Advance in Drug Delivery for Ageing Skeletal Muscle.
Ontology highlight
ABSTRACT:
SUBMITTER: Li Y
PROVIDER: S-EPMC7360840 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Advance in Drug Delivery for Ageing Skeletal Muscle.
Li Yi Y Chen Ming M Zhao Yanpeng Y Li Ming M Qin Yong Y Cheng Shi S Yang Yanyu Y Yin Pengbin P Zhang Licheng L Tang Peifu P
Frontiers in pharmacology 20200708
The age-related loss of skeletal muscle, sarcopenia, is characterized by progressive loss of muscle mass, reduction in muscle strength, and dysfunction of physical performance. It has become a global health problem leading to several adverse outcomes in the ageing population. Research on skeletal muscle loss prevention and treatment is developing quickly. However, the current clinical approaches to sarcopenia are limited. Recently, novel drug delivery systems offer new possibilities for treating ...[more]
Similar Datasets
Project description:BACKGROUND:Ageing skeletal muscle undergoes chronic denervation, and the neuromuscular junction (NMJ), the key structure that connects motor neuron nerves with muscle cells, shows increased defects with ageing. Previous studies in various species have shown that with ageing, type II fast-twitch skeletal muscle fibres show more atrophy and NMJ deterioration than type I slow-twitch fibres. However, how this process is regulated is largely unknown. A better understanding of the mechanisms regulating skeletal muscle fibre-type specific denervation at the NMJ could be critical to identifying novel treatments for sarcopenia. Cardiac troponin T (cTnT), the heart muscle-specific isoform of TnT, is a key component of the mechanisms of muscle contraction. It is expressed in skeletal muscle during early development, after acute sciatic nerve denervation, in various neuromuscular diseases and possibly in ageing muscle. Yet the subcellular localization and function of cTnT in skeletal muscle is largely unknown. METHODS:Studies were carried out on isolated skeletal muscles from mice, vervet monkeys, and humans. Immunoblotting, immunoprecipitation, and mass spectrometry were used to analyse protein expression, real-time reverse transcription polymerase chain reaction was used to measure gene expression, immunofluorescence staining was performed for subcellular distribution assay of proteins, and electromyographic recording was used to analyse neurotransmission at the NMJ. RESULTS:Levels of cTnT expression in skeletal muscle increased with ageing in mice. In addition, cTnT was highly enriched at the NMJ region-but mainly in the fast-twitch, not the slow-twitch, muscle of old mice. We further found that the protein kinase A (PKA) RI? subunit was largely removed from, while PKA RII? and RII? are enriched at, the NMJ-again, preferentially in fast-twitch but not slow-twitch muscle in old mice. Knocking down cTnT in fast skeletal muscle of old mice: (i) increased PKA RI? and reduced PKA RII? at the NMJ; (ii) decreased the levels of gene expression of muscle denervation markers; and (iii) enhanced neurotransmission efficiency at NMJ. CONCLUSIONS:Cardiac troponin T at the NMJ region contributes to NMJ functional decline with ageing mainly in the fast-twitch skeletal muscle through interfering with PKA signalling. This knowledge could inform useful targets for prevention and therapy of age-related decline in muscle function.
| S-EPMC5659053 | biostudies-literature
Project description:Healthy skeletal muscle can regenerate after ischaemic, mechanical, or toxin-induced injury, but ageing impairs that regeneration potential. This has been largely attributed to dysfunctional satellite cells and reduced myogenic capacity. Understanding which signalling pathways are associated with reduced myogenesis and impaired muscle regeneration can provide valuable information about the mechanisms driving muscle ageing and prompt the development of new therapies. To investigate this, we developed a high-throughput in vitro model to assess muscle regeneration in chemically injured C2C12 and human myotube-derived young and aged myoblast cultures. We observed a reduced regeneration capacity of aged cells, as indicated by an attenuated recovery towards preinjury myotube size and myogenic fusion index at the end of the regeneration period, in comparison with younger muscle cells that were fully recovered. RNA-sequencing data showed significant enrichment of KEGG signalling pathways, PI3K-Akt, and downregulation of GO processes associated with muscle development, differentiation, and contraction in aged but not in young muscle cells. Data presented here suggests that repair in response to in vitro injury is impaired in aged vs. young muscle cells. Our study establishes a framework that enables further understanding of the factors underlying impaired muscle regeneration in older age.
2023-07-05 | E-MTAB-12248 | biostudies-arrayexpress
Project description:Motor unit remodelling involving repeated denervation and re-innervation occurs throughout life. The efficiency of this process declines with age contributing to neuromuscular deficits. This study investigated differentially expressed genes (DEG) in muscle following peroneal nerve crush to model motor unit remodelling in C57BL/6 J mice. Muscle RNA was isolated at 3 days post-crush, RNA libraries were generated using poly-A selection, sequenced and analysed using gene ontology and pathway tools. Three hundred thirty-four DEG were found in quiescent muscle from (26mnth) old compared with (4-6mnth) adult mice and these same DEG were present in muscle from adult mice following nerve crush. Peroneal crush induced 7133 DEG in muscles of adult and 699 DEG in muscles from old mice, although only one DEG (ZCCHC17) was found when directly comparing nerve-crushed muscles from old and adult mice. This analysis revealed key differences in muscle responses which may underlie the diminished ability of old mice to repair following nerve injury.
| S-EPMC8800362 | biostudies-literature
Project description:Frailty is associated with future cardiovascular events in older adults. This cross-sectional study examined the relationship between subclinical vasculopathy with measures of skeletal muscle mass and function. Asymptomatic community-dwelling Asians ≥55 years underwent assessments for subclinical vasculopathy (carotid intima-media thickness (cIMT), aortic and carotid stiffness, and endothelial function), muscle mass (calf circumference adjusted for body mass index) and function (knee extension strength, 6-meter fast gait speed). Multivariable regression analyses for associates of muscle mass/function controlled for demographics and cardiometabolic risk factors. Among 336 participants (median age 62 years, 55.1% male, 3.6% sarcopenia), cIMT, aortic and carotid stiffness inversely correlated with muscle mass, strength and gait speed; cIMT remained independently associated with gait speed (β=-0.26) in multivariable analyses. Age and sex significantly modified the relationship between subclinical vasculopathy and muscle mass/function. Associations, only found in those aged ≥70, included cIMT with gait speed (β=-0.48) and knee strength (β=-9.33), and aortic augmentation index and aortic stiffness composite z-score with gait speed (β=-0.11 and β=-0.19 respectively). Among males, cIMT correlated with gait speed (β=-0.31). The association of subclinical vasculopathy with skeletal muscle mass and function in asymptomatic adults ≥55 years is best reflected by cIMT. The roles of mediating pathways deserve further evaluation.
| S-EPMC8221343 | biostudies-literature
Project description:The targeted delivery of enzyme-responsive nanoparticles to specific tissues can be a valuable, minimally invasive approach for imaging or drug delivery applications. In this study, we show for the first time enzyme-directed assembly of intravenously (IV) delivered nanoparticles in ischemic skeletal muscle, which has applications for drug delivery to damaged muscle of the type prevalent in peripheral artery disease (PAD). Specifically, micellar nanoparticles are cleavable by matrix metalloproteinases (MMPs), causing them to undergo a morphological switch and thus aggregate in tissues where these enzymes are upregulated, like ischemic muscle. Here, we demonstrated noninvasive in vivo imaging of these IV-injected nanoparticles through near-infrared dye labeling and in vivo imaging (IVIS) particle tracking in a rat hindlimb ischemia model. Polymer peptide amphiphilic nanoparticles were synthesized and optimized for both MMP cleavage efficiency and near-IR fluorescence. Nanoparticles were injected 4 days after unilateral hindlimb ischemia and were monitored over 28 days using IVIS imaging. Nanoparticles targeted to ischemic muscle over healthy muscle, and ex vivo biodistribution analysis at 7 and 28 days post-injection confirmed targeting to the ischemic muscle as well as off target accumulation in the liver and spleen. Ex vivo histology confirmed particle localization in ischemic but not healthy muscle. Altering the surface charge of the nanoparticles through addition of zwitterionic dye species resulted in improved targeting to the ischemic muscle. To our knowledge, this is the first study to demonstrate the targeted delivery and long term retention of nanoparticles using an enzyme-directed morphology switch. This has implications for noninvasive drug delivery vehicles for treating ischemic muscle, as no minimally invasive, non-surgical options currently exist.
| S-EPMC5662209 | biostudies-literature
Project description:This study aimed to explore the set of variables related to skeletal muscle mass (SMM) in both sexes, and to create age- and sex-related models of changes in SMM, using the most representative indicator of muscular status. Body composition was assessed in 8733 subjects (? = 3370 and ? = 5363), allocated into subsamples according to age: 18-29.9, 30-39.9, 40-49.9, 50-59.9, 60-69.9, and 70.0-79.9 years. Nine variables were used: protein mass, protein percent, protein mass index, SMM, percent of SMM, SMM index, fat-free mass, fat-free mass index, and protein/fat index. Univariate and multivariate analysis of variance (ANOVA and MANOVA) were used to determine between- and within-sex difference in all variables by age. Correlation analysis established the relationship between age and muscularity variables. Principal Component Analysis extracted the variables that loaded highest in explaining muscularity, while regression analysis determined the linearity of association between the age and indicators of muscular status. Variables SMMI and PSMM were extracted as the most sensitive to age, with SMMI being gender-independent while showing the parabolic and sinusoidal form of change as function of ageing in males and females, respectively; and PSMM being sex-dependent while showing a linear trend of decrease in both sexes.
| S-EPMC7460401 | biostudies-literature
Project description:There is a scarcity of studies that have investigated the role of multiple single nucleotide polymorphisms (SNPs) on a range of muscle phenotypes in an elderly population. The present study investigated the possible association of 24 SNPs with skeletal muscle phenotypes in 307 elderly Caucasian women (aged 60-91 years, 66.3 ± 11.3 kg). Skeletal muscle phenotypes included biceps brachii thickness, vastus lateralis cross-sectional areas, maximal hand grip strength, isometric knee extension and elbow flexion torque. Genotyping for 24 SNPs, chosen on their skeletal muscle structural or functional links, was conducted on DNA extracted from blood or saliva. Of the 24 SNPs, 10 were associated with at least one skeletal muscle phenotype. HIF1A rs11549465 was associated with three skeletal muscle phenotypes and PTK2 rs7460 and ACVR1B rs10783485 were each associated with two phenotypes. PTK2 rs7843014, COL1A1 rs1800012, CNTF rs1800169, NOS3 rs1799983, MSTN rs1805086, TRHR rs7832552 and FTO rs9939609 were each associated with one. Elderly women possessing favourable genotypes were 3.6-13.2% stronger and had 4.6-14.7% larger muscle than those with less favourable genotypes. These associations, together with future work involving a broader range of SNPs, may help identify individuals at particular risk of an age-associated loss of independence.
| S-EPMC7762041 | biostudies-literature
Project description:Key pointsHealthy older adults exhibit lower cardiorespiratory fitness ( V̇O2peak ) than young in the absence of any age-related difference in skeletal muscle mitochondrial capacity, suggesting central haemodynamics plays a larger role in age-related declines in V̇O2peak . Total physical activity did not differ by age, but moderate-to-vigorous physical activity was lower in older compared to young adults. Moderate-to-vigorous physical activity is associated with V̇O2peak and muscle oxidative capacity, but physical inactivity cannot entirely explain the age-related reduction in V̇O2peak .AbstractDeclining fitness ( V̇O2peak ) is a hallmark of ageing and believed to arise from decreased oxygen delivery and reduced muscle oxidative capacity. Physical activity is a modifiable lifestyle factor that is critical when evaluating the effects of age on parameters of fitness and energy metabolism. The objective was to evaluate the effects of age and sex on V̇O2peak , muscle mitochondrial physiology, and physical activity in young and older adults. An additional objective was to assess the contribution of skeletal muscle oxidative capacity to age-related reductions in V̇O2peak and determine if age-related variation in V̇O2peak and muscle oxidative capacity could be explained on the basis of physical activity levels. In 23 young and 52 older men and women measurements were made of V̇O2peak , mitochondrial physiology in permeabilized muscle fibres, and free-living physical activity by accelerometry. Regression analyses were used to evaluate associations between age and V̇O2peak , mitochondrial function, and physical activity. Significant age-related reductions were observed for V̇O2peak (P < 0.001), but not muscle mitochondrial capacity. Total daily step counts did not decrease with age, but older adults showed lower moderate-to-vigorous physical activity, which was associated with V̇O2peak (R2 = 0.323, P < 0.001) and muscle oxidative capacity (R2 = 0.086, P = 0.011). After adjusting for sex and physical activity, age was negatively associated with V̇O2peak but not muscle oxidative capacity. Healthy older adults exhibit lower V̇O2peak but preserved mitochondrial capacity compared to young. Physical activity, particularly moderate-to-vigorous, is a key factor in observed age-related changes in fitness and muscle oxidative capacity, but cannot entirely explain the age-related reduction in V̇O2peak .
| S-EPMC8284426 | biostudies-literature
Project description:Global label free analysis of quadricesp skeletal muscle tissue from adult and old mice subjected to 15 min of isometric contractions.
2020-04-15 | PXD010091 | Pride
Project description:The aim of this work was to produce a reproducible molecular signature of human muscle responses to resistance training and examine how such a profile relates to new and established exercise adaptation gene networks. Subjects were recruited from an age range of 18 to 75 y. Before beginning the study all subjects were screened using a medical questionnaire, physical examination and resting ECG with exclusions for overt muscle wasting (>2 SD below age norms)[85], metabolic, respiratory/cardiovascular disorders or other major contraindications to a healthy status. All subjects had normal blood chemistry and were normotensive (BP <140/90). All subjects performed routine activities of daily living and recreation but did not participate in moderate to high intensity aerobic exercise and none had participated in RET in the last 24 months. Body composition was measured at screening and following RET by dual energy X-ray absorptiometry (DEXA) (Lunar Prodigy II, GE Medical Systems). Subject positioning on the DEXA bed was optimized to allow the region of interest (ROI) body compartments to be analyzed separately. The upper leg ROI was selected as the area inferior to the lowest visible point of the coccyx to the mid-point of the patella. The dataset comprises 44 pre-exercise and 44 post-exercise samples. In addition there is a baseline sample NB021_pre-training (D13_NB021F). Therefore there are 89 samples in total. (Note: Singleton baseline sample NB021_pre-training was normalized only using all baseline samples.) Derby dataset.
2013-06-12 | E-GEOD-47881 | biostudies-arrayexpress