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Senotherapy
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Senotherapy is an early-stage basic research field for development of possible therapeutic agents and strategies to specifically target cellular senescence, 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". 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,oxidative stress,proteotoxic stress,telomere shortening (i.e. telomerase activators).
- SASP inhibitors – agents interfering with pro-inflammatory senescence-associated secretory phenotype (SASP) production, including:
- Glucocorticoids as potent suppressors of selected components of the SASP
- Statins such as simvastatin, that can reduce the expression of pro-inflammatory cytokines (IL-6, IL-8, and MCP-1)
- JAK1/2 inhibitors such as ruxolitinib
- NF-κB and p38 inhibitors
- IL-1α blockers
- Mitochondrial depleters in the case of impaired mitophagy
- Senolytics – small molecules that specifically induce cell death in senescent cells, targeting survival pathways and anti-apoptotic mechanisms,antibodies and antibody-mediated drug delivery medications. Unlike SASP inhibitors, senolytics can be effective by intermittent rather than continuous application.
- Senomorphics – small molecules that suppress senescent phenotypes without cell killing
- 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
See also
Further reading
- Kirkland JL, Tchkonia T (2016). "The Way Forward: Translation". Advances in Geroscience. Springer International Publishing. pp. 593–622. doi:10.1007/978-3-319-23246-1_19. 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. doi:10.1016/j.drudis.2017.01.004. PMID 28111332.
- Niedernhofer LJ, Robbins PD (May 2018). "Senotherapeutics for healthy ageing". Nature Reviews. Drug Discovery. 17 (5): 377. doi:10.1038/nrd.2018.44. 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. doi:10.1007/s13659-022-00339-y. PMC 9086005. 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. doi:10.1111/febs.16350. PMID 35015337. S2CID 245900209.