logo
Медицинский вестник
Северного Кавказа
Научно-практический журнал
Зарегистрирован в Федеральной службе
по надзору за соблюдением законодательства
в сфере массовых коммуникаций
и охране культурного наследия
ПИ №ФС77-26521 от 7 декабря 2006 года
ISSN 2073-8137
rus
русский
eng
english

Поиск по сайту




Адрес редакции
355017, Ставрополь, улица Мира, 310.

Телефоны
(8652) 35-25-11, 35-32-29.

E-mail
medvestnik@stgmu.ru

Рейтинг@Mail.ru

Исследование геропротекторных свойств ингибиторов активности связанных со старением сигнальных каскадов на модельных организмах

[Обзоры]
Москалев Алексей Александрович; Шапошников Михаил Вячеславович; Соловьёв Илья Андреевич;

Согласно базам данных DrugAge (http://genomics.senescence.info/drugs/) и Geroprotectors.org (http://geroprotectors.org/) на сегодня известно более 200 соединений, увеличивающих продолжительность жизни модельных организмов. Одним из многообещающих экспериментальных подходов для поиска новых эффективных геропротекторных средств может быть скрининг соединений, мишенями которых являются белки, участвующие в старение-ассоциированных сигнальных путях (инсулин/IGF-1, mTOR, NF-κB, PI3k и др.). В настоящем обзоре обобщены сведения о геропротекторах, модулирующих активность внутриклеточных сигнальных путей, вовлеченных в стресс-ответ, обмен веществ, рост клеток и организма, воспаление, апоптоз и др. Рассмотрены данные литературы и результаты собственных исследований по использованию таргетного подхода на примере моделей Drosophila melanogaster и Caenorhabditis elegans.

Скачать

Список литературы:
1. Aliper A., Belikov A. V., Garazha A. [et al.] In search for geroprotectors: in silico screening and in vitro validation of signalome-level mimetics of young healthy state. Aging (Albany NY). 2016;8(9):2127-2152. doi:10.18632/aging.101047
2. Ayyadevara S., Alla R., Thaden J. J., Shmookler Reis R. J. Remarkable longevity and stress resistance of nematode PI3K-null mutants. Aging Cell. 2008;7(1):13-22. doi: 10.1111/j.1474-9726.2007.00348.x
3. Balistreri C. R., Madonna R., Melino G., Caruso C. The emerging role of Notch pathway in ageing: Focus on the related mechanisms in age-related diseases. Ageing Res Rev. 2016;29:50-65. doi: 10.1016/j.arr.2016.06.004
4. Barardo D., Thornton D., Thoppil H. [et al.] The DrugAge database of aging-related drugs. Aging Cell. 2017;16(3):594-597. doi: 10.1111/acel.12585
5. Barardo D. G., Newby D., Thornton D. [et al.] Machine learning for predicting lifespan-extending chemical compounds. Aging (Albany NY). 2017;9(7):1721-1737. doi: 10.18632/aging.101264
6. Bartke A., Brown-Borg H. Life extension in the dwarf mouse. Curr. Top. Dev. Biol. 2004;63:189-225. doi: 10.1016/S0070-2153(04)63006-7
7. Bikadi Z., Hazai E. Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDock. J. Cheminform. 2009;1:15. doi:10.1186/1758-2946-1-15
8. Bitto A., Ito T. K., Pineda V. V. [et al.] Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. Elife. 2016;5. doi: 10.7554/eLife.16351
9. Blagosklonny M. V. An anti-aging drug today: from senescence-promoting genes to anti-aging pill. Drug Discov. Today. 2007;12(5-6):218-224. doi: 10.1016/j.drudis.2007.01.004
10. Blagosklonny M. V. From rapalogs to anti-aging formula. Oncotarget. 2017;8(22):35492-35507. doi: 10.18632/oncotarget18033
11. Danilov A., Shaposhnikov M., Plyusnina E. [et al.] Selective anticancer agents suppress aging in Drosophila. Oncotarget. 2013;4(9):1507-1526. doi:10.18632/oncotarget1272
12. Danilov A., Shaposhnikov M., Shevchenko O. [et al.] Influence of non-steroidal anti-inflammatory drugs on Drosophila melanogaster longevity. Oncotarget. 2015;6(23):19428-19444. doi: 10.18632/oncotarget5118
13. Dessale T., Batchu K. C., Barardo D. [et al.] Slowing ageing using drug synergy in C. elegans. bioRxiv. 2017. doi: 10.1101/153205
14. Fomenko A. N., Proshkina E. N., Fedintsev A. Y. [et al.] Potential geroproteсtors. – Sankt-Peterburg, 2016.
15. Gardner T. S. The effect of yeast nucleic acid on the survival time of 600 day old albino mice. Journal of Gerontology. 1946;1(Pt 1 4):445-452. doi: 10.1093/geronj/1.4_Part_2.205
16. Gardner T. S. The use of Drosophila melanogaster as a screening agent for longevity factors: II. The effects of biotin, pyridoxine, sodium yeast nucleate, and pantothenic acid on the life span of the fruit fly. Journal of Gerontology. 1948;3(1):9-13. doi: 10.1093/geronj/3.1.9
17. Gardner T. S. The use of Drosophila melanogaster as a screening agent for longevity factors; pantothenic acid as a longevity factor in royal jelly. Journal of Gerontology. 1948;3(1):1-8. doi: 10.1093/geronj/3.1.1
18. Gardner T. S., Forbes F. B. The effect of sodium thiocyanate and yeast nucleic acid on the survival time of 700 day old albino mice. Journal of Gerontology. 1946;1(Pt 1 4):453-456. doi: 10.1093/geronj/1.4_Part_2.209
19. Grosdidier A., Zoete V., Michielin O. SwissDock, a protein-small molecule docking web service based on EADock DSS. Nucleic Acids Res. 2011;39(Web Server issue):W270-277. doi: 10.1093/nar/gkr366
20. Gruber J., Yee Z., Tolwinski N. Developmental Drift and the Role of Wnt Signaling in Aging. Cancers. 2016;8(8):73. doi: 10.3390/cancers8080073
21. Harman D. Aging: a theory based on free radical and radiation chemistry. J. Gerontol. 1956;11(3):298-300. doi: 10.1093/geronj/11.3.298
22. Hartenfeller M., Schneider G. De novo drug design. Methods Mol. Biol. 2011;672:299-323. doi: 10.1007/978-1-60761-839-3_12
23. He C., Tsuchiyama S. K., Nguyen Q. T., Plyusnina E. N. [et al.] Enhanced longevity by ibuprofen, conserved in multiple species, occurs in yeast through inhibition of tryptophan import. PLoS Genet. 2014;10(12):e1004860. doi:10.1371/journal.pgen.1004860
24. Herce H. D., Schumacher D., Schneider A. F. L. [et al.] Cell-permeable nanobodies for targeted immunolabelling and antigen manipulation in living cells. Nat. Chem. 2017;9(8):762-771. doi: 10.1038/nchem.2811
25. Hill S. M., Hao X., Liu B., Nystrom T. Life-span extension by a metacaspase in the yeast Saccharomyces cerevisiae. Science. 2014;344(6190):1389-1392. doi:10.1126/science.1252634
26. Honoki K., Fujii H., Tsukamoto S. [et al.] Crossroads of hallmarks in aging and cancer: Anti-aging and anticancer target pathways can be shared. Trends in Cancer Research. 2016;11:39-59.
27. Huang X., Leggas M., Dickson R. C. Drug synergy drives conserved pathways to increase fission yeast lifespan. PLoS ONE. 2015;10(3):e0121877. doi: 10.1371/journal. pone.0121877
28. Huang X., Liu J., Withers B. R. [et al.] Reducing signs of aging and increasing lifespan by drug synergy. Aging Cell. 2013;12(4):652-660. doi:10.1111/acel.12090
29. Huhne R., Thalheim T., Suhnel J. AgeFactDB – the JenAge Ageing Factor Database – towards data integration in ageing research. Nucleic Acids Res. 2014;42(Database issue):D892-896. doi: 10.1093/nar/gkt1073
30. Lashmanova E., Proshkina E., Zhikrivetskaya S. [et al.] Fucoxanthin increases lifespan of Drosophila melanogaster and Caenorhabditis elegans. Pharmacol. Res. 2015;100:228-241. doi: 10.1016/j.phrs.2015.08.009
31. Liao C., Sitzmann M., Pugliese A., Nicklaus M. C. Software and resources for computational medicinal chemistry. Future Med. Chem. 2011;3(8):1057-1085. doi:10.4155/fmc.11.63
32. López-Otín C., Blasco M. A., Partridge L. [et al.] The hallmarks of aging. Cell. 2013;153(6):1194-1217. doi: 10.1016/j.cell.2013.05.039
33. Medina-Franco J. L., Giulianotti M. A., Welmaker G. S., Houghten R. A. Shifting from the single to the multitarget paradigm in drug discovery. Drug Discov. Today. 2013;18(9-10):495-501. doi: 10.1016/j.drudis.2013.01.008
34. Meng X. Y., Zhang H. X., Mezei M., Cui M. Molecular docking: a powerful approach for structure-based drug discovery. Curr. Comput. Aided. Drug Des. 2011;7(2): 146-157. doi: 10.2174/157340911795677602
35. Metchnikoff E., Mitchell P. C. The prolongation of life: optimistic studies. – New York & London: G. P. Putnam’s Sons, 1910.
36. Moskalev A., Chernyagina E., de Magalhaes J. P. [et al.] Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease. Aging (Albany NY). 2015;7(9):616-628. doi: 10.18632/aging.100799
37. Moskalev A., Chernyagina E., Kudryavtseva A., Shaposhnikov M. Geroprotectors: A Unified Concept and Screening Approaches. Aging Dis. 2017;8(3):354-363. doi: 10.14336/AD.2016.1022
38. Moskalev A., Chernyagina E., Tsvetkov V. [et al.] Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic. Aging Cell. 2016;15(3):407-415. doi: 10.1111/acel.12463
39. Moskalev A., Shaposhnikov M. Pharmacological inhibition of NF-κB prolongs lifespan of Drosophila melanogaster. Aging (Albany NY). 2011;3(4):391-394. doi:10.18632/aging.100314
40. Moskalev A. A., Aliper A. M., Smit-McBride Z. [et al.] Genetics and epigenetics of aging and longevity. Cell. Cycle. 2014;13(7):1063-1077. doi:10.4161/cc.28433
41. Moskalev A. A., Shaposhnikov M. V. Pharmacological inhibition of phosphoinositide 3 and TOR kinases improves survival of Drosophila melanogaster. Rejuvenation Res. 2010;13(2-3):246-247. doi: 10.1089/rej.2009.0903
42. Moskalev A. A., Shaposhnikov M. V. Pharmacological inhibition of phosphoinositide 3 and TOR kinases improves survival of Drosophila melanogaster. Rejuvenation Res. 2010;13(2-3):246-247. doi: 10.1089/rej.2009.0903
43. Murakami S., Johnson T. E. Life extension and stress resistance in Caenorhabditis elegans modulated by the tkr-1 gene. Curr Biol. 1998;8(19):1091-1094. doi: 10.1016/S0960-9822(98)70448-8
44. Neafsey P. J. Longevity hormesis. A review. Mech Ageing Dev. 1990;51(1):1-31. doi: 10.1016/0047-6374(90)90158-C
45. Plyusnina E. N., Shaposhnikov M. V., Moskalev A. A. Increase of Drosophila melanogaster lifespan due to D-GADD45 overexpression in the nervous system. Biogerontology. 2011;12(3):211-226. doi: 10.1007/s10522-010-9311-6
46. Powers R. W., Kaeberlein M., Caldwell S. D. [et al.] Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes. Dev. 2006;20(2):174-184. doi: 10.1101/gad.1381406
47. Proshkina E. N., Shaposhnikov M. V., Sadritdinova A. F. [et al.] Basic mechanisms of longevity: A case study of Drosophila pro-longevity genes. Ageing Res. Rev. 2015;24(Pt B):218-231. doi: 10.1016/j.arr.2015.08.005
48. Robida-Stubbs S., Glover-Cutter K., Lamming D. W. [et al.] TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell. Metab. 2012;15(5):713-724. doi: 10.1016/j.cmet2012.04.007
49. Rogina B., Reenan R. A., Nilsen S. P., Helfand S. L. Extended life-span conferred by cotransporter gene mutations in Drosophila. Science. 2000;290(5499):2137-2140. doi: 10.1126/science.290.5499.2137
50. Schmidt F., Matter H., Hessler G., Czich A. Predictive in silico off-target profiling in drug discovery. Future Med. Chem. 2014;6(3):295-317. doi:10.4155/fmc.13.202
51. Shaposhnikov M., Latkin D., Plyusnina E. [et al.] The effects of pectins on life span and stress resistance in Drosophila melanogaster. Biogerontology. 2014;15(2):113-127. doi: 10.1007/s10522-013-9484-x
52. Shmookler Reis R. J., Bharill P., Tazearslan C., Ayyadevara S. Extreme-longevity mutations orchestrate silencing of multiple signaling pathways. Biochim Biophys Acta. 2009;1790(10):1075-1083. doi: 10.1016/j.bbagen.2009.05.011
53. Simko G. I., Gyurko D., Veres D. V. [et al.] Network strategies to understand the aging process and help age-related drug design. Genome Med. 2009;1(9):90. doi: 10.1186/gm90
54. Van Bockstaele F., Holz J. B., Revets H. The development of nanobodies for therapeutic applications. Curr Opin Investig Drugs. 2009;10(11):1212-1224. doi: 10.2217/nnm.13.86
55. Wang X., Chrysovergis K., Kosak J. [et al.] hNAG-1 increases lifespan by regulating energy metabolism and insulin/IGF-1/mTOR signaling. Aging (Albany NY). 2014;6(8):690-704. doi: 10.18632/aging.100687
56. Wei D., Jiang X., Zhou L. [et al.] Discovery of multitarget inhibitors by combining molecular docking with common pharmacophore matching. J. Med. Chem. 2008;51(24):7882-7888. doi: 10.1021/jm8010096
57. Wei M., Fabrizio P., Hu J. [et al.] Life span extension by calorie restriction depends on Rim15 and transcription factors downstream of Ras/PKA, Tor, and Sch9. PLoS Genet. 2008;4(1):e13. doi: 10.1371/journal. pgen.0040013
58. Yanai H., Budovsky A., Barzilay T. [et al.] Widescale comparative analysis of longevity genes and interventions. Aging Cell. 2017; doi: 10.1111/acel.12659

Ключевые слова: долголетие, старение, геропротекторы, сигнальные каскады, модельные организмы


Учредители:
Ставропольская государственная медицинская академия
Государственный научно-исследовательский институт курортологии
Пятигорская государственная фармацевтическая академия