Skip to main content
Top
Published in: Journal of Inflammation 1/2011

Open Access 01-12-2011 | Research

Ageing prolongs inflammatory marker expression in regenerating rat skeletal muscles after injury

Authors: Chris van der Poel, Luc E Gosselin, Jonathan D Schertzer, James G Ryall, Kristy Swiderski, Meron Wondemaghen, Gordon S Lynch

Published in: Journal of Inflammation | Issue 1/2011

Login to get access

Abstract

Background

Some of the most serious consequences of normal ageing relate to its effects on skeletal muscle, particularly significant wasting and associated weakness, termed "sarcopenia". The underlying mechanisms of sarcopenia have yet to be elucidated completely but an altered muscle inflammatory response after injury is a likely contributing factor. In this study we investigated age-related changes in the expression of numerous inflammatory markers linked to successful muscle regeneration.

Methods

Right extensor digitorum longus (EDL) muscles from young (3 month), adult (12 month) and old (24 month) male F344 rats were injected with bupivacaine hydrochloride to cause complete muscle fibre degeneration, then excised 12, 24, 36, and 72 hours later (n = 5/age group/time point). We used qRT-PCR to quantify the mRNA expression levels of the inflammatory markers TNFα, IFNγ, IL1, IL18, IL6, and CD18 as well as regenerative markers MyoD and myogenin.

Results

Inflammatory markers were all increased significantly in all age groups after myotoxic injury. There was a trend for expression of inflammatory markers to be higher in uninjured muscles of old rats, especially at 72 hours post injury where the expression levels of several markers was significantly higher in old compared with young and adult rats. There was also a decrease in the expression of regenerative markers in old rats at 72 hours post injury.

Conclusion

Our findings identify a prolonged inflammatory signature in injured muscles from old compared with young and adult rats together with a blunted expression of key markers of regeneration in muscles of old rats. Importantly, our findings identify potential targets for future therapeutic strategies for improving the regenerative capacity of skeletal muscle during ageing.
Appendix
Available only for authorised users
Literature
1.
2.
go back to reference Tidball JG: Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol. 2005, 288: R345-53.PubMedCrossRef Tidball JG: Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol. 2005, 288: R345-53.PubMedCrossRef
3.
go back to reference Chargé SB, Rudnicki MA: Cellular and molecular regulation of muscle regeneration. Physiol Rev. 2004, 84: 209-38. 10.1152/physrev.00019.2003.PubMedCrossRef Chargé SB, Rudnicki MA: Cellular and molecular regulation of muscle regeneration. Physiol Rev. 2004, 84: 209-38. 10.1152/physrev.00019.2003.PubMedCrossRef
4.
go back to reference Summan M, Warren GL, Mercer RR, Chapman R, Hulderman T, Van Rooijen N, Simeonova PP: Macrophages and skeletal muscle regeneration: a clodronate-containing lipsome depletion study. Am J Physiol Reg Int Comp Physiol. 2006, 290: R1488-95. 10.1152/ajpregu.00465.2005.CrossRef Summan M, Warren GL, Mercer RR, Chapman R, Hulderman T, Van Rooijen N, Simeonova PP: Macrophages and skeletal muscle regeneration: a clodronate-containing lipsome depletion study. Am J Physiol Reg Int Comp Physiol. 2006, 290: R1488-95. 10.1152/ajpregu.00465.2005.CrossRef
5.
go back to reference Tidball JG, Wehling-Hendricks M: Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo. J Physiol. 2007, 578: 327-36.PubMedPubMedCentralCrossRef Tidball JG, Wehling-Hendricks M: Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo. J Physiol. 2007, 578: 327-36.PubMedPubMedCentralCrossRef
6.
go back to reference Lu H, Huang D, Saederup N, Charo IF, Ransohoff RM, Zhou L: Macrophages recruited via CCR2 produce insulin-like growth factor-1 to repair acute skeletal muscle injury. FASEB J. 2011, 25: 358-69. 10.1096/fj.10-171579.PubMedPubMedCentralCrossRef Lu H, Huang D, Saederup N, Charo IF, Ransohoff RM, Zhou L: Macrophages recruited via CCR2 produce insulin-like growth factor-1 to repair acute skeletal muscle injury. FASEB J. 2011, 25: 358-69. 10.1096/fj.10-171579.PubMedPubMedCentralCrossRef
7.
go back to reference Lapointe BM, Fremont P, Côte CH: Adaptation to lengthening contractions is independent of voluntary muscle recruitment but relies on inflammation. Am J Physiol Regul Integr Comp Physiol. 2002, 282: R323-9.PubMedCrossRef Lapointe BM, Fremont P, Côte CH: Adaptation to lengthening contractions is independent of voluntary muscle recruitment but relies on inflammation. Am J Physiol Regul Integr Comp Physiol. 2002, 282: R323-9.PubMedCrossRef
8.
go back to reference Lapointe BM, Frenette J, Côte CH: Lengthening contraction-induced inflammation is linked to secondary damage but devoid of neutrophil invasion. J Appl Physiol. 2002, 92: 1995-2004. 10.1063/1.1494845.PubMedCrossRef Lapointe BM, Frenette J, Côte CH: Lengthening contraction-induced inflammation is linked to secondary damage but devoid of neutrophil invasion. J Appl Physiol. 2002, 92: 1995-2004. 10.1063/1.1494845.PubMedCrossRef
9.
go back to reference Lynch GS: Sarcopenia - age-related muscle wasting and weakness. Mechanisms and treatments. 2011, Springer (Germany), 479-CrossRef Lynch GS: Sarcopenia - age-related muscle wasting and weakness. Mechanisms and treatments. 2011, Springer (Germany), 479-CrossRef
10.
go back to reference Conboy IM, Conboy MJ, Smythe GM, Rando TA: Notch-mediated restoration of regenerative potential to aged muscle. Science. 2003, 302: 1575-7. 10.1126/science.1087573.PubMedCrossRef Conboy IM, Conboy MJ, Smythe GM, Rando TA: Notch-mediated restoration of regenerative potential to aged muscle. Science. 2003, 302: 1575-7. 10.1126/science.1087573.PubMedCrossRef
11.
go back to reference Conboy IM, Rando TA: Aging, stem cells and tissue regeneration: lessons from muscle. Cell Cycle. 2005, 4: 407-10. 10.4161/cc.4.3.1518.PubMedCrossRef Conboy IM, Rando TA: Aging, stem cells and tissue regeneration: lessons from muscle. Cell Cycle. 2005, 4: 407-10. 10.4161/cc.4.3.1518.PubMedCrossRef
12.
go back to reference Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C, Rando TA: Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science. 2007, 317: 807-10. 10.1126/science.1144090.PubMedCrossRef Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C, Rando TA: Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science. 2007, 317: 807-10. 10.1126/science.1144090.PubMedCrossRef
13.
go back to reference Ryall JG, Schertzer JD, Lynch GS: Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness. Biogerontology. 2008, 9: 213-28. 10.1007/s10522-008-9131-0.PubMedCrossRef Ryall JG, Schertzer JD, Lynch GS: Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness. Biogerontology. 2008, 9: 213-28. 10.1007/s10522-008-9131-0.PubMedCrossRef
14.
go back to reference Giresi PG, Stevenson EJ, Theilhaber J, Koncarevic A, Parkington J, Fielding RA, Kandarian SC: Identification of a molecular signature of sarcopenia. Physiol Genomics. 2005, 21: 253-63. 10.1152/physiolgenomics.00249.2004.PubMedCrossRef Giresi PG, Stevenson EJ, Theilhaber J, Koncarevic A, Parkington J, Fielding RA, Kandarian SC: Identification of a molecular signature of sarcopenia. Physiol Genomics. 2005, 21: 253-63. 10.1152/physiolgenomics.00249.2004.PubMedCrossRef
15.
go back to reference Hamada K, Vannier E, Sacheck JM, Witsell AL, Roubenoff R: Senescence of human skeletal muscle impairs the local inflammatory cytokine response to acute eccentric exercise. FASEB J. 2005, 19: 264-6.PubMed Hamada K, Vannier E, Sacheck JM, Witsell AL, Roubenoff R: Senescence of human skeletal muscle impairs the local inflammatory cytokine response to acute eccentric exercise. FASEB J. 2005, 19: 264-6.PubMed
16.
go back to reference Carlson BM, Faulkner JA: The regeneration of noninnervated muscle grafts and marcaine-treated muscles in young and old rats. J Gerontol A Biol Sci Med Sci. 1996, 51: B43-9.PubMedCrossRef Carlson BM, Faulkner JA: The regeneration of noninnervated muscle grafts and marcaine-treated muscles in young and old rats. J Gerontol A Biol Sci Med Sci. 1996, 51: B43-9.PubMedCrossRef
17.
go back to reference Shavlakadze T, McGeachie J, Grounds MD: Delayed but excellent myogenic stem cell response of regenerating geriatric skeletal muscles in mice. Biogerontology. 2010, 11: 363-76. 10.1007/s10522-009-9260-0.PubMedCrossRef Shavlakadze T, McGeachie J, Grounds MD: Delayed but excellent myogenic stem cell response of regenerating geriatric skeletal muscles in mice. Biogerontology. 2010, 11: 363-76. 10.1007/s10522-009-9260-0.PubMedCrossRef
18.
go back to reference Beitzel F, Gregorevic P, Ryall JG, Plant DR, Sillence MN, Lynch GS: β2-Adrenoceptor agonist fenoterol enhances functional repair of regenerating rat skeletal muscle after injury. J Appl Physiol. 2004, 96: 1385-92. 10.1152/japplphysiol.01081.2003.PubMedCrossRef Beitzel F, Gregorevic P, Ryall JG, Plant DR, Sillence MN, Lynch GS: β2-Adrenoceptor agonist fenoterol enhances functional repair of regenerating rat skeletal muscle after injury. J Appl Physiol. 2004, 96: 1385-92. 10.1152/japplphysiol.01081.2003.PubMedCrossRef
19.
go back to reference Gregorevic P, Plant DR, Stupka N, Lynch GS: Changes in contractile activation characteristics of rat fast and slow skeletal muscle fibres during regeneration. J Physiol Lond. 2004, 558: 549-60. 10.1113/jphysiol.2004.066217.PubMedPubMedCentralCrossRef Gregorevic P, Plant DR, Stupka N, Lynch GS: Changes in contractile activation characteristics of rat fast and slow skeletal muscle fibres during regeneration. J Physiol Lond. 2004, 558: 549-60. 10.1113/jphysiol.2004.066217.PubMedPubMedCentralCrossRef
20.
go back to reference Plant DR, Beitzel F, Lynch GS: Length-tension relationships are altered in regenerating muscles of the rat after bupivacaine injection. J Appl Physiol. 2005, 98: 1998-2003. 10.1152/japplphysiol.01381.2004.PubMedCrossRef Plant DR, Beitzel F, Lynch GS: Length-tension relationships are altered in regenerating muscles of the rat after bupivacaine injection. J Appl Physiol. 2005, 98: 1998-2003. 10.1152/japplphysiol.01381.2004.PubMedCrossRef
21.
go back to reference Pizza FX, Peterson JM, Baas JH, Koh TJ: Neutrophils contribute to muscle injury and impair its resolution after lengthening contractions in mice. J Physiol Lond. 2005, 562: 899-913.PubMedPubMedCentralCrossRef Pizza FX, Peterson JM, Baas JH, Koh TJ: Neutrophils contribute to muscle injury and impair its resolution after lengthening contractions in mice. J Physiol Lond. 2005, 562: 899-913.PubMedPubMedCentralCrossRef
22.
go back to reference Sadeh M: Effects of aging on skeletal muscle regeneration. J Neurol Sci. 1988, 87: 67-74. 10.1016/0022-510X(88)90055-X.PubMedCrossRef Sadeh M: Effects of aging on skeletal muscle regeneration. J Neurol Sci. 1988, 87: 67-74. 10.1016/0022-510X(88)90055-X.PubMedCrossRef
23.
go back to reference Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick EM, Newman AB, Nevitt M, Harris TB: Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci. 2002, 57: M326-32. 10.1093/gerona/57.5.M326.PubMedCrossRef Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick EM, Newman AB, Nevitt M, Harris TB: Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci. 2002, 57: M326-32. 10.1093/gerona/57.5.M326.PubMedCrossRef
24.
go back to reference Przybyla B, Gurley C, Harvey JF, Bearden E, Kortebein P, Evans WJ, Sullivan DH, Peterson CA, Dennis RA: Aging alters macrophage properties in human skeletal muscle both at rest and in response to acute resistance exercise. Exp Gerontol. 2006, 41: 320-7. 10.1016/j.exger.2005.12.007.PubMedCrossRef Przybyla B, Gurley C, Harvey JF, Bearden E, Kortebein P, Evans WJ, Sullivan DH, Peterson CA, Dennis RA: Aging alters macrophage properties in human skeletal muscle both at rest and in response to acute resistance exercise. Exp Gerontol. 2006, 41: 320-7. 10.1016/j.exger.2005.12.007.PubMedCrossRef
25.
go back to reference Thompson RW, McClung JM, Baltgalvis KA, Davis JM, Carson JA: Modulation of overload-induced inflammation by aging and anabolic steroid administration. Exp Gerontol. 2006, 41: 1136-48. 10.1016/j.exger.2006.08.013.PubMedCrossRef Thompson RW, McClung JM, Baltgalvis KA, Davis JM, Carson JA: Modulation of overload-induced inflammation by aging and anabolic steroid administration. Exp Gerontol. 2006, 41: 1136-48. 10.1016/j.exger.2006.08.013.PubMedCrossRef
26.
go back to reference Pedersen M, Bruunsgaard H, Weis N, Hendel HW, Andreassen BU, Eldrup E, Dela F, Pedersen BK: Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes. Mech Ageing Dev. 2003, 124: 495-502. 10.1016/S0047-6374(03)00027-7.PubMedCrossRef Pedersen M, Bruunsgaard H, Weis N, Hendel HW, Andreassen BU, Eldrup E, Dela F, Pedersen BK: Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes. Mech Ageing Dev. 2003, 124: 495-502. 10.1016/S0047-6374(03)00027-7.PubMedCrossRef
27.
go back to reference Jozsi AC, Dupont-Versteegden EE, Taylor-Jones JM, Evans WJ, Trappe TA, Campbell WW, Peterson CA: Aged human muscle demonstrates an altered gene expression profile consistent with an impaired response to exercise. Mech Ageing Dev. 2000, 120: 45-56. 10.1016/S0047-6374(00)00178-0.PubMedCrossRef Jozsi AC, Dupont-Versteegden EE, Taylor-Jones JM, Evans WJ, Trappe TA, Campbell WW, Peterson CA: Aged human muscle demonstrates an altered gene expression profile consistent with an impaired response to exercise. Mech Ageing Dev. 2000, 120: 45-56. 10.1016/S0047-6374(00)00178-0.PubMedCrossRef
28.
go back to reference Dennis RA, Przybyla B, Gurley C, Kortebein PM, Simpson P, Sullivan DH, Peterson CA: Aging alters gene expression of growth and remodeling factors in human skeletal muscle both at rest and in response to acute resistance exercise. Physiol Genomics. 2008, 32: 393-400.PubMedCrossRef Dennis RA, Przybyla B, Gurley C, Kortebein PM, Simpson P, Sullivan DH, Peterson CA: Aging alters gene expression of growth and remodeling factors in human skeletal muscle both at rest and in response to acute resistance exercise. Physiol Genomics. 2008, 32: 393-400.PubMedCrossRef
29.
go back to reference Dennis RA, Zhu H, Kortebein PM, Bush HM, Harvey JF, Sullivan DH, Peterson CA: Muscle expression of genes associated with inflammation, growth, and remodeling is strongly correlated in older adults with resistance training outcomes. Physiol Genomics. 2009, 38: 169-75. 10.1152/physiolgenomics.00056.2009.PubMedPubMedCentralCrossRef Dennis RA, Zhu H, Kortebein PM, Bush HM, Harvey JF, Sullivan DH, Peterson CA: Muscle expression of genes associated with inflammation, growth, and remodeling is strongly correlated in older adults with resistance training outcomes. Physiol Genomics. 2009, 38: 169-75. 10.1152/physiolgenomics.00056.2009.PubMedPubMedCentralCrossRef
30.
go back to reference Bicer S, Reiser PJ, Ching S, Quan N: Induction of muscle weakness by local inflammation: an experimental animal model. Inflamm Res. 2009, 58: 175-83. 10.1007/s00011-008-8093-7.PubMedPubMedCentralCrossRef Bicer S, Reiser PJ, Ching S, Quan N: Induction of muscle weakness by local inflammation: an experimental animal model. Inflamm Res. 2009, 58: 175-83. 10.1007/s00011-008-8093-7.PubMedPubMedCentralCrossRef
31.
go back to reference Adams GR, Caiozzo VJ, Haddad F, Baldwin KM: Cellular and molecular responses to increased skeletal muscle loading after irradiation. Am J Physiol Cell Physiol. 2002, 283: C1182-95.PubMedCrossRef Adams GR, Caiozzo VJ, Haddad F, Baldwin KM: Cellular and molecular responses to increased skeletal muscle loading after irradiation. Am J Physiol Cell Physiol. 2002, 283: C1182-95.PubMedCrossRef
32.
33.
go back to reference Musaro A, Cusella De Angelis MG, Germani A, Germani A, Ciccarelli C, Molinaro M, Zani BM: Enhanced expression of myogenic regulatory genes in aging skeletal muscle. Exp Cell Res. 1995, 221: 241-8. 10.1006/excr.1995.1372.PubMedCrossRef Musaro A, Cusella De Angelis MG, Germani A, Germani A, Ciccarelli C, Molinaro M, Zani BM: Enhanced expression of myogenic regulatory genes in aging skeletal muscle. Exp Cell Res. 1995, 221: 241-8. 10.1006/excr.1995.1372.PubMedCrossRef
34.
go back to reference Alway SE, Lowe DA, Chen KD: The effects of age and hindlimb supension on the levels of expression of the myogenic regulatory factors MyoD and myogenin in rat fast and slow skeletal muscles. Exp Physiol. 2001, 86: 509-17. 10.1113/eph8602235.PubMedCrossRef Alway SE, Lowe DA, Chen KD: The effects of age and hindlimb supension on the levels of expression of the myogenic regulatory factors MyoD and myogenin in rat fast and slow skeletal muscles. Exp Physiol. 2001, 86: 509-17. 10.1113/eph8602235.PubMedCrossRef
35.
go back to reference Lowe DA, Lund T, Always SE: Hypertrophy-stimulated myogenic regulatory factor mRNA increases are attenuated in fast muscle of aged quails. Am J Physiol. 1998, 275: C155-62.PubMed Lowe DA, Lund T, Always SE: Hypertrophy-stimulated myogenic regulatory factor mRNA increases are attenuated in fast muscle of aged quails. Am J Physiol. 1998, 275: C155-62.PubMed
36.
go back to reference Tamaki T, Uchiyama S, Uchiyama Y, Akatsuka A, Yoshimura S, Roy RR, Edgerton VR: Limited myogenic response to a single bout of weight-lifting exercise in old rats. Am J Physiol Cell Physiol. 2000, 278: C1143-52.PubMed Tamaki T, Uchiyama S, Uchiyama Y, Akatsuka A, Yoshimura S, Roy RR, Edgerton VR: Limited myogenic response to a single bout of weight-lifting exercise in old rats. Am J Physiol Cell Physiol. 2000, 278: C1143-52.PubMed
37.
go back to reference Bigot A, Jacquemin V, Debacq-Chainiaux F, Butler-Browne GS, Toussaint O, Furling D, Mouly V: Replicative aging down-regulates the myogenic regulatory factors in human myoblasts. Biol Cell. 2008, 100: 189-99. 10.1042/BC20070085.PubMedCrossRef Bigot A, Jacquemin V, Debacq-Chainiaux F, Butler-Browne GS, Toussaint O, Furling D, Mouly V: Replicative aging down-regulates the myogenic regulatory factors in human myoblasts. Biol Cell. 2008, 100: 189-99. 10.1042/BC20070085.PubMedCrossRef
Metadata
Title
Ageing prolongs inflammatory marker expression in regenerating rat skeletal muscles after injury
Authors
Chris van der Poel
Luc E Gosselin
Jonathan D Schertzer
James G Ryall
Kristy Swiderski
Meron Wondemaghen
Gordon S Lynch
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2011
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/1476-9255-8-41

Other articles of this Issue 1/2011

Journal of Inflammation 1/2011 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.