CISD2 - Revision history

Andrea: category change

2022-12-27T11:45:44Z

category change

← Older revision		Revision as of 11:45, 27 December 2022
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	== Natural compounds that can upregulate CISD2 expression ==		== Natural compounds that can upregulate CISD2 expression ==
	CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice.<ref name=”Rejuvenation”>Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014. https://doi.org/10.3390/ijms232214014</ref>		CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice.<ref name=”Rejuvenation”>Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014. https://doi.org/10.3390/ijms232214014</ref>
	Treatment with dietary '''hesperetin''', starting at 19–21 month old, has shown to enhance CISD2 gene expression and extend the lifespan and healthspan of mice. In addition, hesperidin and its aglycone, hesperetin treatment appears to attenuate whole-body metabolic decline, reducing fat and improving glucose homeostasis, as well as slowing down heart and skeletal muscle aging.<ref name=”Hesperetin”>Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., ... & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. PMID: 35871686 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310407 9310407] DOI: 10.1186/s12929-022-00838-7</ref><ref name=”Rejuvenation”/> Hesperetin has various beneficial biological properties, which confer cardioprotective<ref>Liu, P., Li, J., Liu, M., Zhang, M., Xue, Y., Zhang, Y., ... & Chu, L. (2021). Hesperetin modulates the Sirt1/Nrf2 signaling pathway in counteracting myocardial ischemia through suppression of oxidative stress, inflammation, and apoptosis. Biomedicine & Pharmacotherapy, 139, 111552. PMID: 33839495 DOI:[https://doi.org/10.1016/j.biopha.2021.111552 10.1016/j.biopha.2021.111552]</ref>, anticancer,<ref>Pandey, P., & Khan, F. (2021). A mechanistic review of the anticancer potential of hesperidin, a natural flavonoid from citrus fruits. Nutrition Research, 92, 21-31. PMID: 34273640 DOI:[https://doi.org/10.1016/j.nutres.2021.05.011 10.1016/j.nutres.2021.05.011]</ref><ref>Yap, K. M., Sekar, M., Wu, Y. S., Gan, S. H., Rani, N. N. I. M., Seow, L. J., ... & Lum, P. T. (2021). Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects. Saudi Journal of Biological Sciences, 28(12), 6730-6747 PMID:34866972 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626310 PMC8626310] DOI: 10.1016/j.sjbs.2021.07.046.</ref> antidiabetic effects,<ref>Yang, H., Wang, Y., Xu, S., Ren, J., Tang, L., Gong, J., ... & Su, D. (2022). Hesperetin, a promising treatment option for diabetes and related complications: A literature review. Journal of Agricultural and Food Chemistry, 70(28), 8582-8592. PMID:35801973 DOI:[https://doi.org/10.1021/acs.jafc.2c03257 10.1021/acs.jafc.2c03257]</ref><ref name=”Wdowiak”>Wdowiak, K., Walkowiak, J., Pietrzak, R., Bazan-Woźniak, A., & Cielecka-Piontek, J. (2022). Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review. Nutrients, 14(13), 2647. PMID: 35807828 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268531 9268531] DOI: 10.3390/nu14132647</ref> protective effect against bone loss,<ref>Ortiz, A. D. C., Fideles, S. O. M., Reis, C. H. B., Bellini, M. Z., Pereira, E. D. S. B. M., Pilon, J. P. G., ... & Buchaim, R. L. (2022). Therapeutic Effects of Citrus Flavonoids Neohesperidin, Hesperidin and Its Aglycone, Hesperetin on Bone Health. Biomolecules, 12(5), 626. PMID:35625554 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138288/ 9138288] DOI: 10.3390/biom12050626</ref> skin aging<ref>Man, M. Q., Yang, B., & Elias, P. M. (2019). Benefits of hesperidin for cutaneous functions. Evidence-Based Complementary and Alternative Medicine, 2019. PMID: 31061668 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466919 6466919] DOI: 10.1155/2019/2676307</ref> and also against neurodegeneration triggered by aging<ref name=”Wdowiak”/><ref>Evans, J. A., Mendonca, P., & Soliman, K. F. (2022). Neuroprotective Effects and Therapeutic Potential of the Citrus Flavonoid Hesperetin in Neurodegenerative Diseases. Nutrients, 14(11), 2228. PMID:35684025 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183194 9183194] DOI: 10.3390/nu14112228</ref>		Treatment with dietary '''hesperetin''', starting at 19–21 month old, has shown to enhance CISD2 gene expression and extend the lifespan and healthspan of mice. In addition, hesperidin and its aglycone, hesperetin treatment appears to attenuate whole-body metabolic decline, reducing fat and improving glucose homeostasis, as well as slowing down heart and skeletal muscle aging.<ref name=”Hesperetin”>Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., ... & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. PMID: 35871686 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310407 9310407] DOI: 10.1186/s12929-022-00838-7</ref><ref name=”Rejuvenation”/> Hesperetin has various beneficial biological properties, which confer cardioprotective<ref>Liu, P., Li, J., Liu, M., Zhang, M., Xue, Y., Zhang, Y., ... & Chu, L. (2021). Hesperetin modulates the Sirt1/Nrf2 signaling pathway in counteracting myocardial ischemia through suppression of oxidative stress, inflammation, and apoptosis. Biomedicine & Pharmacotherapy, 139, 111552. PMID: 33839495 DOI:[https://doi.org/10.1016/j.biopha.2021.111552 10.1016/j.biopha.2021.111552]</ref>, anticancer,<ref>Pandey, P., & Khan, F. (2021). A mechanistic review of the anticancer potential of hesperidin, a natural flavonoid from citrus fruits. Nutrition Research, 92, 21-31. PMID: 34273640 DOI:[https://doi.org/10.1016/j.nutres.2021.05.011 10.1016/j.nutres.2021.05.011]</ref><ref>Yap, K. M., Sekar, M., Wu, Y. S., Gan, S. H., Rani, N. N. I. M., Seow, L. J., ... & Lum, P. T. (2021). Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects. Saudi Journal of Biological Sciences, 28(12), 6730-6747 PMID:34866972 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626310 PMC8626310] DOI: 10.1016/j.sjbs.2021.07.046.</ref> antidiabetic effects,<ref>Yang, H., Wang, Y., Xu, S., Ren, J., Tang, L., Gong, J., ... & Su, D. (2022). Hesperetin, a promising treatment option for diabetes and related complications: A literature review. Journal of Agricultural and Food Chemistry, 70(28), 8582-8592. PMID:35801973 DOI:[https://doi.org/10.1021/acs.jafc.2c03257 10.1021/acs.jafc.2c03257]</ref><ref name=”Wdowiak”>Wdowiak, K., Walkowiak, J., Pietrzak, R., Bazan-Woźniak, A., & Cielecka-Piontek, J. (2022). Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review. Nutrients, 14(13), 2647. PMID: 35807828 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268531 9268531] DOI: 10.3390/nu14132647</ref> protective effect against bone loss,<ref>Ortiz, A. D. C., Fideles, S. O. M., Reis, C. H. B., Bellini, M. Z., Pereira, E. D. S. B. M., Pilon, J. P. G., ... & Buchaim, R. L. (2022). Therapeutic Effects of Citrus Flavonoids Neohesperidin, Hesperidin and Its Aglycone, Hesperetin on Bone Health. Biomolecules, 12(5), 626. PMID:35625554 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138288/ 9138288] DOI: 10.3390/biom12050626</ref> skin aging<ref>Man, M. Q., Yang, B., & Elias, P. M. (2019). Benefits of hesperidin for cutaneous functions. Evidence-Based Complementary and Alternative Medicine, 2019. PMID: 31061668 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466919 6466919] DOI: 10.1155/2019/2676307</ref> and also against neurodegeneration triggered by aging.<ref name=”Wdowiak”/><ref>Evans, J. A., Mendonca, P., & Soliman, K. F. (2022). Neuroprotective Effects and Therapeutic Potential of the Citrus Flavonoid Hesperetin in Neurodegenerative Diseases. Nutrients, 14(11), 2228. PMID:35684025 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183194 9183194] DOI: 10.3390/nu14112228</ref>

	The beneficial anti-aging effects of hesperidin and its aglycone, hesperetin are largely dependent on CISD2 as revealed from transcriptomic analysis - most (79%) of the genes influenced by hesperetin lost their differential expression patterns in the absence of CISD2.<ref name=”Hesperetin”/><ref name=”Rejuvenation”/> It would be interesting to check in the same way if the anti-aging effects of naringenin also depend on CISD2.<ref>ur Rehman, M. F., Batool, A. I., Qadir, R., & Aslam, M. (2021). Hesperidin and naringenin. In A centum of valuable plant bioactives (pp. 403-444). Academic Press. https://doi.org/10.1016/B978-0-12-822923-1.00027-3 </ref>		The beneficial anti-aging effects of hesperidin and its aglycone, hesperetin are largely dependent on CISD2 as revealed from transcriptomic analysis - most (79%) of the genes influenced by hesperetin lost their differential expression patterns in the absence of CISD2.<ref name=”Hesperetin”/><ref name=”Rejuvenation”/> It would be interesting to check in the same way if the anti-aging effects of naringenin also depend on CISD2.<ref>ur Rehman, M. F., Batool, A. I., Qadir, R., & Aslam, M. (2021). Hesperidin and naringenin. In A centum of valuable plant bioactives (pp. 403-444). Academic Press. https://doi.org/10.1016/B978-0-12-822923-1.00027-3 </ref>
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	Inclusion complexes of hesperidin or hesperetin with hydroxypropyl β-cyclodextrin<ref>Wdowiak, K., Rosiak, N., Tykarska, E., Żarowski, M., Płazińska, A., Płaziński, W., & Cielecka-Piontek, J. (2022). Amorphous Inclusion Complexes: Molecular Interactions of Hesperidin and Hesperetin with HP-Β-CD and Their Biological Effects. International journal of molecular sciences, 23(7), 4000. PMID: 35409360 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000012 9000012] DOI: 10.3390/ijms23074000</ref> or Soluplus®, alginate sodium, and hydroxypropylmethylcellulose in a 1:5 w/w ratio,<ref>Rosiak, N., Wdowiak, K., Tykarska, E., & Cielecka-Piontek, J. (2022). Amorphous Solid Dispersion of Hesperidin with Polymer Excipients for Enhanced Apparent Solubility as a More Effective Approach to the Treatment of Civilization Diseases. International Journal of Molecular Sciences, 23(23), 15198. https://doi.org/10.3390/ijms232315198</ref> increase solubility and antioxidant potential. Such solid dispersions are promising delivery systems of hesperidin, and they can pose a more effective approach to treating civilization diseases.		Inclusion complexes of hesperidin or hesperetin with hydroxypropyl β-cyclodextrin<ref>Wdowiak, K., Rosiak, N., Tykarska, E., Żarowski, M., Płazińska, A., Płaziński, W., & Cielecka-Piontek, J. (2022). Amorphous Inclusion Complexes: Molecular Interactions of Hesperidin and Hesperetin with HP-Β-CD and Their Biological Effects. International journal of molecular sciences, 23(7), 4000. PMID: 35409360 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000012 9000012] DOI: 10.3390/ijms23074000</ref> or Soluplus®, alginate sodium, and hydroxypropylmethylcellulose in a 1:5 w/w ratio,<ref>Rosiak, N., Wdowiak, K., Tykarska, E., & Cielecka-Piontek, J. (2022). Amorphous Solid Dispersion of Hesperidin with Polymer Excipients for Enhanced Apparent Solubility as a More Effective Approach to the Treatment of Civilization Diseases. International Journal of Molecular Sciences, 23(23), 15198. https://doi.org/10.3390/ijms232315198</ref> increase solubility and antioxidant potential. Such solid dispersions are promising delivery systems of hesperidin, and they can pose a more effective approach to treating civilization diseases.

	The principal bright yellow compound obtained from the root of turmeric (''Curcuma longa'') named '''curcumin''' also was found to increase the CISD2 protein level in the astrocytes of the spinal cords of old mice<ref>Lin, C. C., Chiang, T. H., Chen, W. J., Sun, Y. Y., Lee, Y. H., & Lin, M. S. (2015). CISD2 serves a novel role as a suppressor of nitric oxide signalling and curcumin increases CISD2 expression in spinal cord injuries. Injury, 46(12), 2341-2350. PMID: 26387034 DOI:[https://doi.org/10.1016/j.injury.2015.07.040 10.1016/j.injury.2015.07.040]</ref><ref> Lin, C. C., Chiang, T. H., Sun, Y. Y., & Lin, M. S. (2019). Protective effects of CISD2 and influence of curcumin on CISD2 expression in aged animals and inflammatory cell model. Nutrients, 11(3), 700. PMID: 30934593 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470567 6470567] DOI: 10.3390/nu11030700</ref>		The principal bright yellow compound obtained from the root of turmeric (''Curcuma longa'') named '''curcumin''' also was found to increase the CISD2 protein level in the astrocytes of the spinal cords of old mice.<ref>Lin, C. C., Chiang, T. H., Chen, W. J., Sun, Y. Y., Lee, Y. H., & Lin, M. S. (2015). CISD2 serves a novel role as a suppressor of nitric oxide signalling and curcumin increases CISD2 expression in spinal cord injuries. Injury, 46(12), 2341-2350. PMID: 26387034 DOI:[https://doi.org/10.1016/j.injury.2015.07.040 10.1016/j.injury.2015.07.040]</ref><ref> Lin, C. C., Chiang, T. H., Sun, Y. Y., & Lin, M. S. (2019). Protective effects of CISD2 and influence of curcumin on CISD2 expression in aged animals and inflammatory cell model. Nutrients, 11(3), 700. PMID: 30934593 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470567 6470567] DOI: 10.3390/nu11030700</ref>

	== References ==		== References ==
	<references />		<references />
	[[Category:~~Genes affecting longevity~~]]		[[Category:Main list]]
	[[Category:Longevity]]		[[Category:Longevity genes]]

Dmitry Dzhagarov: /* Natural compounds that can upregulate CISD2 expression */

2022-12-12T10:07:33Z

Natural compounds that can upregulate CISD2 expression

← Older revision		Revision as of 10:07, 12 December 2022
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	== Natural compounds that can upregulate CISD2 expression ==		== Natural compounds that can upregulate CISD2 expression ==
	CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice.<ref name=”Rejuvenation”>Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014. https://doi.org/10.3390/ijms232214014</ref>		CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice.<ref name=”Rejuvenation”>Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014. https://doi.org/10.3390/ijms232214014</ref>
	Treatment with dietary '''hesperetin''', starting at 19–21 month old, has shown to enhance CISD2 gene expression and extend the lifespan and healthspan of mice. ~~In addition,~~ In addition, hesperidin and its aglycone, hesperetin treatment appears to attenuate whole-body metabolic decline, reducing fat and improving glucose homeostasis, as well as slowing down heart and skeletal muscle aging.<ref name=”Hesperetin”>Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., ... & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. PMID: 35871686 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310407 9310407] DOI: 10.1186/s12929-022-00838-7</ref><ref name=”Rejuvenation”/> Hesperetin has various beneficial biological properties, which confer cardioprotective<ref>Liu, P., Li, J., Liu, M., Zhang, M., Xue, Y., Zhang, Y., ... & Chu, L. (2021). Hesperetin modulates the Sirt1/Nrf2 signaling pathway in counteracting myocardial ischemia through suppression of oxidative stress, inflammation, and apoptosis. Biomedicine & Pharmacotherapy, 139, 111552. PMID: 33839495 DOI:[https://doi.org/10.1016/j.biopha.2021.111552 10.1016/j.biopha.2021.111552]</ref>, anticancer,<ref>Pandey, P., & Khan, F. (2021). A mechanistic review of the anticancer potential of hesperidin, a natural flavonoid from citrus fruits. Nutrition Research, 92, 21-31. PMID: 34273640 DOI:[https://doi.org/10.1016/j.nutres.2021.05.011 10.1016/j.nutres.2021.05.011]</ref><ref>Yap, K. M., Sekar, M., Wu, Y. S., Gan, S. H., Rani, N. N. I. M., Seow, L. J., ... & Lum, P. T. (2021). Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects. Saudi Journal of Biological Sciences, 28(12), 6730-6747 PMID:34866972 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626310 PMC8626310] DOI: 10.1016/j.sjbs.2021.07.046.</ref> antidiabetic effects,<ref>Yang, H., Wang, Y., Xu, S., Ren, J., Tang, L., Gong, J., ... & Su, D. (2022). Hesperetin, a promising treatment option for diabetes and related complications: A literature review. Journal of Agricultural and Food Chemistry, 70(28), 8582-8592. PMID:35801973 DOI:[https://doi.org/10.1021/acs.jafc.2c03257 10.1021/acs.jafc.2c03257]</ref><ref name=”Wdowiak”>Wdowiak, K., Walkowiak, J., Pietrzak, R., Bazan-Woźniak, A., & Cielecka-Piontek, J. (2022). Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review. Nutrients, 14(13), 2647. PMID: 35807828 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268531 9268531] DOI: 10.3390/nu14132647</ref> protective effect against bone loss<ref>Ortiz, A. D. C., Fideles, S. O. M., Reis, C. H. B., Bellini, M. Z., Pereira, E. D. S. B. M., Pilon, J. P. G., ... & Buchaim, R. L. (2022). Therapeutic Effects of Citrus Flavonoids Neohesperidin, Hesperidin and Its Aglycone, Hesperetin on Bone Health. Biomolecules, 12(5), 626. PMID:35625554 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138288/ 9138288] DOI: 10.3390/biom12050626</ref> skin aging<ref>Man, M. Q., Yang, B., & Elias, P. M. (2019). Benefits of hesperidin for cutaneous functions. Evidence-Based Complementary and Alternative Medicine, 2019. PMID: 31061668 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466919 6466919] DOI: 10.1155/2019/2676307</ref> and also against neurodegeneration triggered by aging<ref name=”Wdowiak”/><ref>Evans, J. A., Mendonca, P., & Soliman, K. F. (2022). Neuroprotective Effects and Therapeutic Potential of the Citrus Flavonoid Hesperetin in Neurodegenerative Diseases. Nutrients, 14(11), 2228. PMID:35684025 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183194 9183194] DOI: 10.3390/nu14112228</ref>		Treatment with dietary '''hesperetin''', starting at 19–21 month old, has shown to enhance CISD2 gene expression and extend the lifespan and healthspan of mice. In addition, hesperidin and its aglycone, hesperetin treatment appears to attenuate whole-body metabolic decline, reducing fat and improving glucose homeostasis, as well as slowing down heart and skeletal muscle aging.<ref name=”Hesperetin”>Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., ... & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. PMID: 35871686 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310407 9310407] DOI: 10.1186/s12929-022-00838-7</ref><ref name=”Rejuvenation”/> Hesperetin has various beneficial biological properties, which confer cardioprotective<ref>Liu, P., Li, J., Liu, M., Zhang, M., Xue, Y., Zhang, Y., ... & Chu, L. (2021). Hesperetin modulates the Sirt1/Nrf2 signaling pathway in counteracting myocardial ischemia through suppression of oxidative stress, inflammation, and apoptosis. Biomedicine & Pharmacotherapy, 139, 111552. PMID: 33839495 DOI:[https://doi.org/10.1016/j.biopha.2021.111552 10.1016/j.biopha.2021.111552]</ref>, anticancer,<ref>Pandey, P., & Khan, F. (2021). A mechanistic review of the anticancer potential of hesperidin, a natural flavonoid from citrus fruits. Nutrition Research, 92, 21-31. PMID: 34273640 DOI:[https://doi.org/10.1016/j.nutres.2021.05.011 10.1016/j.nutres.2021.05.011]</ref><ref>Yap, K. M., Sekar, M., Wu, Y. S., Gan, S. H., Rani, N. N. I. M., Seow, L. J., ... & Lum, P. T. (2021). Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects. Saudi Journal of Biological Sciences, 28(12), 6730-6747 PMID:34866972 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626310 PMC8626310] DOI: 10.1016/j.sjbs.2021.07.046.</ref> antidiabetic effects,<ref>Yang, H., Wang, Y., Xu, S., Ren, J., Tang, L., Gong, J., ... & Su, D. (2022). Hesperetin, a promising treatment option for diabetes and related complications: A literature review. Journal of Agricultural and Food Chemistry, 70(28), 8582-8592. PMID:35801973 DOI:[https://doi.org/10.1021/acs.jafc.2c03257 10.1021/acs.jafc.2c03257]</ref><ref name=”Wdowiak”>Wdowiak, K., Walkowiak, J., Pietrzak, R., Bazan-Woźniak, A., & Cielecka-Piontek, J. (2022). Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review. Nutrients, 14(13), 2647. PMID: 35807828 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268531 9268531] DOI: 10.3390/nu14132647</ref> protective effect against bone loss,<ref>Ortiz, A. D. C., Fideles, S. O. M., Reis, C. H. B., Bellini, M. Z., Pereira, E. D. S. B. M., Pilon, J. P. G., ... & Buchaim, R. L. (2022). Therapeutic Effects of Citrus Flavonoids Neohesperidin, Hesperidin and Its Aglycone, Hesperetin on Bone Health. Biomolecules, 12(5), 626. PMID:35625554 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138288/ 9138288] DOI: 10.3390/biom12050626</ref> skin aging<ref>Man, M. Q., Yang, B., & Elias, P. M. (2019). Benefits of hesperidin for cutaneous functions. Evidence-Based Complementary and Alternative Medicine, 2019. PMID: 31061668 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466919 6466919] DOI: 10.1155/2019/2676307</ref> and also against neurodegeneration triggered by aging<ref name=”Wdowiak”/><ref>Evans, J. A., Mendonca, P., & Soliman, K. F. (2022). Neuroprotective Effects and Therapeutic Potential of the Citrus Flavonoid Hesperetin in Neurodegenerative Diseases. Nutrients, 14(11), 2228. PMID:35684025 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183194 9183194] DOI: 10.3390/nu14112228</ref>

	The beneficial anti-aging effects of hesperidin and its aglycone, hesperetin are largely dependent on CISD2 as revealed from transcriptomic analysis - most (79%) of the genes influenced by hesperetin lost their differential expression patterns in the absence of CISD2.<ref name=”Hesperetin”/><ref name=”Rejuvenation”/> It would be interesting to check in the same way if the anti-aging effects of naringenin also depend on CISD2.<ref>ur Rehman, M. F., Batool, A. I., Qadir, R., & Aslam, M. (2021). Hesperidin and naringenin. In A centum of valuable plant bioactives (pp. 403-444). Academic Press. https://doi.org/10.1016/B978-0-12-822923-1.00027-3 </ref>		The beneficial anti-aging effects of hesperidin and its aglycone, hesperetin are largely dependent on CISD2 as revealed from transcriptomic analysis - most (79%) of the genes influenced by hesperetin lost their differential expression patterns in the absence of CISD2.<ref name=”Hesperetin”/><ref name=”Rejuvenation”/> It would be interesting to check in the same way if the anti-aging effects of naringenin also depend on CISD2.<ref>ur Rehman, M. F., Batool, A. I., Qadir, R., & Aslam, M. (2021). Hesperidin and naringenin. In A centum of valuable plant bioactives (pp. 403-444). Academic Press. https://doi.org/10.1016/B978-0-12-822923-1.00027-3 </ref>

Dmitry Dzhagarov: /* Natural compounds that can upregulate CISD2 expression */

2022-12-12T10:04:36Z

Natural compounds that can upregulate CISD2 expression

← Older revision		Revision as of 10:04, 12 December 2022
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	== Natural compounds that can upregulate CISD2 expression ==		== Natural compounds that can upregulate CISD2 expression ==
	CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice.<ref name=”Rejuvenation”>Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014. https://doi.org/10.3390/ijms232214014</ref>		CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice.<ref name=”Rejuvenation”>Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014. https://doi.org/10.3390/ijms232214014</ref>
	Treatment with dietary '''hesperetin''', starting at 19–21 month old, has shown to enhance CISD2 gene expression and extend the lifespan and healthspan of mice. In addition, hesperetin treatment appears to attenuate whole-body metabolic decline, reducing fat and improving glucose homeostasis, as well as slowing down heart and skeletal muscle aging.<ref name=”Hesperetin”>Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., ... & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. PMID: 35871686 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310407 9310407] DOI: 10.1186/s12929-022-00838-7</ref><ref name=”Rejuvenation”/> Hesperetin has various beneficial biological properties, which confer cardioprotective<ref>Liu, P., Li, J., Liu, M., Zhang, M., Xue, Y., Zhang, Y., ... & Chu, L. (2021). Hesperetin modulates the Sirt1/Nrf2 signaling pathway in counteracting myocardial ischemia through suppression of oxidative stress, inflammation, and apoptosis. Biomedicine & Pharmacotherapy, 139, 111552. PMID: 33839495 DOI:[https://doi.org/10.1016/j.biopha.2021.111552 10.1016/j.biopha.2021.111552]</ref>, anticancer,<ref>Pandey, P., & Khan, F. (2021). A mechanistic review of the anticancer potential of hesperidin, a natural flavonoid from citrus fruits. Nutrition Research, 92, 21-31. PMID: 34273640 DOI:[https://doi.org/10.1016/j.nutres.2021.05.011 10.1016/j.nutres.2021.05.011]</ref><ref>Yap, K. M., Sekar, M., Wu, Y. S., Gan, S. H., Rani, N. N. I. M., Seow, L. J., ... & Lum, P. T. (2021). Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects. Saudi Journal of Biological Sciences, 28(12), 6730-6747 PMID:34866972 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626310 PMC8626310] DOI: 10.1016/j.sjbs.2021.07.046.</ref> antidiabetic effects,<ref>Yang, H., Wang, Y., Xu, S., Ren, J., Tang, L., Gong, J., ... & Su, D. (2022). Hesperetin, a promising treatment option for diabetes and related complications: A literature review. Journal of Agricultural and Food Chemistry, 70(28), 8582-8592. PMID:35801973 DOI:[https://doi.org/10.1021/acs.jafc.2c03257 10.1021/acs.jafc.2c03257]</ref><ref name=”Wdowiak”>Wdowiak, K., Walkowiak, J., Pietrzak, R., Bazan-Woźniak, A., & Cielecka-Piontek, J. (2022). Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review. Nutrients, 14(13), 2647. PMID: 35807828 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268531 9268531] DOI: 10.3390/nu14132647</ref> protective effect against bone loss<ref>Ortiz, A. D. C., Fideles, S. O. M., Reis, C. H. B., Bellini, M. Z., Pereira, E. D. S. B. M., Pilon, J. P. G., ... & Buchaim, R. L. (2022). Therapeutic Effects of Citrus Flavonoids Neohesperidin, Hesperidin and Its Aglycone, Hesperetin on Bone Health. Biomolecules, 12(5), 626. PMID:35625554 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138288/ 9138288] DOI: 10.3390/biom12050626</ref> and also against neurodegeneration triggered by aging<ref name=”Wdowiak”/><ref>Evans, J. A., Mendonca, P., & Soliman, K. F. (2022). Neuroprotective Effects and Therapeutic Potential of the Citrus Flavonoid Hesperetin in Neurodegenerative Diseases. Nutrients, 14(11), 2228. PMID:35684025 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/ 9183194] DOI: 10.3390/nu14112228</ref>		Treatment with dietary '''hesperetin''', starting at 19–21 month old, has shown to enhance CISD2 gene expression and extend the lifespan and healthspan of mice. In addition, In addition, hesperidin and its aglycone, hesperetin treatment appears to attenuate whole-body metabolic decline, reducing fat and improving glucose homeostasis, as well as slowing down heart and skeletal muscle aging.<ref name=”Hesperetin”>Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., ... & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. PMID: 35871686 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310407 9310407] DOI: 10.1186/s12929-022-00838-7</ref><ref name=”Rejuvenation”/> Hesperetin has various beneficial biological properties, which confer cardioprotective<ref>Liu, P., Li, J., Liu, M., Zhang, M., Xue, Y., Zhang, Y., ... & Chu, L. (2021). Hesperetin modulates the Sirt1/Nrf2 signaling pathway in counteracting myocardial ischemia through suppression of oxidative stress, inflammation, and apoptosis. Biomedicine & Pharmacotherapy, 139, 111552. PMID: 33839495 DOI:[https://doi.org/10.1016/j.biopha.2021.111552 10.1016/j.biopha.2021.111552]</ref>, anticancer,<ref>Pandey, P., & Khan, F. (2021). A mechanistic review of the anticancer potential of hesperidin, a natural flavonoid from citrus fruits. Nutrition Research, 92, 21-31. PMID: 34273640 DOI:[https://doi.org/10.1016/j.nutres.2021.05.011 10.1016/j.nutres.2021.05.011]</ref><ref>Yap, K. M., Sekar, M., Wu, Y. S., Gan, S. H., Rani, N. N. I. M., Seow, L. J., ... & Lum, P. T. (2021). Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects. Saudi Journal of Biological Sciences, 28(12), 6730-6747 PMID:34866972 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626310 PMC8626310] DOI: 10.1016/j.sjbs.2021.07.046.</ref> antidiabetic effects,<ref>Yang, H., Wang, Y., Xu, S., Ren, J., Tang, L., Gong, J., ... & Su, D. (2022). Hesperetin, a promising treatment option for diabetes and related complications: A literature review. Journal of Agricultural and Food Chemistry, 70(28), 8582-8592. PMID:35801973 DOI:[https://doi.org/10.1021/acs.jafc.2c03257 10.1021/acs.jafc.2c03257]</ref><ref name=”Wdowiak”>Wdowiak, K., Walkowiak, J., Pietrzak, R., Bazan-Woźniak, A., & Cielecka-Piontek, J. (2022). Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review. Nutrients, 14(13), 2647. PMID: 35807828 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268531 9268531] DOI: 10.3390/nu14132647</ref> protective effect against bone loss<ref>Ortiz, A. D. C., Fideles, S. O. M., Reis, C. H. B., Bellini, M. Z., Pereira, E. D. S. B. M., Pilon, J. P. G., ... & Buchaim, R. L. (2022). Therapeutic Effects of Citrus Flavonoids Neohesperidin, Hesperidin and Its Aglycone, Hesperetin on Bone Health. Biomolecules, 12(5), 626. PMID:35625554 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138288/ 9138288] DOI: 10.3390/biom12050626</ref> skin aging<ref>Man, M. Q., Yang, B., & Elias, P. M. (2019). Benefits of hesperidin for cutaneous functions. Evidence-Based Complementary and Alternative Medicine, 2019. PMID: 31061668 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466919 6466919] DOI: 10.1155/2019/2676307</ref> and also against neurodegeneration triggered by aging<ref name=”Wdowiak”/><ref>Evans, J. A., Mendonca, P., & Soliman, K. F. (2022). Neuroprotective Effects and Therapeutic Potential of the Citrus Flavonoid Hesperetin in Neurodegenerative Diseases. Nutrients, 14(11), 2228. PMID:35684025 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183194 9183194] DOI: 10.3390/nu14112228</ref>

	The beneficial anti-aging effects of hesperetin are largely dependent on CISD2 as revealed from transcriptomic analysis - most (79%) of the genes influenced by hesperetin lost their differential expression patterns in the absence of CISD2.<ref name=”Hesperetin”/><ref name=”Rejuvenation”/> It would be interesting to check in the same way if the anti-aging effects of naringenin also depend on CISD2.<ref>ur Rehman, M. F., Batool, A. I., Qadir, R., & Aslam, M. (2021). Hesperidin and naringenin. In A centum of valuable plant bioactives (pp. 403-444). Academic Press. https://doi.org/10.1016/B978-0-12-822923-1.00027-3 </ref>		The beneficial anti-aging effects of hesperidin and its aglycone, hesperetin are largely dependent on CISD2 as revealed from transcriptomic analysis - most (79%) of the genes influenced by hesperetin lost their differential expression patterns in the absence of CISD2.<ref name=”Hesperetin”/><ref name=”Rejuvenation”/> It would be interesting to check in the same way if the anti-aging effects of naringenin also depend on CISD2.<ref>ur Rehman, M. F., Batool, A. I., Qadir, R., & Aslam, M. (2021). Hesperidin and naringenin. In A centum of valuable plant bioactives (pp. 403-444). Academic Press. https://doi.org/10.1016/B978-0-12-822923-1.00027-3 </ref>

	Hesperetin is a well-known bioflavonoid that is found in ~~small amounts~~ in ~~sauerkraut~~, as well as in numerous types of citrus fruits including- oranges, grapefruit, and tangerines upon ingestion.<ref>Erlund, I. (2004). Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutrition research, 24(10), 851-874. https://doi.org/10.1016/j.nutres.2004.07.005</ref><ref>Sohel, M., Sultana, H., Sultana, T., Al Amin, M., Aktar, S., Ali, M. C., ... & Dash, R. (2022). Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: a comprehensive review. Heliyon, e08815.PMID: 35128104 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810372 8810372] DOI: 10.1016/j.heliyon.2022.e08815</ref><ref name=”Wdowiak”/>		Hesperetin is a well-known bioflavonoid that is found in dried peppermint leaves (60-200 mg/100 g),<ref>[http://phenol-explorer.eu/contents/show/2/207/732 Hesperidin in Peppermint, dried]</ref> as well as in numerous types of citrus fruits including- oranges, grapefruit, and tangerines upon ingestion, also in small amounts in sauerkraut.<ref>Erlund, I. (2004). Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutrition research, 24(10), 851-874. https://doi.org/10.1016/j.nutres.2004.07.005</ref><ref>Sohel, M., Sultana, H., Sultana, T., Al Amin, M., Aktar, S., Ali, M. C., ... & Dash, R. (2022). Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: a comprehensive review. Heliyon, e08815.PMID: 35128104 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810372 8810372] DOI: 10.1016/j.heliyon.2022.e08815</ref><ref name=”Wdowiak”/>

			Inclusion complexes of hesperidin or hesperetin with hydroxypropyl β-cyclodextrin<ref>Wdowiak, K., Rosiak, N., Tykarska, E., Żarowski, M., Płazińska, A., Płaziński, W., & Cielecka-Piontek, J. (2022). Amorphous Inclusion Complexes: Molecular Interactions of Hesperidin and Hesperetin with HP-Β-CD and Their Biological Effects. International journal of molecular sciences, 23(7), 4000. PMID: 35409360 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000012 9000012] DOI: 10.3390/ijms23074000</ref> or Soluplus®, alginate sodium, and hydroxypropylmethylcellulose in a 1:5 w/w ratio,<ref>Rosiak, N., Wdowiak, K., Tykarska, E., & Cielecka-Piontek, J. (2022). Amorphous Solid Dispersion of Hesperidin with Polymer Excipients for Enhanced Apparent Solubility as a More Effective Approach to the Treatment of Civilization Diseases. International Journal of Molecular Sciences, 23(23), 15198. https://doi.org/10.3390/ijms232315198</ref> increase solubility and antioxidant potential. Such solid dispersions are promising delivery systems of hesperidin, and they can pose a more effective approach to treating civilization diseases.

	The principal bright yellow compound obtained from the root of turmeric (''Curcuma longa'') named '''curcumin''' also was found to increase the CISD2 protein level in the astrocytes of the spinal cords of old mice<ref>Lin, C. C., Chiang, T. H., Chen, W. J., Sun, Y. Y., Lee, Y. H., & Lin, M. S. (2015). CISD2 serves a novel role as a suppressor of nitric oxide signalling and curcumin increases CISD2 expression in spinal cord injuries. Injury, 46(12), 2341-2350. PMID: 26387034 DOI:[https://doi.org/10.1016/j.injury.2015.07.040 10.1016/j.injury.2015.07.040]</ref><ref> Lin, C. C., Chiang, T. H., Sun, Y. Y., & Lin, M. S. (2019). Protective effects of CISD2 and influence of curcumin on CISD2 expression in aged animals and inflammatory cell model. Nutrients, 11(3), 700. PMID: 30934593 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470567 6470567] DOI: 10.3390/nu11030700</ref>		The principal bright yellow compound obtained from the root of turmeric (''Curcuma longa'') named '''curcumin''' also was found to increase the CISD2 protein level in the astrocytes of the spinal cords of old mice<ref>Lin, C. C., Chiang, T. H., Chen, W. J., Sun, Y. Y., Lee, Y. H., & Lin, M. S. (2015). CISD2 serves a novel role as a suppressor of nitric oxide signalling and curcumin increases CISD2 expression in spinal cord injuries. Injury, 46(12), 2341-2350. PMID: 26387034 DOI:[https://doi.org/10.1016/j.injury.2015.07.040 10.1016/j.injury.2015.07.040]</ref><ref> Lin, C. C., Chiang, T. H., Sun, Y. Y., & Lin, M. S. (2019). Protective effects of CISD2 and influence of curcumin on CISD2 expression in aged animals and inflammatory cell model. Nutrients, 11(3), 700. PMID: 30934593 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470567 6470567] DOI: 10.3390/nu11030700</ref>

Dmitry Dzhagarov: /* Cisd2 level is a key determinant of lifespan and healthspan */

2022-12-11T12:23:43Z

Cisd2 level is a key determinant of lifespan and healthspan

← Older revision		Revision as of 12:23, 11 December 2022
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	CISD2 knockout mice also show accelerated aging, blindness, an abnormal skeleton, and muscle atrophy, effects that are very similar to those described in the WFS2 patients.<ref name=”diseases”/> <ref>Amr, S., Heisey, C., Zhang, M., Xia, X. J., Shows, K. H., Ajlouni, K., ... & Shiang, R. (2007). A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. The American Journal of Human Genetics, 81(4), 673-683. https://doi.org/10.1086/520961</ref>		CISD2 knockout mice also show accelerated aging, blindness, an abnormal skeleton, and muscle atrophy, effects that are very similar to those described in the WFS2 patients.<ref name=”diseases”/> <ref>Amr, S., Heisey, C., Zhang, M., Xia, X. J., Shows, K. H., Ajlouni, K., ... & Shiang, R. (2007). A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. The American Journal of Human Genetics, 81(4), 673-683. https://doi.org/10.1086/520961</ref>
	== Cisd2 level is a key determinant of lifespan and healthspan ==		== Cisd2 level is a key determinant of lifespan and healthspan ==
	Mouse Cisd2 deficiency shortens lifespan and accelerates aging that results in premature aging.<ref>Chen, Y. F., Kao, C. H., Chen, Y. T., Wang, C. H., Wu, C. Y., Tsai, C. Y., ... & Tsai, T. F. (2009). Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes & development, 23(10), 1183-1194. PMID: 19451219 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685531 2685531] DOI: 10.1101/gad.1779509 </ref>		Mouse Cisd2 deficiency shortens lifespan and accelerates aging that results in premature aging.<ref>Chen, Y. F., Kao, C. H., Chen, Y. T., Wang, C. H., Wu, C. Y., Tsai, C. Y., ... & Tsai, T. F. (2009). Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes & development, 23(10), 1183-1194. PMID: 19451219 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685531 2685531] DOI: 10.1101/gad.1779509 </ref>
	[[File:CISD2 activator.jpg\|thumb\|Beneficial effects of exercise and Cisd2 overexpression delay aging in skeletal muscle.<ref name="Teng">Teng, Y. C., Wang, J. Y., Chi, Y. H., & Tsai, T. F. (2020). Exercise and the Cisd2 Prolongevity Gene: Two Promising Strategies to Delay the Aging of Skeletal Muscle. Int. J. Mol. Sci, 21, 9059. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731423/ https://doi.org/10.3390/ijms21239059</ref>]]		[[File:CISD2 activator.jpg\|thumb\|Beneficial effects of exercise and Cisd2 overexpression delay aging in skeletal muscle.<ref name="Teng">Teng, Y. C., Wang, J. Y., Chi, Y. H., & Tsai, T. F. (2020). Exercise and the Cisd2 Prolongevity Gene: Two Promising Strategies to Delay the Aging of Skeletal Muscle. Int. J. Mol. Sci, 21, 9059. PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731423/ 7731423] Doi:[https://doi.org/10.3390/ijms21239059 10.3390/ijms21239059]</ref>]]
	Cisd2 is essential to delaying cardiac aging and to maintaining heart functions. Cisd2 deficiency causes intercalated disc defects and leads to degeneration of the mitochondria and sarcomeres, thereby impairing its electromechanical functioning. Cisd2 deficiency also disrupts Ca<sup>2+</sup> homeostasis via dysregulation of sarco/endoplasmic reticulum Ca<sup>2+</sup>-ATPase activity, resulting in an increased level of basal cytosolic Ca<sup>2+</sup> and mitochondrial Ca<sup>2+</sup> overload in cardiomyocytes.<ref>Yeh, C. H., Shen, Z. Q., Hsiung, S. Y., Wu, P. C., Teng, Y. C., Chou, Y. J., ... & Tsai, T. F. (2019). Cisd2 is essential to delaying cardiac aging and to maintaining heart functions. PLoS biology, 17(10), e3000508. </ref>		Cisd2 is essential to delaying cardiac aging and to maintaining heart functions. Cisd2 deficiency causes intercalated disc defects and leads to degeneration of the mitochondria and sarcomeres, thereby impairing its electromechanical functioning. Cisd2 deficiency also disrupts Ca<sup>2+</sup> homeostasis via dysregulation of sarco/endoplasmic reticulum Ca<sup>2+</sup>-ATPase activity, resulting in an increased level of basal cytosolic Ca<sup>2+</sup> and mitochondrial Ca<sup>2+</sup> overload in cardiomyocytes.<ref>Yeh, C. H., Shen, Z. Q., Hsiung, S. Y., Wu, P. C., Teng, Y. C., Chou, Y. J., ... & Tsai, T. F. (2019). Cisd2 is essential to delaying cardiac aging and to maintaining heart functions. PLoS biology, 17(10), e3000508. PMID: 31593566 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799937/ 6799937] DOI:[https://doi.org/10.1371/journal.pbio.3000508 10.1371/journal.pbio.3000508]</ref>

	Conversely, a persistently high level of Cisd2 promotes longevity.<ref name=”persistent”>Wu, C. Y., Chen, Y. F., Wang, C. H., Kao, C. H., Zhuang, H. W., Chen, C. C., ... & Tsai, T. F. (2012). A persistent level of Cisd2 extends healthy lifespan and delays aging in mice. Human molecular genetics, 21(18), 3956-3968. PMID: 22661501 DOI:[https://doi.org/10.1093/hmg/dds210 10.1093/hmg/dds210]</ref> CISD2 protects cardiomyocytes from overaccumulation of iron, which is common in aging hearts and can contribute to the pathogenesis of heart failure.<ref name=”iron”> Karmi, O., Rowland, L., King, S. D., Manrique‐Acevedo, C., Cabantchik, I. Z., Nechushtai, R., & Mittler, R. (2022). The [2Fe‐2S] protein CISD2 plays a key role in preventing iron accumulation in cardiomyocytes. FEBS letters, 596(6), 747-761. PMID: 34997963 DOI: [https://doi.org/10.1002/1873-3468.14277 10.1002/1873-3468.14277]</ref>		Conversely, a persistently high level of Cisd2 promotes longevity.<ref name=”persistent”>Wu, C. Y., Chen, Y. F., Wang, C. H., Kao, C. H., Zhuang, H. W., Chen, C. C., ... & Tsai, T. F. (2012). A persistent level of Cisd2 extends healthy lifespan and delays aging in mice. Human molecular genetics, 21(18), 3956-3968. PMID: 22661501 DOI:[https://doi.org/10.1093/hmg/dds210 10.1093/hmg/dds210]</ref> CISD2 protects cardiomyocytes from overaccumulation of iron, which is common in aging hearts and can contribute to the pathogenesis of heart failure.<ref name=”iron”> Karmi, O., Rowland, L., King, S. D., Manrique‐Acevedo, C., Cabantchik, I. Z., Nechushtai, R., & Mittler, R. (2022). The [2Fe‐2S] protein CISD2 plays a key role in preventing iron accumulation in cardiomyocytes. FEBS letters, 596(6), 747-761. PMID: 34997963 DOI: [https://doi.org/10.1002/1873-3468.14277 10.1002/1873-3468.14277]</ref> Cisd2 overexpression modulates a number of aging-related pathways, namely the [[sirtuins]] signaling, [[autophagy]], and [[Cellular senescence\|senescence]] pathways, to bring about [[rejuvenation]] of the [[Aging-associated diseases\|heart as it enters old age]].<ref>Yeh, C. H., Chou, Y. J., Chu, T. K., & Tsai, T. F. (2021). Rejuvenating the aging heart by enhancing the expression of the cisd2 prolongevity gene. International journal of molecular sciences, 22(21), 11487. PMID: 34768917 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583758/ 8583758] DOI:[https://doi.org/10.3390/ijms222111487 10.3390/ijms222111487]</ref>
	Cisd2 ameliorates age-associated degeneration of the skin, skeletal muscles and neurons. <ref name=”persistent” />		Cisd2 ameliorates age-associated degeneration of the skin, skeletal muscles and neurons. <ref name=”persistent” />
	Moreover, Cisd2 protects mitochondria from age-associated damage and functional decline as well as attenuating the age-associated reduction in whole-body energy metabolism. <ref name=”persistent” />		Moreover, Cisd2 protects mitochondria from age-associated damage and functional decline as well as attenuating the age-associated reduction in whole-body energy metabolism. <ref name=”persistent” />

Dmitry Dzhagarov: /* Natural compounds that can upregulate CISD2 expression */

2022-12-09T18:39:08Z

Natural compounds that can upregulate CISD2 expression

← Older revision		Revision as of 18:39, 9 December 2022
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	== Natural compounds that can upregulate CISD2 expression ==		== Natural compounds that can upregulate CISD2 expression ==
	CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice.<ref name=”Rejuvenation”>Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014. https://doi.org/10.3390/ijms232214014</ref>		CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice.<ref name=”Rejuvenation”>Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014. https://doi.org/10.3390/ijms232214014</ref>
	Treatment with dietary hesperetin, starting at 19–21 month old, has shown to enhance CISD2 gene expression and extend the lifespan and healthspan of mice. In addition, hesperetin treatment appears to attenuate whole-body metabolic decline, reducing fat and improving glucose homeostasis, as well as slowing down heart and skeletal muscle aging.<ref name=”Hesperetin”>Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., ... & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. PMID: 35871686 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310407 9310407] DOI: 10.1186/s12929-022-00838-7</ref><ref name=”Rejuvenation”/> Hesperetin has various beneficial biological properties, which confer cardioprotective<ref>Liu, P., Li, J., Liu, M., Zhang, M., Xue, Y., Zhang, Y., ... & Chu, L. (2021). Hesperetin modulates the Sirt1/Nrf2 signaling pathway in counteracting myocardial ischemia through suppression of oxidative stress, inflammation, and apoptosis. Biomedicine & Pharmacotherapy, 139, 111552. PMID: 33839495 DOI:[https://doi.org/10.1016/j.biopha.2021.111552 10.1016/j.biopha.2021.111552]</ref>, anticancer,<ref>Pandey, P., & Khan, F. (2021). A mechanistic review of the anticancer potential of hesperidin, a natural flavonoid from citrus fruits. Nutrition Research, 92, 21-31. PMID: 34273640 DOI:[https://doi.org/10.1016/j.nutres.2021.05.011 10.1016/j.nutres.2021.05.011]</ref><ref>Yap, K. M., Sekar, M., Wu, Y. S., Gan, S. H., Rani, N. N. I. M., Seow, L. J., ... & Lum, P. T. (2021). Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects. Saudi Journal of Biological Sciences, 28(12), 6730-6747 PMID:34866972 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626310 PMC8626310] DOI: 10.1016/j.sjbs.2021.07.046.</ref> antidiabetic effects,<ref>Yang, H., Wang, Y., Xu, S., Ren, J., Tang, L., Gong, J., ... & Su, D. (2022). Hesperetin, a promising treatment option for diabetes and related complications: A literature review. Journal of Agricultural and Food Chemistry, 70(28), 8582-8592. PMID:35801973 DOI:[https://doi.org/10.1021/acs.jafc.2c03257 10.1021/acs.jafc.2c03257]</ref><ref name=”Wdowiak”>Wdowiak, K., Walkowiak, J., Pietrzak, R., Bazan-Woźniak, A., & Cielecka-Piontek, J. (2022). Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review. Nutrients, 14(13), 2647. PMID: 35807828 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268531 9268531] DOI: 10.3390/nu14132647</ref> protective effect against bone loss<ref>Ortiz, A. D. C., Fideles, S. O. M., Reis, C. H. B., Bellini, M. Z., Pereira, E. D. S. B. M., Pilon, J. P. G., ... & Buchaim, R. L. (2022). Therapeutic Effects of Citrus Flavonoids Neohesperidin, Hesperidin and Its Aglycone, Hesperetin on Bone Health. Biomolecules, 12(5), 626. PMID:35625554 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138288/ 9138288] DOI: 10.3390/biom12050626</ref> and also against neurodegeneration triggered by aging<ref name=”Wdowiak”/><ref>Evans, J. A., Mendonca, P., & Soliman, K. F. (2022). Neuroprotective Effects and Therapeutic Potential of the Citrus Flavonoid Hesperetin in Neurodegenerative Diseases. Nutrients, 14(11), 2228. PMID:35684025 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/ 9183194] DOI: 10.3390/nu14112228</ref>		Treatment with dietary '''hesperetin''', starting at 19–21 month old, has shown to enhance CISD2 gene expression and extend the lifespan and healthspan of mice. In addition, hesperetin treatment appears to attenuate whole-body metabolic decline, reducing fat and improving glucose homeostasis, as well as slowing down heart and skeletal muscle aging.<ref name=”Hesperetin”>Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., ... & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. PMID: 35871686 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310407 9310407] DOI: 10.1186/s12929-022-00838-7</ref><ref name=”Rejuvenation”/> Hesperetin has various beneficial biological properties, which confer cardioprotective<ref>Liu, P., Li, J., Liu, M., Zhang, M., Xue, Y., Zhang, Y., ... & Chu, L. (2021). Hesperetin modulates the Sirt1/Nrf2 signaling pathway in counteracting myocardial ischemia through suppression of oxidative stress, inflammation, and apoptosis. Biomedicine & Pharmacotherapy, 139, 111552. PMID: 33839495 DOI:[https://doi.org/10.1016/j.biopha.2021.111552 10.1016/j.biopha.2021.111552]</ref>, anticancer,<ref>Pandey, P., & Khan, F. (2021). A mechanistic review of the anticancer potential of hesperidin, a natural flavonoid from citrus fruits. Nutrition Research, 92, 21-31. PMID: 34273640 DOI:[https://doi.org/10.1016/j.nutres.2021.05.011 10.1016/j.nutres.2021.05.011]</ref><ref>Yap, K. M., Sekar, M., Wu, Y. S., Gan, S. H., Rani, N. N. I. M., Seow, L. J., ... & Lum, P. T. (2021). Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects. Saudi Journal of Biological Sciences, 28(12), 6730-6747 PMID:34866972 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626310 PMC8626310] DOI: 10.1016/j.sjbs.2021.07.046.</ref> antidiabetic effects,<ref>Yang, H., Wang, Y., Xu, S., Ren, J., Tang, L., Gong, J., ... & Su, D. (2022). Hesperetin, a promising treatment option for diabetes and related complications: A literature review. Journal of Agricultural and Food Chemistry, 70(28), 8582-8592. PMID:35801973 DOI:[https://doi.org/10.1021/acs.jafc.2c03257 10.1021/acs.jafc.2c03257]</ref><ref name=”Wdowiak”>Wdowiak, K., Walkowiak, J., Pietrzak, R., Bazan-Woźniak, A., & Cielecka-Piontek, J. (2022). Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review. Nutrients, 14(13), 2647. PMID: 35807828 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268531 9268531] DOI: 10.3390/nu14132647</ref> protective effect against bone loss<ref>Ortiz, A. D. C., Fideles, S. O. M., Reis, C. H. B., Bellini, M. Z., Pereira, E. D. S. B. M., Pilon, J. P. G., ... & Buchaim, R. L. (2022). Therapeutic Effects of Citrus Flavonoids Neohesperidin, Hesperidin and Its Aglycone, Hesperetin on Bone Health. Biomolecules, 12(5), 626. PMID:35625554 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138288/ 9138288] DOI: 10.3390/biom12050626</ref> and also against neurodegeneration triggered by aging<ref name=”Wdowiak”/><ref>Evans, J. A., Mendonca, P., & Soliman, K. F. (2022). Neuroprotective Effects and Therapeutic Potential of the Citrus Flavonoid Hesperetin in Neurodegenerative Diseases. Nutrients, 14(11), 2228. PMID:35684025 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/ 9183194] DOI: 10.3390/nu14112228</ref>

	The beneficial anti-aging effects of hesperetin are largely dependent on CISD2 as revealed from transcriptomic analysis - most (79%) of the genes influenced by hesperetin lost their differential expression patterns in the absence of CISD2.<ref name=”Hesperetin”/><ref name=”Rejuvenation”/> It would be interesting to check in the same way if the anti-aging effects of naringenin also depend on CISD2.<ref>ur Rehman, M. F., Batool, A. I., Qadir, R., & Aslam, M. (2021). Hesperidin and naringenin. In A centum of valuable plant bioactives (pp. 403-444). Academic Press. https://doi.org/10.1016/B978-0-12-822923-1.00027-3 </ref>		The beneficial anti-aging effects of hesperetin are largely dependent on CISD2 as revealed from transcriptomic analysis - most (79%) of the genes influenced by hesperetin lost their differential expression patterns in the absence of CISD2.<ref name=”Hesperetin”/><ref name=”Rejuvenation”/> It would be interesting to check in the same way if the anti-aging effects of naringenin also depend on CISD2.<ref>ur Rehman, M. F., Batool, A. I., Qadir, R., & Aslam, M. (2021). Hesperidin and naringenin. In A centum of valuable plant bioactives (pp. 403-444). Academic Press. https://doi.org/10.1016/B978-0-12-822923-1.00027-3 </ref>
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	Hesperetin is a well-known bioflavonoid that is found in small amounts in sauerkraut, as well as in numerous types of citrus fruits including- oranges, grapefruit, and tangerines upon ingestion.<ref>Erlund, I. (2004). Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutrition research, 24(10), 851-874. https://doi.org/10.1016/j.nutres.2004.07.005</ref><ref>Sohel, M., Sultana, H., Sultana, T., Al Amin, M., Aktar, S., Ali, M. C., ... & Dash, R. (2022). Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: a comprehensive review. Heliyon, e08815.PMID: 35128104 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810372 8810372] DOI: 10.1016/j.heliyon.2022.e08815</ref><ref name=”Wdowiak”/>		Hesperetin is a well-known bioflavonoid that is found in small amounts in sauerkraut, as well as in numerous types of citrus fruits including- oranges, grapefruit, and tangerines upon ingestion.<ref>Erlund, I. (2004). Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutrition research, 24(10), 851-874. https://doi.org/10.1016/j.nutres.2004.07.005</ref><ref>Sohel, M., Sultana, H., Sultana, T., Al Amin, M., Aktar, S., Ali, M. C., ... & Dash, R. (2022). Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: a comprehensive review. Heliyon, e08815.PMID: 35128104 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810372 8810372] DOI: 10.1016/j.heliyon.2022.e08815</ref><ref name=”Wdowiak”/>

	The principal bright yellow compound obtained from the root of turmeric (''Curcuma longa'') named curcumin also was found to increase the CISD2 protein level in the astrocytes of the spinal cords of old mice<ref>Lin, C. C., Chiang, T. H., Chen, W. J., Sun, Y. Y., Lee, Y. H., & Lin, M. S. (2015). CISD2 serves a novel role as a suppressor of nitric oxide signalling and curcumin increases CISD2 expression in spinal cord injuries. Injury, 46(12), 2341-2350. PMID: 26387034 DOI:[https://doi.org/10.1016/j.injury.2015.07.040 10.1016/j.injury.2015.07.040]</ref><ref> Lin, C. C., Chiang, T. H., Sun, Y. Y., & Lin, M. S. (2019). Protective effects of CISD2 and influence of curcumin on CISD2 expression in aged animals and inflammatory cell model. Nutrients, 11(3), 700. PMID: 30934593 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470567 6470567] DOI: 10.3390/nu11030700</ref>		The principal bright yellow compound obtained from the root of turmeric (''Curcuma longa'') named '''curcumin''' also was found to increase the CISD2 protein level in the astrocytes of the spinal cords of old mice<ref>Lin, C. C., Chiang, T. H., Chen, W. J., Sun, Y. Y., Lee, Y. H., & Lin, M. S. (2015). CISD2 serves a novel role as a suppressor of nitric oxide signalling and curcumin increases CISD2 expression in spinal cord injuries. Injury, 46(12), 2341-2350. PMID: 26387034 DOI:[https://doi.org/10.1016/j.injury.2015.07.040 10.1016/j.injury.2015.07.040]</ref><ref> Lin, C. C., Chiang, T. H., Sun, Y. Y., & Lin, M. S. (2019). Protective effects of CISD2 and influence of curcumin on CISD2 expression in aged animals and inflammatory cell model. Nutrients, 11(3), 700. PMID: 30934593 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470567 6470567] DOI: 10.3390/nu11030700</ref>

	== References ==		== References ==

Dmitry Dzhagarov: /* Natural compounds that can upregulate CISD2 expression */

2022-12-09T18:37:03Z

Natural compounds that can upregulate CISD2 expression

← Older revision		Revision as of 18:37, 9 December 2022
Line 23:		Line 23:
	== Natural compounds that can upregulate CISD2 expression ==		== Natural compounds that can upregulate CISD2 expression ==
	CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice.<ref name=”Rejuvenation”>Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014. https://doi.org/10.3390/ijms232214014</ref>		CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice.<ref name=”Rejuvenation”>Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014. https://doi.org/10.3390/ijms232214014</ref>
	Treatment with dietary [[hesperetin]], starting at 19–21 month old, has shown to enhance CISD2 gene expression and extend the lifespan and healthspan of mice. In addition, hesperetin treatment appears to attenuate whole-body metabolic decline, reducing fat and improving glucose homeostasis, as well as slowing down heart and skeletal muscle aging.<ref name=”Hesperetin”>Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., ... & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. PMID: 35871686 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310407 9310407] DOI: 10.1186/s12929-022-00838-7</ref><ref name=”Rejuvenation”/>		Treatment with dietary hesperetin, starting at 19–21 month old, has shown to enhance CISD2 gene expression and extend the lifespan and healthspan of mice. In addition, hesperetin treatment appears to attenuate whole-body metabolic decline, reducing fat and improving glucose homeostasis, as well as slowing down heart and skeletal muscle aging.<ref name=”Hesperetin”>Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., ... & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. PMID: 35871686 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310407 9310407] DOI: 10.1186/s12929-022-00838-7</ref><ref name=”Rejuvenation”/> Hesperetin has various beneficial biological properties, which confer cardioprotective<ref>Liu, P., Li, J., Liu, M., Zhang, M., Xue, Y., Zhang, Y., ... & Chu, L. (2021). Hesperetin modulates the Sirt1/Nrf2 signaling pathway in counteracting myocardial ischemia through suppression of oxidative stress, inflammation, and apoptosis. Biomedicine & Pharmacotherapy, 139, 111552. PMID: 33839495 DOI:[https://doi.org/10.1016/j.biopha.2021.111552 10.1016/j.biopha.2021.111552]</ref>, anticancer,<ref>Pandey, P., & Khan, F. (2021). A mechanistic review of the anticancer potential of hesperidin, a natural flavonoid from citrus fruits. Nutrition Research, 92, 21-31. PMID: 34273640 DOI:[https://doi.org/10.1016/j.nutres.2021.05.011 10.1016/j.nutres.2021.05.011]</ref><ref>Yap, K. M., Sekar, M., Wu, Y. S., Gan, S. H., Rani, N. N. I. M., Seow, L. J., ... & Lum, P. T. (2021). Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects. Saudi Journal of Biological Sciences, 28(12), 6730-6747 PMID:34866972 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626310 PMC8626310] DOI: 10.1016/j.sjbs.2021.07.046.</ref> antidiabetic effects,<ref>Yang, H., Wang, Y., Xu, S., Ren, J., Tang, L., Gong, J., ... & Su, D. (2022). Hesperetin, a promising treatment option for diabetes and related complications: A literature review. Journal of Agricultural and Food Chemistry, 70(28), 8582-8592. PMID:35801973 DOI:[https://doi.org/10.1021/acs.jafc.2c03257 10.1021/acs.jafc.2c03257]</ref><ref name=”Wdowiak”>Wdowiak, K., Walkowiak, J., Pietrzak, R., Bazan-Woźniak, A., & Cielecka-Piontek, J. (2022). Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review. Nutrients, 14(13), 2647. PMID: 35807828 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268531 9268531] DOI: 10.3390/nu14132647</ref> protective effect against bone loss<ref>Ortiz, A. D. C., Fideles, S. O. M., Reis, C. H. B., Bellini, M. Z., Pereira, E. D. S. B. M., Pilon, J. P. G., ... & Buchaim, R. L. (2022). Therapeutic Effects of Citrus Flavonoids Neohesperidin, Hesperidin and Its Aglycone, Hesperetin on Bone Health. Biomolecules, 12(5), 626. PMID:35625554 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138288/ 9138288] DOI: 10.3390/biom12050626</ref> and also against neurodegeneration triggered by aging<ref name=”Wdowiak”/><ref>Evans, J. A., Mendonca, P., & Soliman, K. F. (2022). Neuroprotective Effects and Therapeutic Potential of the Citrus Flavonoid Hesperetin in Neurodegenerative Diseases. Nutrients, 14(11), 2228. PMID:35684025 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/ 9183194] DOI: 10.3390/nu14112228</ref>

	The beneficial anti-aging effects of hesperetin are largely dependent on CISD2 as revealed from transcriptomic analysis - most (79%) of the genes influenced by hesperetin lost their differential expression patterns in the absence of CISD2.<ref name=”Hesperetin”/><ref name=”Rejuvenation”/> It would be interesting to check in the same way if the anti-aging effects of naringenin also depend on CISD2.<ref>ur Rehman, M. F., Batool, A. I., Qadir, R., & Aslam, M. (2021). Hesperidin and naringenin. In A centum of valuable plant bioactives (pp. 403-444). Academic Press. https://doi.org/10.1016/B978-0-12-822923-1.00027-3 </ref>		The beneficial anti-aging effects of hesperetin are largely dependent on CISD2 as revealed from transcriptomic analysis - most (79%) of the genes influenced by hesperetin lost their differential expression patterns in the absence of CISD2.<ref name=”Hesperetin”/><ref name=”Rejuvenation”/> It would be interesting to check in the same way if the anti-aging effects of naringenin also depend on CISD2.<ref>ur Rehman, M. F., Batool, A. I., Qadir, R., & Aslam, M. (2021). Hesperidin and naringenin. In A centum of valuable plant bioactives (pp. 403-444). Academic Press. https://doi.org/10.1016/B978-0-12-822923-1.00027-3 </ref>

	Hesperetin is a well-known bioflavonoid that is found in small amounts in sauerkraut, as well as in numerous types of citrus fruits including- oranges, grapefruit, and tangerines upon ingestion.<ref>Erlund, I. (2004). Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutrition research, 24(10), 851-874. https://doi.org/10.1016/j.nutres.2004.07.005</ref><ref>Sohel, M., Sultana, H., Sultana, T., Al Amin, M., Aktar, S., Ali, M. C., ... & Dash, R. (2022). Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: a comprehensive review. Heliyon, e08815.PMID: 35128104 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810372 8810372] DOI: 10.1016/j.heliyon.2022.e08815</ref><ref>Wdowiak, K., Walkowiak, J., Pietrzak, R., Bazan-Woźniak, A., & Cielecka-Piontek, J. (2022). Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review. Nutrients, 14(13), 2647. PMID: 35807828 PMC[https:/~~/www.ncbi.nlm.nih.gov/pmc/articles/PMC9268531 9268531] DOI: 10.3390/nu14132647</ref~~>		Hesperetin is a well-known bioflavonoid that is found in small amounts in sauerkraut, as well as in numerous types of citrus fruits including- oranges, grapefruit, and tangerines upon ingestion.<ref>Erlund, I. (2004). Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutrition research, 24(10), 851-874. https://doi.org/10.1016/j.nutres.2004.07.005</ref><ref>Sohel, M., Sultana, H., Sultana, T., Al Amin, M., Aktar, S., Ali, M. C., ... & Dash, R. (2022). Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: a comprehensive review. Heliyon, e08815.PMID: 35128104 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810372 8810372] DOI: 10.1016/j.heliyon.2022.e08815</ref><ref name=”Wdowiak”/>

	The principal bright yellow compound obtained from the root of turmeric (''Curcuma longa'') named curcumin also was found to increase the CISD2 protein level in the astrocytes of the spinal cords of old mice<ref>Lin, C. C., Chiang, T. H., Chen, W. J., Sun, Y. Y., Lee, Y. H., & Lin, M. S. (2015). CISD2 serves a novel role as a suppressor of nitric oxide signalling and curcumin increases CISD2 expression in spinal cord injuries. Injury, 46(12), 2341-2350. PMID: 26387034 DOI:[https://doi.org/10.1016/j.injury.2015.07.040 10.1016/j.injury.2015.07.040]</ref><ref> Lin, C. C., Chiang, T. H., Sun, Y. Y., & Lin, M. S. (2019). Protective effects of CISD2 and influence of curcumin on CISD2 expression in aged animals and inflammatory cell model. Nutrients, 11(3), 700. PMID: 30934593 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470567 6470567] DOI: 10.3390/nu11030700</ref>		The principal bright yellow compound obtained from the root of turmeric (''Curcuma longa'') named curcumin also was found to increase the CISD2 protein level in the astrocytes of the spinal cords of old mice<ref>Lin, C. C., Chiang, T. H., Chen, W. J., Sun, Y. Y., Lee, Y. H., & Lin, M. S. (2015). CISD2 serves a novel role as a suppressor of nitric oxide signalling and curcumin increases CISD2 expression in spinal cord injuries. Injury, 46(12), 2341-2350. PMID: 26387034 DOI:[https://doi.org/10.1016/j.injury.2015.07.040 10.1016/j.injury.2015.07.040]</ref><ref> Lin, C. C., Chiang, T. H., Sun, Y. Y., & Lin, M. S. (2019). Protective effects of CISD2 and influence of curcumin on CISD2 expression in aged animals and inflammatory cell model. Nutrients, 11(3), 700. PMID: 30934593 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470567 6470567] DOI: 10.3390/nu11030700</ref>

Dmitry Dzhagarov: /* Cisd2 level is a key determinant of lifespan and healthspan */

2022-12-06T20:09:16Z

Cisd2 level is a key determinant of lifespan and healthspan

← Older revision		Revision as of 20:09, 6 December 2022
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	CISD2 knockout mice also show accelerated aging, blindness, an abnormal skeleton, and muscle atrophy, effects that are very similar to those described in the WFS2 patients.<ref name=”diseases”/> <ref>Amr, S., Heisey, C., Zhang, M., Xia, X. J., Shows, K. H., Ajlouni, K., ... & Shiang, R. (2007). A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. The American Journal of Human Genetics, 81(4), 673-683. https://doi.org/10.1086/520961</ref>		CISD2 knockout mice also show accelerated aging, blindness, an abnormal skeleton, and muscle atrophy, effects that are very similar to those described in the WFS2 patients.<ref name=”diseases”/> <ref>Amr, S., Heisey, C., Zhang, M., Xia, X. J., Shows, K. H., Ajlouni, K., ... & Shiang, R. (2007). A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. The American Journal of Human Genetics, 81(4), 673-683. https://doi.org/10.1086/520961</ref>
	== Cisd2 level is a key determinant of lifespan and healthspan ==		== Cisd2 level is a key determinant of lifespan and healthspan ==
	Mouse Cisd2 deficiency shortens lifespan and accelerates aging that results in premature aging.<ref>Chen, Y. F., Kao, C. H., Chen, Y. T., Wang, C. H., Wu, C. Y., Tsai, C. Y., ... & Tsai, T. F. (2009). Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes & development, 23(10), 1183-1194. PMID: 19451219 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685531 2685531] DOI: 10.1101/gad.1779509 </ref>		Mouse Cisd2 deficiency shortens lifespan and accelerates aging that results in premature aging.<ref>Chen, Y. F., Kao, C. H., Chen, Y. T., Wang, C. H., Wu, C. Y., Tsai, C. Y., ... & Tsai, T. F. (2009). Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes & development, 23(10), 1183-1194. PMID: 19451219 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685531 2685531] DOI: 10.1101/gad.1779509 </ref>
			[[File:CISD2 activator.jpg\|thumb\|Beneficial effects of exercise and Cisd2 overexpression delay aging in skeletal muscle.<ref name="Teng">Teng, Y. C., Wang, J. Y., Chi, Y. H., & Tsai, T. F. (2020). Exercise and the Cisd2 Prolongevity Gene: Two Promising Strategies to Delay the Aging of Skeletal Muscle. Int. J. Mol. Sci, 21, 9059. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731423/ https://doi.org/10.3390/ijms21239059</ref>]]
	Cisd2 is essential to delaying cardiac aging and to maintaining heart functions. Cisd2 deficiency causes intercalated disc defects and leads to degeneration of the mitochondria and sarcomeres, thereby impairing its electromechanical functioning. Cisd2 deficiency also disrupts Ca<sup>2+</sup> homeostasis via dysregulation of sarco/endoplasmic reticulum Ca<sup>2+</sup>-ATPase activity, resulting in an increased level of basal cytosolic Ca<sup>2+</sup> and mitochondrial Ca<sup>2+</sup> overload in cardiomyocytes.<ref>Yeh, C. H., Shen, Z. Q., Hsiung, S. Y., Wu, P. C., Teng, Y. C., Chou, Y. J., ... & Tsai, T. F. (2019). Cisd2 is essential to delaying cardiac aging and to maintaining heart functions. PLoS biology, 17(10), e3000508. </ref>		Cisd2 is essential to delaying cardiac aging and to maintaining heart functions. Cisd2 deficiency causes intercalated disc defects and leads to degeneration of the mitochondria and sarcomeres, thereby impairing its electromechanical functioning. Cisd2 deficiency also disrupts Ca<sup>2+</sup> homeostasis via dysregulation of sarco/endoplasmic reticulum Ca<sup>2+</sup>-ATPase activity, resulting in an increased level of basal cytosolic Ca<sup>2+</sup> and mitochondrial Ca<sup>2+</sup> overload in cardiomyocytes.<ref>Yeh, C. H., Shen, Z. Q., Hsiung, S. Y., Wu, P. C., Teng, Y. C., Chou, Y. J., ... & Tsai, T. F. (2019). Cisd2 is essential to delaying cardiac aging and to maintaining heart functions. PLoS biology, 17(10), e3000508. </ref>

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	Cisd2 ameliorates age-associated degeneration of the skin, skeletal muscles and neurons. <ref name=”persistent” />		Cisd2 ameliorates age-associated degeneration of the skin, skeletal muscles and neurons. <ref name=”persistent” />
	Moreover, Cisd2 protects mitochondria from age-associated damage and functional decline as well as attenuating the age-associated reduction in whole-body energy metabolism. <ref name=”persistent” />		Moreover, Cisd2 protects mitochondria from age-associated damage and functional decline as well as attenuating the age-associated reduction in whole-body energy metabolism. <ref name=”persistent” />
	It was shown that a persistent level of Cisd2 achieved by transgenic expression in mice '''extends their median and maximum lifespan without any apparent deleterious side effects'''.<ref name=”homeostasis”/>		It was shown that a persistent level of Cisd2 achieved by transgenic expression in mice '''extends their median and maximum lifespan without any apparent deleterious side effects'''.<ref name=”homeostasis”/> According to Teng et al., exercise and Cisd2 activation are two very promising strategies as an individual ages to build a healthy lifespan.<ref name="Teng"/>

	== Natural compounds that can upregulate CISD2 expression ==		== Natural compounds that can upregulate CISD2 expression ==

Dmitry Dzhagarov: /* Cisd2 level is a key determinant of lifespan and healthspan */

2022-11-30T20:00:40Z

Cisd2 level is a key determinant of lifespan and healthspan

← Older revision		Revision as of 20:00, 30 November 2022
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	Cisd2 ameliorates age-associated degeneration of the skin, skeletal muscles and neurons. <ref name=”persistent” />		Cisd2 ameliorates age-associated degeneration of the skin, skeletal muscles and neurons. <ref name=”persistent” />
	Moreover, Cisd2 protects mitochondria from age-associated damage and functional decline as well as attenuating the age-associated reduction in whole-body energy metabolism. <ref name=”persistent” />		Moreover, Cisd2 protects mitochondria from age-associated damage and functional decline as well as attenuating the age-associated reduction in whole-body energy metabolism. <ref name=”persistent” />
	It was shown that a persistent level of Cisd2 achieved by transgenic expression in mice '''extends their median and maximum lifespan without any apparent deleterious side effects'''.<ref name=”homeostasis”/>		It was shown that a persistent level of Cisd2 achieved by transgenic expression in mice '''extends their median and maximum lifespan without any apparent deleterious side effects'''.<ref name=”homeostasis”/>

			== Natural compounds that can upregulate CISD2 expression ==
	CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice.<ref name=”Rejuvenation”>Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014. https://doi.org/10.3390/ijms232214014</ref>		CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice.<ref name=”Rejuvenation”>Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014. https://doi.org/10.3390/ijms232214014</ref>
	Treatment with dietary [[hesperetin]], starting at 19–21 month old, has shown to enhance CISD2 gene expression and extend the lifespan and healthspan of mice. In addition, hesperetin treatment appears to attenuate whole-body metabolic decline, reducing fat and improving glucose homeostasis, as well as slowing down heart and skeletal muscle aging.<ref name=”Hesperetin”>Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., ... & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. PMID: 35871686 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310407 9310407] DOI: 10.1186/s12929-022-00838-7</ref><ref name=”Rejuvenation”/>		Treatment with dietary [[hesperetin]], starting at 19–21 month old, has shown to enhance CISD2 gene expression and extend the lifespan and healthspan of mice. In addition, hesperetin treatment appears to attenuate whole-body metabolic decline, reducing fat and improving glucose homeostasis, as well as slowing down heart and skeletal muscle aging.<ref name=”Hesperetin”>Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., ... & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. PMID: 35871686 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310407 9310407] DOI: 10.1186/s12929-022-00838-7</ref><ref name=”Rejuvenation”/>

			The beneficial anti-aging effects of hesperetin are largely dependent on CISD2 as revealed from transcriptomic analysis - most (79%) of the genes influenced by hesperetin lost their differential expression patterns in the absence of CISD2.<ref name=”Hesperetin”/><ref name=”Rejuvenation”/> It would be interesting to check in the same way if the anti-aging effects of naringenin also depend on CISD2.<ref>ur Rehman, M. F., Batool, A. I., Qadir, R., & Aslam, M. (2021). Hesperidin and naringenin. In A centum of valuable plant bioactives (pp. 403-444). Academic Press. https://doi.org/10.1016/B978-0-12-822923-1.00027-3 </ref>

	Hesperetin is a well-known bioflavonoid that is found in small amounts in sauerkraut, as well as in numerous types of citrus fruits including- oranges, grapefruit, and tangerines upon ingestion.<ref>Erlund, I. (2004). Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutrition research, 24(10), 851-874. https://doi.org/10.1016/j.nutres.2004.07.005</ref><ref>Sohel, M., Sultana, H., Sultana, T., Al Amin, M., Aktar, S., Ali, M. C., ... & Dash, R. (2022). Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: a comprehensive review. Heliyon, e08815.PMID: 35128104 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810372 8810372] DOI: 10.1016/j.heliyon.2022.e08815</ref><ref>Wdowiak, K., Walkowiak, J., Pietrzak, R., Bazan-Woźniak, A., & Cielecka-Piontek, J. (2022). Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review. Nutrients, 14(13), 2647. PMID: 35807828 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268531 9268531] DOI: 10.3390/nu14132647</ref>		Hesperetin is a well-known bioflavonoid that is found in small amounts in sauerkraut, as well as in numerous types of citrus fruits including- oranges, grapefruit, and tangerines upon ingestion.<ref>Erlund, I. (2004). Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutrition research, 24(10), 851-874. https://doi.org/10.1016/j.nutres.2004.07.005</ref><ref>Sohel, M., Sultana, H., Sultana, T., Al Amin, M., Aktar, S., Ali, M. C., ... & Dash, R. (2022). Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: a comprehensive review. Heliyon, e08815.PMID: 35128104 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810372 8810372] DOI: 10.1016/j.heliyon.2022.e08815</ref><ref>Wdowiak, K., Walkowiak, J., Pietrzak, R., Bazan-Woźniak, A., & Cielecka-Piontek, J. (2022). Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review. Nutrients, 14(13), 2647. PMID: 35807828 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268531 9268531] DOI: 10.3390/nu14132647</ref>

			The principal bright yellow compound obtained from the root of turmeric (''Curcuma longa'') named curcumin also was found to increase the CISD2 protein level in the astrocytes of the spinal cords of old mice<ref>Lin, C. C., Chiang, T. H., Chen, W. J., Sun, Y. Y., Lee, Y. H., & Lin, M. S. (2015). CISD2 serves a novel role as a suppressor of nitric oxide signalling and curcumin increases CISD2 expression in spinal cord injuries. Injury, 46(12), 2341-2350. PMID: 26387034 DOI:[https://doi.org/10.1016/j.injury.2015.07.040 10.1016/j.injury.2015.07.040]</ref><ref> Lin, C. C., Chiang, T. H., Sun, Y. Y., & Lin, M. S. (2019). Protective effects of CISD2 and influence of curcumin on CISD2 expression in aged animals and inflammatory cell model. Nutrients, 11(3), 700. PMID: 30934593 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470567 6470567] DOI: 10.3390/nu11030700</ref>

	== References ==		== References ==

Dmitry Dzhagarov at 11:45, 25 November 2022

2022-11-25T11:45:14Z

← Older revision		Revision as of 11:45, 25 November 2022
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	'''CISD2 (CDGSH Iron Sulfur Domain 2)''' is an evolutionarily conserved ~~prolongevity~~ gene (also known as: '''ERIS (endoplasmic reticulum intermembrane small protein)''', Miner1, '''NAF-1 (nutrient-deprivation autophagy factor-1)''', WFS2, and ZCD2) that is located at position 24 on the long arm of human chromosome 4 (4q24) – the region significantly contributing to life-span control as has been revealed by a genome-wide linkage scan of long-lived families. <ref>Puca, A. A., Daly, M. J., Brewster, S. J., Matise, T. C., Barrett, J., Shea-Drinkwater, M., ... & Perls, T. (2001). A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4. Proceedings of the National Academy of Sciences, 98(18), 10505-10508. PMID: 11526246 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC56990/ 56990] DOI: 10.1073/pnas.181337598 </ref><ref>Amr, S., Heisey, C., Zhang, M., Xia, X. J., Shows, K. H., Ajlouni, K., ... & Shiang, R. (2007). A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. The American Journal of Human Genetics, 81(4), 673-683. </ref>		'''CISD2 (CDGSH Iron Sulfur Domain 2)''' is an evolutionarily conserved pro-longevity gene (also known as: '''ERIS (endoplasmic reticulum intermembrane small protein)''', Miner1, '''NAF-1 (nutrient-deprivation autophagy factor-1)''', WFS2, and ZCD2) that is located at position 24 on the long arm of human chromosome 4 (4q24) – the region significantly contributing to life-span control as has been revealed by a genome-wide linkage scan of long-lived families. <ref>Puca, A. A., Daly, M. J., Brewster, S. J., Matise, T. C., Barrett, J., Shea-Drinkwater, M., ... & Perls, T. (2001). A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4. Proceedings of the National Academy of Sciences, 98(18), 10505-10508. PMID: 11526246 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC56990/ 56990] DOI: 10.1073/pnas.181337598 </ref><ref>Amr, S., Heisey, C., Zhang, M., Xia, X. J., Shows, K. H., Ajlouni, K., ... & Shiang, R. (2007). A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. The American Journal of Human Genetics, 81(4), 673-683. </ref>
	CISD2 localizes onto the endoplasmic reticulum (ER), the outer mitochondrial membrane and the mitochondria-associated membrane. It plays a crucial role in the regulation of cytosolic Ca<sup>2+</sup> homeostasis, ER integrity and in preventing mitochondrial dysfunction, and also in the activation of autophagy and apoptosis in different cells. <ref>Shen, Z. Q., Chen, Y. F., Chen, J. R., Jou, Y. S., Wu, P. C., Kao, C. H., ... & Tsai, T. F. (2017). CISD2 haploinsufficiency disrupts calcium homeostasis, causes nonalcoholic fatty liver disease, and promotes hepatocellular carcinoma. Cell reports, 21(8), 2198-2211.</ref> <ref name=”calcium”>Yeh, C. H., Chou, Y. J., Kao, C. H., & Tsai, T. F. (2020). Mitochondria and calcium homeostasis: Cisd2 as a big player in cardiac ageing. International Journal of Molecular Sciences, 21(23), 9238. PMID: 33287440 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731030 7731030] DOI: 10.3390/ijms21239238</ref><ref name=”integrity”>Chen, Y. F., Kao, C. H., Kirby, R., & Tsai, T. F. (2009). Cisd2 mediates mitochondrial integrity and life span in mammals. Autophagy, 5(7), 1043-1045. DOI: 10.4161/auto.5.7.9351 </ref><ref>Chen, Y. F., Kao, C. H., Chen, Y. T., Wang, C. H., Wu, C. Y., Tsai, C. Y., ... & Tsai, T. F. (2009). Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes & development, 23(10), 1183-1194. PMID: 19451219 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685531 2685531] DOI: 10.1101/gad.1779509</ref>		CISD2 localizes onto the endoplasmic reticulum (ER), the outer mitochondrial membrane and the mitochondria-associated membrane. It plays a crucial role in the regulation of cytosolic Ca<sup>2+</sup> homeostasis, ER integrity and in preventing mitochondrial dysfunction, and also in the activation of autophagy and apoptosis in different cells. <ref>Shen, Z. Q., Chen, Y. F., Chen, J. R., Jou, Y. S., Wu, P. C., Kao, C. H., ... & Tsai, T. F. (2017). CISD2 haploinsufficiency disrupts calcium homeostasis, causes nonalcoholic fatty liver disease, and promotes hepatocellular carcinoma. Cell reports, 21(8), 2198-2211.</ref> <ref name=”calcium”>Yeh, C. H., Chou, Y. J., Kao, C. H., & Tsai, T. F. (2020). Mitochondria and calcium homeostasis: Cisd2 as a big player in cardiac ageing. International Journal of Molecular Sciences, 21(23), 9238. PMID: 33287440 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731030 7731030] DOI: 10.3390/ijms21239238</ref><ref name=”integrity”>Chen, Y. F., Kao, C. H., Kirby, R., & Tsai, T. F. (2009). Cisd2 mediates mitochondrial integrity and life span in mammals. Autophagy, 5(7), 1043-1045. DOI: 10.4161/auto.5.7.9351 </ref><ref>Chen, Y. F., Kao, C. H., Chen, Y. T., Wang, C. H., Wu, C. Y., Tsai, C. Y., ... & Tsai, T. F. (2009). Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes & development, 23(10), 1183-1194. PMID: 19451219 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685531 2685531] DOI: 10.1101/gad.1779509</ref>
	By functioning as a transport conduit across intracellular membranes for labile iron and calcium, CISD2 protects cells from overaccumulation of iron and calcium excitotoxicity.<ref name=”homeostasis”>Shen, Z. Q., Huang, Y. L., Teng, Y. C., Wang, T. W., Kao, C. H., Yeh, C. H., & Tsai, T. F. (2021). CISD2 maintains cellular homeostasis. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1868(4), 118954. https://doi.org/10.1016/j.bbamcr.2021.118954</ref>		By functioning as a transport conduit across intracellular membranes for labile iron and calcium, CISD2 protects cells from overaccumulation of iron and calcium excitotoxicity.<ref name=”homeostasis”>Shen, Z. Q., Huang, Y. L., Teng, Y. C., Wang, T. W., Kao, C. H., Yeh, C. H., & Tsai, T. F. (2021). CISD2 maintains cellular homeostasis. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1868(4), 118954. https://doi.org/10.1016/j.bbamcr.2021.118954</ref>

Dmitry Dzhagarov: /* Cisd2 level is a key determinant of lifespan and healthspan */

2022-11-25T11:11:04Z

Cisd2 level is a key determinant of lifespan and healthspan

← Older revision		Revision as of 11:11, 25 November 2022
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	CISD2 knockout mice also show accelerated aging, blindness, an abnormal skeleton, and muscle atrophy, effects that are very similar to those described in the WFS2 patients.<ref name=”diseases”/> <ref>Amr, S., Heisey, C., Zhang, M., Xia, X. J., Shows, K. H., Ajlouni, K., ... & Shiang, R. (2007). A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. The American Journal of Human Genetics, 81(4), 673-683. https://doi.org/10.1086/520961</ref>		CISD2 knockout mice also show accelerated aging, blindness, an abnormal skeleton, and muscle atrophy, effects that are very similar to those described in the WFS2 patients.<ref name=”diseases”/> <ref>Amr, S., Heisey, C., Zhang, M., Xia, X. J., Shows, K. H., Ajlouni, K., ... & Shiang, R. (2007). A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. The American Journal of Human Genetics, 81(4), 673-683. https://doi.org/10.1086/520961</ref>
	== Cisd2 level is a key determinant of lifespan and healthspan ==		== Cisd2 level is a key determinant of lifespan and healthspan ==
	Mouse Cisd2 deficiency shortens lifespan and results in premature aging.<ref>Chen, Y. F., Kao, C. H., Chen, Y. T., Wang, C. H., Wu, C. Y., Tsai, C. Y., ... & Tsai, T. F. (2009). Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes & development, 23(10), 1183-1194. PMID: 19451219 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685531 2685531] DOI: 10.1101/gad.1779509 </ref> ~~In mice~~, Cisd2 deficiency ~~shortens lifespan~~ and ~~accelerates~~ aging. Conversely, a persistently high level of Cisd2 promotes longevity. <ref name=”persistent”>Wu, C. Y., Chen, Y. F., Wang, C. H., Kao, C. H., Zhuang, H. W., Chen, C. C., ... & Tsai, T. F. (2012). A persistent level of Cisd2 extends healthy lifespan and delays aging in mice. Human molecular genetics, 21(18), 3956-3968. PMID: 22661501 DOI: 10.1093/hmg/dds210 </ref>		Mouse Cisd2 deficiency shortens lifespan and accelerates aging that results in premature aging.<ref>Chen, Y. F., Kao, C. H., Chen, Y. T., Wang, C. H., Wu, C. Y., Tsai, C. Y., ... & Tsai, T. F. (2009). Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes & development, 23(10), 1183-1194. PMID: 19451219 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685531 2685531] DOI: 10.1101/gad.1779509 </ref>
	~~It was shown that a persistent level~~ of ~~Cisd2 achieved by transgenic expression~~ in ~~mice extends their median~~ and ~~maximum lifespan without any apparent deleterious side effects~~.<ref name=~~”homeostasis”~~/>		Cisd2 is essential to delaying cardiac aging and to maintaining heart functions. Cisd2 deficiency causes intercalated disc defects and leads to degeneration of the mitochondria and sarcomeres, thereby impairing its electromechanical functioning. Cisd2 deficiency also disrupts Ca<sup>2+</sup> homeostasis via dysregulation of sarco/endoplasmic reticulum Ca<sup>2+</sup>-ATPase activity, resulting in an increased level of basal cytosolic Ca<sup>2+</sup> and mitochondrial Ca<sup>2+</sup> overload in cardiomyocytes.<ref>Yeh, C. H., Shen, Z. Q., Hsiung, S. Y., Wu, P. C., Teng, Y. C., Chou, Y. J., ... & Tsai, T. F. (2019). Cisd2 is essential to delaying cardiac aging and to maintaining heart functions. PLoS biology, 17(10), e3000508. </ref>
	Cisd2 ameliorates age-associated degeneration of the skin, skeletal muscles and neurons. <ref name=”persistent” />
	Moreover, Cisd2 protects mitochondria from age-associated damage and functional decline as well as attenuating the age-associated reduction in whole-body energy metabolism. <ref name=”persistent” />		Conversely, a persistently high level of Cisd2 promotes longevity.<ref name=”persistent”>Wu, C. Y., Chen, Y. F., Wang, C. H., Kao, C. H., Zhuang, H. W., Chen, C. C., ... & Tsai, T. F. (2012). A persistent level of Cisd2 extends healthy lifespan and delays aging in mice. Human molecular genetics, 21(18), 3956-3968. PMID: 22661501 DOI:[https://doi.org/10.1093/hmg/dds210 10.1093/hmg/dds210]</ref> CISD2 protects cardiomyocytes from overaccumulation of iron, which is common in aging hearts and can contribute to the pathogenesis of heart failure.<ref name=”iron”> Karmi, O., Rowland, L., King, S. D., Manrique‐Acevedo, C., Cabantchik, I. Z., Nechushtai, R., & Mittler, R. (2022). The [2Fe‐2S] protein CISD2 plays a key role in preventing iron accumulation in cardiomyocytes. FEBS letters, 596(6), 747-761. PMID: 34997963 DOI: [https://doi.org/10.1002/1873-3468.14277 10.1002/1873-3468.14277]</ref>
			Cisd2 ameliorates age-associated degeneration of the skin, skeletal muscles and neurons. <ref name=”persistent” />
			Moreover, Cisd2 protects mitochondria from age-associated damage and functional decline as well as attenuating the age-associated reduction in whole-body energy metabolism. <ref name=”persistent” />
			It was shown that a persistent level of Cisd2 achieved by transgenic expression in mice '''extends their median and maximum lifespan without any apparent deleterious side effects'''.<ref name=”homeostasis”/>

	CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice.<ref name=”Rejuvenation”>Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014. https://doi.org/10.3390/ijms232214014</ref>		CISD2, the expression of which otherwise decreases during natural aging, can be pharmaceutically activated at a late-life stage of aged mice.<ref name=”Rejuvenation”>Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014. https://doi.org/10.3390/ijms232214014</ref>
	Treatment with dietary hesperetin, starting at 19–21 month old, has shown to enhance CISD2 gene expression and extend the lifespan and healthspan of mice. In addition, hesperetin treatment appears to attenuate whole-body metabolic decline, reducing fat and improving glucose homeostasis, as well as slowing down heart and skeletal muscle aging.<ref name=”Hesperetin”>Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., ... & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. PMID: 35871686 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310407 9310407] DOI: 10.1186/s12929-022-00838-7</ref><ref name=”Rejuvenation”/>		Treatment with dietary [[hesperetin]], starting at 19–21 month old, has shown to enhance CISD2 gene expression and extend the lifespan and healthspan of mice. In addition, hesperetin treatment appears to attenuate whole-body metabolic decline, reducing fat and improving glucose homeostasis, as well as slowing down heart and skeletal muscle aging.<ref name=”Hesperetin”>Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., ... & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. PMID: 35871686 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310407 9310407] DOI: 10.1186/s12929-022-00838-7</ref><ref name=”Rejuvenation”/>

	~~CISD2 protects cardiomyocytes from overaccumulation~~ of ~~iron~~, ~~which is common in aging hearts~~ and ~~can contribute to~~ the ~~pathogenesis of heart failure~~.<ref ~~name=”iron”~~> ~~Karmi~~, O., ~~Rowland~~, L., ~~King~~, S. D., ~~Manrique‐Acevedo~~, C., ~~Cabantchik~~, I. Z., ~~Nechushtai~~, R., & ~~Mittler~~, R. (2022). ~~The [2Fe‐2S] protein CISD2 plays~~ a ~~key role in preventing iron accumulation in cardiomyocytes~~. ~~FEBS letters~~, ~~596~~(6), ~~747-761~~. PMID: ~~34997963~~ DOI: 10.~~1002~~/~~1873-3468.14277~~</ref>		Hesperetin is a well-known bioflavonoid that is found in small amounts in sauerkraut, as well as in numerous types of citrus fruits including- oranges, grapefruit, and tangerines upon ingestion.<ref>Erlund, I. (2004). Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutrition research, 24(10), 851-874. https://doi.org/10.1016/j.nutres.2004.07.005</ref><ref>Sohel, M., Sultana, H., Sultana, T., Al Amin, M., Aktar, S., Ali, M. C., ... & Dash, R. (2022). Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: a comprehensive review. Heliyon, e08815.PMID: 35128104 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810372 8810372] DOI: 10.1016/j.heliyon.2022.e08815</ref><ref>Wdowiak, K., Walkowiak, J., Pietrzak, R., Bazan-Woźniak, A., & Cielecka-Piontek, J. (2022). Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review. Nutrients, 14(13), 2647. PMID: 35807828 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268531 9268531] DOI: 10.3390/nu14132647</ref>

	== References ==		== References ==