Table 1.
Senotherapeutics related to intervertebral disc degeneration.
| Drugs | Mechanism | Outcomes | Reference(s) |
|---|---|---|---|
| Quercetin | Nrf2/NF-kB axis | Influencing SASP factor expression and senescence phenotype in NPCs | [82] |
| Dasatinib and Quercetin | Significantly reduced the senescence markers p16INK4a and p19ARF and the SASP molecules IL-6 and MMP13 | [83] | |
| Curcumin and O-vanillin | Expression of SASP factors was decreased, and matrix synthesis increased | [84] | |
| Dehydrocostus lactone | TBK1/NF-κB and MAPK Signaling | Partially attenuated TNF- α Induced ECM degradation and NP cell senescence | [85] |
| ABT-263/Navitoclax | Bcl-2 family | Significant decrease in intervertebral disc SASP (IL-6 and MMP-13) secretion and diminished ECM degradation | [86] |
| 17-DMAG | Hsp90 | Increased PG levels | [87] |
| RG7112（RO5045337） | p53 | Selectively kill senescent intervertebral disc (IVD) cells through apoptosis and reduce the expression of SASP factors in culture, including IFN- γ, IL-6 and CCL24 | [88] |
| SIRT1 | Regulating autophagy as well as counteracting oxidative stress | [89] | |
| Ganciclovir | Selectively remove p16 Ink4a positive senescent cells | Reduction in the number of senescent cells ameliorates multiple age-associated changes within the disc tissue | [90] |
| Rapamycin | mTOR signaling pathway | Reduce p16 expression and reverse the senescent phenotype of human NPCs | [91] |
| Amiloride | non-specific ASIC inhibitor | Reversed the decline in NP-MSC proliferative capacity and cell cycle arrest together with blocking cells from becoming senescent | [92] |
| Klotho | Inhibitor of Wnt/β-catenin | Reduce age-related SASP protein secretion and maintain NPC phenotype and viability | [93] |
| KU55933 | Inhibitor of ATM | Ameliorates myeloid cell senescence and stromal GAG loss | [94,95] |
| SSK1/JHB75B/NaV-Gal | β-gal-targeted prodrug | Selective killing of SNCs | [[96], [97], [98]] |
Nrf2/NF-kB axis: NF-E2-related factor 2/Nuclear factorkappa B; SASP: Senescence-associated secretory phenotype; NPCs: Nucleus pulposus cells;
PG: Proteoglycan; ABT-263: A Bad-like BH3 mimetic; Bcl-2 family: B cell CLL/lymphoma-2 (BCL-2) and its relatives comprise the BCL-2 family of proteins;
17-DMAG: 17-dimethylaminoethylamino-17-demethoxygeldanamycin, a heat shock protein 90 (Hsp90) inhibitor; RG7112: MDM2 Small-Molecule Antagonist;
SIRT1: Sirtuin 1; IFN- γ: Interferon-γ; CCL24: C–C motif chemokine ligand 24; ASIC: Acid-sensing ion channels; NP-MSC: Nucleus pulposus mesenchymal stem cells;
ATM: The ataxia-telangiectasia mutated; GAG: Glycosaminoglycan; SNCs: Senescent cells