Soluble factors released from activated T-lymphocytes regulate C2C12 myoblast proliferation and cellular signalling, but effects are blunted in the elderly

Al-Dabbagh, Sarah; McPhee, Jamie S.; Piasecki, Mathew; Stewart, Claire E.; Al-Shanti, Nasser

Abstract

The key objective of this work was to investigate the impact of young and old human lymphocyte secretomes on C2C12 myoblasts regeneration. Conditioned media (CMs) were harvested from isolated young and older lymphocytes treated with (activated AC), or without (non-activated NA), anti-CD3/CD28 activators for 4 days. AC conditioned media from older lymphocytes had decreased levels of amphiregulin (367±208pg/ml vs. 904±323pg/ml; p=0.018) and IGF-I (845±88ng/ml vs. 1100±48ng/ml; p=0.032) compared with younger AC. AC older vs younger lymphocytes had reduced expression of CD25 (24.6±5.5%; p=0.0003) and increased expression of FoxP3 (35±15.7%; p=0.032). Treatment of C2C12 myoblasts with young AC resulted in decreased expression of MyoD (0.46±0.12; p=0.004) and Myogenin (0.34±0.05; p=0.010) mRNA, increased activation of MEk1 (724±140 MFI; p=0.001) and ERK1/2 (3768±314 MFI; p=0.001) and a decreased activation of Akt (74.5±4 MFI; p=0.009) and mTOR (61.8±7 MFI; p=0.001) compared with old AC. By contrast, C2C12 myoblasts treated with older AC displayed increased expression of MyoD (0.7±0.08; p=0.004) and Myogenin (0.68±0.05; p=0.010) mRNA, decreased phosphorylation of MEk1 and ERK1/2 (528±80 MFI; p=0.008, and 1141±668 MFI; p=0.001, respectively) and increased Akt/mTOR activation (171±35 MFI; p=0.009, and 184±33 MFI; p=0.001, respectively). These data provide new evidence that differences between older and younger lymphocyte secretomes contribute to differential responses of C2C12 myoblasts in culture.

Citation

Al-Dabbagh, S., McPhee, J. S., Piasecki, M., Stewart, C. E., & Al-Shanti, N. (2019). Soluble factors released from activated T-lymphocytes regulate C2C12 myoblast proliferation and cellular signalling, but effects are blunted in the elderly. Journals of Gerontology, Series A, 74(9), 1375–1385. https://doi.org/10.1093/gerona/gly238

• Journal Article Type: Article
• Acceptance Date: Oct 4, 2018
• Online Publication Date: Oct 17, 2018
• Publication Date: Sep 1, 2019
• Deposit Date: Oct 23, 2018
• Publicly Available Date: Oct 18, 2019
• Journal: Journals of Gerontology: Series A
• Print ISSN: 1079-5006
• Electronic ISSN: 1758-535X
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 74
• Issue: 9
• Pages: 1375–1385
• DOI: https://doi.org/10.1093/gerona/gly238
• Keywords: Ageing; Geriatrics and gerontology
• Public URL: https://nottingham-repository.worktribe.com/output/1181104
• Publisher URL: https://academic.oup.com/biomedgerontology/article/74/9/1375/5133697
• Additional Information: This is a pre-copyedited, author-produced version of an article accepted for publication in The Journals of Gerontology Series A following peer review. The version of record Sarah Al-Dabbagh, Jamie S McPhee, Mathew Piasecki, Claire E Stewart, Nasser Al-Shanti, Soluble Factors Released From Activated T Lymphocytes Regulate C2C12 Myoblast Proliferation and Cellular Signaling, but Effects Are Blunted in the Elderly, The Journals of Gerontology: Series A, Volume 74, Issue 9, September 2019, Pages 1375–1385 is available online at: https://academic.oup.com/biomedgerontology/article/74/9/1375/5133697
• Contract Date: Oct 24, 2018