Biology:Senotherapy
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Short description: Basic research field
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-1α blockers
- Mitochondrial depleters in the case of impaired mitophagy[14]
- Senolytics – small molecules that specifically induce cell death in senescent cells,[15][16] targeting survival pathways and anti-apoptotic mechanisms,[17] 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
- Geroprotector
- Senolytic
References
- ↑ 1.0 1.1 "Cellular senescence in aging and age-related disease: from mechanisms to therapy". Nature Medicine 21 (12): 1424–1435. December 2015. doi:10.1038/nm.4000. PMID 26646499.
- ↑ "Zoledronate Attenuates Accumulation of DNA Damage in Mesenchymal Stem Cells and Protects Their Function". Stem Cells 34 (3): 756–767. March 2016. doi:10.1002/stem.2255. PMID 26679354.
- ↑ 3.0 3.1 "PGC-1α Modulates Telomere Function and DNA Damage in Protecting against Aging-Related Chronic Diseases". Cell Reports 12 (9): 1391–1399. September 2015. doi:10.1016/j.celrep.2015.07.047. 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.
- ↑ "Induction of autophagy by spermidine promotes longevity". Nature Cell Biology 11 (11): 1305–1314. November 2009. doi:10.1038/ncb1975. PMID 19801973. https://www.openaccessrepository.it/record/23132.
- ↑ "Long-lived species have improved proteostasis compared to phylogenetically-related shorter-lived species". Biochemical and Biophysical Research Communications 457 (4): 669–675. February 2015. doi:10.1016/j.bbrc.2015.01.046. PMID 25615820.
- ↑ "Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection". Science 350 (6265): 1193–1198. December 2015. doi:10.1126/science.aab3389. PMID 26785477. Bibcode: 2015Sci...350.1193B.
- ↑ "From cell senescence to age-related diseases: differential mechanisms of action of senescence-associated secretory phenotypes". BMB Reports 48 (10): 549–558. October 2015. doi:10.5483/bmbrep.2015.48.10.122. PMID 26129674.
- ↑ "SASP reflects senescence". EMBO Reports 10 (3): 228–230. March 2009. doi:10.1038/embor.2009.22. PMID 19218920.
- ↑ "Glucocorticoids suppress selected components of the senescence-associated secretory phenotype". Aging Cell 11 (4): 569–578. August 2012. doi:10.1111/j.1474-9726.2012.00818.x. PMID 22404905.
- ↑ "Simvastatin suppresses breast cancer cell proliferation induced by senescent cells". Scientific Reports 5: 17895. December 2015. doi:10.1038/srep17895. PMID 26658759. Bibcode: 2015NatSR...517895L.
- ↑ "JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age". Proceedings of the National Academy of Sciences of the United States of America 112 (46): E6301–E6310. November 2015. doi:10.1073/pnas.1515386112. PMID 26578790. Bibcode: 2015PNAS..112E6301X.
- ↑ "Targeting senescent cells enhances adipogenesis and metabolic function in old age". eLife 4: e12997. December 2015. doi:10.7554/eLife.12997. PMID 26687007.
- ↑ "Mitochondria are required for pro-ageing features of the senescent phenotype". The EMBO Journal 35 (7): 724–742. April 2016. doi:10.15252/embj.201592862. 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".
- ↑ "Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors". Aging Cell 15 (3): 428–435. June 2016. doi:10.1111/acel.12445. PMID 26711051.
- ↑ "The Achilles' heel of senescent cells: from transcriptome to senolytic drugs". Aging Cell 14 (4): 644–658. August 2015. doi:10.1111/acel.12344. PMID 25754370.
- ↑ "Regulation of Survival Networks in Senescent Cells: From Mechanisms to Interventions". Journal of Molecular Biology 431 (15): 2629–2643. July 2019. doi:10.1016/j.jmb.2019.05.036. PMID 31153901.
- ↑ "The role of cellular senescence in ageing and endocrine disease". Nature Reviews. Endocrinology 16 (5): 263–275. May 2020. doi:10.1038/s41574-020-0335-y. PMID 32161396.
- ↑ "Identification of HSP90 inhibitors as a novel class of senolytics" (in En). Nature Communications 8 (1): 422. September 2017. doi:10.1038/s41467-017-00314-z. PMID 28871086. Bibcode: 2017NatCo...8..422F.
- ↑ "Reduced expression of MYC increases longevity and enhances healthspan". Cell 160 (3): 477–488. January 2015. doi:10.1016/j.cell.2014.12.016. PMID 25619689.
Further reading
- "The Way Forward: Translation". Advances in Geroscience. Springer International Publishing. 2016. pp. 593–622. doi:10.1007/978-3-319-23246-1_19. ISBN 978-3-319-23245-4.
- "Therapeutic interventions for aging: the case of cellular senescence". Drug Discovery Today 22 (5): 786–795. May 2017. doi:10.1016/j.drudis.2017.01.004. PMID 28111332.
- "Senotherapeutics for healthy ageing". Nature Reviews. Drug Discovery 17 (5): 377. May 2018. doi:10.1038/nrd.2018.44. PMID 29651106.
- "Antiaging agents: safe interventions to slow aging and healthy life span extension". Natural Products and Bioprospecting 12 (1): 18. May 2022. doi:10.1007/s13659-022-00339-y. PMID 35534591.
- "Targeting cellular senescence with senotherapeutics: senolytics and senomorphics". The FEBS Journal 290 (5): 1362–1383. January 2022. doi:10.1111/febs.16350. PMID 35015337.
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