Age-related Loss Of Muscle Mass Research Articles

The role of sarcopenia in fragility fractures of the pelvis – is sarcopenia an underestimated risk factor?

BackgroundFragility fractures of the pelvis (FFPs) represent a significant health burden, particularly for the elderly. The role of sarcopenia, an age-related loss of muscle mass and function, in the development and impact of these fractures is not well understood. This study aims to investigate the prevalence and impact of osteoporosis and sarcopenia in patients presenting with FFPs.MethodsThis retrospective study evaluated 140 elderly patients with FFPs. The diagnosis of sarcopenia was assessed by psoas muscle area (PMA) and the height-adjusted psoas muscle index (PMI) measured on computed tomography (CT) scans. Clinical data, radiological findings and functional outcomes were recorded and compared with the presence or absence of sarcopenia and osteoporosis.ResultsOur study cohort comprised 119 female (85.0%) and 21 (15.0%) male patients. The mean age at the time of injury or onset of symptoms was 82.26 ± 8.50 years.Sarcopenia was diagnosed in 68.6% (n = 96) patients using PMA and 68.8% (n = 88) using PMI. 73.6% (n = 103) of our study population had osteoporosis and 20.0% (n = 28) presented with osteopenia. Patients with sarcopenia and osteoporosis had longer hospital stays (p < 0.04), a higher rate of complications (p < 0.048) and functional recovery was significantly impaired, as evidenced by a greater need for assistance in daily living (p < 0.03). However, they were less likely to undergo surgery (p < 0.03) and the type of FFP differed significantly (p < 0.04). There was no significant difference in mortality rate, pre-hospital health status, age or gender.ConclusionOur study highlights the important role of sarcopenia in FFPs in terms of the serious impact on health and quality of life in elderly patients especially when osteoporosis and sarcopenia occur together.Identifying and targeting sarcopenia in older patients may be an important strategy to reduce pelvic fractures and improve recovery. Further research is needed to develop effective prevention and treatment approaches that target muscle health in the elderly.

Musculoskeletal Failure

Osteoarthritis, osteoporosis, and sarcopenia are prevalent musculoskeletal disorders that significantly impact the aging population’s health and quality of life. Osteoarthritis, characterized by joint inflammation, leads to pain, stiffness, and reduced mobility. Osteoporosis, a condition marked by bone density loss, increases fracture susceptibility, especially in postmenopausal women and older adults. Sarcopenia, the age-related loss of muscle mass and function, contributes to frailty and an increased risk of falls. Combined, osteoarthritis, osteoporosis and sarcopenia constitute “Musculoskeletal Failure.” These 3 conditions share common risk factors like aging, genetics, and hormonal changes, as well as unhealthy lifestyle behaviors resulting in systemic chronic inflammation. Healthy lifestyle behaviors, including regular physical activity and a nutritious diet across the lifespan play a crucial role in the prevention and management of musculoskeletal failure. Awareness of the relationship between lifestyle behaviors, systemic chronic inflammation and the development and progression of these 3 common conditions is a key step in prevention, early detection and are essential for addressing the complex interplay of these musculoskeletal disorders. As the global population ages, understanding and effectively preventing and managing osteoarthritis, osteoporosis, and sarcopenia become paramount for promoting healthy aging and mitigating the societal and economic burden associated with these conditions.

GCPII Inhibition in Macrophages Delays Age-related Muscle Atrophy in Mice

Age-related loss of muscle mass and strength (Sarcopenia) significantly impairs quality of life in the elderly, yet lacks effective treatments. We previously demonstrated that inhibition of GCPII delayed muscle function decline and neuromuscular junction (NMJ) denervation in an amyotrophic lateral sclerosis (ALS) animal model. As sarcopenia shares NMJ deterioration with ALS, we tested the potent GCPII inhibitor 2-(phosphonomethyl)-pentanedioic acid (2-PMPA) in aging mice, and found that it also preserved muscle function and NMJ integrity. By immunofluorescent staining, we demonstrated that aged mice muscles were associated with GCPII-positive infiltrating macrophages. We next developed a macrophage-targeting GCPII inhibitor delivery system by covalently attaching 2-PMPA to 4th-generation polyamidoamine (G4-PAMAM) dendrimers (D-2-PMPA). The D-2-PMPA was found to inhibit GCPII with IC50= 3.50±0.05 nM. Aged mice muscle showed increased GCPII activity specifically in CD11b+ enriched macrophage cells (138.6±3.0 vs. 336.6±52.9; p&lt;0.05) but not in CD11b− cells. Systemic D-2-PMPA therapy (20 mg/kg 2-PMPA equivalent; IP 3 × /week) completely inhibited the elevated GCPII activity (336.5±52.8 vs. 21.8±9.2 fmol/mg/h; p&lt;0.001). 5-months of D-2-PMPA therapy initiated with 15-month-old mice significantly preserved calf muscle volume (95.0±0.8% vs. 90.4±0.7%; p &lt;0.001), enhanced isometric force (230.2±13.3 vs. 184.0±9.0 mN, female p&lt;0.05; 257.3±21.0 vs. 189.7±19.3 mN, male p&lt;0.05), improved grip strength (96.1±1.6 vs. 90.2±2.2 % of maximum p&lt;0.001) and increased rotarod latency (119.0±6.6 vs. 93.5±9.3 s, female p&lt;0.05; 104.5±5.2 vs. 79.3±4.2 s, male p&lt;0.001). Age-related decline of nerve signal conductivity to muscles was also delayed with D-2-PMPA as observed by improved compound muscle action potential (CMAP) latency (1.28±0.02 vs. 1.38±0.04 ms; p&lt; 0.05) and amplitude (15.2±0.5 vs. 1.27±0.6 mV; p&lt;0.01). Furthermore, NMJ integrity was preserved with treatment as demonstrated by single fiber jitter (5.4±0.3 vs. 7.5±0.5 μs; p&lt;0.01). Overall, our current results support that excessive GCPII activity in muscle macrophages is associated with age-related muscle atrophy, which is improved by GCPII inhibition. This study highlights GCPII inhibition in macrophages as a new therapeutic approach to delay sarcopenia. R01AG078181, R01AG068130, R01NS093416. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Clinical meaning of sarcopenia in patients undergoing endoscopic treatment.

With increasing global life expectancy, the significance of geriatric assessment parameters has increased. Sarcopenia is a crucial assessment parameter and is defined as the age-related loss of muscle mass and strength. Sarcopenia is widely acknowledged as a risk factor for postoperative complications in diverse advanced malignancies and has a detrimental effect on the long-term prognosis. While most studies have primarily concentrated on the correlation between sarcopenia and advanced cancer, more recent investigations have focused on the relationship between sarcopenia and early-stage cancer. Endoscopic submucosal dissection (ESD), which is less invasive than surgical intervention, is extensively employed in the management of early-stage cancer, although it is associated with complications such as bleeding and perforation. In recent years, several reports have revealed the adverse consequences of sarcopenia in patients with early-stage cancer undergoing ESD. This literature review briefly summarizes the recent studies on the association between sarcopenia and ESD.

A New Challenge in Treatment of Sarcopenic Obesity in Older Adults: A Systematic Review

Introduction: Sarcopenic obesity (SO) defined as a phenotype of coexistence of sarcopenia, is an age-related loss of muscle mass and strength or physical performance, and obesity. It is crucial to determine the best management strategy for sarcopenic obese patients in order to improve life expectancy. The goal of this review is to provide an overview of sarcopenic obesity treatment for older persons. Methods: PubMed searches were conducted for ‘sarcopenic obesity treatment’ and ‘sarcopenic obesity elderly treatment’ from a database through the past 10 years. All articles available in English identified by these searches were then reviewed in detail Result: At present, the optimal treatment of sarcopenic has not been established. Nutritional interventions, such as a hypocaloric diet, and exercise training or physical therapy are the mainstay of SO prevention and treatment to achieve changes in body composition (muscle gain and fat reduction) and improve the functional status and quality of life of elderly patients. Conclusion: To further our understanding of SO, it is essential that clinicians and researchers establish a universal consensus for the definition and diagnosis of SO and focus on SO treatment and promote healthy aging. &#x0D; &#x0D; Keywords: sarcopenic obesity, elderly, treatment

Brief Review: Exploring Avicenna's Recommendations for Preventing Age-Related Sarcopenia and Improving Motor Control: Insights from Persian Medicine

Background: Sarcopenia, the age-related loss of muscle mass and function, is a significant concern in geriatric medicine. Avicenna, a prominent figure in Persian medicine, emphasized healthy living and provided detailed instructions for the elderly. Objectives: This review aims to evaluate the potential effectiveness of Avicenna's recommendations in preserving and improving motor control in the elderly population. Methods: A systematic search was conducted in electronic databases using relevant keywords to identify studies discussing Avicenna's recommendations for individuals over 65 years old. Avicenna suggested maintaining instinctive heat and essential body moisture through a balanced diet, including fresh fruits, vegetables, lean proteins, and whole grains. He also emphasized the importance of physical activity, moderate massage, and herbal remedies. Results: Comparing Avicenna's recommendations with current research on age-related sarcopenia reveals significant overlap. Studies support Avicenna's emphasis on milk and meat consumption for muscle health. Avicenna's recommendations for physical activity align with current exercise guidelines for older adults. Conclusions: Incorporating Avicenna's recommendations into geriatric medicine may lead to improved outcomes for elderly individuals at risk of sarcopenia and motor control issues. Further research is warranted to explore the mechanisms underlying Avicenna's recommendations and their impact on sarcopenia prevention and management, as well as motor control improvement.

Linking sarcopenia, brain structure and cognitive performance: a large-scale UK Biobank study.

Sarcopenia refers to age-related loss of muscle mass and function and is related to impaired somatic and brain health, including cognitive decline and Alzheimer's disease. However, the relationships between sarcopenia, brain structure and cognition are poorly understood. Here, we investigate the associations between sarcopenic traits, brain structure and cognitive performance. We included 33 709 UK Biobank participants (54.2% female; age range 44-82 years) with structural and diffusion magnetic resonance imaging, thigh muscle fat infiltration (n = 30 561) from whole-body magnetic resonance imaging (muscle quality indicator) and general cognitive performance as indicated by the first principal component of a principal component analysis across multiple cognitive tests (n = 22 530). Of these, 1703 participants qualified for probable sarcopenia based on low handgrip strength, and we assigned the remaining 32 006 participants to the non-sarcopenia group. We used multiple linear regression to test how sarcopenic traits (probable sarcopenia versus non-sarcopenia and percentage of thigh muscle fat infiltration) relate to cognitive performance and brain structure (cortical thickness and area, white matter fractional anisotropy and deep and lower brain volumes). Next, we used structural equation modelling to test whether brain structure mediated the association between sarcopenic and cognitive traits. We adjusted all statistical analyses for confounders. We show that sarcopenic traits (probable sarcopenia versus non-sarcopenia and muscle fat infiltration) are significantly associated with lower cognitive performance and various brain magnetic resonance imaging measures. In probable sarcopenia, for the included brain regions, we observed widespread significant lower white matter fractional anisotropy (77.1% of tracts), predominantly lower regional brain volumes (61.3% of volumes) and thinner cortical thickness (37.9% of parcellations), with |r| effect sizes in (0.02, 0.06) and P-values in (0.0002, 4.2e-29). In contrast, we observed significant associations between higher muscle fat infiltration and widespread thinner cortical thickness (76.5% of parcellations), lower white matter fractional anisotropy (62.5% of tracts) and predominantly lower brain volumes (35.5% of volumes), with |r| effect sizes in (0.02, 0.07) and P-values in (0.0002, 1.9e-31). The regions showing the most significant effect sizes across the cortex, white matter and volumes were of the sensorimotor system. Structural equation modelling analysis revealed that sensorimotor brain regions mediate the link between sarcopenic and cognitive traits [probable sarcopenia: P-values in (0.0001, 1.0e-11); muscle fat infiltration: P-values in (7.7e-05, 1.7e-12)]. Our findings show significant associations between sarcopenic traits, brain structure and cognitive performance in a middle-aged and older adult population. Mediation analyses suggest that regional brain structure mediates the association between sarcopenic and cognitive traits, with potential implications for dementia development and prevention.

The Conceptual Definition of Sarcopenia: Delphi Consensus from the Global Leadership Initiative in Sarcopenia (GLIS).

Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of statements using an online survey tool (SurveyMonkey). Statements were categorised based on predefined thresholds: strong agreement (>80%), moderate agreement (70-80%) and low agreement (<70%). Statements with strong agreement were accepted, statements with low agreement were rejected and those with moderate agreement were reintroduced until consensus was reached. 107 participants (mean age: 54 ± 12years [1 missing age], 64% men) from 29 countries across 7 continents/regions completed the Delphi survey. Twenty statements were found to have a strong agreement. These included; 6 statements on 'general aspects of sarcopenia' (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on 'components of sarcopenia' (muscle mass (89.4%), muscle strength (93.1%) and muscle-specific strength (80.8%) should all be a part of the conceptual definition of sarcopenia)) and 11 statements on 'outcomes of sarcopenia' (strongest agreement: sarcopenia increases the risk of impaired physical performance (97.9%)). A key finding of the Delphi survey was that muscle mass, muscle strength and muscle-specific strength were all accepted as 'components of sarcopenia', whereas impaired physical performance was accepted as an 'outcome' rather than a 'component' of sarcopenia. The GLIS has created the first global conceptual definition of sarcopenia, which will now serve to develop an operational definition for clinical and research settings.

MFN2 overexpression in skeletal muscles of young and old mice causes a mild hypertrophy without altering mitochondrial respiration and H2O2 emission.

Sarcopenia, the aging-related loss of muscle mass and function, is a debilitating process negatively impacting the quality of life of affected individuals. Although the mechanisms underlying sarcopenia are incompletely understood, impairments in mitochondrial dynamics, including mitochondrial fusion, have been proposed as a contributing factor. However, the potential of upregulating mitochondrial fusion proteins to alleviate the effects of aging on skeletal muscles remains unexplored. We therefore hypothesized that overexpressing Mitofusin 2 (MFN2) in skeletal muscle invivo would mitigate the effects of aging on muscle mass and improve mitochondrial function. MFN2 was overexpressed in young (7 mo) and old (24 mo) male mice for 4 months through intramuscular injections of an adeno-associated viruses. The impacts of MFN2 overexpression on muscle mass and fiber size (histology), mitochondrial respiration, and H2O2 emission (Oroboros fluororespirometry), and various signaling pathways (qPCR and western blotting) were investigated. MFN2 overexpression increased muscle mass and fiber size in both young and old mice. No sign of fibrosis, necrosis, or inflammation was found upon MFN2 overexpression, indicating that the hypertrophy triggered by MFN2 overexpression was not pathological. MFN2 overexpression even reduced the proportion of fibers with central nuclei in old muscles. Importantly, MFN2 overexpression had no impact on muscle mitochondrial respiration and H2O2 emission in both young and old mice. MFN2 overexpression attenuated the increase in markers of impaired autophagy in old muscles. MFN2 overexpression may be a viable approach to mitigate aging-related muscle atrophy and may have applications for other muscle disorders.

Body Composition in Chronic Liver Disease.

Body composition has recently been attracting people's attention, not only from a cosmetic standpoint but also from the perspective of health and longevity. The body is classified into three components: fat, bone, and lean soft tissue, and it is common to see an increase in body fat and a decrease in total body muscle mass with aging. Aging-related loss of muscle mass and muscle function is referred to as primary sarcopenia, while sarcopenia caused by disease-specific conditions is referred to as secondary sarcopenia. On the other hand, the liver-muscle axis has been attracting attention in recent years, and it has become clear that the liver and the skeletal muscles interact with each other. In particular, patients with cirrhosis are prone to secondary sarcopenia due to protein-energy malnutrition, which is a characteristic pathophysiology of the disease, suggesting the importance of the organ-organ network. In this review, we would like to outline the latest findings in this field, with a focus on body composition in liver diseases such as liver cirrhosis, fatty liver disease, alcoholic liver disease, and hepatocellular carcinoma.

Relationship of Low Vitamin B6 Status with Sarcopenia, Frailty, and Mortality: A Narrative Review.

Marginal vitamin B6 (B6) deficiency is a widespread global concern. Inadequate B6 levels have been linked to an increased risk of age-related chronic diseases such as cardiovascular diseases and cancers. In recent years, the growing concern over sarcopenia (the age-related loss of muscle mass and strength) and frailty (a decline in physiological resilience and increased vulnerability associated with aging) is particularly relevant due to the emergence of super-aged societies in developed countries. Notably, among the thirty-one studies included in this review, twenty-five showed a significant association of B6 status with sarcopenia, frailty, and all-cause mortality in adults (p < 0.05), while six showed no association. Emerging studies have suggested novel mechanisms underlying this association. These mechanisms involve P2X7 receptor-mediated NLRP3 inflammasome signaling, AMPK signaling, PD-L1 signaling, and satellite cell-mediated myogenesis. Furthermore, the modulation of PLP-dependent enzymes due to B6 deficiency is associated with impaired metabolic processes, affecting energy utilization, imidazole peptide production, and hydrogen sulfide production, as well as the kynurenine pathway, all of which play vital roles in skeletal muscle health and pathophysiology. This narrative review provides an up-to-date assessment of our current understanding of the potential role of nutritional B6 status in combating sarcopenia, frailty, and mortality.

A protocol for remote collection of skeletal muscle mass via D3-creatine dilution in community-dwelling postmenopausal women from the Women's Health Initiative.

There is emerging evidence that cancer and its treatments may accelerate the normal aging process, increasing the magnitude and rate of decline in functional capacity. This accelerated aging process is hypothesized to hasten the occurrence of common adverse age-related outcomes in cancer survivors, including loss of muscle mass and decrease in physical function. However, there is no data describing age-related loss of muscle mass and its relation to physical function in the long-term in cancer survivors. This study protocol describes the use of a novel method of muscle mass measurement, D3-creatine dilution method (D3Cr), in a large sample (n~6000) of community dwelling postmenopausal women from the Women's Health Initiative (WHI). D3Cr will be used to obtain a direct measure of muscle mass remotely. Participants will be drawn from two sub-cohorts embedded within the WHI that have recently completed an in-home visit. Cancer survivors will be drawn from the Life and Longevity After Cancer (LILAC) cohort, and cancer-free controls will be drawn from the WHI Long Life Study 2. The overall objective of this study is to examine the antecedents and consequences of low muscle mass in cancer survivors. The study aims are to: 1) create age-standardized muscle mass percentile curves and z-scores to characterize the distribution of D3- muscle mass in cancer survivors and non-cancer controls, 2) compare muscle mass, physical function, and functional decline in cancer survivors and non- cancer controls, and 3) use machine learning approaches to generate multivariate risk-prediction algorithms to detect low muscle mass. The D3Cr method will transform our ability to measure muscle mass in large-scale epidemiologic research. This study is an opportunity to advance our understanding of a key source of morbidity among older and long-term female cancer survivors. This project will fill knowledge gaps, including the antecedents and consequences of low muscle mass, and use innovative methods to overcome common sources of bias in cancer research. The results of this study will be used to develop interventions to mitigate the harmful effects of low muscle mass in older adults and promote healthy survivorship in cancer survivors in the old (>65) and oldest-old (>85) age groups.

SARCOPENIA AND MOBILITY DYSFUNCTION AS INDICATORS OF INCREASED ADRD RISK IN ASYMPTOMATIC DISEASE

Abstract Sarcopenia, the age-related loss of muscle mass and function, affects up to 30% of older adults. In addition to being an established component of frailty and predictor of mobility dysfunction, sarcopenia is associated with cognitive decline and increased risk of cognitive impairment, with ~70% individuals with late-stage dementia having sarcopenia. In this study, we investigated whether sarcopenia differentiates high- vs low- ADRD risk among 141 community-dwelling, older adults who were healthy controls (HC) or had mild cognitive impairment (MCI) (65% female; mean Age=70±11yr; mean Educ=16±3yr). Using the Brain Health Platform (BHP) developed at the Comprehensive Center for Brain Health, we categorized participants based on measures of resilience, vulnerability, cognitive performance as: Low-risk HC (36.9%); High-risk HC (12.8%), and MCI (50.4%). Amyloid positivity increased across risk groups (20% in Low-risk HC; 33.3% in High-risk HC; 39.1% in MCI). Prevalence of sarcopenia was 26.7% and increased by ADRD risk (12.2% vs 18.8% vs 39.1%, p=0.004). The MCI group had lower flexibility compared to both the low-risk (p=0.024) and high-risk HC (p=0.039) groups. Timed Up and Go (TUG) score increased with risk group (p&amp;lt; 0.001MCI vs Low-risk HC; p=0.005MCI vs High-risk HC). Both mobility measures (i.e., flexibility, TUG) showed good discrimination for MCI vs Low-risk HC [AUC=0.77flexibility; AUC=0.78TUG] as well as for MCI vs High-risk HC [AUC=0.71flexibility; AUC=0.73TUG). Findings suggest that sarcopenia and other markers of mobility dysfunction have the potential to identify asymptomatic individuals at increased risk of ADRD, who could benefit from early intervention.

Genetic variants in myostatin and its receptors promote elite athlete status

BackgroundWhile product of the myostatin gene (MSTN) is an important factor influencing muscle growth, which is well confirmed in nonhuman species, it has not been clearly confirmed whether MSTN expression influences interindividual differences in skeletal muscle mass, affects posttraining changes, or plays a role in the age-related loss of muscle mass and function in humans. Although the inconclusive results are usually explained by ethnic differences and the low frequency of some alleles, it is possible that the role of receptors (ACVR2A and ACVR2B) that affect the biological activity of myostatin is crucial. Therefore, we investigated the sequences of the MSTN, ACVR2A, and ACVR2B genes and determined the interaction between allelic variants and athletic performance and competition level in the Caucasian population. One hundred-two athletes were recruited for the sequencing study, and whole-genome sequencing (WGS) was performed. Second, 330 athletes and 365 controls were included, and real-time PCR was performed.ResultsThe sequence analysis revealed two polymorphisms relatively common in the athlete cohort, and the alternate allele showed overrepresentation in athletes: MSTN rs11333758 and ACVR2A rs3764955. Regarding the polymorphic site MSTN rs11333758, there was a significant overrepresentation of the –/– genotype in all high-elite and mixed-sport high-elite athletes. Carriers of the ACVR2A rs3764955 CC and GG genotypes were more likely to be elite and high-elite athletes. In addition, carriers of the CC genotype were more likely to be in the mixed-sport subelite group. The gene‒gene interaction analysis revealed that mixed-sport high elite athletes showed significant underrepresentation of the ACVR2A rs3764955 GC - MSTN rs11333758 AA genotype combination. In the same group, we observed a significant overrepresentation of the ACVR2A rs3764955 GC - MSTN rs11333758 –/– and the ACVR2A rs3764955 CC - MSTN rs11333758 –/– genotype combinations.ConclusionsWe showed that the specific genotypes of the MSTN rs11333758 and ACVR2A rs3764955, either individually or in gene‒gene combination, are significantly associated with athletes’ competition level in the Polish population, especially in the mixed-sports athlete group. Thus, although further research is required, these polymorphisms, alone or in combination with other polymorphisms, are among the numerous candidates that could explain individual variations in muscle phenotypes.

A Critical Review of Current Worldwide Definitions of Sarcopenia.

With the increasing number of elderly individuals worldwide, the prevalence of age-related loss of muscle mass, referred to as sarcopenia, is expected to increase. Sarcopenia is a relatively new recognized syndrome, which is thought to affect 13% individuals worldwide, and the significant efforts made by different groups have advanced our understanding of the diagnosis, treatment, and natural history of this condition. However, the challenge is now to standardize its measurement and diagnosis to facilitate research in this area and a greater understanding of this condition and its management between clinicians and researchers. The Global Leadership Initiative on Sarcopenia (GLIS) is at the forefront of an international effort to produce standardized definition of sarcopenia. Setting a definition for sarcopenia entails several considerations and trade-offs. In this critical review, we have addressed key challenges driving the process of standardizing the definition, while delving into future avenues in sarcopenia research. Establishing a clear consensus on the working definition of sarcopenia is essential not only for advancing research in this field but also for assessing the prognostic implications of diagnosing sarcopenia and determining the most suitable treatment for affected patients.

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

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

Sarkopenia pada Lanjut Usia: Patogenesis, Diagnosis dan Tata Laksana

‘Sarcopenia’ involves a progressive age-related loss of muscle mass and associated muscle weakness that renders frail elders susceptible to serious injury from sudden falls and fractures and losing their functional independence. This disease has a complex multifactorial pathogenesis, which involves not only age-related changes in neuromuscular function, muscle protein turnover, and hormone levels and sensitivity, but also a chronic pro-inflammatory state, oxidative stress, and behavioral factors – in particular, nutritional status and degree of physical activity. In the previous definition by the European Working Group on Sarcopenia in Older People (EWGSOP) in 2010, the diagnosis of sarcopenia requires the presence of both low muscle mass and low muscle function. Since the 2010 definition is difficult to be translated to clinical practice, the EWGSOP uses low muscle strength as the primary parameter of sarcopenia in the 2018 definition; sarcopenia is probable when low muscle strength is detected. A sarcopenia diagnosis is confirmed by the presence of low muscle quantity or quality. When low muscle strength, low muscle quantity/quality and low physical performance are all detected, sarcopenia is considered severe. According to the pathophysiological factors involved in the pathogenesis of sarcopenia, different treatment strategies against sarcopenia are resistance exercise training, increase essential amino acids intake, vitamin D supplementation for those with vitamin D deficiency, polyunsaturated fatty acids (PUFAs) supplementation, testosterone supplementation, angiotensin-converting enzyme inhibitor administration.

AAV1.NT-3 gene therapy in the SOD1KO mouse model of accelerated sarcopenia.

Sarcopenia, an age-related loss of muscle mass, is a critical factor that affects the health of the older adults. The SOD1KO mouse is deficient of Cu/Zn superoxide dismutase, used as an accelerated aging model. We previously showed that NT-3 improves muscle fibre size by activating the mTOR pathway, suggesting a potential for attenuating age-related muscle loss. This study assessed the therapeutic efficacy of AAV1.NT-3 in this accelerated aging model. Twelve 6months old SOD1KO mice were injected intramuscularly with a 1×1011 vg dose of AAV1.tMCK.NT-3, and 13 age-matched SOD1KO mice were used as controls. The treatment effect was evaluated using treadmill, rotarod and gait analyses as well as histological studies assessing changes in muscle fibre, and fibre type switch, in tibialis anterior, gastrocnemius, and triceps muscles, and myelin thickness by calculating G ratio in sciatic and tibial nerves. Molecular studies involved qPCR experiments to analyse the expression levels of mitochondrial and glycolysis markers and western blot experiments to assess the activity of mTORC1 pathway. Treatment resulted in a 36% (154.9 vs. 114.1; P<0.0001) and 76% increase (154.3 vs. 87.6; P<0.0001) in meters ran, with treadmill test at 3 and 6months post gene delivery. In addition, the treated cohort stayed on rotarod 30% (52.7s vs. 40.4s; P=0.0095) and 54% (50.4s vs. 32.7s; P=0.0007) longer, compared with untreated counterparts at 3 and 6months post injection. Gait analysis, performed at endpoint, showed that stride width was normalized to wild type levels (29.3mm) by an 11% decrease, compared with untreated cohort (28.6mm vs. 32.1mm; P=0.0014). Compared with wild-type, SOD1KO mice showed 9.4% and 11.4% fibre size decrease in tibialis anterior and gastrocnemius muscles, respectively, which were normalized to wild type levels with treatment. Fibre diameter increase was observed prominently in FTG fibre type. G ratio analysis revealed hypomyelination in the tibial (0.721) and sciatic (0.676) nerves of SOD1KO model, which was reversed in the NT-3 cohort (0.646 and 0.634, respectively). Fibre size increase correlated with the increase in the p-S6 and p-4E-BP1 levels, and in the glycolysis markers in tibialis anterior. Alterations observed in the mitochondrial markers were not rescued with treatment. Overall, response to NT-3 was subdued in gastrocnemius muscle. This study shows that AAV1.NT-3 gene therapy protected SOD1KO mouse from accelerated aging effects functionally and histologically. We further confirmed that NT-3 has potential to activate the mTOR and glycolytic pathways in muscle.

Hesperidin Ameliorates Sarcopenia through the Regulation of Inflammaging and the AKT/mTOR/FoxO3a Signaling Pathway in 22-26-Month-Old Mice.

Faced with a globally aging society, the maintenance of health and quality of life in older people is very important. The age-related loss of muscle mass and strength, known as sarcopenia, severely reduces quality of life and increases the risks of various diseases. In this study, we investigated the inhibitory effect of hesperidin (HES) on inflammaging, with the intention of evaluating its potential use as a treatment for sarcopenia. We studied 22-26-month-old mice, corresponding to humans aged ≥70 years, with aging-related sarcopenia, and young mice aged 3-6 months. The daily administration of HES for 8 weeks resulted in greater muscle mass and strength and increased the fiber size of the old mice. HES also restored the immune homeostasis that had been disrupted by aging, such as the imbalance in M1/M2 macrophage ratio. In addition, we found that HES ameliorated the sarcopenia by regulating AKT/mammalian target of rapamycin/forkhead box 3a signaling through an increase in insulin-like growth factor (IGF)-1 expression in the old mice. Therefore, HES represents a promising candidate inhibitor of sarcopenia in older people, and its effects are achieved through the maintenance of immune homeostasis.

A scientometric analysis of sarcopenic obesity: Future trends and new perspectives.

Sarcopenic obesity is a complex condition characterized by the combination of age-related loss of muscle mass and high levels of adiposity, or body fat. Up to 30% of older adults may be affected by this condition, and its prevalence varies by gender, race, and ethnicity. It can lead to postural instability and reduced physical activity, increasing the risk of falls, fractures, and functional limitations. The purpose of this study was to evaluate scientific articles on sarcopenic obesity using statistical methods and to assess the topic from a novel perspective. The Web of Science database publications on sarcopenic obesity published between 1980 and 2023 were analyzed using statistical and bibliometric methods. Spearman correlation coefficient was used in correlation analyses. A nonlinear cubic model regression analysis was performed to forecast the number of publications in the following years. Using keyword network visualization maps, recurrent topics, and relationships were identified. Between 1980 and 2023, the search criteria yielded 1013 publications on geriatric malnutrition. Nine hundred of these (articles, reviews, and meeting abstracts) were included in the analysis. Since 2005, the volume of published materials on the topic has increased dramatically and is continuing to rise. The USA and South Korea were the most active nations, Scott D and Prado CMM were the most active authors, and Osteoporosis International was the most active journal on the subject. This research has shown that countries with higher economic development tend to produce more research on the issue, and the number of publications on the topic will rise in the upcoming years. It is an important research topic in an aging society and needs to be further researched. We believe this article may aid clinicians and scientists in comprehending global efforts to combat sarcopenic obesity.