Table 3.
In vivo effect of potential senolytic therapy.
| Group | Drug | Target | Model | Result | Reference |
|---|---|---|---|---|---|
| BH3 mimetics | Navitoclax (ABT-263) | BCL-2, BCL-XL, BCL-W inhibitor | -Body radiation -Normal aging |
-Reduced lung fibrosis -Improved lung tissue elasticity -Improved hematopoietic parameters -Decreased SASP factors |
(Chang et al., 2016; Mikawa et al., 2018) |
| Induced emphysema (porcine pancreatic elastase) | -Improved lung tissue elasticity | ||||
| ABT-737 | BCL-2, BCL-XL, BCL-W inhibitor | -Body radiation -p14ARF-induced senescence |
-Decreased cellular senescence in lungs and skin | (Yosef et al., 2016) | |
| FOXO4 inhibitor | FOXO4-DRI | FOXO4-p53 interaction inhibition | -Doxorubicin -Normal aging -Premature aging model |
-Decreased doxorubicin-induced body weight and liver toxicity -Improved fur density and responsiveness -Improved kidney function |
(Baar et al., 2017) |
| UBX0101 | UBX0101 | MDM2-p53 pathway | -Post-traumatic osteoarthritis (ACLT transection) | -Reduced pain -Decreased cartilage erosion/thinning -Decreased SASP factors |
(Jeon et al., 2017) |
| Flavenoids-TKI combination | Quercetin and Dasatinib | BCL-2 pathway inhibitor (proteasome activator) PI3K and serpine inhibitor Tyrosine kinase inhibitor (EFNB-dependent suppression of apoptosis) |
-Natural aging -Single leg radiation -Premature aging model -Atherosclerosis model -Liver steatosis model -Transplant of senescent adipocytes -Pulmonary fibrosis (bleomycin induced) |
-Decreased osteoclast numbers -Improved left ventricular ejection fraction -Increased exercise time, distance, and total work to exhaustion -Decreased age-related symptoms -Reduced intimal plaque calcification -Improved vascular relaxation -Reduced hepatic fat deposition -Attenuated decrease of physical function -Attenuated weight reduction -Attenuated lung compliance -Increased distance until exhaustion |
(Zhu et al., 2015; Roos et al., 2016; Farr et al., 2017; Ogrodnik et al., 2017; Schafer et al., 2017; Xu et al., 2018) |
| Flavenoids | Fisetin | (hydrophobic groove of) BCL-2 | -Natural aging -Premature aging model |
-Extension of median and maximal lifespan -Reduced senescent mesenchymal stem/progenitor cells -Reduced SASP factors |
(Yousefzadeh et al., 2018) |
| HSP90 inhibitors | 17-DMAG | -Inhibits the molecular chaperone HSP90, leading to AKT and ERK destabilization | -Premature aging model | -Reduced age-related symptoms and increased body condition -Reduced kidney p16Ink4a expression |
(Fuhrmann-Stroissnigg et al., 2017) |