Loss of oxidative defense and potential blockade of satellite cell maturation in the skeletal muscle of patients with cancer but not in the healthy elderly

Joanna Brzeszczyńska, Neil Johns, Alain Schilb, Simone Degen, Martin Degen, Ramon Langen, Annemie Schols, David J. Glass, Ronenn Roubenoff, Carolyn A. Greig, Carsten Jacobi, Kenneth C.H. Fearon, James A. Ross

Research output: Contribution to journalArticle

Abstract

Muscle wasting in old age or cancer may result from failed myofiber regeneration and/or accelerated atrophy. This study aimed to determine from transcriptomic analysis of human muscle the integrity of the cellular stress response system in relation to satellite cell differentiation or apoptosis in patients with cancer (weight-stable (CWS) or weight-losing (CWL)) or healthy elderly (HE) when compared with healthy middle-aged controls (HMA). 28 patients with cancer (CWS: 18 and CWL: 10), HE: 21 and HMA: 20 underwent biopsy of quadriceps muscle. The expression of transcription factors for muscle regeneration (Pax3, Pax7 and MyoD) was increased in CWS and HE compared with HMA (p<0.001). In contrast, the expression of the late myogenic differentiation marker MyoG was reduced in CWS and CWL but increased in HE (p<0.0001). Bax was significantly increased in CWS, CWL and HE (P<0.0001). Expression of the oxidative defense genes SOD2, GCLM, and Nrf2 was decreased in CWS and CWL but increased in HE (p<0.0001). There is evidence for blockade of satellite cell maturation, upregulation of apoptosis and reduced oxidative defense in the muscle of cancer patients. In the healthy elderly the potential for differentiation and oxidative defense is maintained.
Original languageEnglish
Pages (from-to)1690-1702
Number of pages13
JournalAging
Volume8
Issue number8
DOIs
Publication statusPublished - 23 Jul 2016
Externally publishedYes

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Skeletal Muscle
Weights and Measures
Neoplasms
Muscles
Regeneration
Muscle Neoplasms
Apoptosis
Differentiation Antigens
Quadriceps Muscle
Atrophy
Cell Differentiation
Transcription Factors
Up-Regulation
Biopsy
Genes

Cite this

Brzeszczyńska, Joanna ; Johns, Neil ; Schilb, Alain ; Degen, Simone ; Degen, Martin ; Langen, Ramon ; Schols, Annemie ; Glass, David J. ; Roubenoff, Ronenn ; Greig, Carolyn A. ; Jacobi, Carsten ; Fearon, Kenneth C.H. ; Ross, James A. / Loss of oxidative defense and potential blockade of satellite cell maturation in the skeletal muscle of patients with cancer but not in the healthy elderly. In: Aging. 2016 ; Vol. 8, No. 8. pp. 1690-1702.
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abstract = "Muscle wasting in old age or cancer may result from failed myofiber regeneration and/or accelerated atrophy. This study aimed to determine from transcriptomic analysis of human muscle the integrity of the cellular stress response system in relation to satellite cell differentiation or apoptosis in patients with cancer (weight-stable (CWS) or weight-losing (CWL)) or healthy elderly (HE) when compared with healthy middle-aged controls (HMA). 28 patients with cancer (CWS: 18 and CWL: 10), HE: 21 and HMA: 20 underwent biopsy of quadriceps muscle. The expression of transcription factors for muscle regeneration (Pax3, Pax7 and MyoD) was increased in CWS and HE compared with HMA (p<0.001). In contrast, the expression of the late myogenic differentiation marker MyoG was reduced in CWS and CWL but increased in HE (p<0.0001). Bax was significantly increased in CWS, CWL and HE (P<0.0001). Expression of the oxidative defense genes SOD2, GCLM, and Nrf2 was decreased in CWS and CWL but increased in HE (p<0.0001). There is evidence for blockade of satellite cell maturation, upregulation of apoptosis and reduced oxidative defense in the muscle of cancer patients. In the healthy elderly the potential for differentiation and oxidative defense is maintained.",
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Brzeszczyńska, J, Johns, N, Schilb, A, Degen, S, Degen, M, Langen, R, Schols, A, Glass, DJ, Roubenoff, R, Greig, CA, Jacobi, C, Fearon, KCH & Ross, JA 2016, 'Loss of oxidative defense and potential blockade of satellite cell maturation in the skeletal muscle of patients with cancer but not in the healthy elderly' Aging, vol. 8, no. 8, pp. 1690-1702. https://doi.org/10.18632/aging.101006

Loss of oxidative defense and potential blockade of satellite cell maturation in the skeletal muscle of patients with cancer but not in the healthy elderly. / Brzeszczyńska, Joanna; Johns, Neil; Schilb, Alain; Degen, Simone; Degen, Martin; Langen, Ramon; Schols, Annemie; Glass, David J.; Roubenoff, Ronenn; Greig, Carolyn A.; Jacobi, Carsten; Fearon, Kenneth C.H.; Ross, James A.

In: Aging, Vol. 8, No. 8, 23.07.2016, p. 1690-1702.

Research output: Contribution to journalArticle

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T1 - Loss of oxidative defense and potential blockade of satellite cell maturation in the skeletal muscle of patients with cancer but not in the healthy elderly

AU - Brzeszczyńska, Joanna

AU - Johns, Neil

AU - Schilb, Alain

AU - Degen, Simone

AU - Degen, Martin

AU - Langen, Ramon

AU - Schols, Annemie

AU - Glass, David J.

AU - Roubenoff, Ronenn

AU - Greig, Carolyn A.

AU - Jacobi, Carsten

AU - Fearon, Kenneth C.H.

AU - Ross, James A.

PY - 2016/7/23

Y1 - 2016/7/23

N2 - Muscle wasting in old age or cancer may result from failed myofiber regeneration and/or accelerated atrophy. This study aimed to determine from transcriptomic analysis of human muscle the integrity of the cellular stress response system in relation to satellite cell differentiation or apoptosis in patients with cancer (weight-stable (CWS) or weight-losing (CWL)) or healthy elderly (HE) when compared with healthy middle-aged controls (HMA). 28 patients with cancer (CWS: 18 and CWL: 10), HE: 21 and HMA: 20 underwent biopsy of quadriceps muscle. The expression of transcription factors for muscle regeneration (Pax3, Pax7 and MyoD) was increased in CWS and HE compared with HMA (p<0.001). In contrast, the expression of the late myogenic differentiation marker MyoG was reduced in CWS and CWL but increased in HE (p<0.0001). Bax was significantly increased in CWS, CWL and HE (P<0.0001). Expression of the oxidative defense genes SOD2, GCLM, and Nrf2 was decreased in CWS and CWL but increased in HE (p<0.0001). There is evidence for blockade of satellite cell maturation, upregulation of apoptosis and reduced oxidative defense in the muscle of cancer patients. In the healthy elderly the potential for differentiation and oxidative defense is maintained.

AB - Muscle wasting in old age or cancer may result from failed myofiber regeneration and/or accelerated atrophy. This study aimed to determine from transcriptomic analysis of human muscle the integrity of the cellular stress response system in relation to satellite cell differentiation or apoptosis in patients with cancer (weight-stable (CWS) or weight-losing (CWL)) or healthy elderly (HE) when compared with healthy middle-aged controls (HMA). 28 patients with cancer (CWS: 18 and CWL: 10), HE: 21 and HMA: 20 underwent biopsy of quadriceps muscle. The expression of transcription factors for muscle regeneration (Pax3, Pax7 and MyoD) was increased in CWS and HE compared with HMA (p<0.001). In contrast, the expression of the late myogenic differentiation marker MyoG was reduced in CWS and CWL but increased in HE (p<0.0001). Bax was significantly increased in CWS, CWL and HE (P<0.0001). Expression of the oxidative defense genes SOD2, GCLM, and Nrf2 was decreased in CWS and CWL but increased in HE (p<0.0001). There is evidence for blockade of satellite cell maturation, upregulation of apoptosis and reduced oxidative defense in the muscle of cancer patients. In the healthy elderly the potential for differentiation and oxidative defense is maintained.

U2 - 10.18632/aging.101006

DO - 10.18632/aging.101006

M3 - Article

VL - 8

SP - 1690

EP - 1702

JO - Aging

JF - Aging

SN - 0272-3808

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