scholarly journals FTIR Spectroscopy as a Tool to Study Age-Related Changes in Cardiac and Skeletal Muscle of Female C57BL/6J Mice

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6410
Author(s):  
Sandra Magalhães ◽  
Idália Almeida ◽  
Filipa Martins ◽  
Fátima Camões ◽  
Ana R. Soares ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Ftir Spectroscopy ◽  
Conformational Changes ◽  
Molecular Mechanisms ◽  
Protein Secondary Structure ◽  
Multivariate Statistical ◽  
Age Related ◽  
Muscle Tissues ◽  
Aging Studies ◽  
Old Mice

Studying aging is important to further understand the molecular mechanisms underlying this physiological process and, ideally, to identify a panel of aging biomarkers. Animals, in particular mice, are often used in aging studies, since they mimic important features of human aging, age quickly, and are easy to manipulate. The present work describes the use of Fourier Transform Infrared (FTIR) spectroscopy to identify an age-related spectroscopic profile of the cardiac and skeletal muscle tissues of C57BL/6J female mice. We acquired ATR-FTIR spectra of cardiac and skeletal muscle at four different ages: 6; 12; 17 and 24 months (10 samples at each age) and analyzed the data using multivariate statistical tools (PCA and PLS) and peak intensity analyses. The results suggest deep changes in protein secondary structure in 24-month-old mice compared to both tissues in 6-month-old mice. Oligomeric structures decreased with age in both tissues, while intermolecular β-sheet structures increased with aging in cardiac muscle but not in skeletal muscle. Despite FTIR spectroscopy being unable to identify the proteins responsible for these conformational changes, this study gives insights into the potential of FTIR to monitor the aging process and identify an age-specific spectroscopic signature.

scholarly journals Inflamma-miR-21 Negatively Regulates Myogenesis during Ageing

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 345 ◽  
Author(s):  
Maria Borja-Gonzalez ◽  
Jose C. Casas-Martinez ◽  
Brian McDonagh ◽  
Katarzyna Goljanek-Whysall
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Muscle Hypertrophy ◽  
Myogenic Potential ◽  
Age Related ◽  
Primary Myoblasts ◽  
Muscle Homeostasis ◽  
Old Mice

Ageing is associated with disrupted redox signalling and increased circulating inflammatory cytokines. Skeletal muscle homeostasis depends on the balance between muscle hypertrophy, atrophy and regeneration, however during ageing this balance is disrupted. The molecular pathways underlying the age-related decline in muscle regenerative potential remain elusive. microRNAs are conserved robust gene expression regulators in all tissues including skeletal muscle. Here, we studied satellite cells from adult and old mice to demonstrate that inhibition of miR-21 in satellite cells from old mice improves myogenesis. We determined that increased levels of proinflammatory cytokines, TNFα and IL6, as well as H2O2, increased miR-21 expression in primary myoblasts, which in turn resulted in their decreased viability and myogenic potential. Inhibition of miR-21 function rescued the decreased size of myotubes following TNFα or IL6 treatment. Moreover, we demonstrated that miR-21 could inhibit myogenesis in vitro via regulating IL6R, PTEN and FOXO3 signalling. In summary, upregulation of miR-21 in satellite cells and muscle during ageing may occur in response to elevated levels of TNFα and IL6, within satellite cells or myofibrillar environment contributing to skeletal muscle ageing and potentially a disease-related decline in potential for muscle regeneration.

Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness

2008 ◽  
Vol 9 (4) ◽  
pp. 213-228 ◽  
Author(s):  
James G. Ryall ◽  
Jonathan D. Schertzer ◽  
Gordon S. Lynch
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Skeletal Muscle Wasting ◽  
Age Related

scholarly journals The NLRP3 inflammasome contributes to sarcopenia and lower muscle glycolytic potential in old mice

2017 ◽  
Vol 313 (2) ◽  
pp. E222-E232 ◽  
Author(s):  
Marin Jane McBride ◽  
Kevin P. Foley ◽  
Donna M. D’Souza ◽  
Yujin E. Li ◽  
Trevor C. Lau ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Strength ◽  
Nlrp3 Inflammasome ◽  
Skeletal Muscles ◽  
Metabolic Flux ◽  
Caspase 1 ◽  
Gapdh Activity ◽  
Age Related ◽  
Glycolytic Potential ◽  
Old Mice

The mechanisms underpinning decreased skeletal muscle strength and slowing of movement during aging are ill-defined. “Inflammaging,” increased inflammation with advancing age, may contribute to aspects of sarcopenia, but little is known about the participatory immune components. We discovered that aging was associated with increased caspase-1 activity in mouse skeletal muscle. We hypothesized that the caspase-1-containing NLRP3 inflammasome contributes to sarcopenia in mice. Male C57BL/6J wild-type (WT) and NLRP3−/− mice were aged to 10 (adult) and 24 mo (old). NLRP3−/− mice were protected from decreased muscle mass (relative to body mass) and decreased size of type IIB and IIA myofibers, which occurred between 10 and 24 mo of age in WT mice. Old NLRP3−/− mice also had increased relative muscle strength and endurance and were protected from age-related increases in the number of myopathic fibers. We found no evidence of age-related or NLRP3-dependent changes in markers of systemic inflammation. Increased caspase-1 activity was associated with GAPDH proteolysis and reduced GAPDH enzymatic activity in skeletal muscles from old WT mice. Aging did not alter caspase-1 activity, GAPDH proteolysis, or GAPDH activity in skeletal muscles of NLRP3−/− mice. Our results show that the NLRP3 inflammasome participates in age-related loss of muscle glycolytic potential. Deletion of NLRP3 mitigates both the decline in glycolytic myofiber size and the reduced activity of glycolytic enzymes in muscle during aging. We propose that the etiology of sarcopenia involves direct communication between immune responses and metabolic flux in skeletal muscle.

scholarly journals Ultrastructural immunocytochemistry shows impairment of RNA pathways in skeletal muscle nuclei of old mice: A link to sarcopenia?

2021 ◽  
Vol 65 (2) ◽  
Author(s):  
Maria Assunta Lacavalla ◽  
Barbara Cisterna ◽  
Carlo Zancanaro ◽  
Manuela Malatesta
Keyword(s):  
Skeletal Muscle ◽  
Ribonuclease A ◽  
Rrna Genes ◽  
Nuclear Actin ◽  
Ultrastructural Immunocytochemistry ◽  
Nuclear Compartments ◽  
Age Related ◽  
Methyl Cytosine ◽  
Rna Pathways ◽  
Old Mice

During aging, skeletal muscle is affected by sarcopenia, a progressive decline in muscle mass, strength and endurance that leads to loss of function and disability. Cell nucleus dysfunction is a possible factor contributing to sarcopenia because aging-associated alterations in mRNA and rRNA transcription/maturation machinery have been shown in several cell types including muscle cells. In this study, the distribution and density of key molecular factors involved in RNA pathways namely, nuclear actin (a motor protein and regulator of RNA transcription), 5-methyl cytosine (an epigenetic regulator of gene transcription), and ribonuclease A (an RNA degrading enzyme) were compared in different nuclear compartments of late adult and old mice myonuclei by means of ultrastructural immunocytochemistry. In all nuclear compartments, an age-related decrease of nuclear actin suggested altered chromatin structuring and impaired nucleus-to-cytoplasm transport of both mRNA and ribosomal subunits, while a decrease of 5-methyl cytosine and ribonuclease A in the nucleoli of old mice indicated an age-dependent loss of rRNA genes. These findings provide novel experimental evidence that, in the aging skeletal muscle, nuclear RNA pathways undergo impairment, likely hindering protein synthesis and contributing to the onset and progression of sarcopenia.

scholarly journals The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis

2010 ◽  
Vol 205 (3) ◽  
pp. 201-210 ◽  
Author(s):  
Sebastio Perrini ◽  
Luigi Laviola ◽  
Marcos C Carreira ◽  
Angelo Cignarelli ◽  
Annalisa Natalicchio ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Signs And Symptoms ◽  
Well Being ◽  
Serum Levels ◽  
Normal Range ◽  
Gh Secretion ◽  
Skeletal Muscle Wasting ◽  
Age Related ◽  
Age Dependent

The widespread increase in life expectancy is accompanied by an increased prevalence of features of physical frailty. Signs and symptoms may include sarcopenia and osteopenia, reduced exercise capacity, and diminished sense of well-being. The pathogenesis of age-associated sarcopenia and osteopenia is multifactorial, and hormonal decline may be a contributing factor. Aging is associated with a progressive decrease in GH secretion, and more than 30% of elderly people have circulating IGF1 levels below the normal range found in the young. GH acts directly on target tissues, including skeletal muscle and bone among many others, but many effects are mediated indirectly by circulating (liver-derived) or locally produced IGF1. Aging is also associated with reduced insulin sensitivity which, in turn, may contribute to the impairment of IGF1 action. Recent experimental evidence suggests that besides the age-dependent decline in GH and IGF1 serum levels, the dysregulation of GH and IGF1 actions due to impairment of the post-receptor signaling machinery may contribute to the loss of muscle mass and osteopenia. This article will focus on the molecular mechanisms of impaired GH and IGF1 signaling and action in aging, and their role in the pathogenesis of sarcopenia and osteoporosis.

scholarly journals cAMP signaling in skeletal muscle adaptation: hypertrophy, metabolism, and regeneration

2012 ◽  
Vol 303 (1) ◽  
pp. E1-E17 ◽  
Author(s):  
Rebecca Berdeaux ◽  
Randi Stewart
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Molecular Mechanisms ◽  
Muscle Development ◽  
Camp Signaling ◽  
Metabolic Phenotype ◽  
Muscle Adaptation ◽  
Age Related ◽  
Organ Systems

Among organ systems, skeletal muscle is perhaps the most structurally specialized. The remarkable subcellular architecture of this tissue allows it to empower movement with instructions from motor neurons. Despite this high degree of specialization, skeletal muscle also has intrinsic signaling mechanisms that allow adaptation to long-term changes in demand and regeneration after acute damage. The second messenger adenosine 3′,5′-monophosphate (cAMP) not only elicits acute changes within myofibers during exercise but also contributes to myofiber size and metabolic phenotype in the long term. Strikingly, sustained activation of cAMP signaling leads to pronounced hypertrophic responses in skeletal myofibers through largely elusive molecular mechanisms. These pathways can promote hypertrophy and combat atrophy in animal models of disorders including muscular dystrophy, age-related atrophy, denervation injury, disuse atrophy, cancer cachexia, and sepsis. cAMP also participates in muscle development and regeneration mediated by muscle precursor cells; thus, downstream signaling pathways may potentially be harnessed to promote muscle regeneration in patients with acute damage or muscular dystrophy. In this review, we summarize studies implicating cAMP signaling in skeletal muscle adaptation. We also highlight ligands that induce cAMP signaling and downstream effectors that are promising pharmacological targets.

scholarly journals Testosterone Supplementation Reverses Sarcopenia in Aging through Regulation of Myostatin, c-Jun NH2-Terminal Kinase, Notch, and Akt Signaling Pathways

Endocrinology ◽  
2010 ◽  
Vol 151 (2) ◽  
pp. 628-638 ◽  
Author(s):  
Ekaterina L. Kovacheva ◽  
Amiya P. Sinha Hikim ◽  
Ruoqing Shen ◽  
Indranil Sinha ◽  
Indrani Sinha-Hikim
Keyword(s):  
Muscle Mass ◽  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Muscle Growth ◽  
Fiber Types ◽  
Cross Sectional ◽  
Testosterone Treatment ◽  
Age Related ◽  
Muscle Cell Apoptosis ◽  
Old Mice

Aging in rodents and humans is characterized by loss of muscle mass (sarcopenia). Testosterone supplementation increases muscle mass in healthy older men. Here, using a mouse model, we investigated the molecular mechanisms by which testosterone prevents sarcopenia and promotes muscle growth in aging. Aged mice of 22 months of age received a single sc injection of GnRH antagonist every 2 wk to suppress endogenous testosterone production and were implanted subdermally under anesthesia with 0.5 or 1.0 cm testosterone-filled implants for 2 months (n = 15/group). Young and old mice (n = 15/group), of 2 and 22 months of age, respectively, received empty implants and were used as controls. Compared with young animals, a significant (P < 0.05) increase in muscle cell apoptosis coupled with a decrease in gastrocnemius muscles weight (by 16.7%) and muscle fiber cross-sectional area, of both fast and slow fiber types, was noted in old mice. Importantly, such age-related changes were fully reversed by higher dose (1 cm) of testosterone treatment. Testosterone treatment effectively suppressed age-specific increases in oxidative stress, processed myostatin levels, activation of c-Jun NH2-terminal kinase, and cyclin-dependent kinase inhibitor p21 in aged muscles. Furthermore, it restored age-related decreases in glucose-6-phosphate dehydrogenase levels, phospho-Akt, and Notch signaling. These alterations were associated with satellite cell proliferation and differentiation. Collectively these results suggest involvement of multiple signal transduction pathways in sarcopenia. Testosterone reverses sarcopenia through stimulation of cellular metabolism and survival pathway together with inhibition of death pathway.

scholarly journals High Resolution Genome Wide Expression Analysis of Single Myofibers Using SMART-Seq

2019 ◽  
Author(s):  
Darren M. Blackburn ◽  
Felicia Lazure ◽  
Aldo H. Corchado ◽  
Theodore J. Perkins ◽  
Hamed S. Najafabadi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
High Resolution ◽  
Expression Analysis ◽  
Expression Profiles ◽  
Age Related ◽  
Genome Wide ◽  
Heterogeneous Tissue ◽  
Whole Transcriptome ◽  
Old Mice ◽  
Genome Wide Expression

ABSTRACTSkeletal muscle is a heterogeneous tissue. Individual myofibers that make up muscle tissue exhibit variation in their metabolic and contractile properties. Although there are biochemical and histological assays to study myofiber heterogeneity, efficient methods to analyze the whole transcriptome of individual myofibers are lacking. We have developed single myofiber RNA-Seq (smfRNA-Seq) to analyze the whole transcriptome of individual myofibers by combining single fiber isolation with Switching Mechanisms at 5’ end of RNA Template (SMART) technology. Our method provides high-resolution genome wide expression profiles of single myofibers. Using smfRNA-Seq, we have analyzed the differences in the transcriptome of young and old myofibers to validate the effectiveness of this new method. Using smfRNA-Seq, we performed comparative gene expression analysis between single myofibers from young and old mice. Our data suggests that aging leads to significant changes in the expression of metabolic and structural genes in myofibers. Our data suggests that smfRNA-Seq is a powerful tool to study developmental, disease and age-related dynamics in the composition of skeletal muscle.

scholarly journals Aging Triggers H3K27 Trimethylation Hoarding in the Chromatin of Nothobranchius Furzeri Skeletal Muscle

2019 ◽  
Author(s):  
Chiara Cencioni ◽  
Johanna Heid ◽  
Anna Keprelova ◽  
Seyed Mohammad Mahdi Rasa ◽  
Carsten Kuenne ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Skeletal Muscle Function ◽  
Muscle Aging ◽  
Aging Studies ◽  
Nothobranchius Furzeri ◽  
Landscape Alteration ◽  
Epigenetic Analysis ◽  
Skeletal Muscle Aging ◽  
Polycomb Complex

Aging associates with progressive loss of skeletal muscle function leading up to sarcopenia, a process characterized by impaired mobility and weakening of muscle strength. Molecular mechanisms underpinning sarcopenia are still poorly characterized. Since aging associates with profound epigenetic changes, epigenetic landscape alteration analysis in the skeletal muscle promises to highlight molecular mechanisms of age-associated sarcopenia. The study was conducted exploiting the short-lived turquoise killifish Nothobranchius furzeri (Nfu), a relatively new model for aging studies. The epigenetic analysis suggested for a less accessible and more condensed chromatin in old Nfu skeletal muscle. Specifically, an accumulation of heterochromatin regions was observed as consequence of increased levels of H3K27me3, HP1alpha, polycomb complex subunits and senescence associated heterochromatic foci (SAHFs). Consistently, euchromatin histone marks, including H3K9ac, decreased. The integrative bioinformatics analysis of RNASeq and ChIPSeq, related to skeletal muscle of Nfu at different ages, revealed a down-modulation of genes involved in cell cycle, differentiation and DNA repair and an up-regulation of inflammation and senescence genes. Undoubtedly, more studies are needed to disclose the detailed mechanisms, but this approach revealed an unprecedented specific features of Nfu skeletal muscle aging, potentially associated with sarcopenia onset and consequent impairment of swimming and mobility typical of old Nfu.

scholarly journals mRNA-Seq reveals complex patterns of gene regulation and expression in the mouse skeletal muscle transcriptome associated with calorie restriction

2012 ◽  
Vol 44 (6) ◽  
pp. 331-344 ◽  
Author(s):  
Joseph M. Dhahbi ◽  
Hani Atamna ◽  
Dario Boffelli ◽  
David I. K. Martin ◽  
Stephen R. Spindler
Keyword(s):  
Skeletal Muscle ◽  
Gene Regulation ◽  
Calorie Restriction ◽  
Muscle Development ◽  
Mrna Isoforms ◽  
Age Related ◽  
Old Mice ◽  
And Oxidative Stress ◽  
Skeletal Muscle Transcriptome

Sarcopenia is an age-associated loss of skeletal muscle mass and strength that increases the risk of disability. Calorie restriction (CR), the consumption of fewer calories while maintaining adequate nutrition, mitigates sarcopenia and many other age-related diseases. To identify potential mechanisms by which CR preserves skeletal muscle integrity during aging, we used mRNA-Seq for deep characterization of gene regulation and mRNA abundance in skeletal muscle of old mice compared with old mice subjected to CR. mRNA-Seq revealed complex CR-associated changes in expression of mRNA isoforms, many of which occur without a change in total message abundance and thus would not be detected by methods other than mRNA-Seq. Functional annotation of differentially expressed genes reveals CR-associated upregulation of pathways involved in energy metabolism and lipid biosynthesis, and downregulation of pathways mediating protein breakdown and oxidative stress, consistent with earlier microarray-based studies. CR-associated changes not noted in previous studies involved downregulation of genes controlling actin cytoskeletal structures and muscle development. These CR-associated changes reflect generally healthier muscle, consistent with CR's mitigation of sarcopenia. mRNA-Seq generates a rich picture of the changes in gene expression associated with CR, and may facilitate identification of genes that are primary mediators of CR's effects.

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