Table 1.
Therapeutic drugs targeting of senescence.
| Compound | Model | Dose | Drug target | Comments | References | |
|---|---|---|---|---|---|---|
| Senolytics | Dasatinib and Quercetin | Aged C57BL/6 mice (24–27 months) | Treated with Dasatinib (5 mg/kg/day) and Quercetin (50 mg/kg/day) for 3 consecutive days every 2 weeks | The PI3K/AKT pathway | Eliminate senescent cells, inhibit the inflammation, alleviate physiological dysfunction, and increase survival. Increase 36% higher median post-treatment lifespan of mice. But may have side effects such as pulmonary edema | Xu et al.,22 Justice et al.,6 Hickson et al.31 |
| Fisetin | WT f1 C57BL/6:FVB mice at the age of 85 weeks | 500 mg/kg/day | The PI3K/AKT pathway | Induce apoptosis of senescent cells, reduce inflammation and oxidative stress, extend both median and maximum lifespan of mice (percentage not provided) | Zhu et al.,32 Yousefzadeh et al.33 | |
| 17-DMAG | Ercc1−/Δ mice at the age of 6 weeks | 10 mg/kg three times per week every 3 weeks | The PI3K/AKT pathway | Promote senescent cell apoptosis, reduce the incidence of age-related symptoms | Fuhrmann-Stroissnigg et al.34 | |
| Navitoclax, A1331852, A1155463, and ABT737 | Male C57BL/6J and p16-3MR transgenic mice at the age of 2–3 months | 50 mg/kg/d for 7 days per cycle for two cycles with a 2-week interval between the cycles | BCL family | Promote senescent cell apoptosis, but may have side effects such as thrombocytopenia and neutropenia | Chang et al.,35 Zhu et al.,36 Wilson et al.37 | |
| Panobinostat | A549 and FaDu cell lines | 25 nM | BCL family | As a post-chemotherapy senolytic with the potential to kill persistent senescent cells that accumulate during standard chemotherapy | Samaraweera et al.38 | |
| FOXO4-DRI | XpdTTD/TTD mice, p16::3MR mice and the f1 generation of them. At the age of 115–130 weeks | 5 mg/kg three times per day every other day for 30 days in naturally aged mice | P53-FOXO4 interaction | Restore fitness, fur density, and renal function in aging mice | Baar et al.39 | |
| Catechins | Adult bone marrow-derived human mesenchymal stem cells (hMSCs), 3T3-L1 preadipocytes | 50 or 100 µM | Bax/Bcl-2, Nrf2, and PI3K/AKT/mTOR pathways | Reduce ROS production and prevent oxidative stress-induced cellular senescence, inhibit the SASP and induce senescent cell death | Shin et al.,40 Kumar et al.41 | |
| SASP inhibitor | MitoQ | Male C57BL/6J db/db and db/m mice at the age of 12 weeks | 5 mg/kg, twice weekly for 12 weeks | Mitophagy and the Nrf2/PINK pathway | Reduce oxidative-stress damage and improve mitochondrial function | Braakhuis et al.,42 Rossman et al.,43 Xiao et al.44 |
| SS31 | Male Sprague–Dawley rats of ischemia reperfusion injury (IRI) model | 2 mg/kg administered 30 min before onset of ischemia and at the onset of reperfusion, or 2 mg at 30 min/24 h/48 h after ischemia reperfusion | SIRT1/SIRT3 and the NF-κB pathway | Reduce ROS levels, promote the recovery of ATP, alleviate mitochondrial dysfunction and prevent apoptosis | Birk et al.,45 Lee et al.,46 Cho et al.47 | |
| SKQ1 | The laboratory outbred SHR mice and three strains of inbred mice, that is, 129/sv, BALB/c, and C57Bl/6. | 5 or 50 nmol/kg/day in different groups | antioxidant | Increase the lifespan of rodents (percentage not provided) | Anisimov et al.48 | |
| Melatonin | The primary cortical neurons derived from SD rats | 0.1–1 mM | The Keap1/Nrf2/ARE pathway and SIRT1 | Reduce oxidative stress | Maity et al.,49 Chuang et al.50 | |
| Klotho | Male Spraque–Dawley rats, Tg-Kl mice and Kl+/− mice of ischemia reperfusion injury (IRI) model | 0.01 mg/kg 30 or 60 min after reperfusion; | Wnt/β-catenin pathway | Attenuate renal damage and promote recovery | Hu et al.51 | |
| ICG001 | HKC-8 cells lines or HK-2 cells lines | 5 μM | Wnt/β-catenin pathway | Attenuate renal damage and inhibit senescence | Miao et al.,52 Luo et al.53 | |
| Ruxolitinib | Zmpste24 deficient mice | Administered in subcutaneously implanted slow-release pellets | The JAK pathway | Inhibit SASP and reduce inflammation and reduce premature aging phenotypes | Xu et al.,54 Griveau et al.55 | |
| Ganoderma lucidum | Caenorhabditis elegans, male BALB/c mice at the age of 19–21 months | 100 ppm in Caenorhabditis elegans. 50 and 250 mg/kg once daily for 15 days in aged mice. | The Nrf2, mTOR, and MAPK pathways | Promote health, increase vitality, reduce ROS level, exhibit anti-inflammatory and immunomodulatory effects. Extend the lifespan of C. elegans by about 20–30% | Yun et al.,56 Sudheesh et al.,57 Bhardwaj et al.,58 Chuang et al.59 | |
| Equol | Male and OVX female SD rats | 250 ppm for 2 weeks prior to 90-min transient middle cerebral artery occlusion followed by reperfusion | The Nrf2/ARE pathway | Reduce antioxidative stress | Sekikawa et al.,60 Jing et al.,61 Ma et al.62 | |
| Nutrient signalling regulator | Rapamycin | Genetically heterogeneous mice at the age of 9 months, 3xTg-AD mice | 2.24 mg/kg/day in the study of Miller et al. At doses of 4.7, 14, or 42 ppm from age of 9 months and euthanized at 22 months of age in the study of Wilkinson et al. 2.24 mg/kg/day in 3xTg-AD mice for 10 weeks. | The mTOR signaling pathway | Delay many age-related pathological processes, improve cognitive function and retard multiple aspects of aging in mice. Extend median survival by an average of 10% in males and 18% in females in mice. But may have side effects such as immunosuppression, thrombocytopenia and so on | Wilkinson et al.,63 Caccamo et al.,64 Harrison et al.,65 Johnson et al.,66 Miller et al.67 |
| Metformin | Male C57BL/6 mice at the age of one year | 0.1% w/w in diet (~10.6 mg/kg/day) | The AMPK and NF-κB pathways | Delay the development of age-related diseases, extend 5.83% of mean lifespan of mice. | Bannister et al.,68 Martin-Montalvo et al.,69 Ng et al.70 | |
| Resveratrol | Diabetic rat model with coronary heart disease, Saccharomyces cerevisiae | 10 mg/kg/day for 8 weeks in rat model. 2–5 mM in Saccharomyces cerevisiae. | The SIRT1/NF-κB pathway | Extend the lifespans of S. cerevisiae by 70% in S. cerevisiae, prevent age-related diseases | Howitz et al.,71 Huo et al.,72 Szkudelski et al.73 | |
| Lycium barbarum | ARPE-19 cell exposed to ultraviolet B (UVB). C57BL/6J mice with a high-fat diet | Treated with L. barbarum extracts (from 0 to 200 μg/mL) for 2 h in ARPE-19 cell. 100 mg/kg LBP-supplemented diet for 24 weeks in mice. | The AMPK and Nrf2 pathways | Reduce ROS level, alleviate cellular oxidative stress, inflammation and apoptosis | Hsieh et al.,74 Xing et al.,75 Yang et al.76 | |
| Curcumin | Caenorhabditis elegans. Ten-week-old male Wistar rats with endurance training. | 20 mM in Caenorhabditis elegans. 50 or 100 mg/kg /day for 28 days in rats. | The AMPK, sirtuin, PI3K/AKT, NF-κB, and Nrf2 pathways | Reduce ROS level, have anti-apoptotic and anti-inflammatory effects. Increase in 39.3% in mean lifespan and 21.4% in maximum lifespan of C. elegans. | Liao et al.,77 Lee et al.,78 Pluta et al.,79 Ray et al.80 | |
| Spermidine | Wild-type (MAP1S+/+) and MAP1S knockout mice (MAP1S−/−). High glucose -treated HT-22 cells | 3 mM administered orally via drinking water in mice. 0.25 or 1 μM in HT-22 cells. |
The autophagy | Inhibit the oxidative stress, prevent high glucose-induced neurotoxicity and senescence, extend the lifespan. Increase 25% of the median survival time of mice. | Zhu et al.,81 Yue et al.82 |
ROS, reative oxygen species; SASP, senescence-associated secretory phenotype.