Senotherapy
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Senotherapeutics
)Senotherapy is an early-stage basic research field for development of possible therapeutic agents and strategies to specifically target cellular senescence,[1] an altered cell state associated with ageing and age-related diseases. The name derives from intent of the proposed anti-aging drug to halt "senescence".[1] As of 2019, much of the research remains preliminary and there are no drugs approved for this purpose.
Types
Senotherapeutics include:
- Geroprotectors – agents/strategies which prevent or reverse the senescent state by preventing triggers of cellular senescence, such as DNA damage,[2][3][4] oxidative stress,[5] proteotoxic stress,[6] telomere shortening [7] (i.e. telomerase activators).
- SASP inhibitors – agents interfering with pro-inflammatory senescence-associated secretory phenotype (SASP)[8][9] production, including:
- Glucocorticoids as potent suppressors of selected components of the SASP[10]
- Statins such as simvastatin, that can reduce the expression of pro-inflammatory cytokines (IL-6, IL-8, and MCP-1)[11]
- JAK1/2 inhibitors such as ruxolitinib[12][13]
- NF-κB and p38 inhibitors
- IL-1αblockers
- Mitochondrial depleters in the case of impaired mitophagy[14]
- antibodies and antibody-mediated drug delivery medications. Unlike SASP inhibitors, senolytics can be effective by intermittent rather than continuous application.[18]
- Senomorphics – small molecules that suppress senescent phenotypes without cell killing[19]
- Gene therapy strategies – edit the genes of the cells of an organism in order to increase their resistance to aging, senile diseases and to prolong the life of the organism[3][20]
See also
References
- ^ PMID 26646499.
- PMID 26679354.
- ^ PMID 26299964.
- ^ Wahlestedt, M., Pronk, C. J., & Bryder, D. (2015). Concise Review: Hematopoietic Stem Cell Aging and the Prospects for Rejuvenation. Stem cells translational medicine, 4(2), 186-194.
- S2CID 3126330.
- PMID 25615820.
- PMID 26785477.
- PMID 26129674.
- PMID 19218920.
- PMID 22404905.
- PMID 26658759.
- PMID 26578790.
- PMID 26687007.
- PMID 26848154.
60% of the SASP genes which are significantly different between proliferating and senescent were reversed upon mitochondrial depletion, whereas only 5% were exacerbated
- PMID 26711051.
- PMID 25754370.
- S2CID 173993854.
- PMID 32161396.
- PMID 28871086.
- PMID 25619689.
Further reading
- Kirkland JL, Tchkonia T (2016). "The Way Forward: Translation". Advances in Geroscience. Springer International Publishing. pp. 593–622. ISBN 978-3-319-23245-4.
- Soto-Gamez A, Demaria M (May 2017). "Therapeutic interventions for aging: the case of cellular senescence". Drug Discovery Today. 22 (5): 786–795. PMID 28111332.
- Niedernhofer LJ, Robbins PD (May 2018). "Senotherapeutics for healthy ageing". Nature Reviews. Drug Discovery. 17 (5): 377. PMID 29651106.
- Liu JK (May 2022). "Antiaging agents: safe interventions to slow aging and healthy life span extension". Natural Products and Bioprospecting. 12 (1): 18. PMID 35534591.
- Zhang L, Pitcher LE, Prahalad V, Niedernhofer LJ, Robbins PD (January 2022). "Targeting cellular senescence with senotherapeutics: senolytics and senomorphics". The FEBS Journal. 290 (5): 1362–1383. S2CID 245900209.