Cargando…
Senolytic elimination of senescent macrophages restores muscle stem cell function in severely dystrophic muscle
The aging of the immune system, or immunosenescence, was recently verified to have a causal role in driving the aging of solid organs, while the senolytic elimination of senescent immune cells was found to effectively delay systemic aging. Our recent study also showed that immune cells in severely d...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9596208/ https://www.ncbi.nlm.nih.gov/pubmed/36084954 http://dx.doi.org/10.18632/aging.204275 |
_version_ | 1784815819200397312 |
---|---|
author | Liu, Lei Yue, Xianlin Sun, Zewei Hambright, William S. Feng, Qi Cui, Yan Huard, Johnny Robbins, Paul D. Wang, Zhihui Mu, Xiaodong |
author_facet | Liu, Lei Yue, Xianlin Sun, Zewei Hambright, William S. Feng, Qi Cui, Yan Huard, Johnny Robbins, Paul D. Wang, Zhihui Mu, Xiaodong |
author_sort | Liu, Lei |
collection | PubMed |
description | The aging of the immune system, or immunosenescence, was recently verified to have a causal role in driving the aging of solid organs, while the senolytic elimination of senescent immune cells was found to effectively delay systemic aging. Our recent study also showed that immune cells in severely dystrophic muscles develop senescence-like phenotypes, including the increased expression of senescence-associated secretory phenotype (SASP) factors and senescence markers. Here we further investigated whether the specific clearance of senescent immune cells in dystrophic muscle may effectively improve the function of muscle stem cells and the phenotypes of dystrophic muscle. We observed increased percentage of senescent cells in macrophages from mdx/utro(−/−) mice (a murine model for muscular dystrophy disease, dystrophin−/−; utrophin−/−), while the treatment of mdx/utro(−/−) macrophages with senolytic drug fisetin resulted in reduced number of senescent cells. We administrated fisetin to mdx/utro(−/−) mice for 4 weeks, and observed obviously reduced number of senescent immune cells, restored number of muscle cells, and improve muscle phenotypes. In conclusion, our results reveal that senescent immune cells, such as macrophages, are greatly involved in the development of muscle dystrophy by impacting the function of muscle stem cells, and the senolytic ablation of these senescent cells with fisetin can be an effective therapeutic strategy for improving function of muscle stem cells and phenotypes of dystrophic muscles. |
format | Online Article Text |
id | pubmed-9596208 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-95962082022-10-27 Senolytic elimination of senescent macrophages restores muscle stem cell function in severely dystrophic muscle Liu, Lei Yue, Xianlin Sun, Zewei Hambright, William S. Feng, Qi Cui, Yan Huard, Johnny Robbins, Paul D. Wang, Zhihui Mu, Xiaodong Aging (Albany NY) Research Paper The aging of the immune system, or immunosenescence, was recently verified to have a causal role in driving the aging of solid organs, while the senolytic elimination of senescent immune cells was found to effectively delay systemic aging. Our recent study also showed that immune cells in severely dystrophic muscles develop senescence-like phenotypes, including the increased expression of senescence-associated secretory phenotype (SASP) factors and senescence markers. Here we further investigated whether the specific clearance of senescent immune cells in dystrophic muscle may effectively improve the function of muscle stem cells and the phenotypes of dystrophic muscle. We observed increased percentage of senescent cells in macrophages from mdx/utro(−/−) mice (a murine model for muscular dystrophy disease, dystrophin−/−; utrophin−/−), while the treatment of mdx/utro(−/−) macrophages with senolytic drug fisetin resulted in reduced number of senescent cells. We administrated fisetin to mdx/utro(−/−) mice for 4 weeks, and observed obviously reduced number of senescent immune cells, restored number of muscle cells, and improve muscle phenotypes. In conclusion, our results reveal that senescent immune cells, such as macrophages, are greatly involved in the development of muscle dystrophy by impacting the function of muscle stem cells, and the senolytic ablation of these senescent cells with fisetin can be an effective therapeutic strategy for improving function of muscle stem cells and phenotypes of dystrophic muscles. Impact Journals 2022-09-08 /pmc/articles/PMC9596208/ /pubmed/36084954 http://dx.doi.org/10.18632/aging.204275 Text en Copyright: © 2022 Liu et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Liu, Lei Yue, Xianlin Sun, Zewei Hambright, William S. Feng, Qi Cui, Yan Huard, Johnny Robbins, Paul D. Wang, Zhihui Mu, Xiaodong Senolytic elimination of senescent macrophages restores muscle stem cell function in severely dystrophic muscle |
title | Senolytic elimination of senescent macrophages restores muscle stem cell function in severely dystrophic muscle |
title_full | Senolytic elimination of senescent macrophages restores muscle stem cell function in severely dystrophic muscle |
title_fullStr | Senolytic elimination of senescent macrophages restores muscle stem cell function in severely dystrophic muscle |
title_full_unstemmed | Senolytic elimination of senescent macrophages restores muscle stem cell function in severely dystrophic muscle |
title_short | Senolytic elimination of senescent macrophages restores muscle stem cell function in severely dystrophic muscle |
title_sort | senolytic elimination of senescent macrophages restores muscle stem cell function in severely dystrophic muscle |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9596208/ https://www.ncbi.nlm.nih.gov/pubmed/36084954 http://dx.doi.org/10.18632/aging.204275 |
work_keys_str_mv | AT liulei senolyticeliminationofsenescentmacrophagesrestoresmusclestemcellfunctioninseverelydystrophicmuscle AT yuexianlin senolyticeliminationofsenescentmacrophagesrestoresmusclestemcellfunctioninseverelydystrophicmuscle AT sunzewei senolyticeliminationofsenescentmacrophagesrestoresmusclestemcellfunctioninseverelydystrophicmuscle AT hambrightwilliams senolyticeliminationofsenescentmacrophagesrestoresmusclestemcellfunctioninseverelydystrophicmuscle AT fengqi senolyticeliminationofsenescentmacrophagesrestoresmusclestemcellfunctioninseverelydystrophicmuscle AT cuiyan senolyticeliminationofsenescentmacrophagesrestoresmusclestemcellfunctioninseverelydystrophicmuscle AT huardjohnny senolyticeliminationofsenescentmacrophagesrestoresmusclestemcellfunctioninseverelydystrophicmuscle AT robbinspauld senolyticeliminationofsenescentmacrophagesrestoresmusclestemcellfunctioninseverelydystrophicmuscle AT wangzhihui senolyticeliminationofsenescentmacrophagesrestoresmusclestemcellfunctioninseverelydystrophicmuscle AT muxiaodong senolyticeliminationofsenescentmacrophagesrestoresmusclestemcellfunctioninseverelydystrophicmuscle |