bims-aucach 2022-03-27 papers

bims-aucach

Biomed News

on Autophagy and cachexia

Issue of 2022–03–27
sixteen papers selected by
Kleiton Silva, Rowan University

Pectoralis major muscle atrophy is associated with mitochondrial energy wasting in cachectic patients with gastrointestinal cancer.
Review of Mechanisms and Treatment of Cancer-Induced Cardiac Cachexia.
Apoptosis-Inducing Factor Deficiency Induces Tissue-Specific Alterations in Autophagy: Insights from a Preclinical Model of Mitochondrial Disease and Exercise Training Effects.
Unraveling the Metabolic Hallmarks for the Optimization of Protein Intake in Pre-Dialysis Chronic Kidney Disease Patients.
Targeting proteostasis maintenance and autophagy in senescence.
Pharmacological Modulation of Apoptosis and Autophagy in the Treatment of Pancreatic Cancer.
Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response.
Can Biological Drugs Diminish the Risk of Sarcopenia in Psoriatic Patients? A Systematic Review.
Autophagy Agents in Clinical Trials for Cancer Therapy: A Brief Review.
The niacin receptor HCAR2 modulates microglial response and limits disease progression in a mouse model of Alzheimer's disease.
Effects of Soy Milk in Conjunction With Resistance Training on Physical Performance and Skeletal Muscle Regulatory Markers in Older Men.
VLCKD in Combination with Physical Exercise Preserves Skeletal Muscle Mass in Sarcopenic Obesity after Severe COVID-19 Disease: A Case Report.
Roles of nutrition in muscle health of community-dwelling older adults: evidence-based expert consensus from Asian Working Group for Sarcopenia.
Relationship between Low Muscle Strength, and Protein Intake: A Preliminary Study of Elderly Patients with Hip Fracture.
Skeletal muscle myostatin gene expression and sarcopenia in overweight and obese middle-aged and older adults.
Therapeutic effects of functional electrical stimulation on physical performance and muscle strength in post-stroke older adults: a review.

J Cachexia Sarcopenia Muscle. 2022 Mar 22.

Pectoralis major muscle atrophy is associated with mitochondrial energy wasting in cachectic patients with gastrointestinal cancer.

Adeline Dolly, Thierry Lecomte, Nicolas Tabchouri, Morgane Caulet, Nicolas Michot, Benjamin Anon, Romain Chautard, Yoann Desvignes, Mehdi Ouaissi, Gaëlle Fromont-Hankard, Jean-François Dumas, Stéphane Servais.

   BACKGROUND: Cancer cachexia is a multifactorial syndrome characterized by involuntary and pathological weight loss, mainly due to skeletal muscle wasting, resulting in a decrease in patients' quality of life, response to cancer treatments, and survival. Our objective was to investigate skeletal muscle alterations in cachectic cancer patients.
METHODS: This is a prospective study of patients managed for pancreatic or colorectal cancer with an indication for systemic chemotherapy (METERMUCADIG - NCT02573974). One lumbar CT image was used to determine body composition. Patients were divided into three groups [8 noncachectic (NC), 18 with mild cachexia (MC), and 19 with severe cachexia (SC)] based on the severity of weight loss and muscle mass. For each patient, a pectoralis major muscle biopsy was collected at the time of implantable chamber placement. We used high-resolution oxygraphy to measure mitochondrial muscle oxygen consumption on permeabilized muscle fibres. We also performed optical and electron microscopy analyses, as well as gene and protein expression analyses.
RESULTS: Forty-five patients were included. Patients were 67% male, aged 67 years (interquartile range, 59-77). Twenty-three (51%) and 22 (49%) patients were managed for pancreatic and colorectal cancer, respectively. Our results show a positive correlation between median myofibres area and skeletal muscle index (P = 0.0007). Cancer cachexia was associated with a decrease in MAFbx protein expression (P < 0.01), a marker of proteolysis through the ubiquitin-proteasome pathway. Mitochondrial oxygen consumption related to energy wasting was significantly increased (SC vs. NC, P = 0.028) and mitochondrial area tended to increase (SC vs. MC, P = 0.056) in SC patients. On the contrary, mitochondria content and networks remain unaltered in cachectic cancer patients. Finally, our results show no dysfunction in lipid storage and endoplasmic reticulum homeostasis.
CONCLUSIONS: This clinical protocol brings unique data that provide new insight to mechanisms underlying muscle wasting in cancer cachexia. We report for the first time an increase in mitochondrial energy wasting in the skeletal muscle of severe cachectic cancer patients. Additional clinical studies are essential to further the exploring and understanding of these alterations.

Keywords:  Cancer cachexia; Clinical study; Mitochondrial bioenergetics; Myosteatosis; Pectoralis major; Proteolysis

DOI:  https://doi.org/10.1002/jcsm.12984
Cells. 2022 Mar 18. pii: 1040. [Epub ahead of print]11(6):

Review of Mechanisms and Treatment of Cancer-Induced Cardiac Cachexia.

Vignesh Vudatha, Teja Devarakonda, Christopher Liu, Devon C Freudenberger, Andrea N Riner, Kelly M Herremans, Jose G Trevino.

  Cancer cachexia is a multifactorial, paraneoplastic syndrome that impacts roughly half of all cancer patients. It can negatively impact patient quality of life and prognosis by causing physical impairment, reducing chemotherapy tolerance, and precluding them as surgical candidates. While there is substantial research on cancer-induced skeletal muscle cachexia, there are comparatively fewer studies and therapies regarding cardiac cachexia in the setting of malignancy. A literature review was performed using the PubMed database to identify original articles pertaining to cancer-induced cardiac cachexia, including its mechanisms and potential therapeutic modalities. Seventy studies were identified by two independent reviewers based on inclusion and exclusion criteria. While there are multiple studies addressing the pathophysiology of cardiac-induced cancer cachexia, there are no studies evaluating therapeutic options in the clinical setting. Many treatment modalities including nutrition, heart failure medication, cancer drugs, exercise, and gene therapy have been explored in in vitro and mice models with varying degrees of success. While these may be beneficial in cancer patients, further prospective studies specifically focusing on the assessment and treatment of the cardiac component of cachexia are needed.

Keywords:  TNFα; cancer; cardiac cachexia; reactive oxygen species

DOI:  https://doi.org/10.3390/cells11061040
Antioxidants (Basel). 2022 Mar 07. pii: 510. [Epub ahead of print]11(3):

Apoptosis-Inducing Factor Deficiency Induces Tissue-Specific Alterations in Autophagy: Insights from a Preclinical Model of Mitochondrial Disease and Exercise Training Effects.

Sara Laine-Menéndez, Miguel Fernández-de la Torre, Carmen Fiuza-Luces, Aitor Delmiro, Joaquín Arenas, Miguel Ángel Martín, Patricia Boya, Alejandro Lucia, María Morán.

  We analyzed the effects of apoptosis-inducing factor (AIF) deficiency, as well as those of an exercise training intervention on autophagy across tissues (heart, skeletal muscle, cerebellum and brain), that are primarily affected by mitochondrial diseases, using a preclinical model of these conditions, the Harlequin (Hq) mouse. Autophagy markers were analyzed in: (i) 2, 3 and 6 month-old male wild-type (WT) and Hq mice, and (ii) WT and Hq male mice that were allocated to an exercise training or sedentary group. The exercise training started upon onset of the first symptoms of ataxia in Hq mice and lasted for 8 weeks. Higher content of autophagy markers and free amino acids, and lower levels of sarcomeric proteins were found in the skeletal muscle and heart of Hq mice, suggesting increased protein catabolism. Leupeptin-treatment demonstrated normal autophagic flux in the Hq heart and the absence of mitophagy. In the cerebellum and brain, a lower abundance of Beclin 1 and ATG16L was detected, whereas higher levels of the autophagy substrate p62 and LAMP1 levels were observed in the cerebellum. The exercise intervention did not counteract the autophagy alterations found in any of the analyzed tissues. In conclusion, AIF deficiency induces tissue-specific alteration of autophagy in the Hq mouse, with accumulation of autophagy markers and free amino acids in the heart and skeletal muscle, but lower levels of autophagy-related proteins in the cerebellum and brain. Exercise intervention, at least if starting when muscle atrophy and neurological symptoms are already present, is not sufficient to mitigate autophagy perturbations.

Keywords:  Harlequin; OXPHOS; autophagy; brain; cerebellum; heart; mitochondrial diseases; skeletal muscle

DOI:  https://doi.org/10.3390/antiox11030510
Nutrients. 2022 Mar 11. pii: 1182. [Epub ahead of print]14(6):

Unraveling the Metabolic Hallmarks for the Optimization of Protein Intake in Pre-Dialysis Chronic Kidney Disease Patients.

Patricia Gonzalez, Pedro Lozano, Francisco Solano.

  The daily amount and quality of protein that should be administered by enteral nutrition in pre-dialysis chronic kidney disease (CKD) patients is a widely studied but still controversial issue. This is due to a compromise between the protein necessary to maintain muscular proteostasis avoiding sarcopenia, and the minimal amount required to prevent uremia and the accumulation of nitrogenous toxic substances in blood because of the renal function limitations. This review underlines some intracellular and extracellular features that should be considered to reconcile those two opposite factors. On one hand, the physiological conditions and usual side effects associated with CKD, mTOR and other proteins and nutrients involved in the regulation of protein synthesis in the muscular tissue are discussed. On the other hand, the main digestive features of the most common proteins used for enteral nutrition formulation (i.e., whey, casein and soy protein) are highlighted, due to the importance of supplying key amino acids to serum and tissues to maintain their concentration above the anabolic threshold needed for active protein synthesis, thereby minimizing the catabolic pathways leading to urea formation.

Keywords:  CKD; Leu; enteral nutrition; mTOR; muscular proteostasis; oxidative stress; protein ingestion

DOI:  https://doi.org/10.3390/nu14061182
Aging (Albany NY). 2022 Mar 07. 14(5): 2016-2017

Targeting proteostasis maintenance and autophagy in senescence.

Valentin L'Hôte, Carl Mann, Jean-Yves Thuret.



Keywords:  BRAF-V600E; cellular senescence; proteostasis; selective autophagy; senolytics

DOI:  https://doi.org/10.18632/aging.203941
Mini Rev Med Chem. 2022 Mar 24.

Pharmacological Modulation of Apoptosis and Autophagy in the Treatment of Pancreatic Cancer.

Nityaa Selvarajoo, Johnson Stanslas, Mohammad Kaisarul Islam, Sreenivasa Rao Sagineedu, Kok Lian Ho, Jonathan Chee Woei Lim.

   BACKGROUND: Pancreatic cancer is a fatal malignant neoplasm with infrequent signs and symptoms until a progressive stage. In 2020, GLOBOCAN reported that, pancreatic cancer accounts for 4.7% of all cancer deaths. Despite the availability of standard chemotherapy regiments for treatment, the survival benefits are not guaranteed because tumour cells become chemoresistant even due to the development of chemoresistance in tumour cells even with a short treatment course, where apoptosis and autophagy play critical roles.
OBJECTIVE: This review compiled essential information on the regulatory mechanisms and roles of apoptosis and autophagy in pancreatic cancer, as well as drug-like molecules that target different pathways in pancreatic cancer eradication, with an aim of providing ideas to the scientific communities to discover novels and specific drug to treat pancreatic cancer, specifically PDAC. highlight these mechanisms which target different pathways in eradicating pancreatic cancer.
METHOD: Electronic databases that were searched for research articles for this review were Scopus, Science Direct, PubMed, Springer Link, and Google Scholar. The published studies were identified and retrieved using selected keywords. Discussion/ Conclusion: Many small-molecule anticancer agents have been developed to regulate autophagy and apoptosis associated with pancreatic cancer treatment, where most of them target apoptosis directly through EGFR/Ras/Raf/MAPK and PI3K/Akt/mTOR pathways. The cancer drugs that regulate autophagy in treating cancer can be categorized into three groups: i) direct autophagy inducers (e.g., rapamycin), ii) indirect autophagy inducers (e.g., resveratrol), and iii) autophagy inhibitors. Resveratrol persuades both apoptosis and autophagy with cytoprotective effect, while autophagy inhibitors (e.g., 3-methyladenine, chloroquine) can turn off the protective autophagic effect for therapeutic benefits. Several studies showed that autophagy inhibition resulted in a synergistic effect with chemotherapy (e.g., combination of metformin with gemcitabine/5FU) and such drugs possess a unique clinical value in treating pancreatic cancer as well as other autophagy-dependent carcinomas.

Keywords:  Apoptosis; Autophagy; Autophagy modulators; Cancer drugs.; Chemoresistance; Pancreatic cancer

DOI:  https://doi.org/10.2174/1389557522666220324123605
J Exp Clin Cancer Res. 2022 Mar 22. 41(1): 105

Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response.

Milad Ashrafizadeh, Mahshid Deldar Abad Paskeh, Sepideh Mirzaei, Mohammad Hossein Gholami, Ali Zarrabi, Farid Hashemi, Kiavash Hushmandi, Mehrdad Hashemi, Noushin Nabavi, Francesco Crea, Jun Ren, Daniel J Klionsky, Alan Prem Kumar, Yuzhuo Wang.

  Prostate cancer is a leading cause of death worldwide and new estimates revealed prostate cancer as the leading cause of death in men in 2021. Therefore, new strategies are pertinent in the treatment of this malignant disease. Macroautophagy/autophagy is a "self-degradation" mechanism capable of facilitating the turnover of long-lived and toxic macromolecules and organelles. Recently, attention has been drawn towards the role of autophagy in cancer and how its modulation provides effective cancer therapy. In the present review, we provide a mechanistic discussion of autophagy in prostate cancer. Autophagy can promote/inhibit proliferation and survival of prostate cancer cells. Besides, metastasis of prostate cancer cells is affected (via induction and inhibition) by autophagy. Autophagy can affect the response of prostate cancer cells to therapy such as chemotherapy and radiotherapy, given the close association between autophagy and apoptosis. Increasing evidence has demonstrated that upstream mediators such as AMPK, non-coding RNAs, KLF5, MTOR and others regulate autophagy in prostate cancer. Anti-tumor compounds, for instance phytochemicals, dually inhibit or induce autophagy in prostate cancer therapy. For improving prostate cancer therapy, nanotherapeutics such as chitosan nanoparticles have been developed. With respect to the context-dependent role of autophagy in prostate cancer, genetic tools such as siRNA and CRISPR-Cas9 can be utilized for targeting autophagic genes. Finally, these findings can be translated into preclinical and clinical studies to improve survival and prognosis of prostate cancer patients.

Keywords:  Anti-tumor compounds; Autophagy; Biomarker; Non-coding RNAs; Prostate cancer; Therapy response

DOI:  https://doi.org/10.1186/s13046-022-02293-6
Life (Basel). 2022 Mar 16. pii: 435. [Epub ahead of print]12(3):

Can Biological Drugs Diminish the Risk of Sarcopenia in Psoriatic Patients? A Systematic Review.

Zuzanna Piętowska, Danuta Nowicka, Jacek Szepietowski.

  Sarcopenia and psoriasis are different inflammatory diseases that share common comorbidities (e.g., cardiovascular diseases, metabolic syndrome, obesity, autoimmune diseases, depression). Psoriasis is a dermatosis involving the skin, joints, and nails. Its estimated prevalence is 2-4%, and the possibility of progression to psoriatic arthritis reaches 6-42%. Sarcopenia is defined as reduced muscle strength, muscle quantity, and physical performance due to non-ageing related causes. It affects up to 10% of the general population. We conducted a review of the literature to provide up-to-date information about the risk of sarcopenia in psoriasis and to identify risk factors that increase this risk. The search of the literature allowed us to include 51 publications, but only five cross-sectional studies provided quantitative results on the rates of sarcopenia in psoriasis. The prevalence of sarcopenia in psoriasis varied from 9.1% to 61.7%. This wide range was caused by different definitions of sarcopenia and different cut-off values across studies. Prognostic factors include lean mass and fat mass. Further research based on the European Working Group on Sarcopenia in Older People guidelines is required. Such studies should include not only muscle mass and strength but also other factors that may influence the occurrence of sarcopenia and inflammatory markers.

Keywords:  biological therapy; body composition; drugs intake; muscle loss; psoriasis; psoriatic arthritis; sarcopenia

DOI:  https://doi.org/10.3390/life12030435
Curr Oncol. 2022 Mar 05. 29(3): 1695-1708

Autophagy Agents in Clinical Trials for Cancer Therapy: A Brief Review.

Samiha Mohsen, Philip T Sobash, Ghada Fahad Algwaiz, Noor Nasef, Safaa Abed Al-Zeidaneen, Nagla Abdel Karim.

  Autophagy has been of novel interest since it was first demonstrated to have effect in Burkitt's lymphoma. Since that time, the autophagy agents chloroquine and hydroxychloroquine have become the only FDA (Food and Drug Administration)-approved autophagy inhibitors. While not approved for cancer therapy, there are ongoing clinical trials to evaluate their safety and efficacy. Pevonedistat has emerged as a novel inhibitor through the neddylation pathway and is an autophagy activator. This paper summarizes and presents current clinical trials for hydroxychloroquine (HCQ), chloroquine (CQ), and Pevonedistat for the clinician.

Keywords:  autophagy; cancer; chloroquine; clinical trial; hydroxychloroquine; pevonedistat

DOI:  https://doi.org/10.3390/curroncol29030141
Sci Transl Med. 2022 Mar 23. 14(637): eabl7634

The niacin receptor HCAR2 modulates microglial response and limits disease progression in a mouse model of Alzheimer's disease.

Miguel Moutinho, Shweta S Puntambekar, Andy P Tsai, Israel Coronel, Peter B Lin, Brad T Casali, Pablo Martinez, Adrian L Oblak, Cristian A Lasagna-Reeves, Bruce T Lamb, Gary E Landreth.

Increased dietary intake of niacin has been correlated with reduced risk of Alzheimer's disease (AD). Niacin serves as a high-affinity ligand for the receptor HCAR2 (GPR109A). In the brain, HCAR2 is expressed selectively by microglia and is robustly induced by amyloid pathology in AD. The genetic inactivation of Hcar2 in 5xFAD mice, a model of AD, results in impairment of the microglial response to amyloid deposition, including deficits in gene expression, proliferation, envelopment of amyloid plaques, and uptake of amyloid-β (Aβ), ultimately leading to exacerbation of amyloid burden, neuronal loss, and cognitive deficits. In contrast, activation of HCAR2 with an FDA-approved formulation of niacin (Niaspan) in 5xFAD mice leads to reduced plaque burden and neuronal dystrophy, attenuation of neuronal loss, and rescue of working memory deficits. These data provide direct evidence that HCAR2 is required for an efficient and neuroprotective response of microglia to amyloid pathology. Administration of Niaspan potentiates the HCAR2-mediated microglial protective response and consequently attenuates amyloid-induced pathology, suggesting that its use may be a promising therapeutic approach to AD that specifically targets the neuroimmune response.

DOI: https://doi.org/10.1126/scitranslmed.abl7634
Biol Res Nurs. 2022 Mar 25. 10998004211073123

Effects of Soy Milk in Conjunction With Resistance Training on Physical Performance and Skeletal Muscle Regulatory Markers in Older Men.

Nahid Bijeh, Mohsen Mohammadnia-Ahmadi, Babak Hooshamnd-Moghadam, Mozhgan Eskandari, Fateme Golestani.

  Purpose: We aimed to determine the effects of 12 weeks of soy milk consumption combined with resistance training (RT) on body composition, physical performance, and skeletal muscle regulatory markers in older men. Methods: In this randomized clinical trial study, 60 healthy elderly men (age = 65.63 ± 3.16 years) were randomly assigned to four groups: resistance training (RT; n = 15), soy milk consumption (SMC; n = 15), resistance training + soy milk (RSM; n = 15), and control (CON; n = 15) groups. The study was double-blind for the soy milk/placebo. Participants in RT and RSM groups performed resistance training (3 times/week) for 12 weeks. Participants in the SMC and RSM groups consumed 240 mL of soy milk daily. Body composition [body mass (BM), body fat percent (BFP), waist-hip ratio (WHR), and fat mass (FM)], physical performance [upper body strength (UBS), lower body strength (LBS), VO2max, upper anaerobic power, lower anaerobic power, and handgrip strength], and serum markers [follistatin, myostatin, myostatin-follistatin ratio (MFR), and growth and differentiation factor 11 (GDF11)] were evaluated before and after interventions. Results: All 3 interventions significantly (p < 0.05) increased serum follistatin concentrations (RT = 1.7%, SMC = 2.9%, RSM = 7.8%) and decreased serum myostatin (RT = -1.3% SMC = -5.4%, RSM = -0.5%) and GDF11 concentrations (RT = -1.4%, SMC = -1.4%, RSM = -9.0%), and MFR (RT = -2.6%, SMC = -3.2%, RSM = -12%). In addition, we observed significant reduction in all 3 intervention groups in BFP (RT = -3.6%, SMC = -1.4%, RSM = -6.0%), WHR (RT = -2.2%, SMC = -2.1%, RSM = -4.3%), and FM (RT = -9.6%, SMC = -3.8%, RSM = -11.0%). Moreover, results found significant increase only in RT and RSM groups for muscle mass (RT = 3.8% and RSM = 11.8%), UBS (RT = 10.9% and RSM = 21.8%), LBS (RT = 4.3% and RSM = 7.8%), upper anaerobic power (RT = 7.8% and RSM = 10.3%), and lower anaerobic power (RT = 4.6% and RSM = 8.9%). Handgrip strength were significantly increased in all 3 intervention groups (RT = 7.0%, SMC = 6.9%, RSM = 43.0%). VO2max significantly increased only in RSM (1.7%) after 12 weeks of intervention. Additionally, significant differences were observed between the changes for all variables in the RSM group compared to RT, SMC, and CON groups (p < 0.05). Conclusions: There were synergistic effects of soy milk and RT for skeletal muscle regulatory markers, body composition, and physical performance. Results of the present study support the importance of soy milk in conjunction with RT for older men.

Keywords:  aging; hypertrophy; lean body mass; physical performance; supplement

DOI:  https://doi.org/10.1177/10998004211073123
Healthcare (Basel). 2022 Mar 19. pii: 573. [Epub ahead of print]10(3):

VLCKD in Combination with Physical Exercise Preserves Skeletal Muscle Mass in Sarcopenic Obesity after Severe COVID-19 Disease: A Case Report.

Elisabetta Camajani, Alessandra Feraco, Sabrina Basciani, Lucio Gnessi, Luigi Barrea, Andrea Armani, Massimiliano Caprio.

  The prevalence of sarcopenic obesity is increasing worldwide, with a strong impact on public health and the national health care system. Sarcopenic obesity consists of fat depot expansion and associated systemic low-grade inflammation, exacerbating the decline in skeletal muscle mass and strength. Dietary approach and physical exercise represent essential tools for reducing body weight and preserving muscle mass and function in subjects with sarcopenic obesity. This case report describes the effects of a dietary intervention, based on a Very-Low-Calorie Ketogenic Diet (VLCKD) combined with physical exercise, on body composition, cardiometabolic risk factors, and muscle strength in a woman with sarcopenic obesity, two weeks after hospitalization for bilateral interstitial pneumonia due to COVID-19. To our knowledge, this is the first case report to describe the efficacy of a combined approach intervention including VLCKD along with physical exercise, in reducing fat mass, improving metabolic profile, and preserving skeletal muscle performance in a patient with obesity, soon after severe COVID-19 disease.

Keywords:  SARS-CoV-2; ketogenic diet; ketone bodies; obesity; physical training; sarcopenia

DOI:  https://doi.org/10.3390/healthcare10030573
J Cachexia Sarcopenia Muscle. 2022 Mar 20.

Roles of nutrition in muscle health of community-dwelling older adults: evidence-based expert consensus from Asian Working Group for Sarcopenia.

Liang-Kung Chen, Hidenori Arai, Prasert Assantachai, Masahiro Akishita, Samuel T H Chew, Lourdes Carolina Dumlao, Gustavo Duque, Jean Woo.

  General muscle health declines with age, and in particular, sarcopenia-defined as progressive loss of muscle mass and strength/physical performance-is a growing issue in Asia with a rising population of community-dwelling older adults. Several guidelines have addressed early identification of sarcopenia and management, and although nutrition is central to treatment of sarcopenia, there are currently few guidelines that have examined this specifically in the Asian population. Therefore, the Asian Working Group for Sarcopenia established a special interest group (SIG) comprising seven experts across Asia and one from Australia, to develop an evidence-based expert consensus. A systematic literature search was conducted using MEDLINE on the topic of muscle health, from 2016 (inclusive) to July 2021, in Asia or with relevance to healthy, Asian community-dwelling older adults (≥60 years old). Several key topics were identified: (1) nutritional status: malnutrition and screening; (2) diet and dietary factors; (3) nutritional supplementation; (4) lifestyle interventions plus nutrition; and (5) outcomes and assessment. Clinical questions were developed around these topics, leading to 14 consensus statements. Consensus was achieved using the modified Delphi method with two rounds of voting. Moreover, the consensus addressed the impacts of COVID-19 on nutrition, muscle health, and sarcopenia in Asia. These statements encompass clinical expertise and knowledge across Asia and are aligned with findings in the current literature, to provide a practical framework for addressing muscle health in the community, with the overall aim to encourage and facilitate broader access to equitable care for this target population.

Keywords:  Community; Malnutrition; Muscle; Nutrition; Older adults; Sarcopenia

DOI:  https://doi.org/10.1002/jcsm.12981
J Bone Metab. 2022 Feb;29(1): 17-21

Relationship between Low Muscle Strength, and Protein Intake: A Preliminary Study of Elderly Patients with Hip Fracture.

Kyung-A Choi, Eunseo Heu, Hyun-Cheul Nam, Yongsoon Park, Donghyun Kim, Yong-Chan Ha.

   BACKGROUND: The purpose of the present study was to assess the daily protein uptake and its relationship with sarcopenia, as defined by the Asian Working Group for Sarcopenia (AWGS), among elderly patients with hip fractures.
METHODS: Forty-seven elderly patients with hip fractures were enrolled in this retrospective observational study. The main outcome measures included protein uptake, muscle mass, and grip strength for sarcopenia in elderly patients. Sarcopenia was diagnosed according to AWGS. Wholebody densitometry was used to measure skeletal muscle mass, and muscle strength was evaluated using handgrip testing.
RESULTS: Of 47 patients with hip fractures (12 men and 35 women), 37 (79%) patients exhibited insufficient protein intake (range, 0.01-0.588 g/kg/day), and 10 (21%) patients exhibited excessive protein intake (range, 1.215-2.121 g/kg/day). The mean daily protein intake was 56.5 g (range, 7.2-136.0 g). Prevalence of low muscle strength (handgrip strength <18 kg in women and <26 kg in men) was detected in 13 (37%) women and 8 (67%) men (P=0.076). Sarcopenia (lower muscle mass and lower muscle strength) was detected in 9 (26%) women and 6 (50%) men (P=0.119). Although lower protein intake was marginally associated with sarcopenia (P=0.189), it was significantly associated with lower grip strength (P=0.042).
CONCLUSIONS: The present study demonstrated that insufficient protein intake in elderly patients with hip fractures was common, and lower protein intake was significantly associated with lower muscle strength.

Keywords:  Aged; Dietary proteins; Hip fractures; Malnutrition; Sarcopenia

DOI:  https://doi.org/10.11005/jbm.2022.29.1.17
JCSM Clin Rep. 2021 Oct;6(4): 137-142

Skeletal muscle myostatin gene expression and sarcopenia in overweight and obese middle-aged and older adults.

Alice S Ryan, Guoyan Li.

   Background: Myostatin (MSTN) is a key negative regulator of muscle mass in humans and animals, having direct and indirect influences on molecular regulators of atrophy and hypertrophy, thus potentially impacting fitness and physical function. We have shown that myostatin is elevated in conditions of chronic disability (e.g. paretic limb of stroke). Our hypothesis is that myostatin would be elevated in older adults with sarcopenia. The purpose of this study was to examine the role of skeletal muscle myostatin in sarcopenia.
Methods: Sixty-four overweight to obese aged 45-81 years underwent a maximal aerobic capacity (VO2max) test, dual-energy X-ray absorptiometry (DXA) scan to determine appendicular lean tissue (ALM), and vastus lateralis muscle biopsy to determine myostatin mRNA expression by quantitative real time PCR (Q-RT-PCR). Rates of sarcopenia were determined using (ALM/BMI), and sarcopenia was defined as <0.789 in men and <0.512 in women. Subjects had low fitness (VO2max: 22.7 ± 0.7 mL/kg/min) and on average 40.9 ± 1% body fat.
Results: The prevalence of sarcopenia in this cohort was 16%. BMI, % body fat, and fat mass were higher in adults with sarcopenia than those without sarcopenia (all P < 0.001). Myostatin mRNA expression was lower in those without sarcopenia than those with sarcopenia (P < 0.05) and higher in men than women (P < 0.001). Myostatin expression was associated with BMI (r = 0.36, P < 0.01) and mid-thigh intramuscular fat (r = 0.29, P < 0.05).
Conclusion: Given that myostatin is important in muscle atrophy, fat accumulation, and sarcopenia, further work could address its implication in other aging cohorts of disability and chronic disease.

Keywords:  Aging; Fat accumulation; Myostatin; Obesity; Sarcopenia; Skeletal muscle atrophy

DOI:  https://doi.org/10.1002/crt2.43
Ann Geriatr Med Res. 2022 Mar 22.

Therapeutic effects of functional electrical stimulation on physical performance and muscle strength in post-stroke older adults: a review.

Hyung Eun Shin, Miji Kim, Daehyun Lee, Jae Young Jang, Yunsoo Soh, Dong Hwan Yun, Sunyoung Kim, Jisoo Yang, Maeng Kyu Kim, Hooman Lee, Chang Won Won.

  Stroke-related disabilities cause poor physical performance, especially among older adults, and can lead to sarcopenia. Functional electrical stimulation (FES) has been used to improve physical performance in individuals with neurological disorders and increase muscle mass and strength to counteract muscle atrophy. This review covers the principles, underlying mechanisms, and therapeutic effects of FES on physical performance and skeletal muscle function in post-stroke older adults. We found that FES restored weakened dorsiflexor and hip abductor strength during the swing and stance phases of gait, respectively, to help support weight-bearing and upright posture and facilitate static and dynamic balance in this population. FES may also be effective in improving muscle mass and strength to prevent muscle atrophy. However, previous studies on this topic in post-stroke older adults are scarce, and further studies are needed to confirm this supposition.

Keywords:  Aged; Physical performance; Stroke; Therapeutic Electrical Stimulation

DOI:  https://doi.org/10.4235/agmr.22.0006