CASIN - Revision history

Dmitry Dzhagarov: /* See also */

2023-01-11T16:44:15Z

Dmitry Dzhagarov: /* Side effects of CASIN */

2023-01-11T12:18:07Z

Side effects of CASIN

← Older revision		Revision as of 12:18, 11 January 2023
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	Although pharmacological reduction of Cdc42 activity by CASIN can improve the regeneration of aged intestinal epithelium, in particular ''in vivo'' crypt regeneration in aged mice,<ref name="regenerative"/> the prolonged inhibition of Cdc42 reduced colonic Lgr5<sup>+</sup> intestinal epithelial stem cell regeneration and thus inhibited intestinal epithelial cell repair, leading to advanced mucosal inflammation (inflammatory bowel diseases), which could result in intestinal neoplasia.<ref>Zhang, D., Tang, W., Niu, H., Tse, W., Ruan, H. B., Dolznig, H., ... & Han, X. (2023). Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia. Genes & Diseases. Doi: [https://doi.org/10.1016/j.gendis.2022.11.024 10.1016/j.gendis.2022.11.024]</ref><ref>Sakamori, R., Das, S., Yu, S., Feng, S., Stypulkowski, E., Guan, Y., ... & Gao, N. (2012). Cdc42 and Rab8a are critical for intestinal stem cell division, survival, and differentiation in mice. The Journal of clinical investigation, 122(3), 1052-1065. PMID:[https://pubmed.ncbi.nlm.nih.gov/22354172/ 22354172] PMC3287229 DOI: 10.1172/JCI60282</ref>		Although pharmacological reduction of Cdc42 activity by CASIN can improve the regeneration of aged intestinal epithelium, in particular ''in vivo'' crypt regeneration in aged mice,<ref name="regenerative"/> the prolonged inhibition of Cdc42 reduced colonic Lgr5<sup>+</sup> intestinal epithelial stem cell regeneration and thus inhibited intestinal epithelial cell repair, leading to advanced mucosal inflammation (inflammatory bowel diseases), which could result in intestinal neoplasia.<ref>Zhang, D., Tang, W., Niu, H., Tse, W., Ruan, H. B., Dolznig, H., ... & Han, X. (2023). Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia. Genes & Diseases. Doi: [https://doi.org/10.1016/j.gendis.2022.11.024 10.1016/j.gendis.2022.11.024]</ref><ref>Sakamori, R., Das, S., Yu, S., Feng, S., Stypulkowski, E., Guan, Y., ... & Gao, N. (2012). Cdc42 and Rab8a are critical for intestinal stem cell division, survival, and differentiation in mice. The Journal of clinical investigation, 122(3), 1052-1065. PMID:[https://pubmed.ncbi.nlm.nih.gov/22354172/ 22354172] PMC3287229 DOI: 10.1172/JCI60282</ref>
	CASIN may also cause autoimmunity, mimicking regulatory T (Treg) cell-specific homozygous loss of Cdc42.<ref name="immunity">Kalim, K. W., Yang, J. Q., Wunderlich, M., Modur, V., Nguyen, P., Li, Y., ... & Guo, F. (2021). Targeting of Cdc42 GTPase in regulatory T cells unleashes anti-tumor T cell immunity. J Immunother Cancer, 10(11), e004806. PMID: 36427906 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9703354/ PMC9703354] DOI: 10.1136/jitc-2022-004806</ref>		CASIN may also cause autoimmunity, mimicking regulatory T (Treg) cell-specific homozygous loss of Cdc42.<ref name="immunity">Kalim, K. W., Yang, J. Q., Wunderlich, M., Modur, V., Nguyen, P., Li, Y., ... & Guo, F. (2021). Targeting of Cdc42 GTPase in regulatory T cells unleashes anti-tumor T cell immunity. J Immunother Cancer, 10(11), e004806. PMID: 36427906 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9703354/ PMC9703354] DOI: 10.1136/jitc-2022-004806</ref>

			=== See also ===
			* [https://www.fightaging.org/archives/2023/01/casin-alters-epigenetic-state-to-produce-lasting-improvement-in-aged-stem-cell-function/ CASIN Alters Epigenetic State to Produce Lasting Improvement in Aged Stem Cell Function]. https://www.fightaging.org

	== References ==		== References ==

Dmitry Dzhagarov: /* Side effects of CASIN */

2023-01-07T11:44:28Z

Side effects of CASIN

← Older revision		Revision as of 11:44, 7 January 2023
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	=== Side effects of CASIN ===		=== Side effects of CASIN ===
	Although pharmacological reduction of Cdc42 activity by CASIN can improve the regeneration of aged intestinal epithelium, in particular ''in vivo'' crypt regeneration in aged mice,<ref name="regenerative"/> the prolonged inhibition of Cdc42 reduced colonic Lgr5<sup>+</sup> intestinal epithelial stem cell regeneration and thus inhibited intestinal epithelial cell repair, leading to advanced mucosal inflammation (inflammatory bowel diseases), which could result in intestinal neoplasia.<ref>Zhang, D., Tang, W., Niu, H., Tse, W., Ruan, H. B., Dolznig, H., ... & Han, X. (2023). Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia. Genes & Diseases. Doi: [https://doi.org/10.1016/j.gendis.2022.11.024 10.1016/j.gendis.2022.11.024]</ref><ref>Sakamori, R., Das, S., Yu, S., Feng, S., Stypulkowski, E., Guan, Y., ... & Gao, N. (2012). Cdc42 and Rab8a are critical for intestinal stem cell division, survival, and differentiation in mice. The Journal of clinical investigation, 122(3), 1052-1065. PMID:[https://pubmed.ncbi.nlm.nih.gov/22354172/ 22354172] PMC3287229 DOI: 10.1172/JCI60282</ref>		Although pharmacological reduction of Cdc42 activity by CASIN can improve the regeneration of aged intestinal epithelium, in particular ''in vivo'' crypt regeneration in aged mice,<ref name="regenerative"/> the prolonged inhibition of Cdc42 reduced colonic Lgr5<sup>+</sup> intestinal epithelial stem cell regeneration and thus inhibited intestinal epithelial cell repair, leading to advanced mucosal inflammation (inflammatory bowel diseases), which could result in intestinal neoplasia.<ref>Zhang, D., Tang, W., Niu, H., Tse, W., Ruan, H. B., Dolznig, H., ... & Han, X. (2023). Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia. Genes & Diseases. Doi: [https://doi.org/10.1016/j.gendis.2022.11.024 10.1016/j.gendis.2022.11.024]</ref><ref>Sakamori, R., Das, S., Yu, S., Feng, S., Stypulkowski, E., Guan, Y., ... & Gao, N. (2012). Cdc42 and Rab8a are critical for intestinal stem cell division, survival, and differentiation in mice. The Journal of clinical investigation, 122(3), 1052-1065. PMID:[https://pubmed.ncbi.nlm.nih.gov/22354172/ 22354172] PMC3287229 DOI: 10.1172/JCI60282</ref>
			CASIN may also cause autoimmunity, mimicking regulatory T (Treg) cell-specific homozygous loss of Cdc42.<ref name="immunity">Kalim, K. W., Yang, J. Q., Wunderlich, M., Modur, V., Nguyen, P., Li, Y., ... & Guo, F. (2021). Targeting of Cdc42 GTPase in regulatory T cells unleashes anti-tumor T cell immunity. J Immunother Cancer, 10(11), e004806. PMID: 36427906 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9703354/ PMC9703354] DOI: 10.1136/jitc-2022-004806</ref>

	== References ==		== References ==

Dmitry Dzhagarov: /* Studies on health and lifespan */

2023-01-07T10:12:13Z

Studies on health and lifespan

← Older revision		Revision as of 10:12, 7 January 2023
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	Treatment of old (75-week-old) female mice with CASIN for 4 consecutive days increased their mean lifespan by 10%.<ref name="Geiger" /> In the same study, elderly animals treated with CASIN showed a decrease in biological age as observed by their blood cells [[Epigenetic Clocks\|epigenetic clock]].<ref name="Geiger">Florian, M. C., Leins, H., Gobs, M., Han, Y., Marka, G., Soller, K., ... & Zhao, X. (2020). Inhibition of Cdc42 activity extends lifespan and decreases circulating inflammatory cytokines in aged female C57BL/6 mice. Aging cell, 19(9), e13208. https://doi.org/10.1111/acel.13208</ref>		Treatment of old (75-week-old) female mice with CASIN for 4 consecutive days increased their mean lifespan by 10%.<ref name="Geiger" /> In the same study, elderly animals treated with CASIN showed a decrease in biological age as observed by their blood cells [[Epigenetic Clocks\|epigenetic clock]].<ref name="Geiger">Florian, M. C., Leins, H., Gobs, M., Han, Y., Marka, G., Soller, K., ... & Zhao, X. (2020). Inhibition of Cdc42 activity extends lifespan and decreases circulating inflammatory cytokines in aged female C57BL/6 mice. Aging cell, 19(9), e13208. https://doi.org/10.1111/acel.13208</ref>

	Other studies have showed that treatment with CASIN can improve the regeneration of intestinal epithelium, by inhibiting the age-associated Cdc42 activity in intestinal crypts.<ref>Nalapareddy, K., Hassan, A., Sampson, L., Zheng, Y., & Geiger, H. (2021). Suppression of elevated Cdc42 activity promotes the regenerative potential of aged intestinal stem cells. iScience, 102362. https://doi.org/10.1016/j.isci.2021.102362</ref> CASIN treatment of old hair follicle stem cells can also suppress canonical Wnt signaling in hair follicles and lead to hair follicle stem cell rejuvenation.<ref>Tiwari, R. L., Mishra, P., Martin, N., George, N. O., Sakk, V., Soller, K., ... & Geiger, H. (2021). A Wnt5a-Cdc42 axis controls aging and rejuvenation of hair-follicle stem cells. Aging (Albany NY), 13(4), 4778-4793<nowiki/>https://doi.org/10.18632/aging.202694</ref>		Other studies have showed that treatment with CASIN can improve the regeneration of intestinal epithelium, by inhibiting the age-associated Cdc42 activity in intestinal crypts. <ref name="regenerative">Nalapareddy, K., Hassan, A., Sampson, L., Zheng, Y., & Geiger, H. (2021). Suppression of elevated Cdc42 activity promotes the regenerative potential of aged intestinal stem cells. iScience, 102362. https://doi.org/10.1016/j.isci.2021.102362</ref> CASIN treatment of old hair follicle stem cells can also suppress canonical Wnt signaling in hair follicles and lead to hair follicle stem cell rejuvenation.<ref>Tiwari, R. L., Mishra, P., Martin, N., George, N. O., Sakk, V., Soller, K., ... & Geiger, H. (2021). A Wnt5a-Cdc42 axis controls aging and rejuvenation of hair-follicle stem cells. Aging (Albany NY), 13(4), 4778-4793<nowiki/>https://doi.org/10.18632/aging.202694</ref>

	After a short systemic treatment with CASIN, transplanting aged hematopoietic stem cells (HSCs) from treated mice is sufficient to extend the healthspan and lifespan of aged immunocompromised mice without additional treatment. CASIN treatment improves strength and endurance of aged mice by increasing the myogenic regenerative potential of aged skeletal muscle stem cells. Furthermore, CASIN modifies niche localization and H4K16ac polarity of HSCs ''in vivo''.<ref>Montserrat-Vazquez, S., Ali, N.J., Matteini, F. et al. (2022). Transplanting rejuvenated blood stem cells extends lifespan of aged immunocompromised mice. npj Regen Med 7, 78 https://doi.org/10.1038/s41536-022-00275-y</ref>		After a short systemic treatment with CASIN, transplanting aged hematopoietic stem cells (HSCs) from treated mice is sufficient to extend the healthspan and lifespan of aged immunocompromised mice without additional treatment. CASIN treatment improves strength and endurance of aged mice by increasing the myogenic regenerative potential of aged skeletal muscle stem cells. Furthermore, CASIN modifies niche localization and H4K16ac polarity of HSCs ''in vivo''.<ref>Montserrat-Vazquez, S., Ali, N.J., Matteini, F. et al. (2022). Transplanting rejuvenated blood stem cells extends lifespan of aged immunocompromised mice. npj Regen Med 7, 78 https://doi.org/10.1038/s41536-022-00275-y</ref>

			=== Side effects of CASIN ===
			Although pharmacological reduction of Cdc42 activity by CASIN can improve the regeneration of aged intestinal epithelium, in particular ''in vivo'' crypt regeneration in aged mice,<ref name="regenerative"/> the prolonged inhibition of Cdc42 reduced colonic Lgr5<sup>+</sup> intestinal epithelial stem cell regeneration and thus inhibited intestinal epithelial cell repair, leading to advanced mucosal inflammation (inflammatory bowel diseases), which could result in intestinal neoplasia.<ref>Zhang, D., Tang, W., Niu, H., Tse, W., Ruan, H. B., Dolznig, H., ... & Han, X. (2023). Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia. Genes & Diseases. Doi: [https://doi.org/10.1016/j.gendis.2022.11.024 10.1016/j.gendis.2022.11.024]</ref><ref>Sakamori, R., Das, S., Yu, S., Feng, S., Stypulkowski, E., Guan, Y., ... & Gao, N. (2012). Cdc42 and Rab8a are critical for intestinal stem cell division, survival, and differentiation in mice. The Journal of clinical investigation, 122(3), 1052-1065. PMID:[https://pubmed.ncbi.nlm.nih.gov/22354172/ 22354172] PMC3287229 DOI: 10.1172/JCI60282</ref>

	== References ==		== References ==

Dmitry Dzhagarov at 08:44, 7 January 2023

2023-01-07T08:44:08Z

← Older revision		Revision as of 08:44, 7 January 2023
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	\|} ]]		\|} ]]

	CASIN ('''C'''dc42 '''A'''ctivity-'''S'''pecific '''IN'''hibitor), also known as pyrlindole-related compound 2,<ref name="pyrl">Peterson, J. R., Lebensohn, A. M., Pelish, H. E., & Kirschner, M. W. (2006). Biochemical suppression of small-molecule inhibitors: a strategy to identify inhibitor targets and signaling pathway components. Chemistry & biology, 13(4), 443-452. https://doi.org/10.1016/j.chembiol.2006.02.009 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1820768 PMC1820768] </ref> is a compound that selectively inhibits the activity of Cdc42, a Rho GTPase protein involved in the regulation of several cellular functions such as cell cycle, cell migration, cell morphology and endocytosis.		CASIN ('''C'''dc42 '''A'''ctivity-'''S'''pecific '''IN'''hibitor), also known as pyrlindole-related compound 2,<ref name="pyrl">Peterson, J. R., Lebensohn, A. M., Pelish, H. E., & Kirschner, M. W. (2006). Biochemical suppression of small-molecule inhibitors: a strategy to identify inhibitor targets and signaling pathway components. Chemistry & biology, 13(4), 443-452. https://doi.org/10.1016/j.chembiol.2006.02.009 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1820768 PMC1820768] </ref> is a compound that selectively inhibits the activity of Cdc42, a Rho GTPase protein involved in the regulation of several cellular functions such as cell cycle, cell migration, cell morphology and endocytosis.<ref>Umbayev, B., Yermekova, A., Nessipbekova, A., Syzdykova, A., & Askarova, S. (2023). Role of a small GTPase Cdc42 in aging and age-related diseases. Biogerontology, 1-20. PMID:[https://pubmed.ncbi.nlm.nih.gov/36598630/ 36598630] DOI:[https://doi.org/10.1007/s10522-022-10008-9 10.1007/s10522-022-10008-9]</ref>

	During aging, expression and activity of Cdc42 in blood cells are associated with older adults and cardiovascular disease.<ref>Florian, M. C., Klenk, J., Marka, G., Soller, K., Kiryakos, H., Peter, R., ... & Geiger, H. (2017). Expression and activity of the small RhoGTPase Cdc42 in blood cells of older adults are associated with age and cardiovascular disease. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(9), 1196-1200. https://doi.org/10.1093/gerona/glx091</ref> Cdc42 can be used as a strong predictor of survival, and higher levels of Cdc42 have been associated with an increased risk of mortality.<ref>Kerber, R. A., O’Brien, E., & Cawthon, R. M. (2009). Gene expression profiles associated with aging and mortality in humans. Aging Cell, 8(3), 239-250. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759984 PMC2759984] https://doi.org/10.1111/j.1474-9726.2009.00467.x</ref> By inhibiting Cdc42, CASIN has shown able to rejuvenate aged hematopoietic stem cells (HSCs) ''in vitro'' and to reverse age-related phenotypes of HSCs ''in vivo.''<ref name="Florian">Florian, M. C., Dörr, K., Niebel, A., Daria, D., Schrezenmeier, H., Rojewski, M., ... & Zheng, Y. (2012). Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. Cell stem cell, 10(5), 520-530. https://doi.org/10.1016/j.stem.2012.04.007 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348626 PMC3348626]</ref><ref name="Leins">Leins, H., Mulaw, M., Eiwen, K., Sakk, V., Liang, Y., Denkinger, M., ... & Schirmbeck, R. (2018). Aged murine hematopoietic stem cells drive aging-associated immune remodeling. Blood, 132(6), 565-576. https://doi.org/10.1182/blood-2018-02-831065 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137572 PMC6137572] </ref><ref name="Pawelec">Pawelec, G. P. (2018). CASIN the joint: immune aging at the stem cell level. Blood, The Journal of the American Society of Hematology, 132(6), 553-554. https://doi.org/10.1182/blood-2018-06-858696</ref><ref name="Geiger" />		During aging, expression and activity of Cdc42 in blood cells are associated with older adults and cardiovascular disease.<ref>Florian, M. C., Klenk, J., Marka, G., Soller, K., Kiryakos, H., Peter, R., ... & Geiger, H. (2017). Expression and activity of the small RhoGTPase Cdc42 in blood cells of older adults are associated with age and cardiovascular disease. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(9), 1196-1200. https://doi.org/10.1093/gerona/glx091</ref> Cdc42 can be used as a strong predictor of survival, and higher levels of Cdc42 have been associated with an increased risk of mortality.<ref>Kerber, R. A., O’Brien, E., & Cawthon, R. M. (2009). Gene expression profiles associated with aging and mortality in humans. Aging Cell, 8(3), 239-250. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759984 PMC2759984] https://doi.org/10.1111/j.1474-9726.2009.00467.x</ref> By inhibiting Cdc42, CASIN has shown able to rejuvenate aged hematopoietic stem cells (HSCs) ''in vitro'' and to reverse age-related phenotypes of HSCs ''in vivo.''<ref name="Florian">Florian, M. C., Dörr, K., Niebel, A., Daria, D., Schrezenmeier, H., Rojewski, M., ... & Zheng, Y. (2012). Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. Cell stem cell, 10(5), 520-530. https://doi.org/10.1016/j.stem.2012.04.007 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348626 PMC3348626]</ref><ref name="Leins">Leins, H., Mulaw, M., Eiwen, K., Sakk, V., Liang, Y., Denkinger, M., ... & Schirmbeck, R. (2018). Aged murine hematopoietic stem cells drive aging-associated immune remodeling. Blood, 132(6), 565-576. https://doi.org/10.1182/blood-2018-02-831065 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137572 PMC6137572] </ref><ref name="Pawelec">Pawelec, G. P. (2018). CASIN the joint: immune aging at the stem cell level. Blood, The Journal of the American Society of Hematology, 132(6), 553-554. https://doi.org/10.1182/blood-2018-06-858696</ref><ref name="Geiger" />

Dmitry Dzhagarov: /* Studies on health and lifespan */

2022-12-31T20:27:40Z

Studies on health and lifespan

← Older revision		Revision as of 20:27, 31 December 2022
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	Other studies have showed that treatment with CASIN can improve the regeneration of intestinal epithelium, by inhibiting the age-associated Cdc42 activity in intestinal crypts.<ref>Nalapareddy, K., Hassan, A., Sampson, L., Zheng, Y., & Geiger, H. (2021). Suppression of elevated Cdc42 activity promotes the regenerative potential of aged intestinal stem cells. iScience, 102362. https://doi.org/10.1016/j.isci.2021.102362</ref> CASIN treatment of old hair follicle stem cells can also suppress canonical Wnt signaling in hair follicles and lead to hair follicle stem cell rejuvenation.<ref>Tiwari, R. L., Mishra, P., Martin, N., George, N. O., Sakk, V., Soller, K., ... & Geiger, H. (2021). A Wnt5a-Cdc42 axis controls aging and rejuvenation of hair-follicle stem cells. Aging (Albany NY), 13(4), 4778-4793<nowiki/>https://doi.org/10.18632/aging.202694</ref>		Other studies have showed that treatment with CASIN can improve the regeneration of intestinal epithelium, by inhibiting the age-associated Cdc42 activity in intestinal crypts.<ref>Nalapareddy, K., Hassan, A., Sampson, L., Zheng, Y., & Geiger, H. (2021). Suppression of elevated Cdc42 activity promotes the regenerative potential of aged intestinal stem cells. iScience, 102362. https://doi.org/10.1016/j.isci.2021.102362</ref> CASIN treatment of old hair follicle stem cells can also suppress canonical Wnt signaling in hair follicles and lead to hair follicle stem cell rejuvenation.<ref>Tiwari, R. L., Mishra, P., Martin, N., George, N. O., Sakk, V., Soller, K., ... & Geiger, H. (2021). A Wnt5a-Cdc42 axis controls aging and rejuvenation of hair-follicle stem cells. Aging (Albany NY), 13(4), 4778-4793<nowiki/>https://doi.org/10.18632/aging.202694</ref>

	After a short systemic treatment with CASIN, transplanting aged hematopoietic stem cells (HSCs) from treated mice is sufficient to extend the healthspan and lifespan of aged immunocompromised mice without additional treatment. CASIN treatment improves strength and endurance of aged mice by increasing the myogenic regenerative potential of aged skeletal muscle stem cells. Furthermore, CASIN modifies niche localization and H4K16ac polarity of HSCs in vivo.<ref>Montserrat-Vazquez, S., Ali, N.J., Matteini, F. et al. (2022). Transplanting rejuvenated blood stem cells extends lifespan of aged immunocompromised mice. npj Regen Med 7, 78 https://doi.org/10.1038/s41536-022-00275-y</ref>		After a short systemic treatment with CASIN, transplanting aged hematopoietic stem cells (HSCs) from treated mice is sufficient to extend the healthspan and lifespan of aged immunocompromised mice without additional treatment. CASIN treatment improves strength and endurance of aged mice by increasing the myogenic regenerative potential of aged skeletal muscle stem cells. Furthermore, CASIN modifies niche localization and H4K16ac polarity of HSCs ''in vivo''.<ref>Montserrat-Vazquez, S., Ali, N.J., Matteini, F. et al. (2022). Transplanting rejuvenated blood stem cells extends lifespan of aged immunocompromised mice. npj Regen Med 7, 78 https://doi.org/10.1038/s41536-022-00275-y</ref>

	== References ==		== References ==

Dmitry Dzhagarov at 19:58, 31 December 2022

2022-12-31T19:58:44Z

← Older revision		Revision as of 19:58, 31 December 2022
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	[[File:CASIN (Cdc42 activity-specific inhibitor).jpg\|thumb\|~~CASIN]]~~		[[File:CASIN (Cdc42 activity-specific inhibitor).jpg\|thumb\|

	{\| class="wikitable"		{\| class="wikitable"
	! CASIN (Cdc42 activity-specific inhibitor)		! CASIN (Cdc42 activity-specific inhibitor)
	\|-		\|-
	! IUPAC name = 2-[(2,3,4,9-Tetrahydro-6-phenyl-1H-carbazol-1-yl)amino]ethanol		\| IUPAC name 2-[(2,3,4,9-Tetrahydro-6-phenyl-1H-carbazol-1-yl)amino]ethanol
	\|-		\|-
	\| Molecular weight = 306.4 g/mol		\| Molecular weight 306.4 g/mol
	\|-		\|-
	\| CAS number = 425399-05-9		\| CAS number 425399-05-9
	\|-		\|-
	\| Chemical formula = C<sub>20</sub>H<sub>22</sub>N<sub>2</sub>O		\| Chemical formula C<sub>20</sub>H<sub>22</sub>N<sub>2</sub>O
	\|-		\|-
	\|}		\|} ]]

	CASIN ('''C'''dc42 '''A'''ctivity-'''S'''pecific '''IN'''hibitor), also known as pyrlindole-related compound 2,<ref name="pyrl">Peterson, J. R., Lebensohn, A. M., Pelish, H. E., & Kirschner, M. W. (2006). Biochemical suppression of small-molecule inhibitors: a strategy to identify inhibitor targets and signaling pathway components. Chemistry & biology, 13(4), 443-452. https://doi.org/10.1016/j.chembiol.2006.02.009 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1820768 PMC1820768] </ref> is a compound that selectively inhibits the activity of Cdc42, a Rho GTPase protein involved in the regulation of several cellular functions such as cell cycle, cell migration, cell morphology and endocytosis.		CASIN ('''C'''dc42 '''A'''ctivity-'''S'''pecific '''IN'''hibitor), also known as pyrlindole-related compound 2,<ref name="pyrl">Peterson, J. R., Lebensohn, A. M., Pelish, H. E., & Kirschner, M. W. (2006). Biochemical suppression of small-molecule inhibitors: a strategy to identify inhibitor targets and signaling pathway components. Chemistry & biology, 13(4), 443-452. https://doi.org/10.1016/j.chembiol.2006.02.009 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1820768 PMC1820768] </ref> is a compound that selectively inhibits the activity of Cdc42, a Rho GTPase protein involved in the regulation of several cellular functions such as cell cycle, cell migration, cell morphology and endocytosis.
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	Other studies have showed that treatment with CASIN can improve the regeneration of intestinal epithelium, by inhibiting the age-associated Cdc42 activity in intestinal crypts.<ref>Nalapareddy, K., Hassan, A., Sampson, L., Zheng, Y., & Geiger, H. (2021). Suppression of elevated Cdc42 activity promotes the regenerative potential of aged intestinal stem cells. iScience, 102362. https://doi.org/10.1016/j.isci.2021.102362</ref> CASIN treatment of old hair follicle stem cells can also suppress canonical Wnt signaling in hair follicles and lead to hair follicle stem cell rejuvenation.<ref>Tiwari, R. L., Mishra, P., Martin, N., George, N. O., Sakk, V., Soller, K., ... & Geiger, H. (2021). A Wnt5a-Cdc42 axis controls aging and rejuvenation of hair-follicle stem cells. Aging (Albany NY), 13(4), 4778-4793<nowiki/>https://doi.org/10.18632/aging.202694</ref>		Other studies have showed that treatment with CASIN can improve the regeneration of intestinal epithelium, by inhibiting the age-associated Cdc42 activity in intestinal crypts.<ref>Nalapareddy, K., Hassan, A., Sampson, L., Zheng, Y., & Geiger, H. (2021). Suppression of elevated Cdc42 activity promotes the regenerative potential of aged intestinal stem cells. iScience, 102362. https://doi.org/10.1016/j.isci.2021.102362</ref> CASIN treatment of old hair follicle stem cells can also suppress canonical Wnt signaling in hair follicles and lead to hair follicle stem cell rejuvenation.<ref>Tiwari, R. L., Mishra, P., Martin, N., George, N. O., Sakk, V., Soller, K., ... & Geiger, H. (2021). A Wnt5a-Cdc42 axis controls aging and rejuvenation of hair-follicle stem cells. Aging (Albany NY), 13(4), 4778-4793<nowiki/>https://doi.org/10.18632/aging.202694</ref>

			After a short systemic treatment with CASIN, transplanting aged hematopoietic stem cells (HSCs) from treated mice is sufficient to extend the healthspan and lifespan of aged immunocompromised mice without additional treatment. CASIN treatment improves strength and endurance of aged mice by increasing the myogenic regenerative potential of aged skeletal muscle stem cells. Furthermore, CASIN modifies niche localization and H4K16ac polarity of HSCs in vivo.<ref>Montserrat-Vazquez, S., Ali, N.J., Matteini, F. et al. (2022). Transplanting rejuvenated blood stem cells extends lifespan of aged immunocompromised mice. npj Regen Med 7, 78 https://doi.org/10.1038/s41536-022-00275-y</ref>

	== References ==		== References ==

Andrea: category change

2022-12-27T11:41:38Z

category change

← Older revision		Revision as of 11:41, 27 December 2022
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	[[Category:Drugs]]		[[Category:Drugs]]
	[[Category:~~Longevity~~]]		[[Category:Main list]]

Dmitry Dzhagarov at 07:46, 12 November 2022

2022-11-12T07:46:29Z

← Older revision		Revision as of 07:46, 12 November 2022
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	CASIN (~~Cdc42 Activity~~-~~Specific INhibitor~~), also known as pyrlindole-related compound 2,<ref name="pyrl">Peterson, J. R., Lebensohn, A. M., Pelish, H. E., & Kirschner, M. W. (2006). Biochemical suppression of small-molecule inhibitors: a strategy to identify inhibitor targets and signaling pathway components. Chemistry & biology, 13(4), 443-452. https://doi.org/10.1016/j.chembiol.2006.02.009 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1820768 PMC1820768] </ref> is a compound that selectively inhibits the activity of Cdc42, a Rho GTPase protein involved in the regulation of several cellular functions such as cell cycle, cell migration, cell morphology and endocytosis.		CASIN ('''C'''dc42 '''A'''ctivity-'''S'''pecific '''IN'''hibitor), also known as pyrlindole-related compound 2,<ref name="pyrl">Peterson, J. R., Lebensohn, A. M., Pelish, H. E., & Kirschner, M. W. (2006). Biochemical suppression of small-molecule inhibitors: a strategy to identify inhibitor targets and signaling pathway components. Chemistry & biology, 13(4), 443-452. https://doi.org/10.1016/j.chembiol.2006.02.009 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1820768 PMC1820768] </ref> is a compound that selectively inhibits the activity of Cdc42, a Rho GTPase protein involved in the regulation of several cellular functions such as cell cycle, cell migration, cell morphology and endocytosis.

	During aging, expression and activity of Cdc42 in blood cells are associated with older adults and cardiovascular disease.<ref>Florian, M. C., Klenk, J., Marka, G., Soller, K., Kiryakos, H., Peter, R., ... & Geiger, H. (2017). Expression and activity of the small RhoGTPase Cdc42 in blood cells of older adults are associated with age and cardiovascular disease. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(9), 1196-1200. https://doi.org/10.1093/gerona/glx091</ref> Cdc42 can be used as a strong predictor of survival, and higher levels of Cdc42 have been associated with an increased risk of mortality.<ref>Kerber, R. A., O’Brien, E., & Cawthon, R. M. (2009). Gene expression profiles associated with aging and mortality in humans. Aging Cell, 8(3), 239-250. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759984 PMC2759984] https://doi.org/10.1111/j.1474-9726.2009.00467.x</ref> By inhibiting Cdc42, CASIN has shown able to rejuvenate aged hematopoietic stem cells (HSCs) ''in vitro'' and to reverse age-related phenotypes of HSCs ''in vivo.''<ref name="Florian">Florian, M. C., Dörr, K., Niebel, A., Daria, D., Schrezenmeier, H., Rojewski, M., ... & Zheng, Y. (2012). Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. Cell stem cell, 10(5), 520-530. https://doi.org/10.1016/j.stem.2012.04.007 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348626 PMC3348626]</ref><ref name="Leins">Leins, H., Mulaw, M., Eiwen, K., Sakk, V., Liang, Y., Denkinger, M., ... & Schirmbeck, R. (2018). Aged murine hematopoietic stem cells drive aging-associated immune remodeling. Blood, 132(6), 565-576. https://doi.org/10.1182/blood-2018-02-831065 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137572 PMC6137572] </ref><ref name="Pawelec">Pawelec, G. P. (2018). CASIN the joint: immune aging at the stem cell level. Blood, The Journal of the American Society of Hematology, 132(6), 553-554. https://doi.org/10.1182/blood-2018-06-858696</ref><ref name="Geiger" />		During aging, expression and activity of Cdc42 in blood cells are associated with older adults and cardiovascular disease.<ref>Florian, M. C., Klenk, J., Marka, G., Soller, K., Kiryakos, H., Peter, R., ... & Geiger, H. (2017). Expression and activity of the small RhoGTPase Cdc42 in blood cells of older adults are associated with age and cardiovascular disease. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(9), 1196-1200. https://doi.org/10.1093/gerona/glx091</ref> Cdc42 can be used as a strong predictor of survival, and higher levels of Cdc42 have been associated with an increased risk of mortality.<ref>Kerber, R. A., O’Brien, E., & Cawthon, R. M. (2009). Gene expression profiles associated with aging and mortality in humans. Aging Cell, 8(3), 239-250. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759984 PMC2759984] https://doi.org/10.1111/j.1474-9726.2009.00467.x</ref> By inhibiting Cdc42, CASIN has shown able to rejuvenate aged hematopoietic stem cells (HSCs) ''in vitro'' and to reverse age-related phenotypes of HSCs ''in vivo.''<ref name="Florian">Florian, M. C., Dörr, K., Niebel, A., Daria, D., Schrezenmeier, H., Rojewski, M., ... & Zheng, Y. (2012). Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. Cell stem cell, 10(5), 520-530. https://doi.org/10.1016/j.stem.2012.04.007 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348626 PMC3348626]</ref><ref name="Leins">Leins, H., Mulaw, M., Eiwen, K., Sakk, V., Liang, Y., Denkinger, M., ... & Schirmbeck, R. (2018). Aged murine hematopoietic stem cells drive aging-associated immune remodeling. Blood, 132(6), 565-576. https://doi.org/10.1182/blood-2018-02-831065 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137572 PMC6137572] </ref><ref name="Pawelec">Pawelec, G. P. (2018). CASIN the joint: immune aging at the stem cell level. Blood, The Journal of the American Society of Hematology, 132(6), 553-554. https://doi.org/10.1182/blood-2018-06-858696</ref><ref name="Geiger" />

Andrea: Added context, fixed references and organised content in subsections

2022-10-27T15:01:42Z

Added context, fixed references and organised content in subsections

Show changes

← Older revision		Revision as of 16:44, 11 January 2023
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	=== See also ===		=== See also ===
	* [https://www.fightaging.org/archives/2023/01/casin-alters-epigenetic-state-to-produce-lasting-improvement-in-aged-stem-cell-function/ CASIN Alters Epigenetic State to Produce Lasting Improvement in Aged Stem Cell Function]. ~~https://www~~.~~fightaging.org~~		* [https://www.fightaging.org/archives/2023/01/casin-alters-epigenetic-state-to-produce-lasting-improvement-in-aged-stem-cell-function/ CASIN Alters Epigenetic State to Produce Lasting Improvement in Aged Stem Cell Function]. Fight aging.

	== References ==		== References ==