Recent Advances in Pharmacology of Senotherapeutics: A Review

Cellular senescence, a hallmark of ageing, is characterised by irreversible proliferative arrest and the secretion of inflammatory mediators that influence tissue microenvironments. While senescence is protective in development, wound healing, and tumour suppression, the chronic accumulation of senescent cells accelerates inflammation, fibrosis, and organ dysfunction. Senotherapeutics, a novel pharmacological class that encompasses Senolytics and Senomorphics, aims to selectively eliminate senescent cells or suppress their harmful secretory activity. This review, based on seminar discussions and recent literature, outlines the mechanisms of senescence, associated biomarkers, links to chronic diseases, and current advances in Senotherapeutic strategies. Preclinical evidence and early clinical studies suggest their potential to extend health span in humans and animals.

Ageing, Cellular senescence, SASP, Senolytics

1. Alqahtani, S., Alameen, A. A., Alshammari, F. D., Aljohani, N. J., & Alqahtani, M. S. (2025). Senescence-associated secretory phenotype modulation for cellular rejuvenation and tissue restoration. Cells, 14(8), 608. [Google Scholar] [Crossref]

2. Aratani, S., & Nakanishi, M. (2023). Recent advances in senolysis for age-related diseases. Frontiers in Aging, 4, 1–12. [Google Scholar] [Crossref]

3. Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011). Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature, 479(7372), 232–236. [Google Scholar] [Crossref]

4. Guelfi, G., Ferracini, R., Marengo, B., Fato, R., & Picco, F. (2024). Dog aging: A comprehensive review of molecular mechanisms and related pathways. Cells, 13(24), 2101. [Google Scholar] [Crossref]

5. Han, Z., Zhang, H., Tao, Z., & Wang, Y. (2024). Cross-talk of inflammation and cellular senescence. Cell Death Discovery, 10, 49 [Google Scholar] [Crossref]

6. Justice, J. N., et al. (2019). Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label pilot study. EBioMedicine, 40, 554–563. [Google Scholar] [Crossref]

7. Lelarge, V., Bouchard, B., Poirier, M., & Després, J. P. (2024). Senolytics: From pharmacological inhibitors to emerging therapeutic strategies. NPJ Aging and Mechanisms of Disease, 10, 7. [Google Scholar] [Crossref]

8. López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194–1217. [Google Scholar] [Crossref]

9. Matsubayashi, S., Fujita, Y., & Yamamoto, M. (2023). Drugs against metabolic diseases as potential senotherapeutics. Frontiers in Endocrinology, 14, 1149337. [Google Scholar] [Crossref]

10. Muthamil, S., Nirmal, N., & Senthilkumar, K. (2024). Biomarkers of cellular senescence and aging: Current state and future directions. Advanced Biology, 8(1), e2300109. [Google Scholar] [Crossref]

11. Ogrodnik, M., Zhu, Y., Langhi Prata, L. G. P., Tchkonia, T., & Kirkland, J. L. (2024). Guidelines for minimal information on cellular senescence experimentation in vivo (MICSE). Cell, 187(2), 340–356. [Google Scholar] [Crossref]

12. Raffaele, M., & Vinciguerra, M. (2022). The costs and benefits of senotherapeutics for human health. The Lancet Healthy Longevity, 3(1), e67–e77. [Google Scholar] [Crossref]

13. Simon, K. E., Reilly, S., Matheson, A., & Kaeberlein, M. (2024). A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD⁺ precursor combination. Scientific Reports, 14, 1122. [Google Scholar] [Crossref]

14. The Lancet Healthy Longevity. (2022). Pharmacological interventions targeting cellular senescence. The Lancet Healthy Longevity, 3(2), 91–93. [Google Scholar] [Crossref]

15. Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., et al. (2018). Senolytics improve physical function and increase lifespan in old age. Nature Medicine, 24(8), 1246–1256. [Google Scholar] [Crossref]

16. Zhang, L., Pitcher, L. E., Yousefzadeh, M. J., Niedernhofer, L. J., & Robbins, P. D. (2023). Targeting cellular senescence with senotherapeutics. The FEBS Journal, 290(3), 636–657. [Google Scholar] [Crossref]

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