scholarly journals Differentially Methylated Genes in Muscle Associated with Gait Speed in a Non-Human Primate Model of Aging

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 666-667
Author(s):  
Ellen Quillen ◽  
Brett Frye ◽  
Bethany Wildeman ◽  
Maggie Stainback ◽  
Thomas Register ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Gait Speed ◽  
Physical Aging ◽  
Genetic Relatedness ◽  
Vastus Lateralis ◽  
Bone Diseases ◽  
Vervet Monkeys ◽  
Primate Model ◽  
Age Related ◽  
Differentially Methylated Genes

Abstract Age-related changes in DNA methylation are potent regulators of gene expression and may in part explain the onset of disease and disability. Vervet monkeys are a well-described model of neurocognitive and physical aging. Like humans, gait speed declines with age in vervets, and variability in gait speed in older animals is associated with age-related musculoskeletal and cognitive decline. To identify methylation patterns linked to aging-related physical decline, we investigated differentially methylated loci in vastus lateralis biopsies of 29 female vervets aged 8-28 years (~25-90 years in humans). We evaluated 107,490 loci on the Illumina Infinium Methylation EPIC Human Array that aligned with high fidelity to the vervet genome using the R package minfi and fit generalized linear mixed models to account for underlying genetic relatedness. We found 13 CpG methylation sites associated with 12 genes (CALCR, EBF4, GDNF, GMCL1, HAND1, HOXC10, IRX2, LBX2, MPPED2, SHISA6, SOX2, and WNT2) significantly differentially methylated with gait speed. Increased methylation was negatively associated with gait speed for all loci except GMCL1, reflecting the pattern of global hypermethylation of skeletal muscle tissue with age. Several of the associated genes are involved in development and differentiation including HOXC10 and LBX2, which regulates myoblast migration. CACNG8 regulates voltage-dependent calcium gated channels, and GDNF promotes motor neuron innervation of skeletal muscle. Most associations with muscle phenotypes are novel, but several have been linked to age-related bone diseases. We are currently evaluating the relationships of these differentially methylated loci with muscle mRNA expression and protein abundance.

scholarly journals Meta-analysis of genome-wide DNA methylation and integrative OMICs in human skeletal muscle

2020 ◽  
Author(s):  
S Voisin ◽  
M Jacques ◽  
S Landen ◽  
NR Harvey ◽  
LM Haupt ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
Large Scale ◽  
Human Skeletal Muscle ◽  
Meta Analysis ◽  
Total N ◽  
Age Related ◽  
Differentially Methylated Genes ◽  
Comprehensive Picture ◽  
User Friendly

AbstractKnowledge of age-related DNA methylation changes in skeletal muscle is limited, yet this tissue is severely affected by aging in humans. Using a large-scale epigenome-wide association study (EWAS) meta-analysis of age in human skeletal muscle from 10 studies (total n = 908 human muscle methylomes), we identified 9,986 differentially methylated regions at a stringent false discovery rate < 0.005, spanning 8,748 unique genes, many of which related to skeletal muscle structure and development. We then integrated the DNA methylation results with known transcriptomic and proteomic age-related changes in skeletal muscle, and found that even though most differentially methylated genes are not altered at the mRNA or protein level, they are nonetheless strongly enriched for genes showing age-related differential expression. We provide here the most comprehensive picture of DNA methylation aging in human skeletal muscle, and have made our results available as an open-access, user-friendly, web-based tool called MetaMeth (https://sarah-voisin.shinyapps.io/MetaMeth/).

Lower skeletal muscle capillarization and VEGF expression in aged vs. young men

2006 ◽  
Vol 100 (1) ◽  
pp. 178-185 ◽  
Author(s):  
Nicholas A. Ryan ◽  
Kevin A. Zwetsloot ◽  
Lenna M. Westerkamp ◽  
Robert C. Hickner ◽  
Walter E. Pofahl ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Acute Exercise ◽  
Fiber Type ◽  
Vastus Lateralis ◽  
Young Men ◽  
Exercise Bout ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Age Related ◽  
Endothelial Growth Factor

Recently, we observed that muscle capillarization, vascular endothelial growth factor (VEGF) protein, and the VEGF mRNA response to acute exercise were lower in aged compared with young women (Croley AN, Zwetsloot KA, Westerkamp LM, Ryan NA, Pendergast aged men, Hickner RC, Pofahl WE, and Gavin TP. J Appl Physiol 99: 1875–1882, 2005). We hypothesized that similar age-related differences in muscle capillarization and VEGF expression would exist between young and aged men. Skeletal muscle biopsies were obtained from the vastus lateralis before and at 4 h after a submaximal exercise bout for the measurement of morphometry, capillarization, VEGF, KDR, and Flt-1 in seven aged (mean age 65 yr) and eight young (mean age 21 yr) sedentary men. In aged compared with young men, muscle capillary contacts and capillary-to-fiber perimeter exchange index were lower regardless of fiber type. Muscle VEGF mRNA and protein were lower in aged men both at rest and 4 h postexercise. Exercise increased muscle VEGF mRNA and protein and KDR mRNA independent of age group. There were no effects of exercise or age on muscle Flt-1 mRNA or protein or KDR protein. These results confirm that skeletal muscle capillarization and VEGF expression are lower in aged compared with young men.

scholarly journals Microbiopsy Sampling for Examining Age-Related Differences in Skeletal Muscle Fiber Morphology and Composition

2022 ◽  
Vol 12 ◽  
Author(s):  
Garrett M. Hester ◽  
Trisha A. VanDusseldorp ◽  
Phuong L. Ha ◽  
Kaveh Kiani ◽  
Alex A. Olmos ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Vastus Lateralis ◽  
Peak Torque ◽  
Type I ◽  
Type Ii ◽  
Fiber Morphology ◽  
Specific Strength ◽  
Age Related ◽  
Whole Muscle

Introduction: The increasingly popular microbiopsy is an appealing alternative to the more invasive Bergström biopsy given the challenges associated with harvesting skeletal muscle in older populations. Parameters of muscle fiber morphology and composition derived from the microbiopsy have not been compared between young and older adults.Purpose: The purpose of this study was to examine muscle fiber morphology and composition in young (YM) and older (OM) males using the microbiopsy sampling technique. A secondary aim was to determine if specific strength is associated with serum levels of C-terminal agrin fragment [CAF; an indicator of neuromuscular junction (NMJ) degradation].Methods: Thirty healthy, YM (n = 15, age = 20.7 ± 2.2 years) and OM (n = 15, age = 71.6 ± 3.9 years) underwent ultrasound imaging to determine whole-muscle cross-sectional area (CSA) of the vastus lateralis and rectus femoris as well as isometric and isokinetic (60°⋅s–1 and 180°⋅s–1) peak torque testing of the knee extensors. Microbiopsy samples of the vastus lateralis were collected from 13 YM and 11 OM, and immunofluorescence was used to calculate CSA and proportion of type I and type II fibers.Results: Peak torque was lower in OM at all velocities (p ≤ 0.001; d = 1.39–1.86) but only lower at 180°⋅s–1 (p = 0.003; d = 1.23) when normalized to whole-muscle CSA. Whole-muscle CSA was smaller in OM (p = 0.001; d = 1.34), but atrophy was not present at the single fiber level (p &gt; 0.05). Per individual, ∼900 fibers were analyzed, and type I fiber CSA was larger (p = 0.05; d = 0.94) in OM which resulted in a smaller type II/I fiber CSA ratio (p = 0.015; d = 0.95). CAF levels were not sensitive to age (p = 0.159; d = 0.53) nor associated with specific strength or whole-muscle CSA in OM.Conclusion: The microbiopsy appears to be a viable alternative to the Bergström biopsy for histological analyses of skeletal muscle in older adults. NMJ integrity was not influential for age-related differences in specific strength in our healthy, non-sarcopenic older sample.

scholarly journals Advancing our understanding of skeletal muscle across the lifecourse: protocol for the MASS_Lifecourse Study and characteristics of the first 80 participants

2021 ◽  
Author(s):  
Richard M Dodds ◽  
Christopher Hurst ◽  
Susan J Hillman ◽  
Karen Davies ◽  
Terry J Aspray ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Grip Strength ◽  
Vastus Lateralis ◽  
Experimental Medicine ◽  
Vastus Lateralis Muscle ◽  
Physically Active ◽  
North East ◽  
The North ◽  
Treatment And Prevention ◽  
Age Related

Introduction Sarcopenia, the age-related loss of skeletal muscle strength and mass, carries a significant burden for affected individuals. There has been little investigation of sarcopenia using experimental medicine techniques to study human muscle tissue in detail. The aim of the Muscle Ageing Sarcopenia Studies Lifecourse (MASS_Lifecourse) study is to recruit up to 160 participants, equally divided between females and males between ages 45 and 85 years for detailed phenotyping of skeletal muscle health. Here we describe the protocol for the study and the characteristics of the first 80 participants.  Methods We are recruiting participants from three sources in the north-east of England. Study fieldwork comprises a home visit (or videocall) for consent and assessment of health, cognition, lifestyle, and wellbeing. This is followed by a visit to a clinical research facility for assessment of sarcopenia status and collection of samples including a vastus lateralis muscle biopsy. We produced descriptive statistics for the first 80 participants, including expressing their grip strength relative to normative data in the form of Z-scores. Results The first 80 participants (53.8% female) covered the target ages, ranging from 48 to 84 years. They were regularly physically active, reported good physical function and had a prevalence sarcopenia (including probable sarcopenia) of 11.3% based on the revised European consensus. Their grip strength was similar to that in the general population, with a mean Z-score of 0.09 standard deviations (95% CI: -1.64, 1.83) above that expected. Conclusions The MASS_Lifecourse study combines comprehensive health and lifestyle data with a range of biological samples including skeletal muscle. The findings from planned analyses should contribute to improvements in the diagnosis, treatment and prevention of sarcopenia.

scholarly journals Skeletal Muscle Gene Expression in Long-Term Endurance and Resistance Trained Elderly

2020 ◽  
Vol 21 (11) ◽  
pp. 3988 ◽  
Author(s):  
Alessandra Bolotta ◽  
Giuseppe Filardo ◽  
Provvidenza Maria Abruzzo ◽  
Annalisa Astolfi ◽  
Paola De Sanctis ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Physical Exercise ◽  
Signaling Pathways ◽  
Vastus Lateralis ◽  
Mixture Distribution ◽  
Distribution Analysis ◽  
Muscle Gene Expression ◽  
Age Related ◽  
High Level

Physical exercise is deemed the most efficient way of counteracting the age-related decline of skeletal muscle. Here we report a transcriptional study by next-generation sequencing of vastus lateralis biopsies from elderly with a life-long high-level training practice (n = 9) and from age-matched sedentary subjects (n = 5). Unsupervised mixture distribution analysis was able to correctly categorize trained and untrained subjects, whereas it failed to discriminate between individuals who underwent a prevalent endurance (n = 5) or a prevalent resistance (n = 4) training, thus showing that the training mode was not relevant for sarcopenia prevention. KEGG analysis of transcripts showed that physical exercise affected a high number of metabolic and signaling pathways, in particular those related to energy handling and mitochondrial biogenesis, where AMPK and AKT-mTOR signaling pathways are both active and balance each other, concurring to the establishment of an insulin-sensitive phenotype and to the maintenance of a functional muscle mass. Other pathways affected by exercise training increased the efficiency of the proteostatic mechanisms, consolidated the cytoskeletal organization, lowered the inflammation level, and contrasted cellular senescence. This study on extraordinary individuals who trained at high level for at least thirty years suggests that aging processes and exercise training travel the same paths in the opposite direction.

scholarly journals Aging of skeletal muscle: a 12-yr longitudinal study

2000 ◽  
Vol 88 (4) ◽  
pp. 1321-1326 ◽  
Author(s):  
Walter R. Frontera ◽  
Virginia A. Hughes ◽  
Roger A. Fielding ◽  
Maria A. Fiatarone ◽  
William J. Evans ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Strength ◽  
Fiber Type ◽  
Vastus Lateralis ◽  
Analysis Of Covariance ◽  
Muscle Size ◽  
Type I ◽  
Cross Sectional ◽  
Age Related ◽  
Change In Mean

The present study examines age-related changes in skeletal muscle size and function after 12 yr. Twelve healthy sedentary men were studied in 1985–86 (T1) and nine (initial mean age 65.4 ± 4.2 yr) were reevaluated in 1997–98 (T2). Isokinetic muscle strength of the knee and elbow extensors and flexors showed losses ( P < 0.05) ranging from 20 to 30% at slow and fast angular velocities. Computerized tomography ( n = 7) showed reductions ( P < 0.05) in the cross-sectional area (CSA) of the thigh (12.5%), all thigh muscles (14.7%), quadriceps femoris muscle (16.1%), and flexor muscles (14.9%). Analysis of covariance showed that strength at T1 and changes in CSA were independent predictors of strength at T2. Muscle biopsies taken from vastus lateralis muscles ( n = 6) showed a reduction in percentage of type I fibers (T1 = 60% vs. T2 = 42%) with no change in mean area in either fiber type. The capillary-to-fiber ratio was significantly lower at T2 (1.39 vs. 1.08; P = 0.043). Our observations suggest that a quantitative loss in muscle CSA is a major contributor to the decrease in muscle strength seen with advancing age and, together with muscle strength at T1, accounts for 90% of the variability in strength at T2.

scholarly journals Analgesic and Anti-Inflammatory Effects of Aucklandia lappa Root Extracts on Acetic Acid-Induced Writhing in Mice and Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Plants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 42
Author(s):  
Hee-Geun Jo ◽  
Geon-Yeong Lee ◽  
Chae Yun Baek ◽  
Ho Sueb Song ◽  
Donghun Lee
Keyword(s):  
Acetic Acid ◽  
Weight Bearing ◽  
Bone Diseases ◽  
Joint Disease ◽  
Root Extracts ◽  
Raw264.7 Macrophages ◽  
Age Related ◽  
Monosodium Iodoacetate ◽  
Anti Inflammatory

Osteoarthritis (OA) is an age-related joint disease and one of the most common degenerative bone diseases among elderly people. The currently used therapeutic strategies relying on nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids for OA are often associated with gastrointestinal, cardiovascular, and kidney disorders, despite being proven effective. Aucklandia lappa is a well-known traditional medicine. The root of A. lappa root has several bioactive compounds and has been in use as a natural remedy for bone diseases and other health conditions. We evaluated the A. lappa root extracts on OA progression as a natural therapeutic agent. A. lappa substantially reduced writhing numbers in mice induced with acetic acid. Monosodium iodoacetate (MIA) was injected into the rats through their knee joints of rats to induce experimental OA, which shows similar pathological characteristics to OA in human. A. lappa substantially reduced the MIA-induced weight-bearing of hind limb and reversed the cartilage erosion in MIA rats. IL-1β, a representative inflammatory mediator in OA, was also markedly decreased by A. lappa in the serum of MIA rats. In vitro, A. lappa lowered the secretion of NO and suppressed the IL-1β, COX-2, IL-6, and iNOS production in RAW264.7 macrophages activated with LPS. Based on its analgesic and anti-inflammatory effects, A. lappa could be a potential remedial agent against OA.

scholarly journals Molecular Mechanism and Pathogenesis of Sarcopenia: An Overview

2021 ◽  
Vol 22 (6) ◽  
pp. 3032
Author(s):  
Anna Picca ◽  
Riccardo Calvani
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanism ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Strength Function ◽  
Age Related

Sarcopenia involves a progressive age‐related decline of skeletal muscle mass and strength/function [...]

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