Research Paper|Volume 8, Issue 8|pp 1690—1702

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^1,², Neil Johns^1,², Alain Schilb^3,⁴, Simone Degen^3,⁴, Martin Degen^3,⁴, Ramon Langen⁵, Annemie Schols⁵, David J Glass^3,⁴, Ronenn Roubenoff^3,⁴, Carolyn A. Greig⁶, Carsten Jacobi^3,⁴, Kenneth CH. Fearon², James A. Ross^1,²

¹Tissue Injury and Repair Group, Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, Scotland, UK
²Clinical Sciences (Surgery), University of Edinburgh, Edinburgh, Scotland, UK
³Novartis Institutes for Biomedical Research Basel, Novartis Pharma AG, CH-4056 Basel, Switzerland
⁴Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA
⁵NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands
⁶School of Sport, Exercise and Rehabilitation Sciences and MRC-ARUK Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham, UK

* * Equal contribution

Received: May 11, 2016Accepted: July 12, 2016Published: July 23, 2016

https://doi.org/10.18632/aging.101006

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.