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Updated: Nov 12, 2025
Induction and Validation of Cellular Senescence in Primary Human Cells
Published on: June 20, 2018
The struggle of a good friend getting old: cellular senescence in viral responses and therapy
Jaskaren Kohli1, Iris Veenstra1, Marco Demaria1
1European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), Groningen, The Netherlands.
Abstract:
Cellular senescence is a state of stable cell cycle arrest associated with macromolecular alterations and secretion of pro-inflammatory cytokines and molecules. Senescence-associated phenotypes restrict damage propagation and activate immune responses, two essential processes involved in response to viral infections. However, excessive accumulation and persistence of senescent cells can become detrimental and promote pathology and dysfunctions. Various pharmacological interventions, including antiviral therapies, lead to aberrant and premature senescence. Here, we review the molecular mechanisms by which viral infections and antiviral therapy induce senescence. We highlight the importance of these processes in attenuating viral dissemination and damage propagation, but also how prematurely induced senescent cells can promote detrimental adverse effects in humans. We describe which sequelae due to viral infections and treatment can be partly due to excessive and aberrant senescence. Finally, we propose that pharmacological strategies which eliminate senescent cells or suppress their secretory phenotype could mitigate side effects and alleviate the onset of additional morbidities. These strategies can become extremely beneficial in patients recovering from viral infections or undergoing antiviral therapy.
Insights
Cellular senescence, a cell cycle arrest, can be triggered by viral infections and antiviral drugs. While beneficial in limiting viral spread, excessive senescence can cause harm, suggesting senolytic therapies may help mitigate adverse effects.
Area of Science:
- Gerontology
- Virology
- Immunology
Background:
- Cellular senescence is a stable cell cycle arrest state.
- Senescence involves macromolecular changes and secretes pro-inflammatory factors.
- Senescence-associated phenotypes aid in restricting damage and activating immune responses, crucial for viral infections.
Purpose of the Study:
- To review molecular mechanisms of senescence induction by viral infections and antiviral therapy.
- To highlight the dual role of senescence in viral infections: beneficial in limiting spread and detrimental when excessive.
- To discuss sequelae of viral infections and treatments potentially linked to aberrant senescence.
Main Methods:
- Literature review of molecular mechanisms.
- Analysis of the role of senescence in viral infections and antiviral therapy.
- Discussion of potential therapeutic strategies targeting senescent cells.
Main Results:
- Viral infections and antiviral therapies can induce premature or aberrant cellular senescence.
- While senescence can limit viral dissemination and damage, its excessive accumulation is detrimental.
- Prematurely induced senescent cells can lead to adverse effects and pathologies.
Conclusions:
- Pharmacological strategies to eliminate senescent cells or suppress their secretory phenotype may mitigate side effects.
- Targeting senescent cells could alleviate morbidities associated with viral infections and antiviral treatments.
- Senolytics and secretory inhibitors offer potential benefits for patients recovering from viral infections or undergoing antiviral therapy.
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