Age-related and cancer-related sarcopenia: is there a difference?

Purpose Of Review: The aim of this review is the attempt to differentiating the pathophysiologic and clinical features of the aging-related sarcopenia from cancer-related sarcopenia. In fact, there is some controversy among the experts mainly regarding two points: is always sarcopenia, even that aging-related one, the expression of a generalized disease or may exist independently and without major alteration of the muscle function? Are always aging-related and cancer-related sarcopenia completely separated entities?

Recent Findings: Literature shows that sarcopenia, defined as simple skeletal muscle mass loss, may range from a mainly focal problem which is common in many healthy elderly people, to a component of a complex multiorgan syndrome as cancer cachexia. Disuse, malnutrition and (neuro)degenerative processes can account for most of the aging-related sarcopenias while systemic inflammation and secretion of cancer-and immune-related molecules play an additional major role in cachexia.

Loss of psoas muscle during neoadjuvant treatment for rectal cancer is associated with poor oncological and surgical outcomes.

Background: Sarcopenia has been associated with poor outcomes in rectal cancer patients. This study aims to assess the degree of muscle loss during neoadjuvant therapy in patients with rectal cancer, and its relationship with tumour response, post-operative complications and long-term disease recurrence.

Methods: The change in the psoas muscle area was determined by measuring the psoas muscle area at L4 on initial staging PET CT scans and comparing this with the restaging scan 8-10 weeks after radiation treatment had been completed.

Long term quality of life follow-up and functional impairment study in patients with Hirayama disease.

Hirayama Disease (HD) is a focal motor neuron disorder generally affecting young adults with a male predominance who experience weakness and atrophy in distal upper extremity muscles in an asymmetric or unilateral pattern. Progression is insidious though significant weakness occurs during a progressive phase of the disease over 2-5 years. The long-term outcome of HD is not as well-known and, thus, this study presents self-reported outcomes from HD patients years after a diagnosis.

Alteration of LARGE1 abundance in patients and a mouse model of 5q-associated spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by recessive pathogenic variants affecting the survival of motor neuron (SMN1) gene (localized on 5q). In consequence, cells lack expression of the corresponding protein. This pathophysiological condition is clinically associated with motor neuron (MN) degeneration leading to severe muscular atrophy.

[Risdiplam for the treatment of spinal muscular atrophy].

Spinal muscular atrophy (SMA) is a devastating disease that is the leading genetic cause of death in infants and young children. It includes a broad spectrum of phenotypes that are classified into clinical groups based on the age of onset and maximum motor function achieved. The most common form of SMA is due to a defect in the survival motor neuron 1 gene () localized to 5q11.

TransNeT-CGP: A cluster-based comorbid gene prioritization by integrating transcriptomics and network-topological features.

The local disruptions caused by the genes of one disease can influence the pathways associated with the other diseases resulting in comorbidity. For gene therapies, it is necessary to prioritize the key genes that regulate common biological mechanisms to tackle the issues caused by overlapping diseases. This work proposes a clustering-based computational approach for prioritising the comorbid genes within the overlapping disease modules by analyzing Protein-Protein Interaction networks.

Global Risdiplam Compassionate Use Program for Patients with Type 1 or 2 Spinal Muscular Atrophy.

Purpose: Spinal muscular atrophy (SMA) is a genetic neuromuscular disease causing progressive muscle weakness and reducing life expectancy. Risdiplam (Evrysdi; Genentech/F. Hoffmann-La Roche Ltd, Basel, Switzerland) is a drug approved for use in the treatment of patients with SMA.

Mustn1 is a smooth muscle cell-secreted microprotein that modulates skeletal muscle extracellular matrix composition.

Objective: Skeletal muscle plasticity and remodeling are critical for adapting tissue function to use, disuse, and regeneration. The aim of this study was to identify genes and molecular pathways that regulate the transition from atrophy to compensatory hypertrophy or recovery from injury. Here, we have used a mouse model of hindlimb unloading and reloading, which causes skeletal muscle atrophy, and compensatory regeneration and hypertrophy, respectively.

The SMN-ribosome interplay: a new opportunity for Spinal Muscular Atrophy therapies.

The underlying cause of Spinal Muscular Atrophy (SMA) is in the reduction of survival motor neuron (SMN) protein levels due to mutations in the SMN1 gene. The specific effects of SMN protein loss and the resulting pathological alterations are not fully understood. Given the crucial roles of the SMN protein in snRNP biogenesis and its interactions with ribosomes and translation-related proteins and mRNAs, a decrease in SMN levels below a specific threshold in SMA is expected to affect translational control of gene expression.

HucMSCs Delay Muscle Atrophy After Peripheral Nerve Injury Through Exosomes by Repressing Muscle-Specific Ubiquitin Ligases.

Cell therapy based on mesenchymal stem cells (MSCs) alleviate muscle atrophy caused by diabetes and aging; however, the impact of human umbilical cord mesenchymal stem cells on muscle atrophy following nerve injury and the underlying mechanisms remain unclear. In this study, we evaluated the therapeutic efficacy of human umbilical cord MSCs (hucMSCs) and hucMSC-derived exosomes (hucMSC-EXOs) for muscle atrophy following nerve injury and identified the underlying molecular mechanisms. Sciatic nerve crush injury in rats and the induction of myotubes in L6 cells were used to determine the ameliorating effect of hucMSCs and hucMSC-EXOs on muscle atrophy.

Effects of androgen deprivation therapy on elderly men with high-risk prostate cancer: PROSARC observational study.

Introduction: Prostatic carcinoma (PC) is a frequent neoplasm in elderly patients. Although androgen deprivation is associated with survival benefits, it is also related to adverse effects such as osteoporosis, frailty, or sarcopenia, which can negatively affect the patient's quality of life. This study aims to quantify and evaluate the prevalence of osteoporosis, frailty, or sarcopenia in elderly PC patients before and after androgen deprivation.

Imaging mass cytometry analysis of Becker muscular dystrophy muscle samples reveals different stages of muscle degeneration.

Becker muscular dystrophy (BMD) is characterised by fiber loss and expansion of fibrotic and adipose tissue. Several cells interact locally in what is known as the degenerative niche. We analysed muscle biopsies of controls and BMD patients at early, moderate and advanced stages of progression using Hyperion imaging mass cytometry (IMC) by labelling single sections with 17 markers identifying different components of the muscle.

Prognostic value of preoperative sarcopenia in gastric cancer: A 10-year follow-up study.

Background: Preoperative sarcopenia is associated with prognosis in patients with gastric cancer (GC); however, studies with 10-year survival follow-up are lacking.

Methods: Consecutive patients with GC who underwent radical gastrectomy between December 2009-2012 were included retrospectively. Preoperative sarcopenia was diagnosed using computed tomography skeletal muscle index.

Myosteatosis is associated with poor survival after kidney transplantation: a large retrospective cohort validation.

Purpose: We aim to establish diagnostic thresholds of sarcopenia and myosteatosis based on CT measurements, and to validate their prognostic value in a large cohort of kidney transplant recipients.

Methods: Local healthy population with abdominal CT between 2010 and 2022, and patients underwent kidney transplantation between 2015 and 2019 at our center were retrospectively included. The skeletal muscle index and muscle attenuation of abdominal muscles were calculated based on CT image at the middle of the third lumbar vertebra.

MalnutritiOn assessment with biOelectrical impedaNce analysis in gastRic cancer patIentS undergoing multimodaltrEatment (MOONRISE)-Study protocol for a single-arm multicenter cross-sectional longitudinal study.

European data suggests that over 30% of gastric cancer (GC) patients are diagnosed with sarcopenia before surgery, while unintentional weight loss occurs in approximately 30% of patients following gastrectomy. Preoperative sarcopenia significantly increases the risk of major postoperative complications, and preoperative body weight loss remains a superior predictor of outcome and an independent prognostic factor for overall survival (OS) in patients with GC. A standardized approach of nutritional risk screening of GC patients is yet to be established.

Denervation-Induced Sarcopenia Model.

Rheumatoid arthritis (RA) is an important risk factor for sarcopenia. Physical inactivity, systemic inflammatory factors, and medication directly or indirectly induce skeletal muscle loss in RA patients. The sarcopenia-induced systemic or local proinflammatory microenvironment also contributes to the onset and progression of autoimmune disease.

Prevalence of sarcopenia in patients with chronic kidney disease: a global systematic review and meta-analysis.

Sarcopenia is a risk factor for adverse clinical outcomes in chronic kidney disease (CKD) patients, including mortality. Diagnosis depends on adopted consensus definition and cutoff values; thus, prevalence rates are generally heterogeneous. We conducted a systematic review and meta-analysis to investigate the global prevalence of sarcopenia and its traits across the wide spectrum of CKD.

Progressive, multi-organ, and multi-layered nature of cancer cachexia.

Cancer cachexia is a complex, multifaceted condition that negatively impacts the health, treatment efficacy, and economic status of cancer patients. The management of cancer cachexia is an essential clinical need. Cancer cachexia is currently defined mainly according to the severity of weight loss and sarcopenia (i.

The SMA Modifier Plastin 3 Targets Cell Membrane-Associated Proteins in Motoneurons.

Loss of the gene inevitably leads to spinal muscular atrophy (SMA), one of the most common fatal neuromuscular diseases in children with FDA and EMA approved therapies. However, the cellular mechanisms leading to neuromuscular junction (NMJ) dysfunction due to impaired Ca homeostasis in the presynaptic compartment remain largely unexplained. In the last decade, the so-called SMA modifiers have gained attention.

Impact of Skeletal Muscle Loss and Sarcopenia on Outcomes of Locally Advanced Esophageal Cancer during Neoadjuvant Chemoradiation.

Background: The impact of changes in skeletal muscle and sarcopenia on outcomes during neoadjuvant chemoradiotherapy (NACR) for patients with esophageal cancer remains controversial.

Patients And Methods: We retrospectively analyzed the data of patients with locally advanced esophageal squamous cell cancer who received NACR followed by esophagectomy between June 2013 and December 2021. The images at third lumbar vertebra were analyzed to measure the cross-sectional area and calculate skeletal muscle index (SMI) before and after NACR.

Erosive hand osteoarthritis and sarcopenia: data from Osteoarthritis Initiative cohort.

Objectives: There is no evidence linking specific osteoarthritis (OA) types, such as erosive hand OA (EHOA), with distant generalised changes in muscle composition (sarcopenia), which can potentially be modified. This study pioneers the exploration of the association between EHOA and sarcopenia, both of which are predominantly observed in the older adults.

Methods: Using the Osteoarthritis Initiative cohort, we selected hand OA (modified Kellgren and Lawrence (grade ≥2 in ≥1 hand joint) participants with radiographic central erosions in ≥1 joints (EHOA group) and propensity score-matched hand OA participants with no erosion (non-EHOA group).