The effect of young and old ex vivo human serum on cellular protein synthesis and growth in an in vitro model of aging

Author:

Allen Sophie L.12ORCID,Marshall Ryan N.13,Edwards Sophie J.1,Lord Janet M.234ORCID,Lavery Gareth G.2356,Breen Leigh123

Affiliation:

1. School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom

2. National Institute for Health Research, Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, United Kingdom

3. MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham, United Kingdom

4. Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom

5. Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom

6. Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partner, Birmingham, United Kingdom

Abstract

In vitro models of muscle aging are useful for understanding mechanisms of age-related muscle loss and aiding the development of targeted therapies. To investigate mechanisms of age-related muscle loss in vitro utilizing ex vivo human serum, fasted blood samples were obtained from four old (72 ± 1 yr) and four young (26 ± 3 yr) men. Older individuals had elevated levels of plasma CRP, IL-6, HOMA-IR, and lower concentric peak torque and work-per-repetition compared with young participants ( P < 0.05). C2C12 myotubes were serum and amino acid starved for 1 h and conditioned with human serum (10%) for 4 h or 24 h. After 4 h, C2C12 cells were treated with 5 mM leucine for 30 min. Muscle protein synthesis (MPS) was determined through the surface sensing of translation (SUnSET) technique and regulatory signaling pathways were measured via Western blot. Myotube diameter was significantly reduced in myotubes treated with serum from old, in comparison to young donors (84%, P < 0.001). MPS was reduced in myotubes treated with old donor serum, compared with young serum before leucine treatment (32%, P < 0.01). MPS and the phosphorylation of Akt, p70S6K, and eEF2 were increased in myotubes treated with young serum in response to leucine treatment, with a blunted response identified in cells treated with old serum ( P < 0.05). Muscle protein breakdown signaling pathways did not differ between groups. In summary, we show that myotubes conditioned with serum from older individuals had decreased myotube diameter and MPS compared with younger individuals, potentially driven by low-grade systemic inflammation.

Funder

National Institute for Health Research

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

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