p21 induces a senescence program and skeletal muscle dysfunction
Recent work has established associations between elevated p21, the accumulation of senescent cells, and skeletal muscle dysfunction in mice and humans. Using a mouse model of p21 overexpression (p21OE), we examined if p21 mechanistically contributes to cellular senescence and pathological features i...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877822002216 |
| _version_ | 1811182384528228352 |
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| author | Davis A. Englund Alyssa Jolliffe Zaira Aversa Xu Zhang Ines Sturmlechner Ayumi E. Sakamoto Julianna D. Zeidler Gina M. Warner Colton McNinch Thomas A. White Eduardo N. Chini Darren J. Baker Jan M. van Deursen Nathan K. LeBrasseur |
| author_facet | Davis A. Englund Alyssa Jolliffe Zaira Aversa Xu Zhang Ines Sturmlechner Ayumi E. Sakamoto Julianna D. Zeidler Gina M. Warner Colton McNinch Thomas A. White Eduardo N. Chini Darren J. Baker Jan M. van Deursen Nathan K. LeBrasseur |
| author_sort | Davis A. Englund |
| collection | DOAJ |
| description | Recent work has established associations between elevated p21, the accumulation of senescent cells, and skeletal muscle dysfunction in mice and humans. Using a mouse model of p21 overexpression (p21OE), we examined if p21 mechanistically contributes to cellular senescence and pathological features in skeletal muscle. We show that p21 induces several core properties of cellular senescence in skeletal muscle, including an altered transcriptome, DNA damage, mitochondrial dysfunction, and the senescence-associated secretory phenotype (SASP). Furthermore, p21OE mice exhibit manifestations of skeletal muscle pathology, such as atrophy, fibrosis, and impaired physical function when compared to age-matched controls. These findings suggest p21 alone is sufficient to drive a cellular senescence program and reveal a novel source of skeletal muscle loss and dysfunction. |
| first_indexed | 2024-04-11T09:31:42Z |
| format | Article |
| id | doaj.art-d4615090d69c464288f4371a6d95f0e6 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-04-11T09:31:42Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-d4615090d69c464288f4371a6d95f0e62022-12-22T04:31:53ZengElsevierMolecular Metabolism2212-87782023-01-0167101652p21 induces a senescence program and skeletal muscle dysfunctionDavis A. Englund0Alyssa Jolliffe1Zaira Aversa2Xu Zhang3Ines Sturmlechner4Ayumi E. Sakamoto5Julianna D. Zeidler6Gina M. Warner7Colton McNinch8Thomas A. White9Eduardo N. Chini10Darren J. Baker11Jan M. van Deursen12Nathan K. LeBrasseur13Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USARobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USARobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USARobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USADepartment of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA; Department of Pediatrics, Molecular Genetics Section, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsRobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USARobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA; Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL, USARobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA; Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL, USADivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USARobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USARobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA; Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL, USA; Paul F. Glenn Center for the Biology of Aging at Mayo Clinic, Rochester, MN, USARobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA; Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA; Paul F. Glenn Center for the Biology of Aging at Mayo Clinic, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USADepartment of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USARobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA; Paul F. Glenn Center for the Biology of Aging at Mayo Clinic, Rochester, MN, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA; Corresponding author. Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.Recent work has established associations between elevated p21, the accumulation of senescent cells, and skeletal muscle dysfunction in mice and humans. Using a mouse model of p21 overexpression (p21OE), we examined if p21 mechanistically contributes to cellular senescence and pathological features in skeletal muscle. We show that p21 induces several core properties of cellular senescence in skeletal muscle, including an altered transcriptome, DNA damage, mitochondrial dysfunction, and the senescence-associated secretory phenotype (SASP). Furthermore, p21OE mice exhibit manifestations of skeletal muscle pathology, such as atrophy, fibrosis, and impaired physical function when compared to age-matched controls. These findings suggest p21 alone is sufficient to drive a cellular senescence program and reveal a novel source of skeletal muscle loss and dysfunction.http://www.sciencedirect.com/science/article/pii/S2212877822002216Cellular senescenceDNA damageSenescence-associated secretory phenotypeAgingSarcopeniaPhysical function |
| spellingShingle | Davis A. Englund Alyssa Jolliffe Zaira Aversa Xu Zhang Ines Sturmlechner Ayumi E. Sakamoto Julianna D. Zeidler Gina M. Warner Colton McNinch Thomas A. White Eduardo N. Chini Darren J. Baker Jan M. van Deursen Nathan K. LeBrasseur p21 induces a senescence program and skeletal muscle dysfunction Molecular Metabolism Cellular senescence DNA damage Senescence-associated secretory phenotype Aging Sarcopenia Physical function |
| title | p21 induces a senescence program and skeletal muscle dysfunction |
| title_full | p21 induces a senescence program and skeletal muscle dysfunction |
| title_fullStr | p21 induces a senescence program and skeletal muscle dysfunction |
| title_full_unstemmed | p21 induces a senescence program and skeletal muscle dysfunction |
| title_short | p21 induces a senescence program and skeletal muscle dysfunction |
| title_sort | p21 induces a senescence program and skeletal muscle dysfunction |
| topic | Cellular senescence DNA damage Senescence-associated secretory phenotype Aging Sarcopenia Physical function |
| url | http://www.sciencedirect.com/science/article/pii/S2212877822002216 |
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