Сенотерапевтики
Сенотерапевтики (англ. Senotherapeutics) — это лечебные средства или стратегии, предназначенные для лечения клеточного старения[1][2].
К сенотерапевтикам относятся:
1. геропротекторы — средства для профилактики старения путём ослабления таких триггеров старения как: повреждение ДНК[3][4] , окислительный стресс[5], протеотоксический стресс[6], повреждение теломер[7].
К числу геропротекторов следует также отнести геронейропротекторы такие как фисетин, куркумин, монтелукаст и их производные, такие как CMS121, получаемый из фисетина, и J147, получаемый из куркумина[8][9]
2. агенты, препятствующие секреции SASP (senescence‐associated secretory phenotype)[10][11], так называемые сеноморфики (senomorphics), включая:
- глюкокортикоиды[12],
- статины, такие как симвастатин[13]
- ингибиторы JAK1/2 такие как Ruxolitinib[14][15],
- NF-κB и p38,
- IL-1α и IL-6 блокаторы. Такие как например квебекол или изоквебекол[16],
- активаторы процессов удаления митохондрий[17] и т. д.;
3. средства / стратегии предназначенные для уничтожения постаревших клеток: сенолитики — малые молекулы, которые специфически индуцируют гибель стареющих клеток[18][19], антитела и опосредованная ими доставка лекарств, агенты, которые могут препятствовать ослаблению иммунной системы при старении[20], клетки иммунной системы (NK-клетки, В-клетки[21], Т-клетки).
4. Препараты, которые подавляют фенотип старения у клеток не вызывая изменения количества клеток, называют сеноморфиками[22][23]
5. средства / стратегии генной терапии предназначенные для редактирования генов организма с целью повышения его устойчивости к старению, старческим заболеваниям[24] и продления его жизни[25][25][26][27][28][29][30][31][32][33][34][35].
Примечания
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- Researchers report new methods to identify Alzheimer’s drug candidates that have anti-aging properties
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- Sébastien Cardinal et al., & Normand Voyer (2017). Synthesis and anti-inflammatory activity of isoquebecol. Bioorganic & Medicinal Chemistry
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Литература
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- Niccolò Viviani (2015). Meet the Woman experimenting anti-aging gene therapies (on herself). Exosphere Stories.
- Antonio Regalado (2015). A Tale of Do-It-Yourself Gene Therapy. An American biotech CEO claims she is the first to undergo gene therapy to reverse aging. MIT Technology Review.
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- Baker, D. J., Dawlaty, M. M., Wijshake, T., Jeganathan, K. B., Malureanu, L., van Ree, J. H., … & Behfar, A. (2013). Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan. Nature cell biology,15(1), 96-102. doi:10.1038/ncb2643
- North, B. J., Rosenberg, M. A., Jeganathan, K. B., Hafner, A. V., Michan, S., Dai, J., … & van Deursen, J. M. (2014). SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. The EMBO journal, e201386907. doi:10.15252/embj.201386907
- Wu, J. J., Liu, J., Chen, E. B., Wang, J. J., Cao, L., Narayan, N., … & Lago, C. U. (2013). Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression. Cell reports, 4(5), 913—920 doi:10.1016/j.celrep.2013.07.030
- Pollock, K., Dahlenburg, H., Nelson, H., Fink, K. D., Cary, W., Hendrix, K., … & Nacey, C. (2016). Human Mesenchymal Stem Cells Genetically Engineered to Overexpress Brain-derived Neurotrophic Factor Improve Outcomes in Huntington’s disease Mouse Models. Molecular therapy: the journal of the American Society of Gene Therapy. doi:10.1038/mt.2016.12
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