Functional alterations and transcriptomic changes during zebrafish cardiac aging
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RESEARCH ARTICLE
Functional alterations and transcriptomic changes during zebrafish cardiac aging Xuelian Shao . Yu Fu . Jinmin Ma . Xueyu Li . Chenqi Lu . Ruilin Zhang
Received: 28 January 2020 / Accepted: 25 April 2020 Ó Springer Nature B.V. 2020
Abstract Aging dramatically increases the risk of cardiovascular diseases in human. Animal models are of great value to study cardiac aging, and zebrafish have become a popular model for aging study recently. However, there is limited knowledge about the progression and regulation of cardiac aging in zebrafish. In this study we first validated the effectiveness of a panel of aging-related markers and revealed their spatial-temporal specificity. Using these markers, we discovered that cardiac aging in zebrafish initiated at mid-age around 24 months, followed by a gradual progression marked with increased DNA damage, inflammatory response and reduced mitochondrial function. Furthermore, we showed agingrelated expression profile change in zebrafish hearts was similar to that in rat hearts. Overall, our results provide a deeper insight into the cardiac aging process in zebrafish, which will set up foundation for X. Shao Y. Fu J. Ma X. Li Department of Genetics and Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China C. Lu (&) Department of Biostatistics and Computational Biology, School of Life Sciences, Fudan University, Shanghai, China e-mail: [email protected] R. Zhang (&) School of Basic Medical Sciences, Wuhan University, Wuhan, China e-mail: [email protected]
generating novel cardiac aging models suitable for large scale screening of pharmaceutical targets. Keywords Cardiac aging Aging-related markers Functional alterations Transcriptomic changes
Introduction Cardiovascular diseases have become the leading cause of death worldwide especially for the elderly older than 65 years (Roth et al. 2017). Aging is considered as a great risk factor for cardiovascular diseases including ischemic heart disease, congestive heart failure and atrial fibrillation (Rosamond et al. 2007). It is reported that population aged over 60 years old would double from 2017 to 2050 (United Nations Department of Economic and Social. 2017), which indicates an imminent huge burden of cardiovascular diseases on human welfare. Thus, it is of great importance to understand how cardiac aging progresses and how aging affects cardiac performance in order to develop better prevention and treatment regimens. Nowadays, a panel of markers have been established for assessing aging, and spinal kyphosis is one of the commonly used markers. Although recently proved to have functional roles in development (Rhinn et al. 2019), cellular senescence has long been
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Biogerontology
considered as a hallmark of aging with accumulation of senescent cells detected in certain aged tissues (Lo´pezotı´n et al. 2013). Given that specificity of senescence markers depends on cell type, tissue, developmental stage and species, i
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