Impact of Senescent Cell Subtypes on Tissue Dysfunction and Repair: Importance and Research Questions. (September 2021)

• Record Type: Journal Article
• Authors: Tripathi, Utkarsh; Misra, Avanish; Tchkonia, Tamar; Kirkland, James L.
• Is Part Of: Mechanisms of ageing and development. Volume 198(2021)
• Publication Date: 2021-09
• Subjects: Senolytics -- Cellular senescence -- Deleterious senescent cell subtype -- Helper senescent cell subtype; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2021.111548
• Languages: English
• ISSNs: 0047-6374

Abstract

Highlights: Cellular senescence is a dynamic process and appears to be a heterogenous cell fate. We hypothesize that senescent cells can be of helper (H) or deleterious (D) subtypes. Lowering the burden of the D-subtype below a threshold may alleviate co-morbidities and enhance health-span, while reducing adverse effects from targeting the H-subtype. Abstract: 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.