Senolitik
Senolitik (inglizcha senescence — „qarish“ va -lytic — „parchalanish“ soʻzlaridan olingan) — qarigan hujayralarni tanlab yoʻq qilish va inson salomatligini yaxshilash imkoniyatini aniqlash maqsadida tadqiq etilayotgan kichik molekulalar guruhi[1]. Ushbu tadqiqotlarning maqsadi yosh oʻtishi bilan bogʻliq kasalliklarni kechiktirish, oldini olish, yengillashtirish yoki ularning rivojlanishini ortga qaytarishga xizmat qiladigan vositalarni aniqlash yoki ishlab chiqishdan iborat[2][3]. Shuningdek, senolitiklar yordamida qarigan hujayralarni yoʻq qilish qarish jarayonida immun tizimi faoliyatini yaxshilash usullaridan biri sifatida ham taklif etilgan[4].
Senostatik esa senolitiklarga yaqin tushuncha boʻlib, hujayralarning qarish jarayonini bostirish yoki sekinlashtirish maʼnosini anglatadi[5].
Tadqiqotlar
Ehtimoliy senolitik vositalar hozirda dastlabki ilmiy tadqiqotlar bosqichida boʻlib, ularning ayrimlari insonlarda oʻtkazilayotgan ilk bosqich klinik sinovlarda baholanmoqda[6][7]. Senolitik vositalar sifatida oʻrganilayotgan nomzodlarning aksariyati boshqa maqsadlarda qoʻllanadigan, xususan saratonga qarshi ishlab chiqilgan preparatlar hisoblanadi. Ular qatoriga dasatinib kimyoterapiya preparati hamda tajriba bosqichidagi navitoklaks kabi kichik molekulalar kiradi[8][9].
Eruvchan urokinaza plazminogen aktivatori retseptori qarigan hujayralarda yuqori darajada ifodalanishi aniqlangan. Shu sababli tadqiqotchilar qarigan hujayralarni yoʻq qilish maqsadida sichqonlarda CAR-T hujayralaridan foydalangan[10][11].
Sharhlarga koʻra, senolitik preparatlar uzluksiz qoʻllash oʻrniga vaqti-vaqti bilan qoʻllanganda ham xuddi shunday samarali boʻlishi mumkin. Bu senolitik preparatlarning afzalliklaridan biri hisoblanadi va nojoʻya taʼsirlar, jumladan maqsadli boʻlmagan toʻqimalarga taʼsir etishi xavfini kamaytirishga yordam berishi mumkin[6][12][13][14][15].
Senomorfiklar
Senolitiklar qarigan hujayralarni yoʻq qilsa, senomorfiklar esa ularni yoʻq qilmasdan, ularning xususiyatlarini oʻzgartiradi. Apigenin, rapamitsin va uning analogi everolimus senomorfik vositalar sifatida oʻrganilayotgan nomzodlar qatoriga kiradi. Ular qarigan hujayralarning xususiyatlarini, jumladan SASPni bostirish orqali ularning salbiy taʼsirini kamaytirishga xizmat qiladi[16][17].
Manbalar
- ↑ "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. PMC 4748967. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4748967.
- ↑ "Clinical strategies and animal models for developing senolytic agents". Experimental Gerontology 68: 19–25. August 2015. doi:10.1016/j.exger.2014.10.012. PMID 25446976. PMC 4412760. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4412760.
- ↑ "Senolytic therapies for healthy longevity". Science 364 (6441): 636–637. May 2019. doi:10.1126/science.aaw1299. PMID 31097655. PMC 6816502. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=6816502.
- ↑ "Can blocking inflammation enhance immunity during aging?". The Journal of Allergy and Clinical Immunology 145 (5): 1323–1331. 2020. doi:10.1016/j.jaci.2020.03.016. PMID 32386656. https://discovery.ucl.ac.uk/10108233/3/Akbar_JACI%20review%20280220%20TOP.pdf.
- ↑ Hu, Qinchao; Peng, Jianmin; Jiang, Laibo; Li, Wuguo; Su, Qiao; Zhang, Jiayu; Li, Huan; Song, Ming et al. (28 October 2020). "Metformin as a senostatic drug enhances the anticancer efficacy of CDK4/6 inhibitor in head and neck squamous cell carcinoma". Cell Death & Disease 11 (10): 925. doi:10.1038/s41419-020-03126-0. PMID 33116117. PMC 7595194. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7595194.
- ↑ 6,0 6,1 "Senolytic drugs: from discovery to translation". Journal of Internal Medicine 288 (5): 518–536. November 2020. doi:10.1111/joim.13141. PMID 32686219. PMC 7405395. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7405395.
- ↑ "Rejuvenating senolytics". Nature Reviews. Molecular Cell Biology 19 (9): 543. September 2018. doi:10.1038/s41580-018-0047-5. PMID 30054558.
- ↑ "Selective anti-cancer agents as anti-aging drugs". Cancer Biology & Therapy 14 (12): 1092–1097. December 2013. doi:10.4161/cbt.27350. PMID 24345884. PMC 3912031. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3912031.
- ↑ "Could cancer drugs provide ammunition against aging?". Cell Cycle 15 (2): 153–155. 6 January 2016. doi:10.1080/15384101.2015.1118905. PMID 26587873. PMC 4825846. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4825846.
- ↑ "T cells engineered to target senescence". Nature 583 (7814): 37–38. July 2020. doi:10.1038/d41586-020-01759-x. PMID 32601490.
- ↑ "Senolytic CAR T cells reverse senescence-associated pathologies". Nature 583 (7814): 127–132. July 2020. doi:10.1038/s41586-020-2403-9. PMID 32555459. PMC 7583560. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7583560.
- ↑ "Senolytic drugs: from discovery to translation". Journal of Internal Medicine 288 (5): 518–536. November 2020. doi:10.1111/joim.13141. PMID 32686219. PMC 7405395. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7405395.
- ↑ "Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span". Annual Review of Pharmacology and Toxicology 61 (1): 779–803. January 2021. doi:10.1146/annurev-pharmtox-050120-105018. PMID 32997601. PMC 7790861. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7790861.
- ↑ "Cellular senescence in ageing: from mechanisms to therapeutic opportunities". Nature Reviews. Molecular Cell Biology 22 (2): 75–95. February 2021. doi:10.1038/s41580-020-00314-w. PMID 33328614. PMC 8344376. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=8344376.
- ↑ "Cellular senescence: at the nexus between ageing and diabetes". Diabetologia 62 (10): 1835–1841. October 2019. doi:10.1007/s00125-019-4934-x. PMID 31451866. PMC 6731336. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=6731336.
- ↑ "Cellular senescence in ageing: from mechanisms to therapeutic opportunities". Nature Reviews. Molecular Cell Biology 22 (2): 75–95. February 2021. doi:10.1038/s41580-020-00314-w. PMID 33328614. PMC 8344376. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=8344376.
- ↑ "Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span". Annual Review of Pharmacology and Toxicology 61 (1): 779–803. January 2021. doi:10.1146/annurev-pharmtox-050120-105018. PMID 32997601. PMC 7790861. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7790861.
Adabiyotlar
- "Invariant Natural Killer T cells coordinate removal of senescent cells" (English). Med 2 (8): 938–950. August 2021. doi:10.1016/j.medj.2021.04.014. PMID 34617070. PMC 8491998. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=8491998.
- "Senolytic drugs: from discovery to translation". Journal of Internal Medicine 288 (5): 518–536. November 2020. doi:10.1111/joim.13141. PMID 32686219. PMC 7405395. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7405395., a review that is open access and features a list of senolytics candidates
- "Orally-active, clinically-translatable senolytics restore α-Klotho in mice and humans" (English). eBioMedicine 77. March 2022. doi:10.1016/j.ebiom.2022.103912. PMID 35292270. PMC 9034457. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=9034457.
- "Could getting rid of old cells turn back the clock on aging?" (en). Knowable Magazine. 2022-12-21. doi:10.1146/knowable-122122-1. https://knowablemagazine.org/article/health-disease/2022/could-getting-rid-old-cells-turn-back-clock-aging?mc_cid=b691ff690b&mc_eid=6e7303fddd.
- Wong, Carissa (2024-05-15). "How to kill the 'zombie' cells that make you age" (en). Nature 629 (8012): 518–520. doi:10.1038/d41586-024-01370-4. PMID 40796952. https://www.nature.com/articles/d41586-024-01370-4.