Senescent-like microglia limit remyelination through the senescence associated secretory phenotype [preprint]
Authors
Gross, Phillip SDuran-Laforet, Violeta
Manavi, Zeeba
Zia, Sameera
Lee, Sung Hyun
Shults, Nataliia
Selva, Sean
Alvarez, Enrique
Plemel, Jason R
Schafer, Dorothy P
Huang, Jeffrey K
Document Type
PreprintPublication Date
2024-05-26
Metadata
Show full item recordAbstract
The capacity to regenerate myelin in the central nervous system (CNS) diminishes with age. This decline is particularly evident in multiple sclerosis (MS), which has been suggested to exhibit features of accelerated biological aging. Whether cellular senescence, a hallmark of aging, contributes to remyelination impairment remains unknown. Here, we show that senescent cells (SCs) accumulate within demyelinated lesions after injury, and their elimination enhances remyelination in young mice but not in aged mice. In young mice, we observed the upregulation of senescence-associated transcripts primarily in microglia after demyelination, followed by their reduction during remyelination. However, in aged mice, senescence-associated factors persisted within lesions, correlating with inefficient remyelination. We found that SC elimination enhanced remyelination in young mice but was ineffective in aged mice. Proteomic analysis of senescence-associated secretory phenotype (SASP) revealed elevated levels of CCL11/Eotaxin-1 in lesions, which was found to inhibit efficient oligodendrocyte maturation. These results suggest therapeutic targeting of SASP components, such as CCL11, may improve remyelination in aging and MS.Source
Gross PS, Laforet VD, Manavi Z, Zia S, Lee SH, Shults N, Selva S, Alvarez E, Plemel JR, Schafer DP, Huang JK. Senescent-like microglia limit remyelination through the senescence associated secretory phenotype. bioRxiv [Preprint]. 2024 May 26:2024.05.23.595605. doi: 10.1101/2024.05.23.595605. PMID: 38826296; PMCID: PMC11142216.DOI
10.1101/2024.05.23.595605Permanent Link to this Item
http://hdl.handle.net/20.500.14038/53641PubMed ID
38826296Notes
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.Rights
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.ae974a485f413a2113503eed53cd6c53
10.1101/2024.05.23.595605