A Natural Model of Mouse Cardiac Myocyte Senescence

Wang, Zunzhe; Rong, Xing; Luo, Biao; Qin, Shanshan; Lü, Lili; Zhang, Xiuli; Sun, Yang; Hu, Qin; Zhang, Chunxiang

doi:10.1007/s12265-016-9711-3

Cited by 13 publications

(15 citation statements)

References 5 publications

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“…Overall, our results correspond with Wang et al, who have already described the culture of neonatal cardiomyocytes derived from C57Bl/6 mice over 28 days as a model system of cardiac senescence[40]. The herein presented results supplement the literature by the data of p16, p21 and autofluorescence in cultured neonatal cardiomyocytes and clarify the temporal course of the commonly used markers of cellular senescence over 21 days.…”

supporting

confidence: 91%

“…In contrast to their adult state, mammalian neonatal cardiomyocytes allow the maintenance of a prolonged, physiologically contractive culture [36]. Murine neonatal cardiomyocytes have already been used to mimic diverse states of cardiac dysfunction, such as myocardial ischemia [37], ventricular hypertrophy [38], arrhythmia [39], and cellular senescence [40]. As studies on protein homeostasis (proteostasis) and contractility in cardiomyocyte aging remain a challenging task, culture of neonatal cardiomyocytes offers an optimal approach for manipulation studies under controlled conditions.…”

Section: Introductionmentioning

confidence: 99%

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Cardiomyocyte Contractility and Autophagy in a Premature Senescence Model of Cardiac Aging

Häseli

Deubel

Jung

et al. 2020

Oxidative Medicine and Cellular Longevity

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Globally, cardiovascular diseases are the leading cause of death in the aging population. While the clinical pathology of the aging heart is thoroughly characterized, underlying molecular mechanisms are still insufficiently clarified. The aim of the present study was to establish an in vitro model system of cardiomyocyte premature senescence, culturing heart muscle cells derived from neonatal C57Bl/6J mice for 21 days. Premature senescence of neonatal cardiac myocytes was induced by prolonged culture time in an oxygen-rich postnatal environment. Age-related changes in cellular function were determined by senescence-associated β-galactosidase activity, increasing presence of cell cycle regulators, such as p16, p53, and p21, accumulation of protein aggregates, and restricted proteolysis in terms of decreasing (macro-)autophagy. Furthermore, the culture system was functionally characterized for alterations in cell morphology and contractility. An increase in cellular size associated with induced expression of atrial natriuretic peptides demonstrated a stress-induced hypertrophic phenotype in neonatal cardiomyocytes. Using the recently developed analytical software tool Myocyter, we were able to show a spatiotemporal constraint in spontaneous contraction behavior during cultivation. Within the present study, the 21-day culture of neonatal cardiomyocytes was defined as a functional model system of premature cardiac senescence to study age-related changes in cardiomyocyte contractility and autophagy.

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supporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Cardiomyocyte Contractility and Autophagy in a Premature Senescence Model of Cardiac Aging

Häseli

Deubel

Jung

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Recent studies have suggested that not only mitotic, but also postmitotic cells are capable of entering a state of senescence. This has been observed in a number of cell types from the CNS (Jurk et al, 2012), bone (Farr et al, 2017), cardiac (Wang et al, 2016), and adipose tissue (Minamino et al, 2009).…”

Section: Discussionmentioning

confidence: 72%

Loss of SATB1 Induces a p21 Dependent Cellular Senescence Phenotype in Dopaminergic Neurons

Rießland

Kolisnyk

et al. 2018

Preprint

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Cellular senescence is a mechanism used by mitotic cells to prevent uncontrolled cell division. As senescent cells persist in tissues, they cause local inflammation and are harmful to surrounding cells, contributing to aging. Generally, neurodegenerative diseases, such as Parkinson's, are disorders of aging. The contribution of cellular senescence to neurodegeneration is still unclear. SATB1 is a DNA binding protein associated with Parkinson's disease. We report that SATB1 prevents cellular senescence in post-mitotic dopaminergic neurons. Loss of SATB1 causes activation of a cellular senescence transcriptional program in dopamine neurons, both in human stem cell-derived dopaminergic neurons and in mice. We observed phenotypes which are central to cellular senescence in SATB1 knockout dopamine neurons in vitro and in vivo. Moreover, we found that SATB1 directly represses expression of the pro-senescence factor, p21, in dopaminergic neurons. Our data implicate senescence of dopamine neurons as a contributing factor to the pathology of Parkinson's disease. hESC shows normal appearance. Scale bar: 200 µm. (D) Immunolabeling of DA precursor markers in WT and SATB1 KO hESC derived DA neurons after 16 days of differentiation reveals no difference in marker expression. (E) Depiction of spontaneous action potentials of WT and SATB1 KO DA neurons at different time points show that both genotypes differentiate into mature DA neurons between day 35 and 40. Scale bar: 20 mV, 2 s. (F) DA neurons at day 40 show significant differences in maintenance of response to positive current injections. Scale bar: 20 mV, 200 ms. (G) Longitudinal comparison of cell survival of WT vs. SATB1 KO DA neurons revealed a significant reduction in SATB1 KO survival between day 30 and 40, reaching a plateau at ~50%. Data are represented as mean ± SEM. (H) Quantification of neurite morphology and complexity in WT and SATB1 KO DA neurons. Data are represented as mean ± SEM. (I) Triple immunolabeling of cortical shows that both WT as well as SATB1 KO neurons express the essential markers for cortical neurons. Scale bar: 50 µm. (J) SATB1 KO cortical neurons show no significant change in survival during differentiation. Data are represented as mean ± SEM. (K) Quantification of neurite morphology and complexity in WT and SATB1 KO CTX neurons. (L)Representative western blot and quantification depicts that WT DA neurons express significantly higher levels of SATB1 than WT cortical neurons, suggesting a higher demand in DA neurons. Data are represented as mean ± SEM. See also Figure S1.

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“…This has been observed in a number of cell types from the CNS (Jurk et al, 2012), bone Figure S7. (Farr et al, 2017), cardiac (Wang et al, 2016), and adipose tissue (Minamino et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Loss of SATB1 Induces p21-Dependent Cellular Senescence in Post-mitotic Dopaminergic Neurons

Rießland¹,

Kolisnyk²,

Kim³

et al. 2019

Cell Stem Cell

124

122

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A Natural Model of Mouse Cardiac Myocyte Senescence

Cited by 13 publications

References 5 publications

Cardiomyocyte Contractility and Autophagy in a Premature Senescence Model of Cardiac Aging

Cardiomyocyte Contractility and Autophagy in a Premature Senescence Model of Cardiac Aging

Loss of SATB1 Induces a p21 Dependent Cellular Senescence Phenotype in Dopaminergic Neurons

Loss of SATB1 Induces p21-Dependent Cellular Senescence in Post-mitotic Dopaminergic Neurons

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