p = 0.0004), measured by the short physical performance battery of 1.50%, 95% CI (1.05, 1.95), measured by the EuroQoL 5-dimension of (SMD = 0.27, 95% CI [-0.10, 0.65], p = 0.16), suggesting that Chinese herbal medicine alone or combined with conventional treatment has ameliorating effect on sarcopenia. Chinese herbal medicine is a potential therapeutic strategy in sarcopenia. The funnel plot and Egger's test indicated publication bias. To confirm our conclusions, further high-quality studies should be conducted.

Branched-chain amino acid supplementation does not improve measures of sarcopenia in cirrhosis: results of a randomised controlled trial.

BACKGROUND: Sarcopenia is associated with adverse outcomes in cirrhosis. Branched-chain amino acids (BCAA) target several pathways that lead to muscle loss in this population. AIMS: We aimed to evaluate the impact of BCAA supplementation on sarcopenia measures in patients with cirrhosis. METHODS: We conducted a 12-month double-blinded, randomised, controlled trial of BCAA supplementation (30 g daily) compared to an equicaloric, equi-nitrogenous whey protein in volunteers with cirrhosis and reduced muscle strength. The primary endpoint was an increase in grip strength and upper limb lean mass measured on DEXA. Mean-adjusted differences (MAD, 95% CI) between groups at 6 and 12 months are reported as treatment effect using a linear mixed model for repeated measures. RESULTS: A total of 150 volunteers entered the trial (74 BCAA, 76 control), with a median age of 58 years [IQR 48; 63] and MELD of 14 [12; 17]. At 12 months, 57% in the BCAA arm and 61% in the control arm met the primary endpoint (p = 0.80). No significant between-group difference was found in grip strength (MAD -0.15 kg [-0.37; 0.06], p = 0.29) or upper limb lean mass (1.7 kg [-0.2; 3.6], p = 0.22) at 12 months. No significant differences in other body composition parameters, physical performance, frailty, rates of hospitalisation or mortality were found between the BCAA and the control group. Fatigue improved across the entire cohort, without significant between-group differences. 15% of volunteers reported side effects, with distaste higher in the BCAA arm (p = 0.045). CONCLUSION: BCAA supplementation did not improve measures of muscle strength, mass or performance or physical frailty compared to a whey protein supplement in a randomised controlled setting. ACTRN12618000802202.

Ashwagandha Ethanol Extract Attenuates Sarcopenia-Related Muscle Atrophy in Aged Mice.

The investigation focused on the impact of Withania somnifera (ashwagandha) extract (WSE) on age-related mechanisms affecting skeletal muscle sarcopenia-related muscle atrophy in aged mice. Beyond evaluating muscular aspects, the study explored chronic low-grade inflammation, muscle regeneration, and mitochondrial biogenesis. WSE administration, in comparison to the control group, demonstrated no significant differences in body weight, diet, or water intake, affirming its safety profile. Notably, WSE exhibited a propensity to reduce epidermal and abdominal fat while significantly increasing muscle mass at a dosage of 200 mg/kg. The muscle-to-fat ratio, adjusted for body weight, increased across all treatment groups. WSE administration led to a reduction in the pro-inflammatory cytokines TNF-α and IL-1ß, mitigating inflammation-associated muscle atrophy. In a 12-month-old mouse model equivalent to a 50-year-old human, WSE effectively preserved muscle strength, stabilized grip strength, and increased muscle tissue weight. Positive effects were observed in running performance and endurance. Mechanistically, WSE balanced muscle protein synthesis/degradation, promoted fiber differentiation, and enhanced mitochondrial biogenesis through the IGF-1/Akt/mTOR pathway. This study provides compelling evidence for the anti-sarcopenic effects of WSE, positioning it as a promising candidate for preventing sarcopenia pending further clinical validation.

Steamed Ginseng Berry Powder Ameliorates Skeletal Muscle Atrophy via Myogenic Effects.

Sarcopenia is an age-related loss of muscle mass and function for which there is no approved pharmacological treatment. We tested direct efficacy by evaluating grip strength improvement in a sarcopenia mouse model rather than drug screening, which inhibits specific molecular mechanisms. Various physiological functions of ginseng berries are beneficial to the human body. The present study aimed to evaluate the efficacy and safety of steamed ginseng berry powder (SGBP). SGBP administration increased myotube diameter and suppressed the mRNA expression of sarcopenia-inducing molecules. SGBP also reduced the levels of inflammatory transcription factors and cytokines that are known to induce sarcopenia. Oral administration of SGBP improved muscle mass and physical performance in a mouse model of sarcopenia. In summary, our data suggest that SGBP is a novel therapeutic candidate for the amelioration of muscle weakness, including sarcopenia.

The association of testosterone with sarcopenia and frailty in chronic liver disease.

BACKGROUND: Testosterone is an important anabolic hormone responsible for maintaining body composition and muscle mass and circulates mostly albumin-bound, or sex hormone binding globulin (SHBG)-bound or free in the plasma. Of these fractions, the latter is bioactive and exerts the androgenic effects on male population. Liver cirrhosis, the advanced stage of any chronic liver disease characterized by permanent distortions to the hepatic architecture, disrupts the hypothalamic-pituitary-gonadal axis, leading to diminished levels of free testosterone and hypogonadism. METHODS: We retrieved the PubMed database to provide a synopsis of testosterone's physiology and action and summarize the effect of sarcopenia in pre-cirrhotic and cirrhotic patients. Moreover, we scoped to provide insight into the relationship of testosterone levels with sarcopenia, frailty and survival in cirrhotic and non-cirrhotic population as well as to discuss the efficacy of exogenous testosterone supplementation on the anthropometric parameters and survival of those patients. RESULTS: Low testosterone levels have been associated with sarcopenia, reduced body lean mass, decreased bone mineral density and frailty, thus leading to increased morbidity and mortality especially among cirrhotic patients. Furthermore, exogenous testosterone administration significantly ameliorated body composition on patients with chronic hepatic disease, without significant adverse effects. However, the current literature does not suggest any significant effect on survival of those patients. Moreover, the long-term safety of testosterone use remains an open question. CONCLUSION: Low serum testosterone is strongly correlated with sarcopenia, frailty, higher rate of hepatic decompensation and mortality. Nonetheless, exogenous supplementation of testosterone did not ameliorate the liver-related outcomes and complications.

Current Nutritional and Pharmacological Approaches for Attenuating Sarcopenia.

Sarcopenia is characterized by a gradual slowing of movement due to loss of muscle mass and quality, decreased power and strength, increased risk of injury from falls, and often weakness. This review will focus on recent research trends in nutritional and pharmacological approaches to controlling sarcopenia. Because nutritional studies in humans are fairly limited, this paper includes many results from nutritional studies in mammals. The combination of resistance training with supplements containing amino acids is the gold standard for preventing sarcopenia. Amino acid (HMB) supplementation alone has no significant effect on muscle strength or muscle mass in sarcopenia, but the combination of HMB and exercise (whole body vibration stimulation) is likely to be effective. Tea catechins, soy isoflavones, and ursolic acid are interesting candidates for reducing sarcopenia, but both more detailed basic research on this treatment and clinical studies in humans are needed. Vitamin D supplementation has been shown not to improve sarcopenia in elderly individuals who are not vitamin D-deficient. Myostatin inhibitory drugs have been tried in many neuromuscular diseases, but increases in muscle mass and strength are less likely to be expected. Validation of myostatin inhibitory antibodies in patients with sarcopenia has been positive, but excessive expectations are not warranted.

Exploring traditional Chinese medicine as a potential treatment for sarcopenia: A network pharmacology and data mining analysis of drug selection and efficacy.

Sarcopenia, as an increasingly pressing clinical issue, can be ameliorated through employment of traditional Chinese medicines. However, the current lack of specific pharmacological interventions for Sarcopenia necessitates further exploration of novel possibilities in traditional Chinese medicine for the treatment of this condition, utilizing advanced methodologies such as web pharmacology and data mining. Screening the essential targets of Sarcopenia, conducting matching between target and active molecules, as well as active molecules and herbs. Employing data mining techniques to analyze the screening outcomes, and molecular docking to compare the binding activities of active molecules with target proteins. The approach of using herbs for the treatment of Sarcopenia involves 13 targets, with 414 active compounds and 367 types of herbs. Data mining reveals that the herbs used in treating Sarcopenia are primarily characterized by their bitter taste, exerting their effects through dispelling dampness and promoting blood circulation. Moreover, 2 new formulas are postulated. Furthermore, molecular docking analysis indicates that the main active components of the herbs can be observed to tightly bind with the targets. Through network pharmacology and molecular docking, our findings reveal that herbs contain 15 key active components and 5 key targets, which correspond to 7 major herbs and 2 new formulas. Academically, these findings hold significant reference value for the development of novel drugs targeting Sarcopenia.

Potential of Fatty Acids in Treating Sarcopenia: A Systematic Review.

This paper presents a systematic review of studies investigating the effects of fatty acid supplementation in potentially preventing and treating sarcopenia. PubMed, Embase, and Web of Science databases were searched using the keywords 'fatty acid' and 'sarcopenia'. Results: A total of 14 clinical and 11 pre-clinical (including cell and animal studies) studies were included. Of the 14 clinical studies, 12 used omega-3 polyunsaturated fatty acids (PUFAs) as supplements, 1 study used ALA and 1 study used CLA. Seven studies combined the use of fatty acid with resistant exercises. Fatty acids were found to have a positive effect in eight studies and they had no significant outcome in six studies. The seven studies that incorporated exercise found that fatty acids had a better impact on elderlies. Four animal studies used novel fatty acids including eicosapentaenoic acid, trans-fatty acid, and olive leaf extraction as interventions. Three animal and four cell experiment studies revealed the possible mechanisms of how fatty acids affect muscles by improving regenerative capacity, reducing oxidative stress, mitochondrial and peroxisomal dysfunctions, and attenuating cell death. Conclusion: Fatty acids have proven their value in improving sarcopenia in pre-clinical experiments. However, current clinical studies show controversial results for its role on muscle, and thus the mechanisms need to be studied further. In the future, more well-designed randomized controlled trials are required to assess the effectiveness of using fatty acids in humans.

The potential of traditional herbal active ingredients in the treatment of sarcopenia animal models: focus on therapeutic effects and mechanisms.

Sarcopenia is a major global public health problem that harms individual physical function. In 2018, the European Working Group on Sarcopenia in the Elderly 2 classified sarcopenia into primary and secondary sarcopenia. However, information on the pathogenesis and effective treatment of primary and secondary sarcopenia is limited. Traditional herbal active ingredients have biological activities that promote skeletal muscle health, showing potential preventive and therapeutic effects on sarcopenia. Therefore, this narrative review aims to provide a comprehensive overview of global traditional herbal active ingredients' beneficial therapeutic effects and molecular mechanisms on sarcopenia-related animal models. For this purpose, we conducted a literature search in three databases, PubMed, Web of Science, and Embase, consistent with the review objectives. After the screening, 12 animal studies met the review themes. The review results showed that the pathological mechanisms in sarcopenia-related animal models include imbalanced protein metabolism, oxidative stress, inflammation, apoptosis, insulin resistance, endoplasmic reticulum stress, impaired mitochondrial biogenesis, and autophagy-lysosome system aggravation. Eleven traditional herbal active ingredients exerted positive anti-sarcopenic effects by ameliorating these pathological mechanisms. This narrative review will provide meaningful insight into future studies regarding traditional herbal active ingredients for treating sarcopenia.

Current Research on Vitamin D Supplementation against Sarcopenia: A Review of Clinical Trials.

Vitamin D plays an important role in skeletal muscle function and metabolism. The aim of this review was A) to discuss the clinical evidence of vitamin D supplementation either alone or combined with other strategies in the prevention of sarcopenia in non-sarcopenic individuals and B) to critically discuss the clinical evidence on the effect of vitamin D combined with other strategies on muscle strength, mass and function in sarcopenic individuals without vitamin D deficiency. Sparse clinical data on non-sarcopenic individuals indicate that vitamin D alone has a subtle beneficial effect on knee extensor strength at doses 880-1600 IU/day without improving handgrip strength or muscle mass. When co-administered with other supplements such as protein, mixed effects appear to prevent the decline of muscle mass, possibly delaying the onset of sarcopenia in non-sarcopenic individuals, at doses of 800-1,000 IU/day over 6-12 weeks. In sarcopenic individuals, vitamin D 100-1,000 IU/day co-supplementation with protein results in increased handgrip strength between 9.8-40.5%. However, there is no strong clinical evidence that vitamin D dosage correlates with changes in muscle strength or mass. Potential sources of discrepancy among studies are discussed. Future studies with appropriate experimental design are essential to dissect the net effect of vitamin D on sarcopenia.

The Effect of Omega-3 Fatty Acids on Sarcopenia: Mechanism of Action and Potential Efficacy.

Sarcopenia, a progressive disease characterized by a decline in muscle strength, quality, and mass, affects aging population worldwide, leading to increased morbidity and mortality. Besides resistance exercise, various nutritional strategies, including omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation, have been sought to prevent this condition. This narrative review summarizes the current evidence on the effect and mechanism of n-3 PUFA on musculoskeletal health. Despite conflicting evidence, n-3 PUFA is suggested to benefit muscle mass and volume, with more evident effects with higher supplementation dose (>2 g/day). n-3 PUFA supplementation likely improves handgrip and quadriceps strength in the elderly. Improved muscle functions, measured by walking speed and time-up-to-go test, are also observed, especially with longer duration of supplementation (>6 months), although the changes are small and unlikely to be clinically meaningful. Lastly, n-3 PUFA supplementation may positively affect muscle protein synthesis response to anabolic stimuli, alleviating age-related anabolic resistance. Proposed mechanisms by which n-3 PUFA supplementation improves muscle health include 1. anti-inflammatory properties, 2. augmented expression of mechanistic target of rapamycin complex 1 (mTORC1) pathway, 3. decreased intracellular protein breakdown, 4. improved mitochondrial biogenesis and function, 5. enhanced amino acid transport, and 6. modulation of neuromuscular junction activity. In conclusion, n-3 PUFAs likely improve musculoskeletal health related to sarcopenia, with suggestive effect on muscle mass, strength, physical performance, and muscle protein synthesis. However, the interpretation of the findings is limited by the small number of participants, heterogeneity of supplementation regimens, and different measuring protocols.

Effect of Coenzyme Q10 Supplementation on Sarcopenia, Frailty, and Falls: A Scoping Review.

Coenzyme Q10 (CoQ10) is well-known for its antioxidant effects and has been highlighted in research related to aging and many age-related conditions. However, there is limited research on the benefit of CoQ10 supplementation in conditions impacting the physical robustness of older adults, such as sarcopenia, frailty, falls and osteoporosis. This scoping review identified and summarized 4 studies that assessed the effects of exogenous CoQ10 on outcomes relating to sarcopenia, frailty, and falls. Results of the studies showed statistically significant improvements in a variety of physical robustness related outcomes, however several limitations of these studies prevent conclusive recommendations from being drawn regarding the benefit of CoQ10 supplementation in these conditions. A well-designed randomized control trial assessing the benefit of CoQ10 supplementation on clinically relevant outcomes related to sarcopenia, frailty, and falls may be warranted.

A Brief Narrative Review of the Underlying Mechanisms Whereby Omega-3 Fatty Acids May Influence Skeletal Muscle: From Cell Culture to Human Interventions.

Skeletal muscle is essential for human locomotion as well as maintaining metabolic homeostasis. Age-related reduction in skeletal muscle mass, strength, and function (i.e., sarcopenia) is a result of pathophysiological processes that include inflammation, alteration of molecular signaling for muscle protein synthesis and degradation, changes in insulin sensitivity, as well as altered skeletal muscle satellite cell activity. Finding strategies to mitigate skeletal muscle loss with age is deemed paramount as the percentage of the population continues to shift towards having more older adults with sarcopenia. Recent research indicates omega-3 fatty acid supplementation can influence anabolic or catabolic pathways in skeletal muscle. Our brief review will provide a synopsis of some underlying mechanisms that may be attributed to omega-3 fatty acid supplementation's effects on skeletal muscle. We will approach this review by focusing on cell culture, animal (pre-clinical models), and human studies evaluating omega-3 fatty acid supplementation, with suggestions for future research. In older adults, omega-3 fatty acids may possess some potential to modify pathophysiological pathways associated with sarcopenia; however, it is highly likely that omega-3 fatty acids need to be combined with other anabolic interventions to effectively ameliorate sarcopenia.

Tetrahedral Framework Nucleic Acids Inhibit Muscular Mitochondria-Mediated Apoptosis and Ameliorate Muscle Atrophy in Sarcopenia.

Sarcopenia is known as age-related muscle atrophy, which influences over a quarter of the elderly population worldwide. It is characterized by a progressive decline in muscle mass, strength, and performance. To date, clinical treatments in sarcopenia are limited to rehabilitative interventions and dietary supplements. Tetrahedral framework nucleic acids (tFNAs) represent a novel kind of DNA-based nanomaterial with superior antiapoptosis capacity in cells, tissues, organs, and systems. In our study, the therapeutic effect of tFNAs treatment on sarcopenia was evaluated both in vivo and in vitro. Results from muscular biophysiological characteristics demonstrated significant improvement in muscle function and endurance in the aged mouse model, and histologic examinations also showed beneficial morphological changes in muscle fibers. In vitro, DEX-induced sarcopenic myotube atrophy was also ameliorated through the inhibition of mitochondria-mediated cell apoptosis. Collectively, tFNAs treatment might serve as an alternative option to deal with sarcopenia in the near future.

Omega-3 polyunsaturated fatty acids in sarcopenia management: A network meta-analysis of randomized controlled trials.

Sarcopenia frequently occurs with aging and leads to major adverse impacts on activities of daily living and quality of life in elderly individuals. Omega-3 polyunsaturated fatty acid (omega-3 PUFAs) supplements are considered promising therapeutic agents for sarcopenia management; however, the evidence remains inconsistent. We reviewed randomized controlled trials (RCTs) about omega-3 PUFA supplementation in patients with sarcopenia or in those at high risk for sarcopenia. Network meta-analysis (NMA) procedures were conducted using a frequentist model. The primary outcomes were (1) upper-extremity muscle strength and (2) lower-extremity physical function. The NMA of 16 RCTs showed that the high-dose (more than 2.5 g/day omega-3 PUFAs) group yielded the greatest improvement in both upper-extremity muscle strength and lower-extremity physical function [compared to placebo/standard care groups, standardized mean difference (SMD)= 1.68, 95% confidence interval (95%CI)= 0.03-3.33, and SMD= 0.73, 95%CI= 0.16-1.30, respectively], and the effects were reaffirmed in subgroup analyses of placebo-controlled RCTs or those excluding concurrent resistance training programs. None of the investigated omega-3 PUFAs supplementation was associated with significantly increased skeletal muscle mass, fat mass, or overall body weight. Our findings provide a basis for future large-scale RCTs to investigate the dose effects and clinical application of omega-3 PUFA supplementation in sarcopenia management. TRIAL REGISTRATION: The current study was approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (TSGHIRB No. B-109-29) and registered in PROSPERO (CRD42022347161).

The Impact of Whey Protein Supplementation on Sarcopenia Progression among the Elderly: A Systematic Review and Meta-Analysis.

We conducted a systematic literature review and meta-analysis to investigate the role of whey protein supplementation in the functioning of the elderly with sarcopenia. The aim was to investigate the available scientific evidence and determine the best recommendations with respect to whey protein supplementation in sarcopenic patients. Methods: Databases, including CINAHL, Embase PubMed, and Web of Science, were searched from database inception until 31 December 2022 for randomised controlled trials (RCTs) comparing the efficacy of whey protein supplementation in the elderly with sarcopenia. Data on study design, risk of bias, patient, illness, and treatment characteristics from each study were independently extracted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The tool "assessing risk of bias" from the Cochrane Handbook was used to evaluate the quality of the included papers. Results: The search identified 629 records; 590 articles were excluded as duplicates or after evaluation at the title or abstract level. Out of 39 full-text articles that were reviewed, 29 were excluded for not fulfilling the inclusion criteria. There is some evidence that whey protein supplementation combined with age-appropriate physical exercise might improve muscle mass and lower limb function in the elderly with sarcopenia. The present meta-analysis demonstrated overall that whey supplementation does not improve any of the tested sarcopenia-linked parameters. However, we found that study duration (weeks) and age significantly affect the handgrip strength rate and the chair and stand test rate, respectively, so consideration should be given to oral supplementation combined with the age of participants and an appropriate physical activity as a form of sarcopenia prevention in the high-risk group.