TABLE 2.
Senolytics on anti-aging therapy.
| Senolytics | Targets | Preclinical and clinical research of OA and others |
|---|---|---|
| Dasatinib | Tyrosine kinase | The combination of dasatinib and quercetin reduced age-related bone loss Farr et al. (2017). |
| Improved articular cartilage integrity in post-traumatic OA rats Dai et al. (2020). | ||
| Showed promising effects in clinical trials in idiopathic pulmonary fibrosis patients and diabetic nephropathy patients Hickson et al. (2019); Justice et al. (2019). | ||
| Quercetin | PI3K | As above |
| Fisetin | PI3K/AKT/mTOR; SIRT1; NF-κB | Reduced IL-1β-induced inflammatory response and human chondrocyte ECM degradation; delayed OA progression in mice Zheng et al. (2017). |
| The clinical trial of fisetin for the treatment of OA is recruiting (https://clinicaltrials.gov/ct2/show/NCT04210986). | ||
| Piperlongumin | OXR1 | Protected articular cartilage in OA rats Ye et al. (2020). |
| ABT-737 | BCL-2; BCL-XL; BCL-W | Induced apoptosis of multiple senescent cells Yosef et al. (2016). |
| ABT-263 (Navitoclax) | BCL-2; BCL-XL; BCL-W | Induced apoptosis of senescent chondrocytes isolated human OA articular cartilage and protected articular cartilage in OA rats Yang et al. (2020). |
| A1331852 | BCL-XL | Killed several tumor cells Leverson et al. (2015). |
| A1155463 | BCL-XL | Killed several tumor cells Leverson et al. (2015). |
| ABT-199 (Venetoclax) | BCL-2 | FDA approved for chronic lymphocytic leukemia Cang et al. (2015). |
| UBX0101 | MDM2/p53 | Induced apoptosis of senescent chondrocytes isolated from cartilage of OA patients and reduced erosion of articular cartilage in OA mice Jeon et al. (2017). |
| Reduced joint pain of OA patients in the phase I clinical trial Hsu et al. (2020). | ||
| The phase II clinical trial failed (https://clinicaltrials.gov/ct2/show/NCT04349956). | ||
| FOXO4-DRI | FOXO4/p53 | Eliminated senescent cells restored tissue homeostasis in aged mice Baar et al. (2017). |
| 17-DMAG (Alvespimycin) | HSP90; p21 | Extended the lifespan of Ercc1-/Δ premature aging mouse Fuhrmann-Stroissnigg et al. (2017). |
| Promoted auricular cartilage formation in the mice Bertram et al. (2018). | ||
| Celastrol | HSP90; TP53; mTOR; MAPK1; STAT3; NF-κB | Attenuated inflammatory responses in human OA chondrocytes Ding et al. (2013). |
| Reduced articular cartilage destruction in OA rats Jin et al. (2020). | ||
| Fenofibrate | PPARα | Induced apoptosis of senescent human OA chondrocytes and alleviated joint pain and joint destruction in OA patients Nogueira-Recalde et al. (2019). |
| Gal-encapsulated cytotoxic | SA-β-Gal | Killed senescent cells specifically and reduced off-targets Muñoz-Espín et al. (2018). |
| Gal-encapsulated navitoclax | SA-β-Gal | Killed senescent cells specifically and reduced off-targets González-Gualda et al. (2020). |