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Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
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DNA-damage-induced type I interferon promotes senescence and inhibits stem cell function.
Qiujing Yu1, Yuliya V Katlinskaya1, Christopher J Carbone1
1Department of Animal Biology, School of Veterinary Medicine, Abramson Family Cancer Research Institute, Basser Research Center for BRCA, Perelman School of Medicine, University of Pennsylvania, 380 S. University Ave, Philadelphia, PA 19104, USA.
Cell Reports
|April 30, 2015
Summary
DNA damage triggers type I interferons (IFNs), which amplify DNA damage responses, promote aging, and inhibit stem cell function. Blocking this interferon pathway delays aging and extends lifespan in mice.
Area of Science:
- Molecular Biology
- Immunology
- Aging Research
Background:
- Type I interferons (IFNs) are induced by DNA-damaging agents, but the underlying mechanisms and biological significance remain unclear.
- DNA damage is implicated in aging and cellular senescence, but the molecular links are not fully elucidated.
Purpose of the Study:
- To investigate the role of interferon signaling in response to DNA damage.
- To explore the connection between DNA damage, interferon production, and aging phenotypes.
Main Methods:
- Investigated the activation of transcription factor IRF3 in response to double-stranded DNA breaks.
- Assessed endogenous IFN-β production in cells and tissues with DNA damage.
- Examined the effects of IFN signaling on DNA damage responses, p53 activation, senescence, and stem cell function.
- Utilized Terc knockout mice to study the impact of IFN pathway inactivation on aging and lifespan.
Main Results:
- Activated IRF3 stimulates cell-autonomous IFN-β expression following double-stranded DNA breaks.
- Accumulating DNA damage leads to endogenous IFN-β production and IFN signaling in vitro and in vivo.
- IFN signaling amplifies DNA damage responses, activates the p53 pathway, promotes senescence, and inhibits stem cell function.
- Inactivating the IFN pathway prevented progeric phenotypes and extended lifespan in Terc knockout mice.
Conclusions:
- DNA-damage-response-induced IFN signaling is a critical mechanism linking DNA damage accumulation to senescence and premature aging.
- Interferon signaling plays a significant role in mediating the aging process in response to cellular stress.
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