4.5 Article

Impact of Senescent Cell Subtypes on Tissue Dysfunction and Repair: Importance and Research Questions

Journal

MECHANISMS OF AGEING AND DEVELOPMENT
Volume 198, Issue -, Pages -

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2021.111548

Keywords

Senolytics; Cellular senescence; Deleterious senescent cell subtype; Helper senescent cell subtype

Funding

  1. National Institutes of Health [R37 AG13925, R33 AG61456, R01 AG072301, R01 AG61414, P01 AG62413, UH3 AG56933]
  2. Noaber Foundation
  3. Connor Fund

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Cellular senescence is a dynamic process with diverse functional characteristics that can be influenced by various factors. Understanding the background information about senescent cells is crucial for identifying rational therapeutic strategies.
Cellular senescence, first observed and defined through cell culture studies, is a cell fate associated with essentially permanent cell cycle arrest and that can be triggered by a variety of inducers. Emerging evidence suggests senescence is a dynamic process with diverse functional characteristics. Depending on the tissue, type of inducer, and time since induction, senescent cells can promote tissue repair and re-modeling, prevent tumor development, or contribute to age-related disorders and chronic diseases, including cancers. Senescent cell characteristics appear to depend on multiple factors and be influenced by the milieu and other senescent cells locally and at a distance. We review diverse phenotypes of senescent cells originating from different cell types, senescence inducers over time since induction of senescence, and across conditions and diseases. This background is essential to inform further understanding about senescent cell subtypes and will point towards rational senescence-modulating strategies for achieving therapeutic benefit.

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