Cell Senescence-Independent Changes of Human Skin Fibroblasts with Age

Fullard, Nicola; Wordsworth, James; Welsh, Ciaran; Maltman, Victoria; Bascom, Charlie; Tasseff, Ryan; Isfort, Robert; Costello, Lydia; Scanlan, Rebekah-Louise; Przyborski, Stefan; Shanley, Daryl

Abstract

Skin ageing is defined, in part, by collagen depletion and fragmentation that leads to a loss of mechanical tension. This is currently believed to reflect, in part, the accumulation of senescent cells. We compared the expression of genes and proteins for components of the extracellular matrix (ECM) as well as their regulators and found that in vitro senescent cells produced more matrix metalloproteinases (MMPs) than proliferating cells from adult and neonatal donors. This was consistent with previous reports of senescent cells contributing to increased matrix degradation with age; however, cells from adult donors proved significantly less capable of producing new collagen than neonatal or senescent cells, and they showed significantly lower myofibroblast activation as determined by the marker α-SMA. Functionally, adult cells also showed slower migration than neonatal cells. We concluded that the increased collagen degradation of aged fibroblasts might reflect senescence, the reduced collagen production likely reflects senescence-independent processes.

Citation

Fullard, N., Wordsworth, J., Welsh, C., Maltman, V., Bascom, C., Tasseff, R., …Shanley, D. (2024). Cell Senescence-Independent Changes of Human Skin Fibroblasts with Age. Cells, 13(8), Article 659. https://doi.org/10.3390/cells13080659

• Journal Article Type: Article
• Acceptance Date: Mar 20, 2024
• Online Publication Date: Apr 9, 2024
• Publication Date: Apr 2, 2024
• Deposit Date: Apr 18, 2024
• Publicly Available Date: Apr 19, 2024
• Journal: Cells
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 8
• Article Number: 659
• DOI: https://doi.org/10.3390/cells13080659
• Keywords: skin, ageing, senescence, fibroblast, TGF, collagen, metalloproteinase, fibrosis, extracellular matrix, myofibroblast
• Public URL: https://durham-repository.worktribe.com/output/2388226