Fermented Yak-Kong using derived from Korean infant intestine effectively relieves muscle atrophy in an aging mouse model.
Food & function
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 subsp. 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 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.
10.1039/d3fo04204a
New Horizons in the Treatment of Age-Associated Obesity, Sarcopenia and Osteoporosis.
Drugs & aging
The rapid increase in both the lifespan and proportion of older adults in developed countries is accompanied by the dramatic growth of age-associated chronic diseases, including obesity, sarcopenia, and osteoporosis. Hence, prevention and treatment of age-associated chronic diseases has become increasingly urgent. The key to achieving this goal is a better understanding of the mechanisms underlying their pathophysiology, some aspects of which, despite extensive investigation, are still not fully understood. Aging, obesity, sarcopenia, and osteoporosis are characterized by the creation of a systemic, chronic, low-grade inflammation (SCLGI). The common mechanisms that govern the development of these chronic conditions include a failed resolution of inflammation. Physiologically, the process of inflammation resolution is provided mainly by specialized pro-resolving mediators (SPMs) acting via cognate G protein-coupled receptors (GPCRs). Noteworthy, SPM levels and the expression of their receptors are significantly reduced in aging and the associated chronic disorders. In preclinical studies, supplementation of SPMs or their stable, small-molecule SPM mimetics and receptor agonists reveals clear beneficial effects in inflammation-related obesity and sarcopenic and osteoporotic conditions, suggesting a translational potential. Age-associated chronic disorders are also characterized by gut dysbiosis and the accumulation of senescent cells in the adipose tissue, skeletal muscle, and bones. Based on these findings, we propose SCLGI resolution as a novel strategy for the prevention/treatment of age-associated obesity, sarcopenia, and osteoporosis. Our approach entails the enhancement of inflammation resolution by SPM mimetics and receptor agonists in concert with probiotics/prebiotics and compounds that eliminate senescent cells and their pro-inflammatory activity.
10.1007/s40266-022-00960-z
Lactobacillus delbrueckii alleviates lipopolysaccharide-induced muscle inflammation and atrophy in weaned piglets associated with inhibition of endoplasmic reticulum stress and protein degradation.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Pro-inflammatory cytokines in muscle play a pivotal role in physiological responses and in the pathophysiology of inflammatory disease and muscle atrophy. Lactobacillus delbrueckii (LD), as a kind of probiotics, has inhibitory effects on pro-inflammatory cytokines associated with various inflammatory diseases. This study was conducted to explore the effect of dietary LD on the lipopolysaccharide (LPS)-induced muscle inflammation and atrophy in piglets and to elucidate the underlying mechanism. A total of 36 weaned piglets (Duroc × Landrace × Large Yorkshire) were allotted into three groups with six replicates (pens) of two piglets: (1) Nonchallenged control; (2) LPS-challenged (LPS); (3) 0.2% LD diet and LPS-challenged (LD+LPS). On d 29, the piglets were injected intraperitoneally with LPS or sterilized saline, respectively. All piglets were slaughtered at 4 h after LPS or saline injection, the blood and muscle samples were collected for further analysis. Our results showed that dietary supplementation of LD significantly attenuated LPS-induced production of pro-inflammatory cytokines IL-6 and TNF-α in both serum and muscle of the piglets. Concomitantly, pretreating the piglets with LD also clearly inhibited LPS-induced nuclear translocation of NF-κB p65 subunits in the muscle, which correlated with the anti-inflammatory effects of LD on the muscle of piglets. Meanwhile, LPS-induced muscle atrophy, indicated by a higher expression of muscle atrophy F-box, muscle RING finger protein (MuRF1), forkhead box O 1, and autophagy-related protein 5 (ATG5) at the transcriptional level, whereas pretreatment with LD led to inhibition of these upregulations, particularly genes for MuRF1 and ATG5. Moreover, LPS-induced mRNA expression of endoplasmic reticulum stress markers, such as eukaryotic translational initiation factor 2α (eIF-2α) was suppressed by pretreatment with LD, which was accompanied by a decrease in the protein expression levels of IRE1α and GRP78. Additionally, LD significantly prevented muscle cell apoptotic death induced by LPS. Taken together, our data indicate that the anti-inflammatory effect of LD supply on muscle atrophy of piglets could be likely regulated by inhibiting the secretion of pro-inflammatory cytokines through the inactivation of the ER stress/NF-κB singling pathway, along with the reduction in protein degradation.
10.1096/fj.202400969RR
Probiotics Supplements Improve the Sarcopenia-Related Quality of Life in Older Adults with Age-Related Muscle Decline.
Calcified tissue international
A pathological increase in intestinal leak is implicated in age-associated muscle loss, termed sarcopenia, and reduced sarcopenia-related quality-of-life (SarQoL). However, the potential therapies remain elusive. We investigated the effects of probiotic supplementation on sarcopenia and SarQoL in geriatric older adults. We randomized sarcopenic men into placebo (age = 71.4 ± 3.9 years, n = 63) and probiotic (age = 73 ± 4.1 years, n = 60) groups for 16 weeks. The probiotic used was one capsule daily of Vivomix 112 billion for 16 weeks. We measured sarcopenia parameters of handgrip strength (HGS) and skeletal mass index (SMI), plasma zonulin (marker of the intestinal leak), and SarQoL using a targeted questionnaire. Probiotics improved the SarQoL scores for locomotion, functionality, and activities of daily living and prevented a decline in cumulative SarQoL observed in the placebo group (all p < 0.05). Probiotic supplementation also reduced plasma zonulin and marker of systemic bacterial load. These changes were accompanied by an increase in HGS and maintenance of gait speed in the probiotic group compared to the placebo group. Correlation analysis revealed significant associations of cumulative SarQoL scores with plasma zonulin and HGS in the probiotic group. Collectively, probiotics improved SarQoL and HGS by repairing pathological intestinal leak. Future studies may further dissect the relation between intestinal leak and SarQoL in older adults taking probiotics.
10.1007/s00223-024-01211-6
Faecal microbiota transplantation from young rats attenuates age-related sarcopenia revealed by multiomics analysis.
Journal of cachexia, sarcopenia and muscle
BACKGROUND:Gut microbiota plays a key role in the development of sarcopenia via the 'gut-muscle' axis, and probiotics-based therapy might be a strategy for sarcopenia. Fecal microbiota transplantation from young donors (yFMT) has attracted much attention because of its probiotic function. However, whether or not yFMT is effective for sarcopenia in old recipients is largely unknown. Thus, we aimed to investigate the effect and mechanism of yFMT on age-related sarcopenia. METHODS:The fecal microbiota of either young (12 weeks) or old (88 weeks) donor rats was transplanted into aged recipient rats for 8 weeks. Then, muscle mass, muscle strength, muscle function, muscle atrophy, and muscle regeneration capacity were measured. Analysis of fecal 16 s rRNA, serum non-targeted metabolomic, gut barrier integrity, and muscle transcriptome was conducted to elucidate the interaction between gut microbiota and skeletal muscles. RESULTS:As evaluated by magnetic resonance imaging examination, grip strength test (P < 0.01), rotarod test (P < 0.05), and exhaustive running test (P < 0.05), we found that yFMT mitigated muscle mass loss, muscle strength weakness, and muscle function impairment in aged rats. yFMT also countered age-related atrophy and poor regeneration capacity in fast- and slow-switch muscles, which were manifested by the decrease in slow-switch myofibres (both P < 0.01) and muscle interstitial fibrosis (both P < 0.05) and the increase in the cross-section area of myofibres (both P < 0.001), fast-switch myofibres (both P < 0.01), and muscle satellite cells (both P < 0.001). In addition, yFMT ameliorated age-related dysbiosis of gut microbiota and metabolites by promoting the production of beneficial bacteria and metabolites-Akkermansia, Lactococcus, Lactobacillus, γ-glutamyltyrosine, 3R-hydroxy-butanoic acid, and methoxyacetic acid and inhibiting the production of deleterious bacteria and metabolites-Family_XIII_AD3011_group, Collinsella, indoxyl sulfate, indole-3-carboxilic acid-O-sulphate, and trimethylamine N-oxide. Also, yFMT prevented age-related destruction of gut barrier integrity by increasing the density of goblet cells (P < 0.0001) and the expression levels of mucin-2 (P < 0.0001) and tight junctional proteins (all P < 0.05). Meanwhile, yFMT attenuated age-related impairment of mitochondrial biogenesis and function in fast- and slow-switch muscles. Correlation analysis revealed that yFMT-induced alterations of gut microbiota and metabolites might be closely related to mitochondria-related genes and sarcopenia-related phenotypes. CONCLUSIONS:yFMT could reshape the dysbiosis of gut microbiota and metabolites, maintain gut barrier integrity, and improve muscle mitochondrial dysfunction, eventually alleviating sarcopenia in aged rats. yFMT might be a new therapeutic strategy for age-related sarcopenia.
10.1002/jcsm.13294
Nutritional Strategies for Muscle Atrophy: Current Evidence and Underlying Mechanisms.
Molecular nutrition & food research
Skeletal muscle can undergo detrimental changes in various diseases, leading to muscle dysfunction and atrophy, thus severely affecting people's lives. Along with exercise, there is a growing interest in the potential of nutritional support against muscle atrophy. This review provides a brief overview of the molecular mechanisms driving skeletal muscle atrophy and summarizes recent advances in nutritional interventions for preventing and treating muscle atrophy. The nutritional supplements include amino acids and their derivatives (such as leucine, β-hydroxy, β-methylbutyrate, and creatine), various antioxidant supplements (like Coenzyme Q10 and mitoquinone, resveratrol, curcumin, quercetin, Omega 3 fatty acids), minerals (such as magnesium and selenium), and vitamins (such as vitamin B, vitamin C, vitamin D, and vitamin E), as well as probiotics and prebiotics (like Lactobacillus, Bifidobacterium, and 1-kestose). Furthermore, the study discusses the impact of a combined approach involving nutritional support and physical therapy to prevent muscle atrophy, suggests appropriate multi-nutritional and multi-modal interventions based on individual conditions to optimize treatment outcomes, and enhances the recovery of muscle function for patients. By understanding the molecular mechanisms behind skeletal muscle atrophy and implementing appropriate interventions, it is possible to enhance the recovery of muscle function and improve patients' quality of life.
10.1002/mnfr.202300347
Gut microbiota as a promising therapeutic target for age-related sarcopenia.
Ageing research reviews
Sarcopenia is characterized by a progressive loss of skeletal muscle mass and function with aging. Recently, sarcopenia has been shown to be closely related with gut microbiota. Strategies such as probiotics and fecal microbiota transplantation have shown potential to ameliorate the muscle loss. This review will focus on the age-related sarcopenia, in particular on the relationship between gut microbiota and age-related sarcopenia, how gut microbiota is engaged in sarcopenia, and the potential role of gut microbiota in the treatment of age-related sarcopenia.
10.1016/j.arr.2022.101739
Gut Microbiota, Muscle Mass and Function in Aging: A Focus on Physical Frailty and Sarcopenia.
Ticinesi Andrea,Nouvenne Antonio,Cerundolo Nicoletta,Catania Pamela,Prati Beatrice,Tana Claudio,Meschi Tiziana
Nutrients
Human gut microbiota is able to influence the host physiology by regulating multiple processes, including nutrient absorption, inflammation, oxidative stress, immune function, and anabolic balance. Aging is associated with reduced microbiota biodiversity, increased inter-individual variability, and over-representation of pathobionts, and these phenomena may have great relevance for skeletal muscle mass and function. For this reason, the presence of a gut-muscle axis regulating the onset and progression of age-related physical frailty and sarcopenia has been recently hypothesized. In this narrative review, we summarize the studies supporting a possible association between gut microbiota-related parameters with measures of muscle mass, muscle function, and physical performance in animal models and humans. Reduced muscle mass has been associated with distinct microbiota composition and reduced fermentative capacity in mice, and the administration of probiotics or butyrate to mouse models of muscle wasting has been associated with improved muscle mass. However, no studies have targeted the human microbiome associated with sarcopenia. Limited evidence from human studies shows an association between microbiota composition, involving key taxa such as and , and grip strength. Similarly, few studies conducted on patients with parkinsonism showed a trend towards a different microbiota composition in those with reduced gait speed. No studies have assessed the association of fecal microbiota with other measures of physical performance. However, several studies, mainly with a cross-sectional design, suggest an association between microbiota composition and frailty, mostly assessed according to the deficit accumulation model. Namely, frailty was associated with reduced microbiota biodiversity, and lower representation of butyrate-producing bacteria. Therefore, we conclude that the causal link between microbiota and physical fitness is still uncertain due to the lack of targeted studies and the influence of a large number of covariates, including diet, exercise, multimorbidity, and polypharmacy, on both microbiota composition and physical function in older age. However, the relationship between gut microbiota and physical function remains a very promising area of research for the future.
10.3390/nu11071633
Gut microbes and muscle function: can probiotics make our muscles stronger?
Journal of cachexia, sarcopenia and muscle
Evidence suggests that gut microbiota composition and diversity can be a determinant of skeletal muscle metabolism and functionality. This is true in catabolic (sarcopenia and cachexia) or anabolic (exercise or in athletes) situations. As gut microbiota is known to be causal in the development and worsening of metabolic dysregulation phenotypes such as obesity or insulin resistance, it can regulate, at least partially, skeletal muscle mass and function. Skeletal muscles are physiologically far from the gut. Signals generated by the gut due to its interaction with the gut microbiome (microbial metabolites, gut peptides, lipopolysaccharides, and interleukins) constitute links between gut microbiota activity and skeletal muscle and regulate muscle functionality via modulation of systemic/tissue inflammation as well as insulin sensitivity. The probiotics able to limit sarcopenia and cachexia or promote health performances in rodents are mainly lactic acid bacteria and bifidobacteria. In humans, the same bacteria have been tested, but the scarcity of the studies, the variability of the populations, and the difficulty to measure accurately and with high reproducibility muscle mass and function have not allowed to highlight specific strains able to optimize muscle mass and function. Further studies are required on more defined population, in order to design personalized nutrition. For elderly, testing the efficiency of probiotics according to the degree of frailty, nutritional state, or degree of sarcopenia before supplementation is essential. For exercise, selection of probiotics capable to be efficient in recreational and/or elite athletes, resistance, and/or endurance exercise would also require further attention. Ultimately, a combination of strategies capable to optimize muscle functionality, including bacteria (new microbes, bacterial ecosystems, or mix, more prone to colonize a specific gut ecosystem) associated with prebiotics and other 'traditional' supplements known to stimulate muscle anabolism (e.g. proteins), could be the best way to preserve muscle functionality in healthy individuals at all ages or patients.
10.1002/jcsm.12964