Senotherapeutics to Counteract Senescent Cells Are Prominent Topics in the Context of Anti-Ageing Strategies
Abstract
:1. Introduction
2. Cell Senescence
2.1. SCs as Positive Effectors
2.2. Role in Tumorigenesis
2.3. SCs Molecular Biomarkers
2.4. Senescence Cell Antiapoptotic Pathways (SCAPs)
2.5. SASPs
3. Senotherapeutic Drugs
3.1. Senolytics
3.2. Senomorphics
3.3. Immune Therapies
3.3.1. Immune Cell Response
3.3.2. CAR-T Cells
3.3.3. NK and CAR NK Cells
3.3.4. Monoclonal Antibodies
4. Nutritional Senotherapeutics
5. Nanoparticles
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Senolytic Compounds | ||
---|---|---|
Actions: induce apoptosis of SCs disabling SCAPs or other molecular signals involved in SCs rising | Examples: HSP90, dasatinib, quercetin, fisetin, curcumin | [60,61] |
Positive effects | Reduce the amount of SCs and tissue-related dysfunction | |
Negative effects | Reduction in positive effects of SCs (anticancer, antifibrotic, embryogenetic) | |
Senomorphic Compounds | ||
Actions: inhibit senescence markers (i.e., NF-κB, IKK, JAK) and SASPs | Examples: rapamycin | [60] |
Positive effects | Low impact on positive aspects of SCs; reduction in the paracrine role of SASPs on neighboured cells | |
Negative effects | The necessity of continuous administration; the possibility of side effects | |
Immuno-Based Approaches | ||
Actions: improve immune response toward SCs | Examples: CAR-T cells, NK cells, monoclonal antibodies | [25,62,63,64] |
Positive effects | Targeting specifically SCs; impact directly or indirectly on SCs, without affecting their positive actions | |
Negative effects | It is necessary to know specific markers and act in specific sites to avoid side effects |
Nutritional Senotherapeutic | Effects | References |
---|---|---|
Senomorphics | ||
Resveratrol | Inhibits NF-κB and activates Nrf-2; increases OXPHOS and SIRT1 activation; acts on FOXO and IGF pathway | [61,91] |
Genistein | Regulation of FOXO3 | |
Isoflavone | Modulation of apoptosis pathways | |
Kaempferol | Acts on inhibition of NF-κB through IRAK1/IKB-α | |
Apigenin | Acts on inhibition of NF-κB through IL-1rα modulation acting on IRAK1/p38MAPK | |
EGCG | Inhibition of AMPK activation through the modulation of AKT/PI3k/mTOR signalling pathway. Inhibition of ROS, SASPs, NF-κB, and COX | |
Fisetin | Antioxidant and anti-inflammatory action through modulation of NF-κB and Nrf-2 | |
Curcumin | Anti-inflammatory activity on NF-κB and antioxidative effects on Nrf-2. | |
Piperlongumine | Antioxidant activity inhibiting ROS production |
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Calabrò, A.; Accardi, G.; Aiello, A.; Caruso, C.; Galimberti, D.; Candore, G. Senotherapeutics to Counteract Senescent Cells Are Prominent Topics in the Context of Anti-Ageing Strategies. Int. J. Mol. Sci. 2024, 25, 1792. https://doi.org/10.3390/ijms25031792
Calabrò A, Accardi G, Aiello A, Caruso C, Galimberti D, Candore G. Senotherapeutics to Counteract Senescent Cells Are Prominent Topics in the Context of Anti-Ageing Strategies. International Journal of Molecular Sciences. 2024; 25(3):1792. https://doi.org/10.3390/ijms25031792
Chicago/Turabian StyleCalabrò, Anna, Giulia Accardi, Anna Aiello, Calogero Caruso, Damiano Galimberti, and Giuseppina Candore. 2024. "Senotherapeutics to Counteract Senescent Cells Are Prominent Topics in the Context of Anti-Ageing Strategies" International Journal of Molecular Sciences 25, no. 3: 1792. https://doi.org/10.3390/ijms25031792
APA StyleCalabrò, A., Accardi, G., Aiello, A., Caruso, C., Galimberti, D., & Candore, G. (2024). Senotherapeutics to Counteract Senescent Cells Are Prominent Topics in the Context of Anti-Ageing Strategies. International Journal of Molecular Sciences, 25(3), 1792. https://doi.org/10.3390/ijms25031792