title: 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.
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.
authors.affiliation: Tissue Injury and Repair Group, Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, Scotland, UK.|Clinical Sciences (Surgery), University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Brzeszczyńska
authors.affiliation: Tissue Injury and Repair Group, Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, Scotland, UK.|Clinical Sciences (Surgery), University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Johns
authors.affiliation: Novartis Institutes for Biomedical Research Basel, Novartis Pharma AG, CH-4056 Basel, Switzerland.|Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
authors.forename: Alain
authors.initials: A
authors.lastname: Schilb
authors.affiliation: Novartis Institutes for Biomedical Research Basel, Novartis Pharma AG, CH-4056 Basel, Switzerland.|Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Degen
authors.affiliation: Novartis Institutes for Biomedical Research Basel, Novartis Pharma AG, CH-4056 Basel, Switzerland.|Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Degen
authors.affiliation: NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Ramon
authors.initials: R
authors.lastname: Langen
authors.affiliation: NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Annemie
authors.initials: A
authors.lastname: Schols
authors.affiliation: Novartis Institutes for Biomedical Research Basel, Novartis Pharma AG, CH-4056 Basel, Switzerland.|Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Glass
authors.affiliation: Novartis Institutes for Biomedical Research Basel, Novartis Pharma AG, CH-4056 Basel, Switzerland.|Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
authors.forename: Ronenn
authors.initials: R
authors.lastname: Roubenoff
authors.affiliation: School of Sport, Exercise and Rehabilitation Sciences and MRC-ARUK Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham, UK.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Greig
authors.affiliation: Novartis Institutes for Biomedical Research Basel, Novartis Pharma AG, CH-4056 Basel, Switzerland.|Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
authors.forename: Carsten
authors.initials: C
authors.lastname: Jacobi
authors.affiliation: Clinical Sciences (Surgery), University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: Kenneth Ch
authors.initials: KCh
authors.lastname: Fearon
authors.affiliation: Tissue Injury and Repair Group, Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, Scotland, UK.|Clinical Sciences (Surgery), University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Ross
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002100:Cachexia / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism* / Q000473:pathology
keywords: cachexia; elderly; oxidative stress; satellite cells