Progressive Loss Of Muscle Mass Research Articles

Advance in Drug Delivery for Ageing Skeletal Muscle.

The age-related loss of skeletal muscle, sarcopenia, is characterized by progressive loss of muscle mass, reduction in muscle strength, and dysfunction of physical performance. It has become a global health problem leading to several adverse outcomes in the ageing population. Research on skeletal muscle loss prevention and treatment is developing quickly. However, the current clinical approaches to sarcopenia are limited. Recently, novel drug delivery systems offer new possibilities for treating aged muscle loss. Herein, we briefly recapitulate the potential therapeutic targets of aged skeletal muscle and provide a concise advance in the drug delivery systems, mainly focus on the use of nano-carriers. Furthermore, we elaborately discuss the prospect of aged skeletal muscle treatment by nanotechnology approaches.

Mtorc1 Sensitivity To Amino Acids In Skeletal Muscle And Myotubes Derived From Young And Older Men

Ageing is associated with a progressive loss of muscle mass termed sarcopenia, increasing morbidity and mortality. Although multifactorial in nature, dysregulated sensing of amino acids (AAs) after nutrient ingestion, coupled with blunted mTORC1 activation and muscle protein synthesis (MPS), is undoubtedly a major contributing factor in the development and progression of sarcopenia. However, it is unknown whether this is a result of poor AA delivery to the muscle or diminished AA sensing intrinsic to aged muscle cells. Exercise has been shown to increase the sensitivity of muscle to AAs, and conversely, reductions in physical activity appear to drastically impair this response. Since there is typically a reduction in habitual physical activity in the elderly, the impaired muscle growth response to AAs may be a consequence of a lack of physical activity rather than ageing. PURPOSE: To determine the roles that age and physical activity levels play in the activation of anabolic pathways within skeletal muscle and myotube cultures in response to AAs. METHODS: A cross-sectional study was used to compare mTORC1 signaling in response to ingestion of whey protein in 7 young active (Y, 23±2 yrs), 8 older active (OA, 71±4 yrs) and 3 older inactive (OI, 71±5 yrs) men. To determine if mTORC1 sensitivity is intrinsically regulated and remembered by skeletal muscle cells, myoblasts were isolated from biopsies from these participants and differentiated to form myotubes. Myotube cultures were then deprived of serum and AAs, re-stimulated with AAs, and subsequently lysed temporally for mTORC1 analysis. RESULTS: Our preliminary data indicates that phosphorylation of ribosomal protein s6 (RPS6), a downstream mTORC1 substrate, was increased in myotube cultures from Y and OA men with a reduced response in OI men (Y= 7.2 + 7.3, AO= 9.8 + 4.5, IO = 6.0 + 5.6 -fold). We are currently analysing muscle tissue from these same individuals to understand if mTORC1 signaling is comparable between biopsy tissue and myotube cultures. CONCLUSION: Sustained physical activity levels in older individuals and regular structured exercise may diminish age-related mTORC1 desensitisation of skeletal muscle in response to AA ingestion in cultured myotubes.

Sarcopenic obesity in ageing: cardiovascular outcomes and mortality.

Obesity is a major public health issue with prevalence increasing worldwide. Obesity is a well-established risk factor for CVD and mortality in adult populations. However, the impact of being overweight or obese in the elderly on CVD and mortality is controversial. Some studies even suggest that overweight and obesity, measured by BMI, are apparently associated with a decreased mortality risk (known as the obesity paradox). Ageing is associated with an increase in visceral fat and a progressive loss of muscle mass. Fat mass is positively associated and lean mass is negatively associated with risk of mortality. Therefore, in older adults BMI is not a good indicator of obesity. Sarcopenia has been defined as the degenerative loss of muscle mass, quality and strength with age and is of major concern in ageing populations. Sarcopenia has previously been associated with increased risks of metabolic impairment, cardiovascular risk factors, physical disability and mortality. It is possible for sarcopenia to co-exist with obesity, and sarcopenic obesity is a new class of obesity in older adults who have high adiposity levels together with low muscle mass, quality or strength. Therefore, sarcopenia with obesity may act together to increase their effect on metabolic disorders, CVD and mortality. This review will discuss the available evidence for the health implications of sarcopenic obesity on CVD and mortality in older adults.

Age-related biochemical and histological changes in the soleus muscle of male mice

During aging, skeletal muscle is subjected to progressiveloss of muscle mass and strength (sarcopenia) and a decline in thefunctional ability. The reduction in the antioxidative capacity ofthe skeletal muscle resulting in an abnormal accumulation of thereactive oxygen species (ROS) that is one of the possible causesof the decline in muscle performance. In this study thehistological changes in the soleus muscles of male mice at the ageof 1st and 15th old were examined and the activities of theantioxidant enzymes, CAT and SOD, non- enzymatic antioxidantGPH and MDA level were measured to clarify the age-relatedchanges in healthy subjects. Results showed that there is asignificant reduction (P ≤ 0.05) in the antioxidants SOD, CATand GPH and there is a significant increase (P ≤ 0.05) in MDAlevel at the age of 15th month when compared to 1st month old.We concluded that the activities of the antioxidants were affectedby aging. Moreover, there is age- related lipid peroxidation.

Characterizing Exon Skipping Efficiency in DMD Patient Samples in Clinical Trials of Antisense Oligonucleotides

Duchenne muscular dystrophy (DMD) is a degenerative muscle disease that causes progressive loss of muscle mass, leading to premature death. The mutations often cause a distorted reading frame and premature stop codons, resulting in an almost total lack of dystrophin protein. The reading frame can be corrected using antisense oligonucleotides (AONs) that induce exon skipping. The morpholino AON viltolarsen (code name: NS-065/NCNP-01) has been shown to induce exon 53 skipping, restoring the reading frame for patients with exon 52 deletions. We recently administered NS-065/NCNP-01 intravenously to DMD patients in an exploratory investigator-initiated, first-in-human trial of NS-065/NCNP-01. In this methods article, we present the molecular characterization of dystrophin expression using Sanger sequencing, RT-PCR, and western blotting in the clinical trial. The characterization of dystrophin expression was fundamental in the study for showing the efficacy since no functional outcome tests were performed.

Zingiber Officinale Roscoe Prevents Cellular Senescence of Myoblasts in Culture and Promotes Muscle Regeneration.

Background Ageing resulted in a progressive loss of muscle mass and strength. Increased oxidative stress in ageing affects the capacity of the myoblast to differentiate leading to impairment of muscle regeneration. Zingiber officinale Roscoe (ginger) has potential benefits in reversing muscle ageing due to its antioxidant property. This study aimed to determine the effect of ginger in the prevention of cellular senescence and promotion of muscle regeneration. Methods Myoblast cells were cultured into young and senescent state before treated with different concentrations of ginger standardised extracts containing different concentrations of 6-gingerol and 6-shogaol. Analysis on cellular morphology and myogenic purity was carried out besides determination of SA-β-galactosidase expression and cell cycle profile. Myoblast differentiation was quantitated by determining the fusion index, maturation index, and myotube size. Results Treatment with ginger extracts resulted in improvement of cellular morphology of senescent myoblasts which resembled the morphology of young myoblasts. Our results also showed that ginger treatment caused a significant reduction in SA-β-galactosidase expression on senescent myoblasts indicating prevention of cellular senescence, while cell cycle analysis showed a significant increase in the percentage of cells in the G0/G1 phase and reduction in the S-phase cells. Increased myoblast regenerative capacity was observed as shown by the increased number of nuclei per myotube, fusion index, and maturation index. Conclusions Ginger extracts exerted their potency in promoting muscle regeneration as indicated by prevention of cellular senescence and promotion of myoblast regenerative capacity.

The Prevalence of Sarcopenia in Bipolar Disorder.

BackgroundSarcopenia (SP) is a syndrome described as generalized and progressive loss of muscle mass and strength that may cause fall, fractures, disability and death. Oxidative stress might be a probable etiologic factor in SP as well. SP is a comorbid syndrome that is seen in chronic illnesses. If these two considerations are taken together, one may also think that SP could be also seen in bipolar disorder (BD), because it is a chronic disorder and oxidative stress was related to both illnesses. In our study, we proposed to investigate the prevalence of SP in BD patients.MethodsWe recruited 111 consecutive BD patients who registered in Mood Disorders Unit of Çukurova University. Blood tests were taken from patients to exclude the possible confounding factor related to SP. Socio-demographic variable forms were filled out. Every patient underwent physical mass, strength, and performance tests for the diagnosis of SP, which was determined by the criteria of European consensus.ResultsThe mean age of the patients was 38.00 ±11.44 years (18–68). Among the participants 69 (62.2%) were female, and 42 (37.8%) were male. Pre-SP was 6.3% (n=7), SP was 9.0% (n=10), and severe SP was 1.8% (n=2) in BD patients. The prevalence of pre-SP, SP and severe SP in BD patients was 7.1%, 16.7% and 2.4% in men and 5.8%, 4.3% and 1.4% in women, respectively. Although it was not marginally significant, a difference was observed in SP patients as they had more median psychotic features and median number of episodes per year for BD.ConclusionThis is the first study that investigated SP in BD patients. Sarcopenia was found more frequently in BD patients than in the general population.

Sarcopenia: What a Surgeon Should Know.

Sarcopenia is an increasingly frequent syndrome characterized by generalized and progressive loss of muscle mass, reduction in muscle strength, and resultant functional impairment. This condition is associated with increased risk of falls and fractures, disability, and increased risk of death. When a sarcopenic patient undergoes major surgery, it has a higher risk of complications and postoperative mortality because of less resistance to surgical stress. It is not easy to recognize a sarcopenic patient preoperatively, but this is essential to evaluate the correct risk to benefit ratio. The role of sarcopenia in surgical patients has been studied for both oncological and non-oncological surgery. For correct surgical planning, data about sarcopenia are essential to design a correct tailored treatment.

Sarcopenia in patients with chronic obstructive pulmonary disease: A study of prevalence and associated factors in Western Greek population.

Background:Chronic obstructive pulmonary disease (COPD) is associated with a progressive loss of muscle mass and function and a systemic inflammatory process that can cause sarcopenia.Objective:The objective of this study is to estimate the prevalence rate of sarcopenia in COPD patients and to determine the factors associated with sarcopenic patients living in Western Greece.Methods:European Working Group on Sarcopenia in Older People criteria were applied to 69 outpatients with stable COPD. Body composition, exercise capacity, functional performance, physical activity, and health status were also assessed. COPD disease severity (COPD stage) was evaluated with the Global Initiative for chronic obstructive lung disease. The study protocol was approved by the Ethical Committee of the Technological Educational Institute of Western Greece.Results:The sample comprised 69 patients (59 women and 10 men), with a mean age of 71.33 ± 7.48 years. The prevalence of sarcopenia was 24.6% (n = 17). A high percentage (82.6%; n = 57) of the 69 Greek participants did not perform any regular exercise. The findings of this study demonstrated that sarcopenia was positively associated with COPD, age, body mass index, skeletal muscle mass, hand grip strength, and 4 m test.Conclusions:In conclusion, there is a 24.6% prevalence of sarcopenia in patients with COPD. Further research with larger samples would be indicated to clarify the precise association of specific characteristics of patients with sarcopenia and COPD.

Isolation, Culture, and Differentiation of Primary Myoblasts Derived from Muscle Satellite Cells

The skeletal muscle is key for body mobility and motor performance, but aging and diseases often lead to progressive loss of muscle mass due to wasting or degeneration of muscle cells. Muscle satellite cells (MuSCs) represent a population of tissue stem cells residing in the skeletal muscles and are responsible for homeostatic maintenance and regeneration of skeletal muscles. Growth, injury, and degenerative signals activate MuSCs, which then proliferate (proliferating MuSCs are called myoblasts), differentiate and fuse with existing multinuclear muscle cells (myofibers) to mediate muscle growth and repair. Here, we describe a protocol for isolating MuSCs from skeletal muscles of mice for in vitro analysis. In addition, we provide a detailed protocol on how to culture and differentiate primary myoblasts into myotubes and an immunofluorescent staining procedure to characterize the cells. These methods are essential for modeling regenerative myogenesis in vitro to understand the dynamics, function and molecular regulation of MuSCs.

Sarcopenia in COPD: a systematic review and meta-analysis.

COPD is associated with a progressive loss of muscle mass and function. However, there is an unmet need to define and standardise methods to estimate the prevalence of sarcopenia in COPD patients.We performed a systematic review and meta-analysis of the prevalence of this extrapulmonary manifestation in COPD patients. We searched Embase, Medline (Ovid), CINAHL (EBSCO), Web of Science, Scopus and Google Scholar for studies published up to January 17, 2019, assessing sarcopenia in COPD patients based on low muscle mass and decreased muscle function. Interventional studies, in vitro experiments, protocols or reviews and meta-analyses were excluded. We estimated heterogeneity (I2) and assessed significance (Q) using a Chi-squared test for estimates obtained from random-effects models.4465 articles were initially identified. After removing the duplicates and applying the selection criteria, we reviewed 62 full-text articles. Finally, 10 articles (n=2565 COPD patients) were included in this systematic review and meta-analyses. Overall, the prevalence of sarcopenia in patients with COPD was 21.6% (95% CI 14.6-30.9%, I2=94%), ranging from 8% in population-based to 21% in clinic-based studies, and 63% in COPD patients residing in nursing homes.Sarcopenia is frequently observed in COPD patients, with varying prevalence across population settings. Sarcopenia in COPD should be assessed using standardised tests and cut-off points from sarcopenia consensus criteria for clinical practice and international comparisons.

Progressive loss of muscle mass could be an adverse prognostic factor of 28-day mortality in septic shock patients

A decrease in skeletal muscle mass has been shown to increase hospital mortality. Nevertheless, little is known about the association between progressive muscle loss over time and clinical outcomes. We aimed to evaluate whether progressive loss of muscle mass in septic shock patients was associated with mortality. We reviewed prospectively enrolled registry of septic shock which had 817 consecutive patients. Of these, 175 patients who had computed tomography (CT) at a time of admission as well as 3–6 months prior to admission were included. Between these two CTs, the change in total abdominal muscle area index (TAMAI) was evaluated for progressive muscle loss. The change in TAMAI was higher in the non-survivors (−7.6 cm2/m2, 19.0% decrease) than the survivors (−4.0 cm2/m2, 10.5% decrease) with statistical significance (p = 0.002). Multiple logistic regression showed that the patients who had more than a 6.4 cm2/m2 (16.7%) reduction of TAMAI had a 4.42-fold higher risk for mortality at 28 days (OR, 4.42; 95% CI, 1.41–13.81, p = 0.011). Our study suggested that progressive loss of muscle mass might be a useful prognostic factor for septic shock patients. This implication will need to be further explored in future prospective studies.

Low Appendicular Lean Mass Index and Associations with Metabolic and Demographic Parameters in Wheelchair Athletes with Spinal Cord Injury.

People suffering from spinal cord injury (SCI) undergo metabolic and physical disturbances that target the skeletal muscle, causing a progressive loss of muscle mass. To estimate the appendicular lean mass index (ALMI) in athletes with traumatic (T-group) and non-traumatic (NT-group) SCI, and its association with metabolic and demographic parameters. Wheelchair athletes with SCI aged 18 to 52 years old were included (n = 62). From DEXA assessment, we estimated the ALM index (ALMI = appendicular lean mass/height2) and classified participants according to the degree of muscle loss (ALMI < 2 SD from the reference populations). Fasting blood was assayed for glycaemia, insulin, cortisol, and IGF-1 serum levels. Data were compared by T-test and Fisher's Exact Test; predictors of ALMI were investigated by linear regression models. The frequency of low ALMI was 63% in overall sample, 55% T-group and 71% NT-group. Low ALMI had no significant association with the origin of injury (X2 = 1.1, p = 0.29). Linear regression analyses showed significant association, in the whole sample, between ALMI and serum levels of IGF-1 (Beta = 0.69; p < 0.001), age (Beta=-5.8; p < 0.001), percentage fat mass (Beta=-0.26; p = 0.001), and energy intake (Beta = 0.32; p = 0.02). These significances were not maintained in the NT-group sub-analyses. Low ALMI was very frequent in our SCI participants, despite exercising and independently of the type of injury. Metabolic and demographic variables associated with low ALMI were different according to the origin of injury, which possibly relies on physiopathology particularities. More studies are necessary to clarify our findings.

246 A Clinical Audit of Detection and Management of Sarcopenia in Older Persons’ Specialist Rehabilitation Services in an Academic Teaching Hospital

Abstract Background Sarcopenia, characterised by progressive loss of muscle mass and strength, is associated with increased morbidity, mortality and poorer quality of life. International and European clinical practice guidelines on diagnosis and management of sarcopenia suggest the algorithm: Find Cases through screening, Assess Strength with validated outcome measures, Confirm Diagnosis with muscle quantity analysis and Determine Severity with validated physical performance measures (PPMs). Treatment recommendations include progressive resistance training (PRT) and a protein-rich diet. This audit aimed to investigate our specialist gerontological services’ adherence to these guidelines. Methods Using a custom-designed audit tool, patient medical records (PMRs) were reviewed in two inpatient rehabilitation wards and one Day Hospital (DH). Patients were included if under the care of a geriatrician and reviewed two or more times by a physiotherapist. Results Thirty PMRs were reviewed (18 DH, 12 inpatient). 0% of patients were screened for sarcopenia using a validated screening tool. 83.3% (n=15) of DH patients and 33.3% (n=4) of inpatients underwent a validated strength assessment. 0% of patients underwent muscle quantity analysis. 66.6% (n=12) of DH patients and 33.3% (n=4) of inpatients had validated PPMs performed. Probable sarcopenia was identified in 75% of DH and 100% of inpatients who had PPMs conducted. PRT was prescribed in 94% (n=17) and 50% (n=6) of DH patients and inpatients respectively. 16.6% (n=3) of DH patients and 75% (n=9) of inpatients were referred for nutritional assessment. 100% (n=9) of patients assessed by clinical nutrition were prescribed a high-protein/high-calorie diet. Conclusion This audit demonstrates limitations in identifying and managing sarcopenia as per the most recent international and European clinical practice guidelines. It is recognised that a multi-disciplinary approach is required to improve adherence to these guidelines. A multi-disciplinary sarcopenia management pathway is being implemented to facilitate this. Re-audit is planned to ensure the effectiveness of this pathway.

Efficacy of Nutritional Interventions as Stand-Alone or Synergistic Treatments with Exercise for the Management of Sarcopenia.

Sarcopenia is an age-related and accelerated process characterized by a progressive loss of muscle mass and strength/function. It is a multifactorial process associated with several adverse outcomes including falls, frailty, functional decline, hospitalization, and mortality. Hence, sarcopenia represents a major public health problem and has become the focus of intense research. Unfortunately, no pharmacological treatments are yet available to prevent or treat this age-related condition. At present, the only strategies for the management of sarcopenia are mainly based on nutritional and physical exercise interventions. The purpose of this review is, thus, to provide an overview on the role of proteins and other key nutrients, alone or in combination with physical exercise, on muscle parameters.

The Biological Foundations of Sarcopenia: Established and Promising Markers.

Sarcopenia, the progressive loss of muscle mass and strength, is one of the major health issues in older adults, given its high prevalence accompanied by huge clinical and socioeconomic implications. Age-related changes in skeletal muscle can be attributed to mechanisms both directly and indirectly related to muscle homeostasis. Indeed, a wide spectrum of age-related modifications in the organism was shown to play a key role in the pathogenesis of sarcopenia. Not surprisingly, sarcopenia has sometimes been indicated as a syndrome stemming from the aging process, and not as univocal standalone disease. Due to the multidimensionality of sarcopenia, a single biomarker approach is not enough to explain the biology of this condition. The aim of this review is to suggest innovative and promising sarcopenia markers investigating the link between skeletal muscle and brain. Indeed, as a neurological origin of sarcopenia has been hypothesized, a new perspective on sarcopenia biomarkers may focus on the dysfunction of the neuromuscular junctions (NMJs). The core SNARE synaptosomal-associated protein of 25 kDa (SNAP25) accumulates in the plasma membrane of nerve terminals at NMJs and regulates exocytosis at peripheral and central synapses. Interestingly, mice studies have shown that SNAP25 affects the neuromuscular function. SNARE complex and, in particular, SNAP25 may represent a promising pathway to explore the molecular and cellular mechanisms regulating muscular homeostasis and concur at profiling the sarcopenia biological background.

Ounce Equivalent Protein Ingestion Does Not Result in Equivalent Responses of Protein Kinetics (OR27-05-19)

Abstract Objectives The progressive loss of muscle mass, or sarcopenia, is inherent to aging and related to functionality and independence. It is well established that the loss of muscle mass can be mitigated with adequate dietary protein intake. To help the consumers meet protein requirements utilizing a variety of protein food sources, the Dietary Guidelines for Americans (DGAs) published an “ounce equivalents” recommendation for protein food sources. However, the actual equivalency of these varied protein food groups has not been established. We examined the responses of protein kinetics in response to consumption of ounce equivalents of ground beef, sirloin, eggs, pork loin, kidney beans, peanut butter, tofu, and mixed nuts in young subjects. Methods Subjects adhered to 3 days of activity and dietary control, and were then studied using an 8.5 h metabolic study which included a 4.5 h basal overnight-fasted period followed by a 4 h post-meal period. All groups were balanced by sex (4 males/4 females). Results Consumption of animal-based protein food sources resulted in higher whole body net balance than the plant-based protein food sources (P &lt; 0.05). Consumption of beef sirloin, eggs, and pork loin induced a higher whole-body anabolic response than ground beef and the plant- based proteins. Consumption of tofu (soy-protein) induced a higher whole-body anabolic response than the other plant proteins (P &lt; 0.05). The improvement in whole-body net balance with animal-based protein sources and tofu was due to a significant increase in protein synthesis (P &lt; 0.05) as well as a significant suppression of protein breakdown in most protein sources (P &lt; 0.05). Whole-body net balance was related to higher plasma EAA concentrations with animal-based protein sources and tofu realizing greater peripheral concentrations (P &lt; 0.05). Conclusions The results of this study indicate that the “ounce equivalents” as expressed in the DGAs do not produce equivalent anabolic responses, nor are they equivalent in terms of the amount of protein provided, or the caloric cost of protein consumption. The magnitude of anabolic response appears to be largely determined by the amount of essential amino acids per gram of protein food source. Funding Sources The Beef Checkoff, National Pork Board, and Egg Nutrition Center.

Accelerated sarcopenia and outcomes in older adults with cancer: The Health ABC Study.

11526 Background: Progressive loss of muscle mass and strength (sarcopenia) is a well-known phenomenon of aging; however, little is known about the contribution of a cancer diagnosis to sarcopenia and its subsequent impact on disability. Using a prospective cohort of older adults from pre- to post-cancer diagnosis and a similarly-followed non-cancer cohort, we examined the trajectory of sarcopenia measures and their association with overall survival (OS) and major disability among those with cancer. Methods: The Health, Aging, and Body Composition (Health ABC) Study is a prospective longitudinal study where 3,075 community-dwelling older adults (70-79y) underwent 6 annual assessments of body composition and were followed for development of sentinel events (cancer, disability, death). Appendicular lean mass (ALM [kg]) was a sum of DXA-based lean tissue of all extremities. Hand grip strength (HGS [kg]) was averaged from 2 trials per hand. Gait speed (GS) was evaluated over a 20m course. We used linear mixed effect models to compare the change in ALM, HGS, and GS between individuals who subsequently developed cancer and those who did not, adjusting for age, race, gender, enrollment site. Among patients with cancer, we used multivariable cox regression for time from cancer diagnosis to mortality and major disability (cane/walker, inability to walk 0.25 mile/climb 10 steps, assistance with activities of daily living) treating sarcopenia measures as time-varying covariates. Results: Mean age at enrollment was 75y; 52% female; 42% black; 515 new cancers (prostate: 23%, colorectal: 15%, lung: 13%, breast: 11%). Compared with non-cancer controls, we found significantly steeper declines in HGS ( p= 0.03) and GS ( p&lt; 0.001), and a trend in ALM ( p= 0.07) prior to cancer diagnosis; and a significantly steeper decline in ALM ( p&lt; 0.001), but no difference in HGS ( p= 0.6) or GS ( p= 0.4) after cancer diagnosis. Slow GS was associated with a 44% increase in mortality ( p= 0.02) and a 70% increase in disability ( p= 0.02), but not ALM or HGS. Conclusions: Accelerated loss in sarcopenia measures both prior to and after a cancer diagnosis, and association with disability and mortality in older adults with cancer, present opportunities for targeted interventions.

Tetra-linoleoyl cardiolipin depletion plays a major role in the pathogenesis of sarcopenia

Sarcopenia, the progressive loss of muscle mass, strength, and physical performance that occurs during aging, is highly prevalent among the elderly. Sarcopenia increases the risk of falls, disability, and death. The biological basis for sarcopenia is not well understood. There are no specific preventive or therapeutic strategies for sarcopenia except exercise. The elucidation of biological pathways and identification of therapeutic targets for treating or preventing sarcopenia remain a high priority in aging research. Mitochondria play a critical role in skeletal muscle by providing energy in the form of ATP, regulation of signaling, calcium homeostasis, autophagy, and other functions. Cardiolipin, a unique dimeric phospholipid specific to mitochondria and an essential component of mitochondrial membranes, is involved in mitochondrial protein transport, maintaining structural organization of mitochondrial membranes, cellular signaling, regulating enzymes involved in β-oxidation of fatty acids, and facilitating normal electron transport chain (ETC) function and generation of ATP. The fatty acid species composition of cardiolipin is critical to mitochondrial bioenergetics, as cardiolipin affects membrane biophysical properties, binds and stabilizes ETC protein complexes, and shapes the curvature of the mitochondrial cristae. Tetra-linoleoyl cardiolipin (18:2)4 comprises ∼80% of cardiolipin in mitochondria in normal human skeletal and cardiac muscle and is optimal for effective ETC function and ATP generation. Aging is associated with a decrease in cardiolipin content, decrease in tetra-linoleoyl cardiolipin (18:2)4 and replacement of linoleic acid (18:2) with other fatty acids in cardiolipin composition, decline of ETC function, and increased generation of reactive oxygen species in muscle. Together, these findings from the literature prompt the hypothesis that depletion of the cardiolipin (18:2)4 species may be at the root of mitochondrial dysfunction with aging, in turn leading to sarcopenia. Corroboration of the tetra-linoleoyl cardiolipin depletion hypothesis suggests new leads for the prevention and treatment of sarcopenia by enhancing the biosynthesis, accretion, and integrity of tetra-linoleoyl cardiolipin.

Economic Impact of Hospitalizations in US Adults with Sarcopenia

BackgroundSarcopenia is characterized by progressive loss of muscle mass with corresponding decline in strength and/or physical function. The economic burden of sarcopenia-associated disability is considerable in the US.ObjectiveTo estimate the cost of hospitalizations in US adults with sarcopenia categorized by age, sex, and race/ethnicity.Design, setting and participantsA retrospective, prevalence based, economic burden study, consisting of 4011 adults aged ≥40 years with and without sarcopenia.MethodsData on prevalence of low lean mass, functional limitations, and hospitalizations were obtained from the National Health and Nutrition Examination Survey (1999–2004); cost of hospitalizations was obtained from the Healthcare Cost and Utilization Project — National Inpatient Sample (2014), and population estimates were obtained from the US Census (2014). Probability and cost of hospitalizations were estimated by multiple logistic regression and negative binomial regression models, respectively.ResultsThe total estimated cost of hospitalizations in individuals with sarcopenia was USD $40.4 billion with an average per person cost of USD $260. Within this category, average per person cost was highest for Hispanic women (USD $548) and lowest for Non-Hispanic Black women (USD $25); average per person cost was higher for older adults (≥65 years) (USD $375) than younger adults (40–64 years) (USD $204) with sarcopenia. The total cost of hospitalizations in individuals with sarcopenia (≥65 years) was USD $19.12 billion. Individuals with sarcopenia had greater odds of hospitalization (OR, 1.95; p<.001) compared to those without and had an annual marginal increase in cost of USD $2315.7 per person compared to individuals without sarcopenia.ConclusionSarcopenia places considerable economic burden on the US healthcare system. The ethnic disparity and economic burden associated with sarcopenia warrant further investigation.