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Senescence and the SASP: many therapeutic avenues
Jodie Birch1,2, Jesús Gil1,2
1MRC London Institute of Medical Sciences (LMS), London W12 0NN, United Kingdom.
Abstract:
Cellular senescence is a stress response that elicits a permanent cell cycle arrest and triggers profound phenotypic changes such as the production of a bioactive secretome, referred to as the senescence-associated secretory phenotype (SASP). Acute senescence induction protects against cancer and limits fibrosis, but lingering senescent cells drive age-related disorders. Thus, targeting senescent cells to delay aging and limit dysfunction, known as "senotherapy," is gaining momentum. While drugs that selectively kill senescent cells, termed "senolytics" are a major focus, SASP-centered approaches are emerging as alternatives to target senescence-associated diseases. Here, we summarize the regulation and functions of the SASP and highlight the therapeutic potential of SASP modulation as complimentary or an alternative to current senolytic approaches.
Insights
Cellular senescence, a state of irreversible cell cycle arrest, can be beneficial or detrimental. Targeting the senescence-associated secretory phenotype (SASP) offers a novel therapeutic strategy for age-related diseases.
Area of Science:
- Cellular biology
- Aging research
- Molecular medicine
Background:
- Cellular senescence is a stress-induced permanent cell cycle arrest.
- It involves the senescence-associated secretory phenotype (SASP), a bioactive secretome.
- While acute senescence is protective, chronic senescent cells contribute to age-related diseases.
Purpose of the Study:
- To summarize the regulation and functions of the SASP.
- To highlight the therapeutic potential of SASP modulation.
- To explore SASP-centered approaches as alternatives or complements to senolytics.
Main Methods:
- Literature review on cellular senescence.
- Analysis of SASP regulation and functions.
- Evaluation of therapeutic strategies targeting SASP.
Main Results:
- SASP comprises various bioactive factors.
- SASP plays a dual role in health and disease.
- SASP modulation presents a promising therapeutic avenue.
Conclusions:
- SASP modulation is a viable senotherapy strategy.
- Targeting SASP can complement or replace senolytics.
- Further research into SASP-centered therapies is warranted.
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