Age-related Muscle Loss Research Articles

Short-chain fatty acids enhance muscle mass and function through the activation of mTOR signalling pathways in sarcopenic mice.

Sarcopenia is a prevalent muscle disorder in old people leading to higher fracture rate, mortality, and other adverse clinical outcomes. Evidence indicates that short-chain fatty acids (SCFAs), which are beneficial gut microbial metabolites, were reduced in old people with sarcopenia. This study aimed to determine whether the use of SCFAs as a supplement can be a therapeutic strategy of sarcopenia in a pre-clinical model. Seven-month-old pre-sarcopenic senescent accelerated mouse prone 8 (SAMP8) mice received daily SCFAs cocktail (acetate, butyrate, and propionate) for 3months. Age-matched senescence accelerated mouse resistant 1 (SAMR1) and SAMP8 mice receiving sodium-matched drinking water were control groups. The gut microbiota composition analysis of aged mice with or without sarcopenia was conducted by 16S rDNA sequencing. Gut barrier-related proteins and lipopolysaccharide (LPS) concentration were biomarkers of gut permeability. Colon inflammation levels, circulatory SCFAs concentration, muscle quality, function, and underlying pathways were detected by cell number counting, RT-qPCR, gas chromatography-mass spectrometry, measurements of muscle wet weight and grip strength, ex vivo functional test, treadmill endurance test, transcriptomic sequencing, morphological and immunofluorescent staining, as well as western blot. To investigate the role of mTOR signalling pathways in SCFAs treatment, C2C12 myotubes were treated with rapamycin. Aged SAMP8 mice had different microbiota composition, and lower serum butyric acid compared with SAMR1 mice (P<0.05). SCFAs treatment reversed the increment of colon inflammation (2.8-fold lower of il-1β) and gut barrier permeability (1.7-fold lower of LPS) in SAMP8 mice. Increased muscle mass, myofibre cross-sectional area, grip strength, twitch and tetanic force were found in SCFAs-treated mice compared with control SAMP8 mice (P<0.05). Anti-fatigue capacity (1.6-fold) and muscle glycogen (2-fold) also improved after SCFAs treatment (P<0.05). Transcriptomic analysis showed that AMPK, insulin, and mTOR pathways were involved in SCFAs treatment (P<0.05). Regulation of AKT/mTOR/S6K1 and AMPK/PGC1α pathways were found. SCFAs attenuated fat infiltration and improved mitochondria biogenesis of atrophic muscle. In vitro studies indicated that SCFAs inhibited FoxO3a/Atrogin1 and activated mTOR pathways to improve myotube growth (P<0.05), and rapamycin attenuated the effect of SCFAs through the inhibition of mTOR pathways. This study demonstrated that bacterial metabolites SCFAs could attenuate age-related muscle loss and dysfunction, and protein synthesis-related mTOR signalling pathways were involved both in vivo and in vitro.

Metformin restores autophagic flux and mitochondrial function in late passage myoblast to impede age-related muscle loss

Sarcopenia, which refers to age-related muscle loss, presents a significant challenge for the aging population. Age-related changes that contribute to sarcopenia include cellular senescence, decreased muscle stem cell number and regenerative capacity, impaired autophagy, and mitochondrial dysfunction. Metformin, an anti-diabetic agent, activates AMP-activated protein kinase (AMPK) and affects various cellular processes in addition to reducing hepatic gluconeogenesis, lowering blood glucose levels, and improving insulin resistance. However, its effect on skeletal muscle cells remains unclear. This study aimed to investigate the effects of metformin on age-related muscle loss using a late passage C2C12 cell model. The results demonstrated that metformin alleviated hallmarks of cellular senescence, including SA-β-gal activity and p21 overexpression. Moreover, treatment with pharmacological concentrations of metformin restored the reduced differentiation capacity in late passage cells, evident through increased myotube formation ability and enhanced expression of myogenic differentiation markers such as MyoD, MyoG, and MHC. These effects of metformin were attributed to enhanced autophagic activity, normalization of mitochondrial membrane potential, and improved mitochondrial respiratory capacity. These results suggest that pharmacological concentrations of metformin alleviate the hallmarks of cellular senescence, restore differentiation capacity, and improve autophagic flux and mitochondrial function. These findings support the potential use of metformin for the treatment of sarcopenia.

Protective Effects of Cervus elaphus and Eucommia ulmoides Mixture (KGC01CE) on Muscle Loss and Function in Aged Rats.

Sarcopenia is a condition characterized by a progressive loss of muscle mass and function which are influenced by certain factors such as aging, nutritional deficiencies, and chronic diseases. Despite numerous efforts to prevent or treat sarcopenia, effective therapeutic options for this disease remain limited. This study aims to evaluate the effects of KGC01CE treatment, a mixture of Cervus elaphus (Ce) and Eucommia ulmoides (Eu), which are well-known traditional herbal medicines in Asia, on age-related muscle loss and functional decline in aged rats. KGC01CE has been found to be more effective than the individual extracts in inhibiting dexamethasone (DEX)-induced muscle atrophy and improving muscle mass and grip strength in C2C12 cells and aged rats. Moreover, animal studies were conducted to determine the minimum effective dose, and a 12-week oral administration of KGC01CE treatment at doses of 50, 100, and 200 mg/kg to 15-month-old aged rats resulted in a dose-dependent increase in lean mass, muscle mass, grip strength, and muscle cross-sectional area (CSA), which had decreased due to aging. Furthermore, it was shown that KGC01CE activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and inhibited the expression of muscle-degrading proteins MuRF, Atrogin-1, and myostatin. These results suggest that KGC01CE treatment may effectively prevent muscle loss and functional decline, providing a novel therapeutic strategy for sarcopenia.

Exploring the Therapeutic Potential of Green Tea (Camellia sinensis L.) in Anti-Aging: A Comprehensive Review of Mechanisms and Findings.

Green tea (GT) is rich in Phyto-active compounds such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), epicatechin (EC), catechin, and tannic acid, which exhibit synergistic effects when combined. Preclinical studies demonstrate that GT and its compounds can reduce reactive oxygen species (ROS), enhance antioxidant capacity, and alleviate aging-related issues such as memory impairments, cognitive decline, and shortened lifespan. Clinical trials corroborate the efficacy of topical GT formulations in improving skin tone, texture, and elasticity and reducing wrinkles. The present manuscript summarizes the recent update on the anti-aging potential of GT and its possible mechanisms. The literature survey suggested that GT consumption is linked to improved cognition, reduced depression levels, and activation of pathways in model organisms like C. elegans. Additionally, tea polyphenols enhance fibroblast mitophagy, boost hippocampal synaptic plasticity in rodents, and mitigate age-related cognitive decline. Moreover, EGCG exhibits anti-aging properties by reducing TNF-induced MMP-1 expression, suppressing ERK signaling, and inhibiting MEK and Src phosphorylation in human dermal fibroblasts. In the context of skin permeation and deposition, optimized transpersonal formulation (TF) incorporating EGCG and hyaluronic acid (HA) demonstrated significantly increased skin permeation and deposition of EGCG compared to plain EGCG. Furthermore, EGCG protects cardiomyocytes via the PPARγ pathway and combats age-related muscle loss through miRNA-486-5p regulation, AKT activation, and FoxO1a-mediated expression of MuRF1 and Atrogin-1. In conclusion, the regular consumption of GT holds promise for promoting physical and mental health, delaying brain and skin aging, and improving overall health by enhancing total antioxidant capacity.

Effect of the combination of Lithospermum erythrorhizon and Lonicera japonica on dexamethasone-induced muscle atrophy in mice

AbstractSkeletal muscle atrophy occurs in several pathological conditions. Among other reasons, high-dose or long-term administration of glucocorticoids increases circulating glucocorticoid levels and causes muscle atrophy. The purpose of this study was to investigate whether Lithospermum erythrorhizon and Lonicera japonica complex extract (LELJ) has a beneficial effect on dexamethasone (Dexa)-induced muscle atrophy. In Dexa-induced myotube atrophy, treatment with LELJ increased myotube diameter, decreased the expression of muscle atrophy markers, and increased the expression of myosin heavy chain (MHC) isoforms. Supplementation with LELJ improved muscle function and performance in mice with Dexa-induced muscle atrophy as demonstrated by grip strength and running tests. Additionally, it increased skeletal muscle mass, size, and expression of MHC isoforms and protein synthesis-related markers. Furthermore, it reduced the upregulated protein levels of skeletal muscle atrophy markers in Dexa-treated mice. Supplementation with LELJ reversed Dexa-induced translocation of the glucocorticoid receptor and forkhead box O3 from the cytosol to the nucleus in skeletal muscles. LELJ also ameliorated age-related muscle loss by extending lifespan and increasing locomotor capacity in Caenorhabditis elegans. We identified loganin and lithospermic acid as bioactive compounds of LELJ and found that treatment with these agents increased myotube diameter, MHC isoform, and puromycin protein levels, and decreased atrophy markers in Dexa-treated myotubes. The current findings underscore how LELJ can prevent Dexa-induced skeletal muscle atrophy, attributing the effects to loganin and lithospermic acid.

Association of Gut Microbiome with Muscle Mass, Muscle Strength, and Muscle Performance in Older Adults: A Systematic Review.

Sarcopenia, characterized by reduced muscle mass, strength, or performance, is a common condition in older adults. The association between the gut microbiome and sarcopenia remains poorly understood. This systematic review aims to evaluate the relationship between muscle parameters and the intestinal microbiome. A systematic search was conducted in PubMed, EMBASE, Cochrane Library, and Google Scholar for studies published between 2002 and 2022 involving participants aged 50+. Studies were included if they assessed sarcopenia using at least one measure of muscle mass (skeletal muscle mass, bioelectrical impedance analysis, MRI), muscle strength, or muscle performance (SARC-F questionnaire, Timed-Up-and-Go Test, Chair Stand Test, grip strength, gait speed, Short Physical Performance Battery, 400 m Walk Test). The microbiome was measured using at least RNA/DNA sequencing or shotgun metagenomic sequencing. Twelve studies were analyzed. Findings revealed that a higher abundance of bacterial species such as Desulfovibrio piger, and Clostridium symbiosum and reduced diversity of butyrate-producing bacteria was associated with sarcopenia severity, as indicated by decreased grip strength, muscle mass, or physical performance. The gut microbiome plays a significant role in age-related muscle loss. Probiotics, prebiotics, and bacterial products could be potential interventions to improve muscle health in older adults.

Maccarone et al.'s comments on Cohort studies using 3D-CT are needed to assess whether "home Gym-Bed" exercises are beneficial against sarcopenia.

We appreciate the insightful comments provided by Josef Finsterer regarding our article on the first evidence on the effects of the Home Full-Body in-Bed Gym protocol as a potential intervention to mitigate age-related muscle loss based on the preliminary positive results of a Padua prospective observational study.1 We acknowledge the importance of the points raised and would like to address them in this response. At the University of Padua, we conducted a study aimed at evaluating the impact of a home-based Full-Body in-Bed Gym protocol on various outcomes in elderly individuals, which was published in 2023.1 The rational of our proposal is based on the fact that functional muscle decay of aging is inevitable, but that the general population is highly hypoactive, let's say "lazy". The increase in daily muscular activity even through "Home In-Bed Gym" recovers at least in part the potential abilities progressively lost. Therefore, it is easy to rejuvenate the "lazy" population, that is, the vast majority of elderlies.[...].

Strategies for minimizing muscle loss during use of incretin-mimetic drugs for treatment of obesity.

The rapid and widespread clinical adoption of highly effective incretin-mimetic drugs (IMDs), particularly semaglutide and tirzepatide, for the treatment of obesity has outpaced the updating of clinical practice guidelines. Consequently, many patients may be at risk for adverse effects and uncertain long-term outcomes related to the use of these drugs. Of emerging concern is the loss of skeletal muscle mass and function that can accompany rapid substantial weight reduction; such losses can lead to reduced functional and metabolic health, weight cycling, compromised quality of life, and other adverse outcomes. Available evidence suggests that clinical trial participants receiving IMDs for the treatment of obesity lost 10% or more of their muscle mass during the 68- to 72-week interventions, approximately equivalent to 20 years of age-related muscle loss. The ability to maintain muscle mass during caloric restriction-induced weight reduction is influenced by two key factors: nutrition and physical exercise. Nutrition therapy should ensure adequate intake and absorption of high-quality protein and micronutrients, which may require the use of oral nutritional supplements. Additionally, concurrent physical activity, especially resistance training, has been shown to effectively minimize loss of muscle mass and function during weight reduction therapy. All patients receiving IMDs for obesity should participate in comprehensive treatment programs emphasizing adequate protein and micronutrient intakes, as well as resistance training, to preserve muscle mass and function, maximize the benefit of IMD therapy, and minimize potential risks.

Betaine delays age-related muscle loss by mitigating Mss51-induced impairment in mitochondrial respiration via Yin Yang1.

Mitochondrial dysfunction is one of the hallmarks of aging and a leading contributor to sarcopenia. Nutrients are essential for improving mitochondrial function and skeletal muscle health during the aging process. Betaine is a nutrient with potential muscle-preserving properties. However, whether and how betaine could regulate the mitochondria function in aging muscle are poorly understood. We aimed to explore the molecular target and underlying mechanism of betaine in attenuating the age-related mitochondrial dysfunction in skeletal muscle. Young mice (YOU, 2months), old mice (OLD, 15months), and old mice with betaine treatment (BET, 15months) were fed for 12weeks. The effects of betaine on muscle mass, strength, function, and subcellular structure of muscle fibres were assessed. RNA sequencing (RNA-seq) was conducted to identify the molecular target of betaine. The impacts of betaine on mitochondrial-related molecules, superoxide accumulation, and oxidative respiration were examined using western blotting (WB), immunofluorescence (IF) and seahorse assay. The underlying mechanism of betaine regulation on the molecular target to maintain mitochondrial function was investigated by luciferase reporter assay, chromatin immunoprecipitation and electrophoretic mobility shift assay. Adenoassociated virus transfection, succinate dehydrogenase staining (SDH), and energy expenditure assessment were performed on 20-month-old mice for validating the mechanism in vivo. Betaine intervention demonstrated anti-aging effects on the muscle mass (P=0.017), strength (P=0.010), and running distance (P=0.013). Mitochondrial-related markers (ATP5a, Sdha, and Uqcrc2) were 1.1- to 1.5-fold higher in BET than OLD (all P≤0.036) with less wasted mitochondrial vacuoles accumulating in sarcomere. Bioinformatic analysis from RNA-seq displayed pathways related to mitochondrial respiration activity was higher enriched in BET group (NES=-0.87, FDR=0.10). The quantitative real time PCR (qRT-PCR) revealed betaine significantly reduced the expression of a novel mitochondrial regulator, Mss51 (-24.9%, P=0.002). In C2C12 cells, betaine restored the Mss51-mediated suppression in mitochondrial respiration proteins (all P≤0.041), attenuated oxygen consumption impairment, and superoxide accumulation (by 20.7%, P=0.001). Mechanically, betaine attenuated aging-induced repression in Yy1 mRNA expression (BET vs. OLD: 2.06 vs. 1.02, P=0.009). Yy1 transcriptionally suppressed Mss51 mRNA expression both in vitro and in vivo. This contributed to the preservation of mitochondrial respiration, improvement for energy expenditure (P=0.008), and delay of muscle loss during aging process. Altogether, betaine transcriptionally represses Mss51 via Yy1, improving age-related mitochondrial respiration in skeletal muscle. These findings suggest betaine holds promise as a dietary supplement to delay skeletal muscle degeneration and improve age-related mitochondrial diseases.

Aging-associated Aberrant Mitochondrial Redox Signaling, Physical Activity, and Sarcopenia.

Aging-related alteration of mitochondrial morphology, impairment in metabolic capacity, bioenergetics, and biogenesis are closely associated with loss of muscle mass and function. Mitochondrial Reactive Oxygen Species (ROS) stimulate muscular redox signaling mechanisms. Bioenergetic integrity of mitochondria and redox signaling dynamics deteriorates in aged skeletal muscle. Mitochondrial bioenergetic impairment leads to excessive ROS levels and induces the generation of defective mitochondria. Higher ROS levels may induce senescence or apoptosis. It is not a resolved issue that mitochondrial dysfunction is either the sole reason or a consequence of muscle loss (or both). However, Increasing evidence emphasizes that dysregulated mitochondrial redox signaling has a central role in age-related muscle loss. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates redox signaling pathways with the expression of antioxidant genes. As the aberrant redox signaling mechanisms in aging skeletal muscle become clearer, new natural and synthetic Nrf2-modulating substances and integrated daily physical activity alternatives are coming into view for preventing muscle loss in the elderly. A comprehensive understanding of the relationship between redox signaling pathways and age-related sarcopenia can help us to prevent sarcopenia and its frailty effects with an optimized exercise program as an innovative non-pharmacological therapeutic approach. A further aspect is necessary to consider both individualized physical training options and alternative Nrf2 signaling modulators. Ameliorating the redox signaling with physical activity and pharmacological interventions may help to prevent sarcopenia and its frailty effects.

3D Mitochondrial Structure in Aging Human Skeletal Muscle: Insights into MFN-2 Mediated Changes.

Age-related atrophy of skeletal muscle, is characterized by loss of mass, strength, endurance, and oxidative capacity during aging. Notably, bioenergetics and protein turnover studies have shown that mitochondria mediate this decline in function. Although exercise has been the only therapy to mitigate sarcopenia, the mechanisms that govern how exercise serves to promote healthy muscle aging are unclear. Mitochondrial aging is associated with decreased mitochondrial capacity, so we sought to investigate how aging affects mitochondrial structure and potential age-related regulators. Specifically, the three-dimensional (3D) mitochondrial structure associated with morphological changes in skeletal muscle during aging requires further elucidation. We hypothesized that aging causes structural remodeling of mitochondrial 3D architecture representative of dysfunction, and this effect is mitigated by exercise. We used serial block-face scanning electron microscopy to image human skeletal tissue samples, followed by manual contour tracing using Amira software for 3D reconstruction and subsequent analysis of mitochondria. We then applied a rigorous in vitro and in vivo exercise regimen during aging. Across 5 human cohorts, we correlate differences in magnetic resonance imaging, mitochondria 3D structure, exercise parameters, and plasma immune markers between young (under 50 years) and old (over 50 years) individuals. We found that mitochondria we less spherical and more complex, indicating age-related declines in contact site capacity. Additionally, aged samples showed a larger volume phenotype in both female and male humans, indicating potential mitochondrial swelling. Concomitantly, muscle area, exercise capacity, and mitochondrial dynamic proteins showed age-related losses. Exercise stimulation restored mitofusin 2 (MFN2), one such of these mitochondrial dynamic proteins, which we show is required for the integrity of mitochondrial structure. Furthermore, we show that this pathway is evolutionarily conserved as Marf, the MFN2 ortholog in Drosophila, knockdown alters mitochondrial morphology and leads to the downregulation of genes regulating mitochondrial processes. Our results define age-related structural changes in mitochondria and further suggest that exercise may mitigate age-related structural decline through modulation of mitofusin 2.

The effects of whey, pea, and collagen protein supplementation beyond the recommended dietary allowance on integrated myofibrillar protein synthetic rates in older males: a randomized controlled trial

BackgroundSkeletal muscle mass is determined predominantly by feeding-induced and activity-induced fluctuations in muscle protein synthesis (MPS). Older individuals display a diminished MPS response to protein ingestion, referred to as age-related anabolic resistance, which contributes to the progression of age-related muscle loss known as sarcopenia. ObjectivesWe aimed to determine the impact of consuming higher-quality compared with lower-quality protein supplements above the recommended dietary allowance (RDA) on integrated MPS rates. We hypothesized that increasing total protein intake above the RDA, regardless of the source, would support higher integrated rates of myofibrillar protein synthesis. MethodsThirty-one healthy older males (72 ± 4 y) consumed a controlled diet with protein intake set at the RDA: control phase (days 1–7). In a double-blind, randomized controlled fashion, participants were assigned to consume an additional 50 g (2 × 25g) of whey (n = 10), pea (n = 11), or collagen (n = 10) protein each day (25 g at breakfast and lunch) during the supplemental phase (days 8–15). Deuterated water ingestion and muscle biopsies assessed integrated MPS and acute anabolic signaling. Postprandial blood samples were collected to determine feeding-induced aminoacidemia. ResultsIntegrated MPS was increased during supplemental with whey (1.59 ± 0.11 %/d; P < 0.001) and pea (1.59 ± 0.14 %/d; P < 0.001) when compared with RDA (1.46 ± 0.09 %/d for the whey group; 1.46 ± 0.10 %/d for the pea group); however, it remained unchanged with collagen. Supplemental protein was sufficient to overcome anabolic signaling deficits (mTORC1 and rpS6), corroborating the greater postprandial aminoacidemia. ConclusionsOur findings demonstrate that supplemental protein provided at breakfast and lunch over the current RDA enhanced anabolic signaling and integrated MPS in older males; however, the source of additional protein may be an important consideration in overcoming age-related anabolic resistance.This trial was registered clinicaltrials.gov as NCT04026607.

Augmented muscle mass blunts aging-induced cerebrovascular oxidant stress and inflammation

Cerebrovascular dysfunction is a key driver in the cognitive and sensorimotor decline that accompanies aging, contributing to the overall progression of vascular dementia. Exercise is an effective intervention to improve brain health and cognitive function, demonstrating positive effects on cerebral vasculature via a reduction in oxidant stress, thus delaying or partially reversing dementia symptoms. Age-related muscle loss (sarcopenia), however, is prevalent in adults over 50 and sarcopenic older individuals are frequently unable to take advantage of regular exercise, the most effective therapy to reduce risk of cognitive impairment, at a level that confers benefit. Interventions that can effectively replicate the effect of exercise are thus urgently needed to address the medical needs of a large population at exceedingly elevated risk for age-related cognitive impairment. The objective of the work is to determine if augmented muscle mass, a by-product of exercise, can ameliorate both skeletal and cerebrovascular dysfunction in an aging mouse model. Myokine myostatin is a potent negative regulator of skeletal muscle growth that contributes to reduced muscle mass in many muscle-wasting diseases, including aging. To date, research has focused on the protective effect of augmented muscle mass, using genetic or pharmaceutical inhibition of myostatin, in young and obese animals. Our hypothesis is that augmented muscle mass, via myostatin deletion, will improve muscle function and further, blunt the increase in oxidant stress and inflammation that drive cerebrovascular dysfunction in the aging brain. Young adult (3 mo.) and aged (24 mo.) male C57Bl/6J mice were used as controls, in combination with aged mice (24 mo.) with myostatin constitutively deleted. Augmented muscle mass and function were assessed using in vivo plantarflexion. Oxidant stress and inflammatory makers were assessed in micro vessels isolated from the whole brain, using commercially available ELISA’s and mRNA expression. Vascular function is being assessed using pressure myography and immunohistochemistry using the middle cerebral artery. Results show that augmented muscle mass, via myostatin deletion, was successful at increasing muscle mass in the aging mouse, blunting sarcopenia, and improving skeletal muscle function. Further, the aging cerebrovasculature had significantly increased expression of two of the NADPH oxidase isoforms (NOX1, NOX4), along with pivotal cytokines/chemokines associated with vascular inflammation, activation of microglia and astrocytes, and neuroinflammation (IL-1β and CCL5/RANTES). Biomarkers of oxidant stress (3-nitrotyrosine and 8-isoprostane) were also significantly elevated with aging. Taken together, augmented muscle mass may be an effective therapeutic target to prevent and rescue cerebrovascular function and inhibit cognitive decline in an aging population. This research gratefully acknowledges support from the NIA (K01 AG064121), OCAST (HR21-045-1) and the Niblack Research Scholars Program. 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.

Effects of High-Intensity Interval Training on Muscle Strength for the Prevention and Treatment of Sarcopenia in Older Adults: A Systematic Review of the Literature.

Sarcopenia is a significant health concern primarily affecting old adult individuals, characterized by age-related muscle loss, and decreased strength, power, and endurance. It has profound negative effects on overall health and quality of life, including reduced independence, mobility, and daily activity performance, osteoporosis, increased fall and fracture risks, metabolic issues, and chronic diseases like diabetes and cardiovascular conditions. Preventive strategies typically involve a combination of proper nutrition and regular physical activity. Among strength training exercises, high-intensity interval training (HIIT) stands out as the most effective approach for improving muscle function in older adults with sarcopenia. The current review identifies and summarizes the studies that have examined the effects of HIIT on muscle strength in older adults as an element of the prevention and treatment of sarcopenia. A systematic search using several computerized databases, namely, MEDLINE/PubMed, Scopus, SPORTDiscus, and Web of Science, was performed on 12 January 2023, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 224 studies were initially retrieved. A total of five studies met the selection criteria. HIIT training shows improvements in body composition and functional and cardiorespiratory capacity, has benefits on muscle strength, increases muscle quality and architecture, and is associated with muscle hypertrophy in healthy older adults. Nonetheless, given the shortcomings affecting primary research in terms of the limited number of studies and the high risk of bias, further research is warranted.

Association between sarcopenia and new-onset chronic kidney disease among middle-aged and elder adults: findings from the China Health and Retirement Longitudinal Study

BackgroundSarcopenia is a senile syndrome of age-related muscle loss. It is thought to affect the development of chronic kidney disease and has a serious impact on the quality of life of the elder adults. Little is known about the association between sarcopenia and new-onset chronic kidney disease in middle-aged and elder adults. Using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted a longitudinal analysis to investigate the association between sarcopenia status and new-onset chronic kidney disease in middle-aged and elder adults in China.MethodsThe study population consisted of 3676 participants aged 45 or older selected from 2011 CHARLS database who had no history of chronic kidney disease at the baseline and completed the follow-up in 2015. A multivariate cox regression model was employed to examine the association between sarcopenia and the incidence of new-onset chronic kidney disease.ResultsFollowed up for 4 years, a total of 873 (22.5%) new cases of chronic kidney disease occurred. Among them, participants diagnosed with sarcopenia (HR1.45; 95% CI 1.15–1.83) were more likely to develop new-onset chronic kidney disease than those without sarcopenia. Similarly, patients with sarcopenia were more likely to develop new-onset chronic kidney disease than those with possible sarcopenia (HR 1.27; 95%CI 1.00-1.60). Subgroup analysis revealed that elder adults aged between 60 and 75 years old (HR 1.666; 95%CI 1.20-22.28), with hypertension (HR 1.57; 95%CI 1.02–2.40), people with sarcopenia had a significantly higher risk of developing new-onset chronic kidney disease than those without sarcopenia (all P < 0.05).ConclusionMiddle-aged and elder adults diagnosed with sarcopenia have a higher risk of developing new-onset chronic kidney disease.

Human myofiber-enriched aging-induced lncRNA FRAIL1 promotes loss of skeletal muscle function.

The loss of skeletal muscle mass during aging is a significant health concern linked to adverse outcomes in older individuals. Understanding the molecular basis of age-related muscle loss is crucial for developing strategies to combat this debilitating condition. Long noncoding RNAs (lncRNAs) are a largely uncharacterized class of biomolecules that have been implicated in cellular homeostasis and dysfunction across a many tissues and cell types. To identify lncRNAs that might contribute to skeletal muscle aging, we screened for lncRNAs whose expression was altered in vastus lateralis muscle from older compared to young adults. We identified FRAIL1 as an aging-induced lncRNA with high abundance in human skeletal muscle. In healthy young and older adults, skeletal muscle FRAIL1 was increased with age in conjunction with lower muscle function. Forced expression of FRAIL1 in mouse tibialis anterior muscle elicits a dose-dependent reduction in skeletal muscle fiber size that is independent of changes in muscle fiber type. Furthermore, this reduction in muscle size is dependent on an intact region of FRAIL1 that is highly conserved across non-human primates. Unbiased transcriptional and proteomic profiling of the effects of FRAIL1 expression in mouse skeletal muscle revealed widespread changes in mRNA and protein abundance that recapitulate age-related changes in pathways and processes that are known to be altered in aging skeletal muscle. Taken together, these findings shed light on the intricate molecular mechanisms underlying skeletal muscle aging and implicate FRAIL1 in age-related skeletal muscle phenotypes.

Biophysical and nutritional combination treatment for myosteatosis in patients with sarcopenia: a study protocol for single-blinded randomised controlled trial

IntroductionSarcopenia is characterised by age-related loss of skeletal muscle and function and is associated with risks of adverse outcomes. The prevalence of sarcopenia increases due to ageing population and effective...

Fermented Yak-Kong using Bifidobacterium animalis derived from Korean infant intestine effectively relieves muscle atrophy in an aging mouse model.

Yak-Kong (YK) is a small black soybean widely cultivated in Korea. It is considered to have excellent health functionality, as it has been reported to have better antioxidant efficacy than conventional black or yellow soybeans. Since YK has been described as good for the muscle health of the elderly in old oriental medicine books, this study sought to investigate the effect of fermented YK with Bifidobacterium animalis subsp. lactis LDTM 8102 (FYK) on muscle atrophy. In C2C12 mouse myoblasts, FYK elevated the expression of MyoD, total MHC, phosphorylated AKT, and PGC1α. In addition, two kinds of in vivo studies were conducted using both an induced and normal aging mouse model. The behavioral test results showed that in the induced aging mouse model, FYK intake alleviated age-related muscle weakness and loss of exercise performance. In addition, FYK alleviated muscle mass decrease and improved the expression of biomarkers including total MHC, myf6, phosphorylated AKT, PGC1α, and Tfam, which are related to myoblast differentiation, muscle protein synthesis, and mitochondrial generation in the muscle. In the normal aging model, FYK consumption did not increase muscle mass, but did upregulate the expression levels of biomarkers related to myoblast differentiation, muscle hypertrophy, and muscle function. Furthermore, it mitigated age-related declines in skeletal muscle force production and functional limitation by enhancing exercise performance and grip strength. Taken together, the results suggest that FYK has the potential to be a new functional food material that can alleviate the loss of muscle mass and strength caused by aging and prevent sarcopenia.

Dark tea extract attenuates age-related muscle loss by suppressing oxidative stress and inflammation in skeletal muscle of mice

Dark tea (DT), a tea post-fermented by the Eurotium cristatum fungus, is known to attenuate oxidative damage and chronic inflammation. It also extends the lifespan of Caenorhabditis elegans fed a high-sugar diet. However, its impact on age-related muscle loss in mice is unclear. We divided 65-week-old male C57BL/6 mice into three groups: old control received the AIN-93 M diet, while the 0.15DT and 0.3DT groups had 0.15 % and 0.3 % DT for 9 weeks. As a result, DT improved grip strength, treadmill performance, muscle weight, and size in aged mice. It reduced cellular senescence, muscle atrophy markers, and angiopoietin-like 2 expression, while increasing sirtuin 1 protein levels in aged mice. Additionally, DT lowered malondialdehyde content and pro-inflammatory cytokine levels and enhanced total antioxidant capacity and enzymes, ultimately attenuating mitochondrial dysfunction in skeletal muscle. Therefore, our results suggest DT attenuates age-related muscle atrophy by alleviating oxidative stress, mitochondrial dysfunction, and inflammation.

Butyrate supplementation reduces sarcopenia by repairing neuromuscular junction in patients with chronic obstructive pulmonary disease

IntroductionChronic obstructive pulmonary disease (COPD) is associated with an intestinal leak and neuromuscular junction (NMJ) degradation, which contributes to physical compromise and accelerated age-related muscle loss, called sarcopenia. However, the relevant interventions partly remain ineffective. We investigated the effects of exogenous butyrate on sarcopenia and physical capacity with relevance to intestinal permeability and NMJ integrity in COPD patients. MethodsCOPD patients were randomized into placebo (n = 67) and butyrate (n = 64) groups in a double-blind manner. The patients in the butyrate group received one 300 mg capsule a day for 12 weeks. We measured circulating markers of intestinal leak (zonulin), systemic bacterial load (LBP), and NMJ loss (CAF22), along with handgrip strength (HGS), and short physical performance battery (SPPB) at baseline and 12 weeks. ResultsButyrate supplementation improved HGS and gait speed in COPD patients. Among SPPB indices, butyrate improved the ability to maintain postural balance and walking and prevented a decline in the ability to rise from a chair. Butyrate also reduced the plasma levels of zonulin, LBP, and CAF22 levels in COPD patients (all p < 0.05). Regression analysis revealed significant associations of plasma zonulin and CAF22 with HGS, gait speed, and cumulative SPPB scores in butyrate group. These changes were associated with reduced markers of inflammation and muscle damage. ConclusionButyrate may provide a therapeutic approach to sarcopenia and physical dependency in COPD by repairing intestinal leak and NMJ loss.