Senomorphics

Definition

Senomorphics are compounds studied for their ability to alter the behaviour of senescent cells, especially their inflammatory and tissue-remodelling signals, without necessarily killing those cells. In practice, the term usually refers to attempts to dampen features such as the senescence-associated secretory phenotype, or SASP, rather than to remove senescent cells outright. [1] [2] [3]

Why It Matters in Ageing Research

Senescent cells can influence nearby tissue through cytokines, growth factors, proteases, and other secreted signals, so some researchers are interested in modifying that phenotype even when cell clearance is incomplete or undesirable. This makes senomorphic strategies conceptually different from approaches that aim to eliminate senescent cells, because the target is the cells' harmful signalling profile rather than the cells themselves. [1] [3] [4]

Common Confusion

• Senomorphics are not the same as senolytics: senolytics are intended to selectively remove senescent cells, whereas senomorphics aim to modify their phenotype. [3] [4]
• The term overlaps with "senostatics" in parts of the literature, and authors do not always use the two labels in exactly the same way. [4] [5]
• A reduction in SASP markers in cell or animal studies does not by itself show broad or durable effects on human ageing outcomes. [3] [5] [6]

Related Reading

• Cellular Senescence
• The SASP Explained
• Immune Clearance of Senescent Cells
• Senescence vs Apoptosis

References

1. Coppé, J. P., et al. (2010). The senescence-associated secretory phenotype: The dark side of tumor suppression. https://www.annualreviews.org/doi/10.1146/annurev-pathol-121808-102144
2. Muñoz-Espín, D., & Serrano, M. (2014). Cellular senescence: From physiology to pathology. https://www.nature.com/articles/nrm3823
3. Kirkland, J. L., & Tchkonia, T. (2020). Senolytic drugs: From discovery to translation. https://onlinelibrary.wiley.com/doi/10.1111/joim.13056
4. Short, S., Fielder, E., Miwa, S., & von Zglinicki, T. (2019). Senolytics and senostatics as adjuvant tumour therapy. https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(19)30024-8/fulltext
5. Calcinotto, A., Kohli, J., Zagato, E., Pellegrini, L., Demaria, M., & Alimonti, A. (2019). Cellular senescence: Aging, cancer, and injury. https://journals.physiology.org/doi/full/10.1152/physrev.00020.2018
6. Gasek, N. S., Kuchel, G. A., Kirkland, J. L., & Xu, M. (2021). Strategies for targeting senescent cells in human disease. https://www.nature.com/articles/s41591-021-01521-0