The senescence-associated secretory phenotype and its physiological and pathological implications
Boshi Wang1, Jin Han2, Jennifer H Elisseeff2
1European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), University of Groningen (RUG), Groningen, Netherlands.
Abstract:
Cellular senescence is a state of terminal growth arrest associated with the upregulation of different cell cycle inhibitors, mainly p16 and p21, structural and metabolic alterations, chronic DNA damage responses, and a hypersecretory state known as the senescence-associated secretory phenotype (SASP). The SASP is the major mediator of the paracrine effects of senescent cells in their tissue microenvironment and of various local and systemic biological functions. In this Review, we discuss the composition, dynamics and heterogeneity of the SASP as well as the mechanisms underlying its induction and regulation. We describe the various biological properties of the SASP, its beneficial and detrimental effects in different physiological and pathological settings, and its impact on overall health span. Finally, we discuss the use of the SASP as a biomarker and of SASP inhibitors as senomorphic interventions to treat cancer and other age-related conditions.
Insights
Cellular senescence, marked by growth arrest and a secretory phenotype (SASP), influences tissue microenvironments. Understanding SASP
Area of Science:
- Cellular biology
- Aging research
- Molecular medicine
Background:
- Cellular senescence is a key aging process.
- It involves growth arrest and the senescence-associated secretory phenotype (SASP).
- SASP mediates paracrine signaling and biological functions.
Purpose of the Study:
- To review the composition, dynamics, and regulation of SASP.
- To explore SASP's biological properties and effects.
- To discuss SASP as a biomarker and therapeutic target.
Main Methods:
- Literature review of cellular senescence and SASP.
- Analysis of SASP induction, regulation, and function.
- Discussion of SASP's role in healthspan and disease.
Main Results:
- SASP is heterogeneous and dynamic, with diverse biological effects.
- SASP contributes to both beneficial and detrimental outcomes in aging and disease.
- SASP modulation offers potential therapeutic strategies.
Conclusions:
- SASP is a critical mediator of senescence.
- Targeting SASP may offer senomorphic interventions for age-related conditions.
- Further research into SASP is crucial for understanding aging and disease.
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