Insights into spinal muscular atrophy from molecular biomarkers

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology

Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.

Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and atrophy.The genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene therapies.SMA was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between individuals.Now,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice versa.Additionally,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

Refractory lipoatrophy treated with autologous whole blood injection:A case report

BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resolve,several treatment options have been suggested for this condition.CASE SUMMARY In this paper,we report a case of corticosteroid injection induced lipoatrophy treated with autologous whole blood(AWB)injection,as the condition had been unresponsive to fractional laser therapy.A 29-year-old female patient visited the dermatology clinic complaining of skin depression on her right buttock area,which had appeared six months earlier.There had been only subtle improvement at the margins after fractional CO2 laser treatment;therefore,after obtaining informed consent from the patient,AWB treatment was initiated.One month after the first AWB injection,the size and depth of the lesion had noticeably improved,and a slight improvement was also observed in discoloration.CONCLUSION Close observation is the initial treatment of choice for steroid induced skin atrophy;however,for patients in need of immediate cosmetic improvement,AWB injection may be a safe and cost-effective alternative.

Strain-dependent alpha-synuclein spreading in Parkinson's disease and multiple system atrophy

Parkinson's disease(PD) and atypical Parkinsonian syndromes,such as multiple system atrophy(MSA) and Dementia with Lewy bodies,are neurodegenerative movement disorders characterized by the accumulation of alphasynuclein(a-syn) aggregates.These a-syn aggregates propagate throughout the brain in a prion-like manner,where pathological a-syn recruits endogenous a-syn to form insoluble aggregates.Oligomeric forms representing intermediates on the way to insoluble aggregates result in the most pronounced neurotoxic effects.

Mitochondria replacement from transplanted amniotic fluid stem cells:a promising therapy for non-neuronal defects in spinal muscular atrophy

Spinal muscular atrophy(SMA)is a genetic disorder that primarily affects infants and leads to muscle weakness,atrophy,and paralysis.The main cause is the homozygous mutation or deletion of the SMN1 gene,resulting in inadequate levels of the survival motor neuron(SMN)protein.Approved treatments focus on restoring SMN levels through various approaches,but there is a need for“SMN-independent”therapies that target other pathological processes.Skeletal muscle is closely involved in SMA pathology,with impaired muscle function observed before motor neuron degeneration.Studies have revealed that SMN loss leads to skeletal muscle mitochondrial structural abnormalities,impaired respiration,and accumulation of reactive oxygen species.

Inverse relationship between platelet Akt activity and hippocampal atrophy:A pilot case-control study in patients with diabetes mellitus

BACKGROUND Akt plays diverse roles in humans.It is involved in the pathogenesis of type 2 diabetes mellitus(T2DM),which is caused by insulin resistance.Akt also plays a vital role in human platelet activation.Furthermore,the hippocampus is closely associated with memory and learning,and a decrease in hippocampal volume is reportedly associated with an insulin-resistant phenotype in T2DM patients without dementia.AIM To investigate the relationship between Akt phosphorylation in unstimulated platelets and the hippocampal volume in T2DM patients.METHODS Platelet-rich plasma(PRP)was prepared from the venous blood of patients with T2DM or age-matched controls.The pellet lysate of the centrifuged PRP was subjected to western blotting to analyse the phosphorylation of Akt,p38 mitogen-activated protein(MAP)kinase and glyceraldehyde 3-phosphate dehydrogenase(GAPDH).Phosphorylation levels were quantified by densitometric analysis.Hippocampal volume was analysed using a voxel-based specific regional analysis system for Alzheimer’s disease on magnetic resonance imaging,which proposes the Z-score as a parameter that reflects hippocampal volume.RESULTS The levels of phosphorylated Akt corrected with phosphorylated p38 MAP kinase were inversely correlated with the Z-scores in the T2DM subjects,whereas the levels of phosphorylated Akt corrected with GAPDH were not.However,this relationship was not observed in the control patients.CONCLUSION These results suggest that an inverse relationship may exist between platelet Akt activation and hippocampal atrophy in T2DM patients.Our findings provide insight into the molecular mechanisms underlying T2DM hippocampal atrophy.

Mitochondrial dysfunction in type 2 diabetes:A neglected path to skeletal muscle atrophy

Over the course of several decades,robust research has firmly established the significance of mitochondrial pathology as a central contributor to the onset of skeletal muscle atrophy in individuals with diabetes.However,the specific intricacies governing this process remain elusive.Extensive evidence highlights that individuals with diabetes regularly confront the severe consequences of skeletal muscle degradation.Deciphering the sophisticated mechanisms at the core of this pathology requires a thorough and meticulous exploration into the nuanced factors intricately associated with mitochondrial dysfunction.

Infantile Spinal Muscular Atrophy at the Albert Royer National Children’s Hospital Center in Dakar

Introduction: Infantile spinal muscular atrophy (ISA) is an autosomal recessive disease caused by primary degeneration of cells in the anterior horn of the spinal cord, leading to muscle weakness and hypotonia. Its incidence is estimated at 1 in 6000 births worldwide. In Africa, particularly in Senegal, there are few studies interested on this pathology. We therefore deemed this study necessary, which set itself the objective of describing the diagnostic, therapeutic and progressive aspects of infantile spinal muscular atrophy at the Albert Royer National Children’s Hospital Center in Dakar (CHNEAR). Methodology: We conducted a retrospective descriptive study over a period of two (2) years from December 2020 to December 2022. Included were all hospitalized patients in whom the diagnosis of spinal muscular atrophy was made with or without genetic confirmation. The data were collected on a pre-established form then entered and analyzed with the following software: Excel 2013 and R version 4.1.3. Results: During our study period, 2100 children were hospitalized, the annual incidence was 0.76%. The average age of our patients was 9 ± 9 months with a range of 3 months to 32 months and the median was 6.5 months. The sex ratio was 7. The notion of family consanguinity was found in 62.5% of cases and the notion of ISA in the family in 25% of cases. Hypotonia and respiratory distress were found at the forefront in equal proportions (50% of cases). Electromyogram (EMG) was performed in 3 patients (37.5%). Symptomatic medical treatment was administered in 100% of patients, 04 patients had benefited from respiratory physiotherapy, i.e. 50% of cases, and genetic counseling was carried out in one patient (12.5%). The evolution was immediately favorable in 2 patients or 25% of cases, unfavorable in 75% of cases with a death rate of 50% and the average age of death was 5.5 months ± 1 with extremes ranging from 3 to 7 months. Conclusion: The number of Infantile spinal muscular atrophy cases remains low in hospitals in Dakar. Diagnostic means are still difficult to access. The course is difficult to predict and is often marked in the long term by respiratory difficulties which can be fatal.

Anesthetic Management of a Patient with Spinal Muscular Atrophy Type III Undergoing Emergent Caesarean Section: A Case Report

In this case report, we describe the anesthetic management for a 36-year-old G2P0010 at 36 weeks gestation with Spinal Muscular Atrophy Type III who underwent an emergent caesarean section due to fetal footling breech position. The patient is a wheelchair-bound quadriplegic with kyphoscoliosis and a lack of cough reflex who required nasal continuous noninvasive ventilatory support (CNVS) for chronic hypercapnic respiratory failure. Surgery was done under general anesthesia due to its emergent nature, and the patient was successfully extubated and transitioned to nasal CNVS in the operating room at the end of the case. Postoperative care was provided in the medical intensive care unit for three days without complication and the patient was discharged home uneventfully.

MiR-194-Loaded Gelatin Nanospheres Target MEF2C to Suppress Muscle Atrophy in Mechanical Unloading Model

There is still no effective therapy for muscle atrophy.It found that miR-194 was significantlydownregulated in muscle atrophy model.miR-194 could promote muscle differentiation,and also inhibit ubiquitin ligases.miR-194 loaded in gelatin nanosphere were injected into the muscle atrophy model to realize controlled release.

Inflammation and apoptosis accelerate progression to irreversible atrophy in denervated intrinsic muscles of the hand compared with biceps: proteomic analysis of a rat model of obstetric brachial plexus palsy

In treating patients with obstetric brachial plexus palsy,we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps.In a rat model of obstetric brachial plexus palsy,denervated intrinsic musculature of the forepaw entered the irreversible atrophy far earlier than denervated biceps.In this study,isobaric tags for relative and absolute quantitation were examined in the intrinsic musculature of forepaw and biceps on denervated and normal sides at 3 and 5 weeks to identify dysregulated proteins.Enrichment of pathways mapped by those proteins was analyzed by Kyoto Encyclopedia of Genes and Genomes analysis.At 3 weeks,119 dysregulated proteins in denervated intrinsic musculature of the forepaw were mapped to nine pathways for muscle regulation,while 67 dysregulated proteins were mapped to three such pathways at 5 weeks.At 3 weeks,27 upregulated proteins were mapped to five pathways involving inflammation and apoptosis,while two upregulated proteins were mapped to one such pathway at 5 weeks.At 3 and 5 weeks,53 proteins from pathways involving regrowth and differentiation were downregulated.At 3 weeks,64 dysregulated proteins in denervated biceps were mapped to five pathways involving muscle regulation,while,five dysregulated proteins were mapped to three such pathways at 5 weeks.One protein mapped to inflammation and apoptotic pathways was upregulated from one pathway at 3 weeks,while three proteins were downregulated from two other pathways at 5 weeks.Four proteins mapped to regrowth and differentiation pathways were upregulated from three pathways at 3 weeks,while two proteins were downregulated in another pathway at 5 weeks.These results implicated inflammation and apoptosis as critical factors aggravating atrophy of denervated intrinsic muscles of the hand during obstetric brachial plexus palsy.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Fudan University,China(approval No.DF-325)in January 2015.

Macular atrophy after combined intravitreal triamcinolone and photodynamic therapy to treat choroidal neovascularization

AIMTo report the appearance of choriocapillaris atrophy after combined high dose intravitreal triamcinolone acetonide (TA) and photodynamic therapy (PDT) to treat choroidal neovascularization (CNV) associated with age related macular degeneration (AMD).

Imaging misdiagnosis and clinical analysis of significant hepatic atrophy after bilioenteric anastomosis: A case report

BACKGROUND The occurrence of long-term bilioenteric anastomotic stenosis can readily induce liver atrophy and hyperplasia,thereby causing significant alterations in the anatomical and morphological aspects of the liver.This condition significantly hampers the accuracy of preoperative imaging diagnosis,while also exacerbating the complexity of surgical procedures and the likelihood of complications.CASE SUMMARY A 60-year-old female patient was admitted to the hospital presenting with recurring epigastric pain accompanied by a high fever.The patient had a history of cholecystectomy,although the surgical records were not accessible.Based on preoperative imaging and laboratory examination,the initial diagnosis indicated the presence of intrahepatic calculi,abnormal right liver morphology,and acute cholangitis.However,during the surgical procedure,it was observed that both the left and right liver lobes exhibited evident atrophy and thinness.Additionally,there was a noticeable increase in the volume of the hepatic caudate lobe,and the original bilioenteric anastomosis was narrowed.The anastomosis underwent enlargement subsequent to hepatectomy.As a consequence of the presence of remaining stones in the caudate lobe,the second stage was effectively executed utilizing ultrasound-guided percutaneous transhepatic catheter drainage.Following the puncture,three days elapsed before the drain tip inadvertently perforated the liver,leading to the development of biliary panperitonitis,subsequently followed by pulmonary infection.The patient and her family strongly refused operation,and she died.CONCLUSION The hepatic atrophy-hypertrophy complex induces notable alterations in the anatomical structure,thereby posing a substantial challenge in terms of imaging diagnosis and surgical procedures.Additionally,the long-term presence of hepatic fibrosis changes heightens the likelihood of complications arising from puncture procedures.

Diagnosis of Progressive Spinal Muscular Atrophy by Using Polymerase Chain Reaction

Objective To understand the deletion in the survival motor neuron gene (SMN) of childhood onset spinal muscular atrophy (SMA) in Chinese, and the value of diagnosis of SMA using polymerase chain reaction restriction fragment length polymorphism (PCR RFLP)method. Methods\ Deletions of SMN gene of exon 7 and 8 in 10 cases of presumed SMA, and 20 normal controls from 6 families and 30 unrelated controls were performed by PCR RFLP analysis. Results\ Deletions of SMN gene detected in 9 of 10 (90%) cases of presumed SMA . No deletions of SMN in the telomere were found in the other members of families and controls.Conclusion\ PCR RFLP is a sensitive, specific and simple method in diagnosis of SMA.\;

Helicobacter pylori infection, glandular atrophy and intestinal metaplasia in superficial gastritis, gastric erosion, erosive gastritis, gastric ulcer and early gastric cancer

AIM: To evaluate the histological features of gastric mucosa, including Helicobacter pylori infection in patients with early gastric cancer and endoscopically found superficial gastritis, gastric erosion, erosive gastritis, gastric ulcer. METHODS: The biopsy specimens were taken from the antrum, corpus and upper angulus of all the patients. Giemsa staining, improved toluidine-blue staining, and Hpylori-specific antibody immune staining were performed as appropriate for the histological diagnosis of H pylori infection. Hematoxylin-eosin staining was used for the histological diagnosis of gastric mucosa inflammation, gastric glandular atrophy and intestinal metaplasia and scored into four grades according to the Updated Sydney System. RESULTS: The overall prevalence of H pylori infection in superficial gastritis was 28.7%, in erosive gastritis 57.7%, in gastric erosion 63.3%, in gastric ulcer 80.8%, in early gastric cancer 52.4%. There was significant difference (P<0.05), except for the difference between early gastric cancer and erosive gastritis. H pylori infection rate in antrum, corpus, angulus of patients with superficial gastritis was 25.9%, 26.2%, 25.2%, respectively; in patients with erosive gastritis 46.9%, 53.5%, 49.0%, respectively; in patients with gastric erosion 52.4%, 61.5%, 52.4%, respectively; in patients with gastric ulcer 52.4%, 61.5%, 52.4%, respectively; in patients with early gastric cancer 35.0%, 50.7%, 34.6%, respectively. No significant difference was found among the different site biopsies in superficial gastritis, but in the other diseases the detected rates were higher in corpus biopsy (P<0.05). The grades of mononuclear cell infiltration and polymorphonuclear cell infiltration, in early gastric cancer patients, were significantly higher than that in superficial gastritis patients, lower than that in gastric erosion and gastric ulcer patients (P<0.01); however, there was no significant difference compared with erosive gastritis. The grades of mucosa glandular atrophy and intestinal metaplasia were significantly highest in early gastric cancer, lower in gastric ulcer, the next were erosive gastritis, gastric erosion, the lowest in superficial gastritis (P<0.01). Furthermore, 53.3% and 51.4% showed glandular atrophy and intestinal metaplasia in angular biopsy specimens, respectively; but only 40.3% and 39.9% were identified in antral biopsy, and 14.1% and 13.6% in corpus biopsy; therefore, the angulus was more reliable for the diagnosis of glandular atrophy and intestinal metaplasia compared with antrum and corpus (P<0.01). The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis with H pyloripositivity was 50.7%, 34.1%; of erosive gastritis 76.1%, 63.0%; of gastric erosion 84.8%, 87.8%; of gastric ulcer 80.6%, 90.9%; and of early gastric cancer 85.5%, 85.3%, respectively. The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis with H pylorinegativity was 9.9%, 6.9%; of erosive gastritis 42.5%, 42.1%; of gastric erosion 51.1%, 61.9%; of gastric ulcer 29.8%, 25.5%; and of early gastric cancer 84.0%, 86.0%, respectively. The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis, erosive gastritis, gastric erosion, and gastric ulcer patients with H pylon positivity was significantly higher than those with H pylori negativity (P<0.01); however, there was no significant difference in patients with early gastric cancer with or without H pylori infection. CONCLUSION: The progression of the gastric pre-cancerous lesions, glandular atrophy and intestinal metaplasia in superficial gastritis, gastric erosion, erosive gastritis and gastric ulcer was strongly related to H pylori infection. In depth studies are needed to evaluate whether eradication of H pylori infection will really diminish the risk of gastric cancer.

-765G > C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia

AIM： To investigate the relationship between the -765G 〉 C COX-2 polymorphism and the development of different gastric lesions： atrophy or intestinal metaplasia and gastric adenocarcinoma. METHODS： A cross-sectional study was performed involving 320 Portuguese individuals （210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia） using a PCR-RFLP method.RESULTS： -765C allele was overrepresented in the patients with gastric adenocarcinoma （51%） when compared either with the control group （38%） or patients with atrophy or intestinal metaplasia （27%）. Callele was found to be very common in our population （0.22）, and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele （OR = 2.67, 95% CI = 1.03-6.93; P = 0.04）.CONCLUSION： -765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.

Serum biomarker tests are useful in delineating between patients with gastric atrophy and normal,healthy stomach

AIM:To study the value of serum biomarker tests to differentiate between patients with healthy or diseased stomach mucosa:i.e.those with Helicobacter pylori(H pylori)gastritis or atrophic gastritis,who have a high risk of gastric cancer or peptic ulcer diseases.METHODS:Among 162 Japanese outpatients,pepsinogen-(Pg-)and(Pg)were measured using a conventional Japanese technique,and the European GastroPanel examination(Pg and Pg,gastrin-17 and H pylori antibodies).Gastroscopy with gastric biopsies was performed to classify the patients into those with healthy stomach mucosa,H pylori non-atrophic gastritis or atrophic gastritis.RESULTS:Pg-and Pg assays with the GastroPanel and the Japanese method showed a highly significant correlation.For methodological reasons,however,serum Pg-,but not Pg,was twice as high with the GastroPanel test as with the Japanese test.The biomarker assays revealed that 5%of subjects had advanced atrophic corpus gastritis which was also verified by endoscopic biopsies.GastroPanel examination revealed an additional seven patients who had either advanced atrophic gastritis limited to the antrum or antrum-predominant H pylori gastritis.When compared to the endoscopic biopsy findings,the GastroPanel examination classified the patients into groups with "healthy" or "diseased" stomach mucosa with 94% accuracy,95% sensitivity and 93% specifi city.CONCLUSION:Serum biomarker tests can be used to differentiate between subjects with healthy and diseased gastric mucosa with high accuracy.

Non-invasive diagnosis of gastric mucosal atrophy in an asymptomatic population with high prevalence of gastric cancer

AIM: To validate a non-invasive method to detect gastric mucosal atrophy in a Chilean population with high prevalence of gastric cancer and a poor survival rate. METHODS: We first determined the optimal cut-off level of serum pepsinogen (PG)-1, PG-1/PG-2 ratio and 17-gastrin in 31 voluntary symptomatic patients (mean age: 66.1 years), of them 61% had histologically confirmed gastric atrophy. Then, in a population-based sample of 536 healthy individuals (209 residents in counties with higher relative risk and 327 residents in counties with lower relative risk for gastric cancer), we measured serum anti-H pylori antibodies, PG and 17-gastrin and estimated their risk of gastric cancer. RESULTS: We found that serum PG-1 < 61.5 μg/L, PG-1/PG-2 ratio < 2.2 and 17-gastrin > 13.3 pmol/L had a high specificity (91%-100%) and a fair sensitivity (56%-78%) to detect corpus-predominant atrophy. Based on low serum PG-1 and PG-1/PG-2 ratio together as diagnostic criteria, 12.5% of the asymptomatic subjects had corpus-predominant atrophy (0% of those under 25 years and 20.2% over 65 years old). The frequency of gastric atrophy was similar (12% vs 13%) but H pylori infection rate was slightly higher (77% vs 71%) in the high-risk compared to the low-risk counties. Based on their estimated gastric cancer risk, individuals were classified as: low-risk group (no H pylori infection and no atrophy; n = 115; 21.4%); moderate-risk group(H pylori infection but no atrophy; n = 354, 66.0%); and high-risk group (gastric atrophy, with or without H pylori infection; n = 67, 12.5%). The high-risk group was significantly older (mean age: 61.9 ± 13.3 years), more frequently men and less educated as compared with the low-risk group. CONCLUSION: We propose to concentrate on an upper gastrointestinal endoscopy for detection of early gastric cancer in the high-risk group. This intervention model could improve the poor prognosis of gastric cancer in Chile.

Apoptosis in skeletal muscle and its relevance to atrophy

Apoptosis is necessary for maintaining the integrity of proliferative tissues, such as epithelial cells of the gastrointestinal system. The role of apoptosis in post mitotic tissues, such as skeletal muscle, is less well defined. Apoptosis during muscle atrophy occurs in both myonuclei and other muscle cell types. Apoptosis of myonuclei likely contributes to the loss of muscle mass, but the mechanisms underlying this process are largely unknown. Caspase-dependent as well as -independent pathways have been implicated and the mode by which atrophy is induced likely determines the apoptotic mechanisms that are utilized. It remains to be determined whether a decrease in apoptosis will alleviate atrophy and distinct research strategies may be required for different causes of skeletal muscle loss.