scholarly journals Short‐term bed rest increases inflammation as evidenced by elevated TLR4, NFκB1 and IL6 expression in skeletal muscle of older adults

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Micah J Drummond ◽  
Kyle L Timmerman ◽  
Melissa M Markofski ◽  
Dillon K Walker ◽  
Jared M Dickinson ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Bed Rest ◽  
Short Term

scholarly journals Short-term bed rest increases TLR4 and IL-6 expression in skeletal muscle of older adults

2013 ◽  
Vol 305 (3) ◽  
pp. R216-R223 ◽  
Author(s):  
Micah J. Drummond ◽  
Kyle L. Timmerman ◽  
Melissa M. Markofski ◽  
Dillon K. Walker ◽  
Jared M. Dickinson ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Inflammatory Cytokines ◽  
Muscle Biopsy ◽  
Lean Mass ◽  
Bed Rest ◽  
Short Term ◽  
Tlr4 Signaling ◽  
Adult Skeletal Muscle ◽  
Healthy Older Adults

Bed rest induces significant loss of leg lean mass in older adults. Systemic and tissue inflammation also accelerates skeletal muscle loss, but it is unknown whether inflammation is associated to inactivity-induced muscle atrophy in healthy older adults. We determined if short-term bed rest increases toll-like receptor 4 (TLR4) signaling and pro-inflammatory markers in older adult skeletal muscle biopsy samples. Six healthy, older adults underwent seven consecutive days of bed rest. Muscle biopsies (vastus lateralis) were taken after an overnight fast before and at the end of bed rest. Serum cytokine expression was measured before and during bed rest. TLR4 signaling and cytokine mRNAs associated with pro- and anti-inflammation and anabolism were measured in muscle biopsy samples using Western blot analysis and qPCR. Participants lost ∼4% leg lean mass with bed rest. We found that after bed rest, muscle levels of TLR4 protein expression and interleukin-6 (IL-6), nuclear factor-κB1, interleukin-10, and 15 mRNA expression were increased after bed rest ( P < 0.05). Additionally, the cytokines interferon-γ, and macrophage inflammatory protein-1β, were elevated in serum samples following bed rest ( P < 0.05). We conclude that short-term bed rest in older adults modestly increased some pro- and anti-inflammatory cytokines in muscle samples while systemic changes in pro-inflammatory cytokines were mostly absent. Upregulation of TLR4 protein content suggests that bed rest in older adults increases the capacity to mount an exaggerated, and perhaps unnecessary, inflammatory response in the presence of specific TLR4 ligands, e.g., during acute illness.

scholarly journals Age-dependent skeletal muscle transcriptome response to bed rest-induced atrophy

2019 ◽  
Vol 126 (4) ◽  
pp. 894-902 ◽  
Author(s):  
Ziad S. Mahmassani ◽  
Paul T. Reidy ◽  
Alec I. McKenzie ◽  
Chris Stubben ◽  
Michael T. Howard ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Cell Adhesion ◽  
Lean Mass ◽  
Muscle Wasting ◽  
Stellate Cell ◽  
Bed Rest ◽  
Muscle Loss ◽  
Short Term ◽  
Adult Skeletal Muscle

Short-term muscle disuse induces significant muscle loss in older adults and in some reports may be more accelerated with aging. Identifying muscle transcriptional events in response to bed rest may help identify therapeutic targets to offset muscle loss. Therefore, we compared the muscle transcriptome between young and older adults after bed rest and identified candidate targets related to changes in muscle loss. RNA was sequenced (HiSeq, Illumina; DESeq, R) from muscle biopsies obtained from young [ n = 9; 23 yr (SD 3)] and older [ n = 18; 68 yr (SD 6)] adults before and after 5-day bed rest. Significantly altered pathways in both young and old subjects relating to mechanosensing and cell adhesion (Actin Cytoskeleton Signaling, ILK Signaling, RhoA Signaling, and Integrin Signaling) were altered (activation z score) to a greater extent in old subjects. Hepatic Fibrosis/Hepatic Stellate Cell Activation was the top regulated pathway significantly altered only in the old. Fifty-one differentially regulated genes were only altered in the young after bed rest and resembled a gene expression profile like that in the old at baseline. Inflammation and muscle wasting genes (CXCL2, GADD45A) were uniquely increased in the old after bed rest, and the macrophage gene MAFB decreased in the old and correlated with the change in leg lean mass. In summary, skeletal muscle dysregulation during bed rest in the old may be driven by alterations in molecules related to fibrosis, inflammation, and cell adhesion. This information may aid in the development of mechanistic-based therapies to combat muscle atrophy during short-term disuse. NEW & NOTEWORTHY Using RNA sequencing and bioinformatics approaches, we identified that older adult skeletal muscle was characterized by dysregulated pathways associated with fibrosis, inflammation (upregulated), and cell adhesion and mechanosensing (downregulated) pathways, with a subset of genes differentially regulated in old and young muscle after bed rest that may describe predisposition to muscle loss. Unique upregulated genes only expressed in old muscle after bed rest indicated increased inflammation and muscle wasting (CXCL2, GADD45A) and decreased MAFB correlated with the change in leg lean mass.

Leucine augments specific skeletal muscle mitochondrial respiratory pathways during recovery following 7 days of physical inactivity in older adults

2021 ◽  
Author(s):  
Emily J. Arentson-Lantz ◽  
Jasmine Mikovic ◽  
Nisha Bhattarai ◽  
Christopher S. Fry ◽  
Séverine Lamon ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Bed Rest ◽  
Metabolic Clearance ◽  
Leucine Supplementation ◽  
Respiratory Capacity ◽  
Antioxidant Defense Systems ◽  
Mitochondrial Respiratory

Leucine supplementation attenuates the loss of skeletal muscle mass and function in older adults during bed rest. We sought to determine if leucine could also preserve and/or restore mitochondrial function and muscle oxidative capacity during periods of disuse and rehabilitation. Healthy older adults (69.1 ± 1.1 years) consumed a structured diet with supplemental leucine (LEU: 0.06 g/ kg body weight/ meal; n=8) or alanine (CON: 0.06 g/ kg body weight/meal; n=8) during 7 days of bed rest and 5 days of inpatient rehabilitation. A 75 g oral glucose tolerance test was performed at baseline (PreBR), after bed rest (PostBR) and rehabilitation (PostRehab) and used to calculate an indicator of insulin sensitivity, metabolic clearance rate. (MCR). Tissue samples from the m. vastus lateralis were collected PreBR, PostBR, and PostRehab to assess mitochondrial respiratory capacity and protein markers of the oxidative phosphorylation and a marker of the antioxidant defense systems. During bed rest, leucine tended to preserve insulin sensitivity (Change in MCR, CON vs. LEU: -3.5 ± 0.82 vs LEU: -0.98 ± 0.88, p=0.054), but had no effect on mitochondrial respiratory capacity (Change in State 3+succinate CON vs. LEU -8.7 ± 6.1 vs. 7.3 ± 4.1 pmol O2/sec/mg tissue, p=0.10) Following rehabilitation, leucine increased ATP-linked respiration (CON vs. LEU: -8.9 ± 6.2 vs. 15.5± 4.4 pmol O2/sec/mg tissue, p=0.0042). While the expression of mitochondrial respiratory and antioxidant proteins was not impacted, leucine supplementation preserved specific pathways of mitochondrial respiration, insulin sensitivity and a marker of oxidative stress during bed rest and rehabilitation.

scholarly journals Reduced physical activity in young and older adults: metabolic and musculoskeletal implications

2019 ◽  
Vol 10 ◽  
pp. 204201881988882 ◽  
Author(s):  
Kelly A. Bowden Davies ◽  
Samuel Pickles ◽  
Victoria S. Sprung ◽  
Graham J. Kemp ◽  
Uazman Alam ◽  
...  
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Older Adults ◽  
Skeletal Muscle ◽  
High Risk ◽  
Physical Inactivity ◽  
Hepatic Insulin Resistance ◽  
Short Term ◽  
Peripheral Insulin Resistance ◽  
Triglyceride Accumulation

Background: Although the health benefits of regular physical activity and exercise are well established and have been incorporated into national public health recommendations, there is a relative lack of understanding pertaining to the harmful effects of physical inactivity. Experimental paradigms including complete immobilization and bed rest are not physiologically representative of sedentary living. A useful ‘real-world’ approach to contextualize the physiology of societal downward shifts in physical activity patterns is that of short-term daily step reduction. Results: Step-reduction studies have largely focused on musculoskeletal and metabolic health parameters, providing relevant disease models for metabolic syndrome, type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), sarcopenia and osteopenia/osteoporosis. In untrained individuals, even a short-term reduction in physical activity has a significant impact on skeletal muscle protein and carbohydrate metabolism, causing anabolic resistance and peripheral insulin resistance, respectively. From a metabolic perspective, short-term inactivity-induced peripheral insulin resistance in skeletal muscle and adipose tissue, with consequent liver triglyceride accumulation, leads to hepatic insulin resistance and a characteristic dyslipidaemia. Concomitantly, various inactivity-related factors contribute to a decline in function; a reduction in cardiorespiratory fitness, muscle mass and muscle strength. Conclusions: Physical inactivity maybe particularly deleterious in certain patient populations, such as those at high risk of T2D or in the elderly, considering concomitant sarcopenia or osteoporosis. The effects of short-term physical inactivity (with step reduction) are reversible on resumption of habitual physical activity in younger people, but less so in older adults. Nutritional interventions and resistance training offer potential strategies to prevent these deleterious metabolic and musculoskeletal effects. Impact: Individuals at high risk of/with cardiometabolic disease and older adults may be more prone to these acute periods of inactivity due to acute illness or hospitalization. Understanding the risks is paramount to implementing countermeasures.

Effect of 10 Days of Bed Rest on Skeletal Muscle in Healthy Older Adults

JAMA ◽  
2007 ◽  
Vol 297 (16) ◽  
pp. 1769 ◽  
Author(s):  
Patrick Kortebein ◽  
Arny Ferrando ◽  
Juan Lombeida ◽  
Robert Wolfe ◽  
William J. Evans
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Bed Rest ◽  
Healthy Older Adults

Short-Term Intensive Rehabilitation Induces Recovery of Physical Function After 7 Days of Bed Rest in Older Adults

2016 ◽  
Vol 7 (4) ◽  
pp. 156-163 ◽  
Author(s):  
Jennifer Barbee Ellison ◽  
Micah Drummond ◽  
Jared M. Dickinson ◽  
Janna Michelle McGaugh ◽  
Doug Paddon-Jones ◽  
...  
Keyword(s):  
Older Adults ◽  
Physical Function ◽  
Bed Rest ◽  
Short Term ◽  
Intensive Rehabilitation

scholarly journals Effects of β-hydroxy-β-methylbutyrate on skeletal muscle mitochondrial content and dynamics, and lipids after 10 days of bed rest in older adults

2017 ◽  
Vol 123 (5) ◽  
pp. 1092-1100 ◽  
Author(s):  
Robert A. Standley ◽  
Giovanna Distefano ◽  
Suzette L. Pereira ◽  
Min Tian ◽  
Owen J. Kelly ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Vastus Lateralis ◽  
Bed Rest ◽  
Disuse Atrophy ◽  
Mitochondrial Content ◽  
Cross Sectional ◽  
Oxphos Complex

Loss of muscle mass during periods of disuse likely has negative health consequences for older adults. We have previously shown that β-hydroxy-β-methylbutyrate (HMB) supplementation during 10 days of strict bed rest (BR) attenuates the loss of lean mass in older adults. To elucidate potential molecular mechanisms of HMB effects on muscle during BR and resistance training rehabilitation (RT), we examined mediators of skeletal muscle mitochondrial dynamics, autophagy and atrophy, and intramyocellular lipids. Nineteen older adults (60–76 yr) completed 10 days BR followed by 8-wk RT rehabilitation. Subjects were randomized to either HMB (3 g/day HMB; n = 11) or control (CON; n = 8) groups. Skeletal muscle cross-sectional area (CSA) was determined by histology from percutaneous vastus lateralis biopsies. We measured protein markers of mitochondrial content [oxidative phosphorylation (OXPHOS)], fusion and fission (MFN2, OPA1, FIS1, and DRP1), autophagy (Beclin1, LC3B, and BNIP3), and atrophy [poly-ubiquinated proteins (poly-ub)] by Western blot. Fatty acid composition of several lipid classes in skeletal muscle was measured by infusion-MS analysis. Poly-ub proteins and OXPHOS complex I increased in both groups following BR ( P < 0.05, main effect for time), and muscle triglyceride content tended to increase following BR in the HMB group ( P = 0.055). RT rehabilitation increased OXPHOS complex II protein ( P < 0.05), and total OXPHOS content tended ( P = 0.0504) to be higher in HMB group. In addition, higher levels of DRP1 and MFN2 were maintained in the HMB group after RT ( P < 0.05). BNIP3 and poly-ub proteins were significantly reduced following rehabilitation in both groups ( P < 0.05). Collectively, these data suggest that HMB influences mitochondrial dynamics and lipid metabolism during disuse atrophy and rehabilitation. NEW & NOTEWORTHY Mitochondrial content and dynamics remained unchanged over 10 days of BR in older adults. HMB stimulated intramuscular lipid storage as triacylglycerol following 10 days of bed rest (BR) and maintained higher mitochondrial OXPHOS content and dynamics during the 8-wk resistance exercise rehabilitation program.

scholarly journals Disuse-induced insulin resistance susceptibility coincides with a dysregulated skeletal muscle metabolic transcriptome

2019 ◽  
Vol 126 (5) ◽  
pp. 1419-1429 ◽  
Author(s):  
Ziad S. Mahmassani ◽  
Paul T. Reidy ◽  
Alec I. McKenzie ◽  
Chris Stubben ◽  
Michael T. Howard ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Amino Acid ◽  
Insulin Sensitivity ◽  
Bed Rest ◽  
High Susceptibility ◽  
Short Term ◽  
Muscle Insulin Resistance ◽  
Skeletal Muscle Insulin Resistance ◽  
Muscle Disuse

Short-term muscle disuse is characterized by skeletal muscle insulin resistance, although this response is divergent across subjects. The mechanisms regulating inactivity-induced insulin resistance between populations that are more or less susceptible to disuse-induced insulin resistance are not known. RNA sequencing was conducted on vastus lateralis muscle biopsies from subjects before and after bed rest ( n = 26) to describe the transcriptome of inactivity-induced insulin resistance. Subjects were separated into Low ( n = 14) or High ( n = 12) Susceptibility Groups based on the magnitude of change in insulin sensitivity after 5 days of bed rest. Both groups became insulin-resistant after bed rest, and there were no differences between groups in nonmetabolic characteristics (body mass, body mass index, fat mass, and lean mass). The High Susceptibility Group had more genes altered >1.5-fold (426 high versus 391 low) and more than twofold (73 high versus 55 low). Twenty-four genes were altered more than twofold in the High Susceptibility Group that did not change in the Low Susceptibility Group. 95 gene changes correlated with the changes in insulin sensitivity; 6 of these genes changed more than twofold in the High Susceptibility Group. Participants in the High Susceptibility Group were uniquely characterized with muscle gene responses described by a decrease in pathways responsible for lipid uptake and oxidation, decreased capacity for triglyceride export (APOB), increased lipogenesis (i.e., PFKFB3, FASN), and increased amino acid export (SLC43A1). These transcriptomic data provide a comprehensive examination of pathways and genes that may be useful biomarkers, or novel targets to offset muscle disuse-induced insulin resistance. NEW & NOTEWORTHY Short-term muscle disuse results in skeletal muscle insulin resistance through mechanisms that are not fully understood. Following a 5-day bed rest intervention, subjects were divided into High and Low Susceptibility Groups to inactivity-induced insulin resistance. This was followed by a genome-wide transcriptional analysis on muscle biopsy samples to gain insight on divergent insulin sensitivity responses. Our primary finding was that the skeletal muscle of subjects who experienced the most inactivity-induced insulin resistance (high susceptibility) was characterized by a decreased preference for lipid oxidation, increased lipogenesis, and increased amino acid export.

Sign in / Sign up

Export Citation Format

Share Document