Rejuvenating the Aging Heart by Enhancing the Expression of the Cisd2 Prolongevity Gene

Aging is the major risk factor for cardiovascular disease, which is the leading cause of mortality worldwide among aging populations. Cisd2 is a prolongevity gene that mediates lifespan in mammals. Previously, our investigations revealed that a persistently high level of ...

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Autores principales:	Chi-Hsiao Yeh, Yi-Ju Chou, Ting-Kuan Chu, Ting-Fen Tsai
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cardiac aging cardiac rejuvenation <i>Cisd2</i> inducible cardiac-specific overexpression Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/28dc4c6dbbcc42778ff77035853f6043
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spelling	oai:doaj.org-article:28dc4c6dbbcc42778ff77035853f60432021-11-11T16:57:03ZRejuvenating the Aging Heart by Enhancing the Expression of the <i>Cisd2</i> Prolongevity Gene10.3390/ijms2221114871422-00671661-6596https://doaj.org/article/28dc4c6dbbcc42778ff77035853f60432021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11487https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Aging is the major risk factor for cardiovascular disease, which is the leading cause of mortality worldwide among aging populations. <i>Cisd2</i> is a prolongevity gene that mediates lifespan in mammals. Previously, our investigations revealed that a persistently high level of <i>Cisd2</i> expression in mice is able to prevent age-associated cardiac dysfunction. This study was designed to apply a genetic approach that induces cardiac-specific <i>Cisd2</i> overexpression (<i>Cisd2</i> icOE) at a late-life stage, namely a time point immediately preceding the onset of old age, and evaluate the translational potential of this approach. Several discoveries are pinpointed. Firstly, <i>Cisd2</i> is downregulated in the aging heart. This decrease in <i>Cisd2</i> leads to cardiac dysfunction and impairs electromechanical performance. Intriguingly, <i>Cisd2</i> icOE prevents an exacerbation of age-associated electromechanical dysfunction. Secondly, <i>Cisd2</i> icOE ameliorates cardiac fibrosis and improves the integrity of the intercalated discs, thereby reversing various structural abnormalities. Finally, <i>Cisd2</i> icOE reverses the transcriptomic profile of the aging heart, changing it from an older-age pattern to a younger pattern. Intriguingly, <i>Cisd2</i> icOE modulates a number of aging-related pathways, namely the sirtuin signaling, autophagy, and senescence pathways, to bring about rejuvenation of the heart as it enters old age. Our findings highlight <i>Cisd2</i> as a novel molecular target for developing therapies targeting cardiac aging.Chi-Hsiao YehYi-Ju ChouTing-Kuan ChuTing-Fen TsaiMDPI AGarticlecardiac agingcardiac rejuvenation<i>Cisd2</i>inducible cardiac-specific overexpressionBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11487, p 11487 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cardiac aging cardiac rejuvenation <i>Cisd2</i> inducible cardiac-specific overexpression Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	cardiac aging cardiac rejuvenation <i>Cisd2</i> inducible cardiac-specific overexpression Biology (General) QH301-705.5 Chemistry QD1-999 Chi-Hsiao Yeh Yi-Ju Chou Ting-Kuan Chu Ting-Fen Tsai Rejuvenating the Aging Heart by Enhancing the Expression of the <i>Cisd2</i> Prolongevity Gene
description	Aging is the major risk factor for cardiovascular disease, which is the leading cause of mortality worldwide among aging populations. <i>Cisd2</i> is a prolongevity gene that mediates lifespan in mammals. Previously, our investigations revealed that a persistently high level of <i>Cisd2</i> expression in mice is able to prevent age-associated cardiac dysfunction. This study was designed to apply a genetic approach that induces cardiac-specific <i>Cisd2</i> overexpression (<i>Cisd2</i> icOE) at a late-life stage, namely a time point immediately preceding the onset of old age, and evaluate the translational potential of this approach. Several discoveries are pinpointed. Firstly, <i>Cisd2</i> is downregulated in the aging heart. This decrease in <i>Cisd2</i> leads to cardiac dysfunction and impairs electromechanical performance. Intriguingly, <i>Cisd2</i> icOE prevents an exacerbation of age-associated electromechanical dysfunction. Secondly, <i>Cisd2</i> icOE ameliorates cardiac fibrosis and improves the integrity of the intercalated discs, thereby reversing various structural abnormalities. Finally, <i>Cisd2</i> icOE reverses the transcriptomic profile of the aging heart, changing it from an older-age pattern to a younger pattern. Intriguingly, <i>Cisd2</i> icOE modulates a number of aging-related pathways, namely the sirtuin signaling, autophagy, and senescence pathways, to bring about rejuvenation of the heart as it enters old age. Our findings highlight <i>Cisd2</i> as a novel molecular target for developing therapies targeting cardiac aging.
format	article
author	Chi-Hsiao Yeh Yi-Ju Chou Ting-Kuan Chu Ting-Fen Tsai
author_facet	Chi-Hsiao Yeh Yi-Ju Chou Ting-Kuan Chu Ting-Fen Tsai
author_sort	Chi-Hsiao Yeh
title	Rejuvenating the Aging Heart by Enhancing the Expression of the <i>Cisd2</i> Prolongevity Gene
title_short	Rejuvenating the Aging Heart by Enhancing the Expression of the <i>Cisd2</i> Prolongevity Gene
title_full	Rejuvenating the Aging Heart by Enhancing the Expression of the <i>Cisd2</i> Prolongevity Gene
title_fullStr	Rejuvenating the Aging Heart by Enhancing the Expression of the <i>Cisd2</i> Prolongevity Gene
title_full_unstemmed	Rejuvenating the Aging Heart by Enhancing the Expression of the <i>Cisd2</i> Prolongevity Gene
title_sort	rejuvenating the aging heart by enhancing the expression of the <i>cisd2</i> prolongevity gene
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/28dc4c6dbbcc42778ff77035853f6043
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Rejuvenating the Aging Heart by Enhancing the Expression of the <i>Cisd2</i> Prolongevity Gene

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