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Cellular senescence in development, regeneration and disease
Abstract
Cellular senescence is a state comprising an essentially irreversible proliferative arrest combined with phenotypic changes and pronounced secretory activity. Although senescence has long been linked with aging, recent studies have uncovered functional roles for senescence in embryonic development, regeneration and reprogramming, and have helped to advance our understanding of this process as a highly coordinated and programmed cellular state. In this Primer article, we summarize some of the key findings in the field and attempt to explain them in a simple model that reconciles the normal and pathological roles for senescence. We discuss how a primary role of cellular senescence is to contribute to normal development, cell plasticity and tissue repair, as a dynamic and tightly regulated cellular program. However, when this process is perturbed, the beneficial effects turn detrimental and can contribute to disease and aging.
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“Of note, senescence also plays a role during embryogenesis in the programmed elimination of specific cells and structures 189 .”
From Hallmarks of aging: An expanding universe (2023) · cites this paper as [189]
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BackgroundClearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · cited 1×
“In recent years, perhaps the most conclusive data linking senescence with organismal aging has come from the use of senescence ‘deletor’ mouse models, in which cells expressing p16INK4A are selectively targeted for elimination (Baker et al., 2016, 2011).”
BackgroundNaturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,876
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Senolytics improve physical function and increase lifespan in old age
Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., Inman, C. L., Ogrodnik, M. B., Hachfeld, C. M., Fraser, D. G., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0092-9 · Cited by 2,287
Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
Narita, M., Nuñez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., & Lowe, S. W. (2003) · Cell · doi:10.1016/s0092-8674(03)00401-x · Cited by 2,278
A complex secretory program orchestrated by the inflammasome controls paracrine senescence
Acosta, J. C., Banito, A., Wuestefeld, T., Georgilis, A., Janich, P., Morton, J. P., Athineos, D., Kang, T.-W., Lasitschka, F., Andrulis, M., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2784 · Cited by 2,278 · cited 3×
“In addition, an accumulated SASP and tissue inflammation in aged tissue likely increases the induction of senescence, and spreads the response (Acosta et al., 2013; Xu et al., 2018), and a decline in phagocytosis during aging might also contribute to impaired removal of senescent cells (Li, 2013).”
BackgroundPersistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232
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Metadata
- Authors
- Rhinn, M., Ritschka, B., & Keyes, W. M.
- Affiliations
- Department of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 1 Rue Laurent Fries, 67404, Illkirch, France
- ORCID
- Keyes, William M.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2019-10-01
- Volume
- 146
- Issue
- 20
- ISSN
- 1477-9129
- 0950-1991
- Cited by
- 279
- References
- 68
- Language
- en
- Funders
- Fondation pour la Recherche Médicale (AJE20160635985)
- Fondation ARC pour la Recherche sur le Cancer (PJA20181208104)
- Université de Strasbourg (IDEX2017)
- La Fondation Schlumberger pour l'Education et la Recherche (FSER 19)
- Agence Nationale de la Recherche (ANR-10-LABX-0030-INRT, ANR-10-IDEX-0002-02)
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