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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

Authors

Sarah Al-Dabbagh

Jamie S. McPhee

Claire E. Stewart

Nasser Al-Shanti



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 Mar 28, 2024
Journal Journals of Gerontology: Series A
Print ISSN 1079-5006
Electronic ISSN 1758-535X
Publisher Oxford University Press (OUP)
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

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