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.

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.

Calorie Restriction and Aging

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. SCI-2-SCI-2
Author(s):  
Rafael de Cabo
Keyword(s):  
Oxidative Stress ◽  
Life Span ◽  
Calorie Restriction ◽  
Stress Proteins ◽  
Conflicts Of Interest ◽  
Caloric Intake ◽  
Tissue Growth ◽  
Age Related ◽  
Underlying Mechanisms ◽  
And Oxidative Stress

Abstract Abstract SCI-2 A prominent manifestation of aging is a reduced ability to respond to environmental stressors, including heat and oxidative stress. Reduced stress tolerance and decreased ability to maintain homeostasis are at least partially responsible for the increased morbidity and mortality that occurs with advancing age. The age-related attenuation of stress pathways and increased expression of stress-response genes with aging are examples of the growing body of evidence linking reduced stress responsiveness to aging. In 1935, McCay and colleagues first reported that reducing the caloric intake of rodents could significantly lengthen their mean and maximal life span, slowing down basic aging processes. The effect of calorie restriction (CR) on delaying aging has been replicated in many animal species including nonhuman primates, although in these, potential life span alterations cannot be ascertained for several more years due to their longevity CR causes a reduction in body weight, tissue growth, blood glucose, insulin levels and body temperature. In addition, CR prevents the age-related decline in tolerance to different stressors such as oxidative and heat, and the age-related reduction in expression of protective heat shock and oxidative stress proteins. While CR is the only intervention that has consistently been shown to increase maximum life span and prevent or delay the onset of age-associated pathophysiological changes in laboratory rodents, the underlying mechanisms remain elusive. Using calorie restriction (CR) as their benchmark research tool, gerontologists are making progress in identifying dietary and pharmacologic interventions that may be applicable to retarding aging processes in humans. Disclosures: No relevant conflicts of interest to declare.

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 Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle

2021 ◽  
Author(s):  
Daniel J Ham ◽  
Anastasiya Boersch ◽  
Kathrin Chojnowska ◽  
Shuo Lin ◽  
Aurel B Leuchtmann ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Calorie Restriction ◽  
Expression Profiles ◽  
Life Quality ◽  
Gene Expression Profiles ◽  
Nutrient Sensing ◽  
Skeletal Muscle Function ◽  
Muscle Gene Expression ◽  
Muscle Aging ◽  
Age Related

As global life expectancy continues to climb, maintaining skeletal muscle function is increasingly essential to ensure a good life quality for aging populations. Calorie restriction (CR) is the most potent and reproducible intervention to extend health and lifespan, but is largely unachievable in humans. Therefore, identification of 'CR mimetics' has received much attention. CR targets nutrient-sensing pathways centering on mTORC1. The mTORC1 inhibitor, rapamycin, has been proposed as a potential CR mimetic and is proven to counteract age-related muscle loss. Therefore, we tested whether rapamycin acts via similar mechanisms as CR to slow muscle aging. Contrary to our expectation, long-term CR and rapamycin-treated geriatric mice display distinct skeletal muscle gene expression profiles despite both conferring benefits to aging skeletal muscle. Furthermore, CR improved muscle integrity in a mouse with nutrient-insensitive sustained muscle mTORC1 activity and rapamycin provided additive benefits to CR in aging mouse muscles. Therefore, RM and CR exert distinct, compounding effects in aging skeletal muscle, opening the possibility of parallel interventions to counteract muscle aging.

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 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.

Characterization of the Age-related Changes in Skeletal Muscle Mitochondrial Function

2007 ◽  
Vol 39 (Supplement) ◽  
pp. S407-S408
Author(s):  
Pedro A. Figueiredo ◽  
Rita M. Ferreira ◽  
Maria P. Mota ◽  
Hans J. Appell ◽  
José A. Duarte
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Age Related ◽  
Age Related Changes
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