Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
David Hood
 + 1513 word(s) 1513 2021-05-20 04:36:54 |
2 update layout and reference
Rita Xu
 Meta information modification 1513 2021-05-21 04:07:13 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Hood, D.; Memme, J. Chronic Muscle Disuse. Encyclopedia. Available online: https://encyclopedia.pub/entry/9922 (accessed on 19 April 2024).
Hood D, Memme J. Chronic Muscle Disuse. Encyclopedia. Available at: https://encyclopedia.pub/entry/9922. Accessed April 19, 2024.
Hood, David, Jonathan Memme. "Chronic Muscle Disuse" Encyclopedia, https://encyclopedia.pub/entry/9922 (accessed April 19, 2024).
Hood, D., & Memme, J. (2021, May 20). Chronic Muscle Disuse. In Encyclopedia. https://encyclopedia.pub/entry/9922
Hood, David and Jonathan Memme. "Chronic Muscle Disuse." Encyclopedia. Web. 20 May, 2021.
Chronic Muscle Disuse
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms22105179

Periods of muscle disuse promote diminished muscle quality along with muscle atrophy that is characterized by reductions in muscle fiber cross-sectional area (CSA). Skeletal muscle disuse may be brought about by chronic sedentarism, periods of immobilization due to injury, bed rest as result of illness, or even exposure to microgravity. Such inactivity elicits functional and metabolic derangements in the affected tissue including marked mitochondrial alterations that contribute to the impaired metabolic health and degree of atrophy in the muscle. These impairments within the tissue prompt a net increase in catabolic processes in conjunction with reductions in skeletal muscle protein synthesis. Skeletal muscle mitochondrial decline and atrophy are underlying features of many diseases and they exacerbate disease progression and reduced mobility with aging. Thus, understanding the molecular underpinnings of muscle mitochondrial deficits with prolonged inactivity is of considerable interest.

skeletal muscle atrophy mitochondrial quality control mitochondrial biogenesis mitophagy autophagy

1. Introduction

The adaptability of skeletal muscle to various external stimuli has profound ramifications for overall health. It is well-established that chronic exercise supports favourable adaptions in muscle that contribute to improved metabolic fitness, longevity and the absence of various diseases. In contrast, chronic muscle inactivity promotes diminished muscle quality along with muscle atrophy that is characterized by reductions in muscle fiber cross-sectional area (CSA), the net result of increased catabolism concomitant with reduced skeletal muscle protein synthesis [1][2][3][4][5][6]. Indeed, muscle atrophy is a prominent feature of numerous pathophysiological conditions, including metabolic diseases, cancers, AIDS, and respiratory diseases, among numerous others, and leads to further disease progression and reduced mobility with aging [7][8]. In the absence of disease, skeletal muscle disuse may be brought about by chronic sedentarism, periods of immobilization due to injury, bed rest as result of illness, or for a select few, exposure to microgravity. In these cases, muscle atrophy may occur in the affected limb or more broadly throughout the body, creating functional and metabolic derangements in the affected tissue. Given the frequent recruitment and activation of slow-twitch oxidative fibers for the maintenance of posture and other routine tasks, muscles with a predominantly type I fiber composition such as the soleus are more susceptible to chronic disuse than muscles with a more mixed fiber complexion, such as the gastrocnemius [9][10][11]. Prolonged inactivity promotes the acquisition of the structural, biochemical and mechanical properties of a glycolytic tissue within these type I fibers, and generates metabolic dysfunction emanating from the mitochondrial network. Thus, the effects of muscle atrophy with prolonged inactivity are variable and determined, in part, by the composition of fiber types within the affected tissue [9][12][13][14].

The World Health Organization posits that insufficient physical activity is the leading risk factor for the advancement of non-communicable diseases and diminished quality of life, and is a global phenomenon that requires a substantial and coordinated effort among nations to remediate the pervasive sedentarism [15]. The consequences of muscle atrophy are substantial, with implications in functional decline, disability, disease and premature death. Even during prescribed periods of muscle disuse, as part of therapeutic intervention following injury or illness, the resultant atrophy in the muscle can prove detrimental by delaying, impairing or even preventing adequate recovery, often despite rehabilitative intervention strategies [16][17][18][19][20].

2. Models of Muscle Disuse

2.1. Human Models of Muscle Disuse

Chronic inactivity in humans provides the most direct study of the conditions that bring about muscle wasting in patient populations. Unilateral limb immobilization/casting, as well as bed rest studies present the two most commonly used approaches for studying muscle wasting conditions in human subjects, and are particularly useful in studying muscle decline in the absence of associated comorbidities. Unilateral limb immobilization involves fixing a joint, such as the elbow or knee, in the flexed position while maintaining the limb suspended above the ground. This approach has been used for decades to compare the effects of muscle disuse in one limb, compared to the contralateral, unaffected limb [21]. The ability to localize muscle disuse with this model closely mimics the unloading that occurs following musculoskeletal injuries in the clinical setting, and allows for direct comparisons within the same subject, while eliciting pronounced reductions in CSA and muscle mass [22][23][24]. In fact, reports indicate that limb immobilization is capable of inducing 0.44% reduction in vastus lateralis mass per day [24][25][26]. Bed rest studies have also long been employed to simulate, not only prolonged periods of inactivity following injury or illness, but additionally, the muscle wasting conditions brought about by space flight [27]. Dry-immersion bed rest studies go one step further by positioning a subject in the supine position within a waterproof barrier and suspending them in thermoneutral water, in order to most accurately recreate the complete unloading that is experienced by astronauts in space [28]. The additional benefit of dry-immersion bed rest is the higher rate and greater extent at which neuromuscular adaptations are achieved, compared to traditional bed rest [28]. Both bed rest and limb immobilization studies allow effective countermeasures to be tested, in order to prevent, offset, or reverse the decline in muscle observed with disuse, while also providing a relevant model of the wasting associated with diseases and aging. In a clinical setting, brought into recent focus as a result of the COVID-19 pandemic, is the significant respiratory muscle atrophy and dysfunction resulting from mechanical ventilation in the intensive care unit. Respiratory muscle atrophy and dysfunction can occur in just 18 h following assisted ventilation [29][30]. Samples derived from these patients, although scarce, allow for direct study of the myopathy that makes these subjects unable to return to normal, unsupported ventilation [31][32].

2.2. Animal Models of Muscle Disuse

In many cases employing animal models of muscle inactivity offers greater flexibility and the ability to control for potential confounding variables, while also mimicking many of the relevant disuse atrophy-generating conditions that may affect humans [33][34]. In animals, hindlimb suspension and hindlimb immobilization are two common approaches for inducing disuse-atrophy, particularly in mice and rats. Hindlimb suspension involves affixing orthopedic tape to the tail of the animal and attaching the tape to a metal swivel located at the top of the cage, thus, allowing for unhindered 360° rotation and movement around the cage using the forelimbs [35][36][37][38]. The hindlimb suspension technique was first developed nearly 50 years ago by the National Aeronautics and Space Agency, in order to simulate weightlessness, and thus, makes the approach particularly useful for studying the effects of musculoskeletal unloading [39][40]. Similar to immobilization in humans, rodent hindlimb immobilization involves fixing one limb with a plastic brace, or within a plastic tube, in order to maintain the joint in a flexed position [36]. In this way, disuse can be accomplished by using, either a fixed dorsiflexion of the ankle joint to induce atrophy of the tibialis anterior and extensor digitorum longus, or fixed plantarflexion to produce atrophy of the gastrocnemius, plantaris, and soleus [41][42][43]. The benefits of employing hindlimb immobilization include the ability to compare the effects of disuse to the contralateral limb of the same animal, while restricting muscle contraction. Additionally, these techniques offer a relatively simple, cost effective approach to induce reductions in muscle CSA, mass, and strength in as little as one week [44]. Another model that may be applied to rodents involves confined housing via small cages that restrict movement, and thus, limit physical activity so as to replicate chronic sedentarism [45][46][47][48]. This model of restricted movement is useful in studies interested in observing the systemic effects of muscle inactivity such as the changes in glucose metabolism and insulin resistance, along with the muscle atrophy and myopathy that ensues [45][48][49]. Likewise, an added benefit to any of these aforementioned rodent models is the ability to study corrective interventions, such as re-training to minimize or to reverse the detrimental effects of muscle disuse.

In contrast to these relatively non-invasive techniques, denervation, or similarly, nerve crushing and tetrodotoxin (TTX) cuffing, provide surgical methods of inducing muscle disuse, and have applicability to severe spinal cord or neuronal injury, as well as aging [50]. Denervation involves the excision of a small (~2–3 mm) segment of the nerve innervating the target muscle. Generally the tibial nerve is targeted in rats, while the sciatic nerve is used in mice, thus, affecting the lower hindlimb muscles [36][51][52]. Denervation of the nerve completely abolishes nerve-muscle communication via neuromotor and neurotrophic inputs, leading to rapid atrophy of the tissue. Nerve crushing is similar to denervation, however it requires the application of a force to the nerve with adequate pressure to temporarily ablate neural input to the muscle, while still allowing for neural regeneration and re-innervation to occur over time [36][53][54]. Alternatively, treatment with the sodium channel blocking drug TTX provides a chemical approach to denervation. TTX cuffing around the nerve maintains axonal continuity to the muscle and vascular beds, along with the flow of trophic factors that are otherwise lost with mechanical denervation, yet eliminates the impulse conduction from the nerve to muscle in order to prevent muscle contraction [53][54]. Each of these approaches are both suitable and sufficient for inducing muscle disuse-induced atrophy as well as metabolic myopathy. However, the choice of which model is best depends on the context and application of the experiments, and any conclusions made using one technique should be carefully applied and contrasted with those obtained via other disuse methodologies or model organisms.

References

  1. Booth, F.W. Effect of limb immobilization on skeletal muscle. J. Appl. Physiol. 1982, 52, 1113–1118.
  2. Kandarian, S.C.; Stevenson, E.J. Molecular Events in Skeletal Muscle During Disuse Atrophy. Exerc. Sport Sci. Rev. 2002, 30, 111–116.
  3. Goldspink, D.F. Muscle proteinase activities during compensatory growth and atrophy. Cell. Mol. Life Sci. 1986, 42, 133–134.
  4. Thomason, D.B.; Biggs, R.B.; Booth, F.W. Protein metabolism and beta-myosin heavy-chain mRNA in unweighted soleus muscle. Am. J. Physiol. Integr. Comp. Physiol. 1989, 257, R300–R305.
  5. Loughna, P.; Goldspink, G.; Goldspink, D.F. Effect of inactivity and passive stretch on protein turnover in phasic and postural rat muscles. J. Appl. Physiol. 1986, 61, 173–179.
  6. Jackman, R.W.; Kandarian, S.C. The molecular basis of skeletal muscle atrophy. Am. J. Physiol. Physiol. 2004, 287, C834–C843.
  7. Carter, H.N.; Chen, C.C.W.; Hood, D.A. Mitochondria, Muscle Health, and Exercise with Advancing Age. Physiology 2015, 30, 208–223.
  8. Atherton, P.J.; Greenhaff, P.L.; Phillips, S.M.; Bodine, S.C.; Adams, C.M.; Lang, C.H. Control of skeletal muscle atrophy in response to disuse: Clinical/preclinical contentions and fallacies of evidence. Am. J. Physiol. Metab. 2016, 311, E594–E604.
  9. Edgerton, V.R.; Roy, R.R.; Allen, D.L.; Monti, R.J. Adaptations in Skeletal Muscle Disuse or Decreased-Use Atrophy. Am. J. Phys. Med. Rehabilit. 2002, 81, S127–S147.
  10. Maier, A.; Eldred, E.; Edgerton, V. The effects on spindles of muscle atrophy and hypertrophy. Exp. Neurol. 1972, 37, 100–123.
  11. Tomanek, R.J.; Lund, D.D. Degeneration of different types of skeletal muscle fibres. I. Denervation. J. Anat. 1973, 116, 395–407.
  12. Booth, F.W.; Kelso, J.R. Cytochrome Oxidase of Skeletal Muscle: Adaptive Response to Chronic Disuse. Can. J. Physiol. Pharmacol. 1973, 51, 679–681.
  13. Trappe, S.; Trappe, T.; Gallagher, P.; Harber, M.; Alkner, B.; Tesch, P. Human single muscle fibre function with 84 day bed-rest and resistance exercise. J. Physiol. 2004, 557, 501–513.
  14. Witzmann, F.A.; Kim, D.H.; Fitts, R.H. Recovery time course in contractile function of fast and slow skeletal muscle after hindlimb immobilization. J. Appl. Physiol. 1982, 52, 677–682.
  15. Guthold, R.; Stevens, G.A.; Riley, L.M.; Bull, F.C. Worldwide trends in insufficient physical activity from 2001 to 2016: A pooled analysis of 358 population-based surveys with 1·9 million participants. Lancet Glob. Health 2018, 6, e1077–e1086.
  16. English, K.L.; Paddon-Jones, D. Protecting muscle mass and function in older adults during bed rest. Curr. Opin. Clin. Nutr. Metab. Care 2010, 13, 34–39.
  17. Bodine, S.C. Disuse-induced muscle wasting. Int. J. Biochem. Cell Biol. 2013, 45, 2200–2208.
  18. Meier, W.; Mizner, R.L.; Marcus, R.L.; E Dibble, L.; Peters, C.; LaStayo, P.C. Total Knee Arthroplasty: Muscle Impairments, Functional Limitations, and Recommended Rehabilitation Approaches. J. Orthop. Sports Phys. Ther. 2008, 38, 246–256.
  19. Petterson, S.C.; Mizner, R.L.; Stevens, J.E.; Raisis, L.; Bodenstab, A.; Newcomb, W.; Snyder-Mackler, L. Improved function from progressive strengthening interventions after total knee arthroplasty: A randomized clinical trial with an imbedded prospective cohort. Arthritis Rheum. 2009, 61, 174–183.
  20. Vandenborne, K.; Bs, M.A.E.; Walter, G.A.; Abdus, S.; Okereke, E.; Pt, M.S.; Tahernia, D.; Esterhai, J.L. Longitudinal study of skeletal muscle adaptations during immobilization and rehabilitation. Muscle Nerve 1998, 21, 1006–1012.
  21. Brioche, T.; Pagano, A.F.; Py, G.; Chopard, A. Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention. Mol. Asp. Med. 2016, 50, 56–87.
  22. Glover, E.I.; Phillips, S.M.; Oates, B.R.; Tang, J.E.; Tarnopolsky, M.A.; Selby, A.; Smith, K.; Rennie, M.J. Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion. J. Physiol. 2008, 586, 6049–6061.
  23. De Boer, M.D.; Selby, A.; Atherton, P.; Smith, K.; Seynnes, O.R.; Maganaris, C.N.; Maffulli, N.; Movin, T.; Narici, M.V.; Rennie, M.J. The temporal responses of protein synthesis, gene expression and cell signalling in human quadriceps muscle and patellar tendon to disuse. J. Physiol. 2007, 585, 241–251.
  24. Hackney, K.J.; Ploutz-Snyder, L.L. Unilateral lower limb suspension: Integrative physiological knowledge from the past 20 years (1991–2011). Graefe’s Arch. Clin. Exp. Ophthalmol. 2011, 112, 9–22.
  25. Wall, B.T.; Dirks, M.L.; van Loon, L.J. Skeletal muscle atrophy during short-term disuse: Implications for age-related sarcopenia. Ageing Res. Rev. 2013, 12, 898–906.
  26. Egerman, M.A.; Glass, D.J. Signaling pathways controlling skeletal muscle mass. Crit. Rev. Biochem. Mol. Biol. 2013, 49, 59–68.
  27. Scott, J.M.; Downs, M.; Buxton, R.; Goetchius, E.; Crowell, B.; Ploutz-Snyder, R.; Hackney, K.J.; Ryder, J.; English, K.; Ploutz-Snyder, L.L. Disuse-Induced Muscle Loss and Rehabilitation: The National Aeronautics and Space Administration Bed Rest Study. Crit. Care Explor. 2020, 2, e0269.
  28. Navasiolava, N.M.; Custaud, M.-A.; Tomilovskaya, E.S.; Larina, I.M.; Mano, T.; Gauquelin-Koch, G.; Gharib, C.; Kozlovskaya, I.B. Long-term dry immersion: Review and prospects. Graefe’s Arch. Clin. Exp. Ophthalmol. 2010, 111, 1235–1260.
  29. Vassilakopoulos, T.; Zakynthinos, S.; Roussos, C. Respiratory muscles and weaning failure. Eur. Respir. J. 1996, 9, 2383–2400.
  30. Powers, S.K.; Kavazis, A.N.; Levine, S. Prolonged mechanical ventilation alters diaphragmatic structure and function. Crit. Care Med. 2009, 37, S347–S353.
  31. Friedrich, O.; Diermeier, S.; Larsson, L. Weak by the machines: Muscle motor protein dysfunction—A side effect of intensive care unit treatment. Acta Physiol. 2018, 222, e12885.
  32. Hussain, S.N.A.; Vassilakopoulos, T. Ventilator-induced cachexia. Am. J. Respir. Crit. Care Med. 2002, 166, 1307–1308.
  33. Powers, S.K.; Wiggs, M.P.; Duarte, J.A.; Zergeroglu, A.M.; Demirel, H.A. Mitochondrial signaling contributes to disuse muscle atrophy. Am. J. Physiol. Metab. 2012, 303, E31–E39.
  34. Shanely, R.A.; Zergeroglu, M.A.; Lennon, S.L.; Sugiura, T.; Yimlamai, T.; Enns, D.; Belcastro, A.; Powers, S.K. Mechanical Ventilation–induced Diaphragmatic Atrophy Is Associated with Oxidative Injury and Increased Proteolytic Activity. Am. J. Respir. Crit. Care Med. 2002, 166, 1369–1374.
  35. Oliveira, J.R.S.; Mohamed, J.S.; Myers, M.J.; Brooks, M.J.; Alway, S.E. Effects of hindlimb suspension and reloading on gastrocnemius and soleus muscle mass and function in geriatric mice. Exp. Gerontol. 2019, 115, 19–31.
  36. Musacchia, X.J.; Steffen, J.M.; Fell, R.D. Disuse atrophy of skeletal muscle: Animal models. Exerc. Sport Sci. Rev. 1988, 16, 61–87.
  37. Alway, S.E.; Degens, H.; Lowe, D.A.; Krishnamurthy, G. Increased myogenic repressor Id mRNA and protein levels in hindlimb muscles of aged rats. Am. J. Physiol. Integr. Comp. Physiol. 2002, 282, R411–R422.
  38. Pistilli, E.E.; Siu, P.M.; Alway, S.E. Interleukin-15 responses to aging and unloading-induced skeletal muscle atrophy. Am. J. Physiol. Physiol. 2007, 292, C1298–C1304.
  39. Morey-Holton, E.R.; Globus, R.K. Hindlimb unloading rodent model: Technical aspects. J. Appl. Physiol. 2002, 92, 1367–1377.
  40. Morey-Holton, E.R.; Globus, R.K. Hindlimb Unloading of Growing Rats: A Model for Predicting Skeletal Changes During Space Flight. Bone 1998, 22, 83S–88S.
  41. Caron, A.Z.; Drouin, G.; Desrosiers, J.; Trensz, F.; Grenier, G. A novel hindlimb immobilization procedure for studying skeletal muscle atrophy and recovery in mouse. J. Appl. Physiol. 2009, 106, 2049–2059.
  42. Ebert, S.M.; Dyle, M.C.; Kunkel, S.D.; Bullard, S.A.; Bongers, K.S.; Fox, D.K.; Dierdorff, J.M.; Foster, E.D.; Adams, C.M. Stress-induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy. J. Biol. Chem. 2012, 287, 27290–27301.
  43. Madaro, L.; Smeriglio, P.; Molinaro, M.; Bouché, M. Unilateral immobilization: A simple model of limb atrophy in mice. Basic Appl. Myol. 2008, 18, 149–153.
  44. Speacht, T.L.; Krause, A.R.; Steiner, J.L.; Lang, C.H.; Donahue, H.J. Combination of hindlimb suspension and immobilization by casting exaggerates sarcopenia by stimulating autophagy but does not worsen osteopenia. Bone 2018, 110, 29–37.
  45. Reidy, P.T.; Monning, J.M.; Pickering, C.E.; Funai, K.; Drummond, M.J. Preclinical rodent models of physical inactivity-induced muscle insulin resistance: Challenges and solutions. J. Appl. Physiol. 2021, 130, 537–544.
  46. Barański, S.; Kwarecki, K.; Szmigielski, S.; Rozyński, J. Histochemistry of skeletal muscle fibres in rats undergoing long-term experimental hypokinesia. Folia Histochem. Cytochem. 1971, 9, 381–386.
  47. Marmonti, E.; Busquets, S.; Toledo, M.; Ricci, M.; Beltrà, M.; Gudiño, V.; Oliva, F.; López-Pedrosa, J.M.; Manzano, M.; Rueda, R.; et al. A Rat Immobilization Model Based on Cage Volume Reduction: A Physiological Model for Bed Rest? Front. Physiol. 2017, 8, 184.
  48. Mondon, C.E.; Dolkas, C.B.; Reaven, G.M. Effect of confinement in small space flight size cages on insulin sensitivity of ex-ercise-trained rats. Aviat. Space. Environ. Med. 1983, 54, 919–922.
  49. Fushiki, T.; Kano, T.; Inoue, K.; Sugimoto, E. Decrease in muscle glucose transporter number in chronic physical inactivity in rats. Am. J. Physiol. Metab. 1991, 260, E403–E410.
  50. Bodine, S.C.; Latres, E.; Baumhueter, S.; Lai, V.K.; Nunez, L.; Clarke, B.A.; Poueymirou, W.T.; Panaro, F.J.; Na, E.; Dharmarajan, K.; et al. Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy. Science 2001, 294, 1704–1708.
  51. Tryon, L.D.; Crilly, M.J.; Hood, D.A. Effect of denervation on the regulation of mitochondrial transcription factor a expression in skeletal muscle. Am. J. Physiol. Physiol. 2015, 309, C228–C238.
  52. Vainshtein, A.; Desjardins, E.M.; Ma, D.E.; Sandri, M.; A Hood, D. PGC-1α modulates denervation-induced mitophagy in skeletal muscle. Skelet. Muscle 2015, 5, 1–17.
  53. Gigo-Benato, D.; Russo, T.L.; Geuna, S.; Domingues, N.R.S.R.; Salvini, T.F.; Parizotto, N.A. Electrical stimulation impairs early functional recovery and accentuates skeletal muscle atrophy after sciatic nerve crush injury in rats. Muscle Nerve 2010, 41, 685–693.
  54. Midrio, M. The denervated muscle: Facts and hypotheses. A historical review. Graefe’s Arch. Clin. Exp. Ophthalmol. 2006, 98, 1–21.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Biochemistry & Molecular Biology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
David Hood
,
Jonathan Memme
View Times: 416
Revisions: 2 times (View History)
Update Date: 21 May 2021
Table of Contents
    1000/1000
    Hot Most Recent
    Feedback