Silencing without clearing: pharmacological modulation of the SASP in aging and disease
4 affiliations
- 1Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czechia
- 2Biomedical Research Centre, University Hospital Hradec Kralove, Hradec Kralove, Czechia
- 3Faculty of Informatics and Management, Center for Basic and Applied Research, University of Hradec Kralove, Hradec Kralove, Czechia
- 4Center of Advanced Innovation Technologies, VSB-Technical University of Ostrava, Ostrava-Poruba, Czechia
Abstract
The global rise in life expectancy has led to an increasing prevalence of age-related diseases, including neurodegenerative disorders, cancer, type 2 diabetes mellitus, and cardiovascular conditions, placing substantial societal and economic burdens on healthcare systems worldwide. A key mechanism underlying both aging and these pathologies is cellular senescence (CS), now recognized as one of the 12 hallmarks of aging. Senescent cells exert their effects largely through the senescence-associated secretory phenotype (SASP), a complex pro-inflammatory secretome that disrupts tissue homeostasis in neighbouring cells and actively promotes disease progression. This review first describes the biology of CS and the SASP in the context of aging and age-related pathologies, with emphasis on key regulatory pathways. We then provide a comprehensive overview of current senomorphic agents, i.e., compounds that modulate the SASP without eliminating senescent cells, covering their mechanisms of action, the signaling pathways they target, and the translational challenges they face. A particular focus is placed on the context-dependent dual role of the SASP. While its proinflammatory components drive tissue damage in chronic disease, SASP factors also contribute to wound healing, immune surveillance, and embryonic development. This duality has important implications for therapeutic design. Although senomorphics hold genuine promise as anti-aging interventions, substantial gaps remain between preclinical observations and clinical applicability. Future research must clarify the functions of individual SASP components, identify robust senescence biomarkers, and develop selective compounds with defined dose-response relationships and acceptable safety profiles.
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BibTeX
@article{fresser2026silencing,
title = {{Silencing without clearing: pharmacological modulation of the SASP in aging and disease}},
author = {Lukas Fresser and Zofia Chrienova and Jan Gebrt and Patrik Oleksak and Kamil Kuca and Eugenie Nepovimova},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1911529},
url = {https://doi.org/10.3389/fphar.2026.1911529},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Silencing without clearing: pharmacological modulation of the SASP in aging and disease
AU - Lukas Fresser
AU - Zofia Chrienova
AU - Jan Gebrt
AU - Patrik Oleksak
AU - Kamil Kuca
AU - Eugenie Nepovimova
PY - 2026
DA - 2026/10/12
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1911529
UR - https://doi.org/10.3389/fphar.2026.1911529
AB - The global rise in life expectancy has led to an increasing prevalence of age-related diseases, including neurodegenerative disorders, cancer, type 2 diabetes mellitus, and cardiovascular conditions, placing substantial societal and economic burdens on healthcare systems worldwide. A key mechanism underlying both aging and these pathologies is cellular senescence (CS), now recognized as one of the 12 hallmarks of aging. Senescent cells exert their effects largely through the senescence-associated secretory phenotype (SASP), a complex pro-inflammatory secretome that disrupts tissue homeostasis in neighbouring cells and actively promotes disease progression. This review first describes the biology of CS and the SASP in the context of aging and age-related pathologies, with emphasis on key regulatory pathways. We then provide a comprehensive overview of current senomorphic agents, i.e., compounds that modulate the SASP without eliminating senescent cells, covering their mechanisms of action, the signaling pathways they target, and the translational challenges they face. A particular focus is placed on the context-dependent dual role of the SASP. While its proinflammatory components drive tissue damage in chronic disease, SASP factors also contribute to wound healing, immune surveillance, and embryonic development. This duality has important implications for therapeutic design. Although senomorphics hold genuine promise as anti-aging interventions, substantial gaps remain between preclinical observations and clinical applicability. Future research must clarify the functions of individual SASP components, identify robust senescence biomarkers, and develop selective compounds with defined dose-response relationships and acceptable safety profiles.
SN - 1663-9812
ER -