Functional alterations and transcriptomic changes during zebrafish cardiac aging

Shao, Xuelian; Fu, Yu; Ma, Jinmin; Li, Xueyu; Lu, Chenqi; Zhang, Ruilin

doi:10.1007/s10522-020-09881-z

Cited by 10 publications

(8 citation statements)

References 40 publications

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“…Differential changes in the expression of a wide range of genes play an important role in this reduction in stress resistance. These genes are involved in detoxification of free radicals, xenobiotics, and toxic metals, a response to DNA damage and unfolded proteins, mitochondrial function, regulation of lipid metabolism, and immune and inflammatory responses [35][36][37][38][39][40][51][52][53][54][55]. Aging is associated with a decrease in the efficiency of repair systems and antioxidant defense [2,3,54,55].…”

Section: Discussionmentioning

confidence: 99%

“…These genes are involved in detoxification of free radicals, xenobiotics, and toxic metals, a response to DNA damage and unfolded proteins, mitochondrial function, regulation of lipid metabolism, and immune and inflammatory responses [35][36][37][38][39][40][51][52][53][54][55]. Aging is associated with a decrease in the efficiency of repair systems and antioxidant defense [2,3,54,55]. This leads to a damage accumulation with age and a tension in the work of compensatory mechanisms.…”

Section: Discussionmentioning

confidence: 99%

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The Resistance of Drosophila melanogaster to Oxidative, Genotoxic, Proteotoxic, Osmotic Stress, Infection, and Starvation Depends on Age According to the Stress Factor

et al. 2020

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We studied how aging affects the ability of Drosophila melanogaster to tolerate various types of stress factors. Data were obtained on the resistance of D. melanogaster to oxidative and genotoxic (separately paraquat, Fe3+, Cu2+, and Zn2+ ions), proteotoxic (hyperthermia, Cd2+ ions), and osmotic (NaCl) stresses, starvation, and infection with the pathological Beauveria bassiana fungus at different ages. In all cases, we observed a strong negative correlation between age and stress tolerance. The largest change in the age-dependent decline in survival occurred under oxidative and osmotic stress. In most experiments, we observed that young Drosophila females have higher stress resistance than males. We checked whether it is possible to accurately assess the biological age of D. melanogaster based on an assessment of stress tolerance. We have proposed a new approach for assessing a biological age of D. melanogaster using a two-parameter survival curve model. For the model, we used an algorithm that evaluated the quality of age prediction for different age and gender groups. The best predictions were obtained for females who were exposed to CdCl2 and ZnCl2 with an average error of 0.32 days and 0.36 days, respectively. For males, the best results were observed for paraquat and NaCl with an average error of 0.61 and 0.68 days, respectively. The average accuracy for all stresses in our model was 1.73 days.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Resistance of Drosophila melanogaster to Oxidative, Genotoxic, Proteotoxic, Osmotic Stress, Infection, and Starvation Depends on Age According to the Stress Factor

et al. 2020

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“…Therefore, we evaluated whether C18 and C18:1 LCAC treatment of zebrafish embryos has an impact on mitochondrial function and subsequently the production of ATP. We first assessed the expression of marker genes such as pparg, ppargc1a, cox4i1 and cox4i2 (Supplementary Table S1), which are known to be downregulated in functionally compromised mitochondria [22,23]. We found that pparg and ppargc1a transcripts were indeed significantly decreased in C18-(0.1 µM: pparg: 0.69 ± 0.07, ppargc1a: 0.81 ± 0.07; 0.5 µM: pparg: 0.50 ± 0.09, ppargc1a: 0.33 ± 0.02, SD, n = 3, p < 0.001, p < 0.0001) and C18:1-treated embryos (0.1 µM: pparg: 0.56 ± 0.09, ppargc1a: 0.64 ± 0.03; 0.5 µM: pparg: 0.69 ± 0.08, ppargc1a: 0.74 ± 0.06, SD, n = 3, p < 0.0001) compared to C3-treated embryos (Figure 2C,D).…”

Section: Mitochondrial Structure In Cardiomyocytes Is Not Impaired By Lcac Treatmentmentioning

confidence: 99%

Long-Chain Acyl-Carnitines Interfere with Mitochondrial ATP Production Leading to Cardiac Dysfunction in Zebrafish

Park

Gahr

Krause

et al. 2021

IJMS

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In the human heart, the energy supplied by the production of ATP is predominately accomplished by ß-oxidation in mitochondria, using fatty acids (FAs) as the primary fuel. Long-chain acylcarnitines (LCACs) are intermediate forms of FA transport that are essential for FA delivery from the cytosol into mitochondria. Here, we analyzed the impact of the LCACs C18 and C18:1 on mitochondrial function and, subsequently, on heart functionality in the in vivo vertebrate model system of zebrafish (Danio rerio). Since LCACs are formed and metabolized in mitochondria, we assessed mitochondrial morphology, structure and density in C18- and C18:1-treated zebrafish and found no mitochondrial alterations compared to control-treated (short-chain acylcarnitine, C3) zebrafish embryos. However, mitochondrial function and subsequently ATP production was severely impaired in C18- and C18:1-treated zebrafish embryos. Furthermore, we found that C18 and C18:1 treatment of zebrafish embryos led to significantly impaired cardiac contractile function, accompanied by reduced heart rate and diminished atrial and ventricular fractional shortening, without interfering with cardiomyocyte differentiation, specification and growth. In summary, our findings provide insights into the direct role of long-chain acylcarnitines on vertebrate heart function by interfering with regular mitochondrial function and thereby energy allocation in cardiomyocytes.

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“…Cardiomyocytes are subjected to continuous mechanical and biochemical stresses which contribute to the physiological aging process ( Sheydina et al, 2011 ; Shao et al, 2020 ). This decline in basal and peak cardiac performance during normal human chronological age is linked with cardiomyocyte loss, deposition of extracellular matrix and adverse myocardial remodelling.…”

Section: Introductionmentioning

confidence: 99%

“…This decline in basal and peak cardiac performance during normal human chronological age is linked with cardiomyocyte loss, deposition of extracellular matrix and adverse myocardial remodelling. It is now recognised that these are secondary to accumulating failures of a wide range of cellular processes, including mitochondrial dysfunction and management of oxidative stress ( Chiao and Rabinovitch, 2015 ; Obas and Vasan, 2018 ; Shao et al, 2020 ). These decreases in cardiac performance are initially only recognised if they limit voluntary activities.…”

Section: Introductionmentioning

confidence: 99%

Exercise, programmed cell death and exhaustion of cardiomyocyte proliferation in aging zebrafish

Murphy

Santos-Ledo

Dhanaseelan

et al. 2021

Disease Models &Amp; Mechanisms

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As the human heart ages, the myocardium undergoes fibrotic remodelling, there is declining cardiovascular performance and eventual heart failure. It is suggested that exercise is an important intervention to ameliorate these changes. In this study we establish zebrafish as a laboratory model to understand how aging and exercise affect cardiomyocyte turnover. We show the zebrafish heart does not exhibit indeterminate growth but follows the pattern seen in human aging. In zebrafish, cardiomyocyte proliferation remains constant, but a late increase cell death underlies the pattern of initial cardiac growth and later fibrosis. These anatomical findings are corelated with the human like decline in cardiovascular performance reflected in voluntary swimming activity, critical swimming speed (Ucrit) and biomarkers of cardiac insufficiency. Whilst the vertebrate heart can respond to injury through cardiomyocyte proliferation, it is not known if a proliferative response occurs when the cardiovascular system is exposed to prolonged severe physiological stress, or if this changes with age. To investigate this, young and old adult zebrafish were challenged by 72 hours of enforced swimming in a purpose-built flume at levels close to maximal Ucrit. Whilst young adult fish produced a significant proliferative response older fish had a dramatically impaired response, provided by a smaller proliferative cardiomyocyte population. Finally, we asked if these aging responses could be improved by increased activity throughout adulthood. Whilst there was some improvement in the aged proliferative response the size of the reduced proliferative cardiomyocyte pool remained unchanged and importantly, there was increased myocardial fibrosis. The zebrafish heart thus provides a laboratory model to study cardiomyocyte turnover during aging and physiological stresses, revealing the important trade-off between preserving cardiovascular fitness through exercise and accelerated fibrotic change, whilst the available proliferative pool of cardiomyocytes continues to diminish.

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Functional alterations and transcriptomic changes during zebrafish cardiac aging

Cited by 10 publications

References 40 publications

The Resistance of Drosophila melanogaster to Oxidative, Genotoxic, Proteotoxic, Osmotic Stress, Infection, and Starvation Depends on Age According to the Stress Factor

The Resistance of Drosophila melanogaster to Oxidative, Genotoxic, Proteotoxic, Osmotic Stress, Infection, and Starvation Depends on Age According to the Stress Factor

Long-Chain Acyl-Carnitines Interfere with Mitochondrial ATP Production Leading to Cardiac Dysfunction in Zebrafish

Exercise, programmed cell death and exhaustion of cardiomyocyte proliferation in aging zebrafish

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