Attenuating Cholinergic Transmission Increases the Number of Satellite Cells and Preserves Muscle Mass in Old Age.
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ABSTRACT:
SUBMITTER: Vaughan SK
PROVIDER: S-EPMC6768977 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Postganglionic sympathetic neurons and satellite glial cells are the two major cell types of the peripheral sympathetic ganglia. Sympathetic neurons project to and provide neural control of peripheral organs and have been implicated in human disorders ranging from cardiovascular disease to peripheral neuropathies. Here we show that satellite glia regulate synaptic activity of cultured postnatal sympathetic neurons, providing evidence for local ganglionic control of sympathetic drive. In addition to modulating neuron-to-neuron cholinergic neurotransmission, satellite glia promote synapse formation and contribute to neuronal survival. Examination of the cellular architecture of the rat sympathetic ganglia in vivo shows this regulation of neuronal properties takes place during a developmental period in which neuronal morphology and density are actively changing and satellite glia enwrap sympathetic neuronal somata. Cultured satellite glia make and release factors that promote neuronal activity and that can partially rescue the neurons from cell death following nerve growth factor deprivation. Thus, satellite glia play an early and ongoing role within the postnatal sympathetic ganglia, expanding our understanding of the contributions of local and target-derived factors in the regulation of sympathetic neuron function.
| S-EPMC6999876 | biostudies-literature
Project description:BackgroundSarcopenia, the age-related, progressive loss of skeletal muscle mass, strength, and function, is a considerable socioeconomic burden by increasing risks of falls, fractures, and frailty. Moreover, sarcopenic patients are often obese and therapeutic options are very limited.MethodsHere, we assessed the efficacy of espindolol on muscle mass in 19-month-old male Wistar Han rats (weight, 555?±?18 g), including safety issues. Rats were randomized to treatment with 3 mg/kg/day espindolol (n?=?8) or placebo (n?=?14) for 31 days.ResultsPlacebo-treated rats progressively lost body weight (-15.5?±?7.2 g), lean mass (-1.5?±?4.2 g), and fat mass (-15.6?±?2.7 g), while espindolol treatment increased body weight (+8.0?±?6.1 g, p?<?0.05), particularly lean mass (+43.4?±?3.5 g, p?<?0.001), and reduced fat mass further (-38.6?±?3.4 g, p?<?0.001). Anabolic/catabolic signaling was assessed in gastrocnemius muscle. Espindolol decreased proteasome and caspase-3 proteolytic activities by approximately 50 % (all p?<?0.05). Western blotting showed a reduced expression of key catabolic regulators, including NF?B, MuRF1, and LC-3 (all p?<?0.01). The 50- and 26-kDa forms of myostatin were downregulated fivefold and 20-fold, respectively (both p?<?0.001). Moreover, 4E-BP-1 was reduced fivefold (p?<?0.01), while phospho-PI3K was upregulated fivefold (p?<?0.001), although Akt expression and phosphorylation were lower compared to placebo (all p?<?0.05). No regulation of p38 and expression of ERK1/2 were observed, while phosphorylation of p38 was reduced (-54 %, p?<?0.001) and ERK1/2 was increased (115 and 83 %, respectively, both p?<?0.01). Espindolol did not affect cardiac function (echocardiography) or clinical plasma parameters.ConclusionEspindolol reversed the effects of aging/sarcopenia, particularly loss of muscle mass and increased fat mass. Thus, espindolol is an attractive candidate drug for the treatment of sarcopenia patients.
| S-EPMC4053568 | biostudies-literature
Project description:Sarcopenia, or skeletal muscle atrophy, is a debilitating comorbidity of many physiological and pathophysiological processes, including normal aging. There are no approved therapies for sarcopenia, but the antihypertrophic myokine myostatin is a potential therapeutic target. Here, we show that treatment of young and old mice with an anti-myostatin antibody (ATA 842) for 4 wk increased muscle mass and muscle strength in both groups. Furthermore, ATA 842 treatment also increased insulin-stimulated whole body glucose metabolism in old mice, which could be attributed to increased insulin-stimulated skeletal muscle glucose uptake as measured by a hyperinsulinemic-euglycemic clamp. Taken together, these studies provide support for pharmacological inhibition of myostatin as a potential therapeutic approach for age-related sarcopenia and metabolic disease.
| S-EPMC4776508 | biostudies-other
Project description:Changes in satellite cell content play a key role in regulating skeletal muscle growth and atrophy. Yet, there is little information on changes in satellite cell content from birth to old age in humans. The present study defines muscle fiber type-specific satellite cell content in human skeletal muscle tissue over the entire lifespan. Muscle biopsies were collected in 165 subjects, from different muscles of children undergoing surgery (<18 years; n?=?13) and from the vastus lateralis muscle of young adult (18–49 years; n?=?50), older (50–69 years; n?=?53), and senescent subjects (70–86 years; n?=?49). In a subgroup of 51 aged subjects (71?±?6 years), additional biopsies were collected after 12 weeks of supervised resistance-type exercise training. Immunohistochemistry was applied to assess skeletal muscle fiber type-specific composition, size, and satellite cell content. From birth to adulthood, muscle fiber size increased tremendously with no major changes in muscle fiber satellite cell content, and no differences between type I and II muscle fibers. In contrast to type I muscle fibers, type II muscle fiber size was substantially smaller with increasing age in adults (r?=??0.56; P?<?0.001). This was accompanied by an age-related reduction in type II muscle fiber satellite cell content (r?=??0.57; P?<?0.001). Twelve weeks of resistance-type exercise training significantly increased type II muscle fiber size and satellite cell content. We conclude that type II muscle fiber atrophy with aging is accompanied by a specific decline in type II muscle fiber satellite cell content. Resistance-type exercise training represents an effective strategy to increase satellite cell content and reverse type II muscle fiber atrophy.
| S-EPMC4039250 | biostudies-literature
Project description:IntroductionCritically ill patients are characterized by increased loss of muscle mass, partially attributed to sepsis and multiple organ failure, as well as immobilization. Recent studies have shown that electrical muscle stimulation (EMS) may be an alternative to active exercise in chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) patients with myopathy. The aim of our study was to investigate the EMS effects on muscle mass preservation of critically ill patients with the use of ultrasonography (US).MethodsForty-nine critically ill patients (age: 59 +/- 21 years) with an APACHE II admission score >or=13 were randomly assigned after stratification upon admission to receive daily EMS sessions of both lower extremities (EMS-group) or to the control group (control group). Muscle mass was evaluated with US, by measuring the cross sectional diameter (CSD) of the vastus intermedius and the rectus femoris of the quadriceps muscle.ResultsTwenty-six patients were finally evaluated. Right rectus femoris and right vastus intermedius CSD decreased in both groups (EMS group: from 1.42 +/- 0.48 to 1.31 +/- 0.45 cm, P = 0.001 control group: from 1.59 +/- 0.53 to 1.37 +/- 0.5 cm, P = 0.002; EMS group: from 0.91 +/- 0.39 to 0.81 +/- 0.38 cm, P = 0.001 control group: from 1.40 +/- 0.64 to 1.11 +/- 0.56 cm, P = 0.004, respectively). However, the CSD of the right rectus femoris decreased significantly less in the EMS group (-0.11 +/- 0.06 cm, -8 +/- 3.9%) as compared to the control group (-0.21 +/- 0.10 cm, -13.9 +/- 6.4%; P < 0.05) and the CSD of the right vastus intermedius decreased significantly less in the EMS group (-0.10 +/- 0.05 cm, -12.5 +/- 7.4%) as compared to the control group (-0.29 +/- 0.28 cm, -21.5 +/- 15.3%; P < 0.05).ConclusionsEMS is well tolerated and seems to preserve the muscle mass of critically ill patients. The potential use of EMS as a preventive and rehabilitation tool in ICU patients with polyneuromyopathy needs to be further investigated.Trial registrationclinicaltrials.gov: NCT00882830.
| S-EPMC2784391 | biostudies-literature
Project description:BackgroundThe gut microbiome and fecal metabolites have been found to influence sarcopenia, but whether there are potential bacteria that can alleviate sarcopenia has been under-investigated, and the molecular mechanism remains unclear.MethodsTo investigate the relationships between the gut microbiome, fecal metabolites and sarcopenia, subjects were selected from observational multi-ethnic study conducted in Western China. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia 2014. The gut microbiome was profiled by shotgun metagenomic sequencing. Untargeted metabolomic analysis was performed to analyse the differences in fecal metabolites. We investigated bacterium with the greatest relative abundance difference between healthy individuals and sarcopenia patients, and the differences in metabolites associated with the bacteria, to verify its effects on muscle mass and function in a mouse model.ResultsThe study included 283 participants (68.90% females, mean age: 66.66 years old) with and without sarcopenia (141 and 142 participants, respectively) and from the Han (98 participants), Zang (88 participants) and Qiang (97 participants) ethnic groups. This showed an overall reduction (15.03% vs. 20.77%, P = 0.01) of Prevotella copri between the sarcopenia and non-sarcopenia subjects across the three ethnic groups. Functional characterization of the differential bacteria showed enrichment (odds ratio = 15.97, P = 0.0068) in branched chain amino acid (BCAA) metabolism in non-sarcopenia group. A total of 13 BCAA and their derivatives have relatively low levels in sarcopenia. In the in vivo experiment, we found that the blood BCAA level was higher in the mice gavaged with live P. copri (LPC) (P < 0.001). The LPC mice had significantly longer wire and grid hanging time (P < 0.02), longer time on rotor (P = 0.0001) and larger grip strength (P < 0.0001), indicating better muscle function. The weight of gastrocnemius mass and rectus femoris mass (P < 0.05) was higher in LPC mice. The micro-computed tomography showed a larger leg area (P = 0.0031), and a small animal analyser showed a higher lean mass ratio in LPC mice (P = 0.0157), indicating higher muscle mass.ConclusionsThe results indicated that there were lower levels of both P. copri and BCAA in sarcopenia individuals. In vivo experiments, gavage with LPC could attenuate muscle mass and function decline, indicating alleviating sarcopenia. This suggested that P. copri may play a therapeutic potential role in the management of sarcopenia.
| S-EPMC10570070 | biostudies-literature
Project description:Purpose of reviewImpaired recovery following an intensive care unit (ICU) admission is thought related to muscle wasting. Nutrition and physical activity are considered potential avenues to attenuate muscle wasting. The aim of this review was to present evidence for these interventions in attenuating muscle loss or improving strength and function.Recent findingsRandomised controlled trials on the impact of nutrition or physical activity interventions in critically ill adult patients on muscle mass, strength or function are presented. No nutrition intervention has shown an effect on strength or function, and the effect on muscle mass is conflicting. RCTs on the effect of physical activity demonstrate conflicting results; yet, there is a signal for improved strength and function with higher levels of physical activity, particularly when commenced early. Further research is needed to elucidate the impact of nutrition and physical activity on muscle mass, strength and function, particularly in combination.
| S-EPMC9522765 | biostudies-literature
Project description:Climate warming is changing plant sexual reproduction, having consequences for species distribution and community dynamics. However, the magnitude and direction of plant reproductive efforts (e.g., number of flowers) and success (e.g., number and mass of fruits or seeds) in response to warming have not been well-characterized. Here, we generated a global dataset of simulated warming experiments, consisting of 477 pairwise comparisons for 164 terrestrial species. We found evidence that warming overall decreased fruit number and increased seed mass, but little evidence that warming influenced flower number, fruit mass, or seed number. The warming effects on seed mass were regulated by the pollination type, and insect-pollinated plants exhibited a stronger response to warming than wind-pollinated plants. We found strong evidence that warming increased the mass of seeds for the nondominant species but no evidence of this for the dominant species. There was no evidence that phylogenetic relatedness explained the effects of warming on plant reproductive effort and success. In addition, the effects of warming on flowering onset negatively related to the responses in terms of the number of fruits and seeds to warming, revealing a cascading effect of plant reproductive development. These findings provide the first quantification of the response of terrestrial plant sexual reproduction to warming and suggest that plants may increase their fitness by producing heavier seeds under a warming climate.
| S-EPMC10099976 | biostudies-literature
Project description:Increased expression of SIRT1 extends the lifespan of lower organisms and delays the onset of age-related diseases in mammals. Here, we show that SRT2104, a synthetic small molecule activator of SIRT1, extends both mean and maximal lifespan of mice fed a standard diet. This is accompanied by improvements in health, including enhanced motor coordination, performance, bone mineral density and insulin sensitivity associated with higher mitochondrial content and decreased inflammation. Short-term SRT2104 treatment preserves bone and muscle mass in an experimental model of atrophy. These results demonstrate it is possible to design a small molecule that can slow aging and delay multiple age-related diseases in mammals, supporting the therapeutic potential of SIRT1 activators in humans. Key words: Sirtuins, lifespan, healthspan, osteoporosis, muscle wasting, inflammation Groups of 28 week old male C57BL6/J mice were maintained for the rest of their lives or until sacrifice on either an ad libitum AIN-93G SD diet, an ad libitum AIN-93G diet supplemented with SRT2104 or a caloric restricted AIN-93G diet consisting of 60% of what the ad lib animals ate. SRT2104 was added at a dose of 1.33 g drug per kg of chow, formulated to provide daily doses of approximately 100 mg drug per kg bodyweight to the mice. 5 mice from each group were selected after 41 weeks and RNA was extracted from both muscle and liver tissue using 1.0mm glass beads in a Precellys 24 Tissue Homogenizer and Qiagen RNeasy Mini Kits for Fibrous Tissue according to manufacturer's specifications. Quality and quantity of the total RNA was checked with the Agilent 2100 bioanalyzer using RNA 6000 Nano chips. RNA samples were labeled using the Illumina TotalPrep RNA Amplification Kit. In short, 0.5ug of total RNA was first converted into single-stranded cDNA with reverse transcriptase using an oligo-dT primer containing the T7 RNA polymerase promoter site and then copied to produce double-stranded cDNA molecules. The double stranded cDNA was cleaned and concentrated with the supplied columns and used in an overnight in-vitro transcription reaction where single-stranded RNA (cRNA) was generated and labeled by incorporation of biotin-16-UTP. Arrays were hybridized using a total of 0.75ug of biotin-labeled cRNA at 58 degrees C for 16 hours to Illumina's Sentrix MouseRef-8 v2 Expression BeadChips. Each BeadChip has ~24,000 well-annotated RefSeq transcripts with approximately 30-fold redundancy. The arrays were washed, blocked and the biotin labeled cRNA was detected by staining with streptavidin-Cy3. Arrays were scanned at a resolution of 0.8um using the Beadstation 500 X from Illumina and the data was extracted using the Illumina GenomeStudio software(v1.6.0). Any spots at or below the background were filtered out using an Illumina detection p value of 0.02 and above. The natural log of all remaining scores were used to find the avg and std of each array and the z-score normalization was calculated and presented below. Z-score = (raw value - avg)/std.
2014-09-22 | E-GEOD-49000 | biostudies-arrayexpress
Project description:BackgroundAlthough muscle regenerative capacity declines with age, the extent to which this is due to satellite cell-intrinsic changes vs. environmental changes has been controversial. The majority of aging studies have investigated hindlimb locomotory muscles, principally the tibialis anterior, in caged sedentary mice, where those muscles are abnormally under-exercised.MethodsWe analyze satellite cell numbers in 8 muscle groups representing locomotory and non-locomotory muscles in young and 2-year-old mice and perform transplantation assays of low numbers of hind limb satellite cells from young and old mice.ResultsWe find that satellite cell density does not decline significantly by 2 years of age in most muscles, and one muscle, the masseter, shows a modest but statistically significant increase in satellite cell density with age. The tibialis anterior and extensor digitorum longus were clear exceptions, showing significant declines. We quantify self-renewal using a transplantation assay. Dose dilution revealed significant non-linearity in self-renewal above a very low threshold, suggestive of competition between satellite cells for space within the pool. Assaying within the linear range, i.e., transplanting fewer than 1000 cells, revealed no evidence of decline in cell-autonomous self-renewal or regenerative potential of 2-year-old murine satellite cells.ConclusionThese data demonstrate the value of comparative muscle analysis as opposed to overreliance on locomotory muscles, which are not used physiologically in aging sedentary mice, and suggest that self-renewal impairment with age is precipitously acquired at the geriatric stage, rather than being gradual over time, as previously thought.
| S-EPMC8418011 | biostudies-literature