Biological aging is a process associated with a gradual decline in tissues’ homeostasis based on the progressive inability of the cells to self-renew. Cellular senescence is one of the hallmarks of the aging process, characterized by an irreversible cell cycle arrest due to reactive oxygen species (ROS) production, telomeres shortening, chronic inflammatory activation, and chromatin modifications. In this review, we will describe the effects of senescence on tissue structure, extracellular matrix (ECM) organization, and nucleus architecture, and see how these changes affect (are affected by) mechano-transduction. In our view, this is essential for a deeper understanding of the progressive pathological evolution of the cardiovascular system and its relationship with the detrimental effects of risk factors, known to act at an epigenetic level.
Last. Corey P. Neu(CU: University of Colorado Boulder)H-Index: 26
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Chromatin of the eukaryotic cell nucleus comprises microscopically dense heterochromatin and loose euchromatin domains, each with distinct transcriptional ability and roles in cellular mechanotransduction. While recent methods are developed to characterize the mechanics of nucleus, measurement of intranuclear mechanics remains largely unknown. Here, the development of "nuclear elastography," which combines microscopic imaging and computational modeling to quantify the relative elasticity of the ...
#1Shaohua Wu(UNMC: University of Nebraska Medical Center)H-Index: 15
#2Virender Kumar(UNMC: University of Nebraska Medical Center)H-Index: 58
Last. Bin Duan(UNMC: University of Nebraska Medical Center)H-Index: 6
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Heart valve disease is a common manifestation of cardiovascular disease and is a significant cause of cardiovascular morbidity and mortality worldwide. The pulmonary valve (PV) is of primary concern because of its involvement in common congenital heart defects, and the PV is usually the site for prosthetic replacement following a Ross operation. Although effects of age on valve matrix components and mechanical properties for aortic and mitral valves have been studied, very little is known about ...
Senolytics are a class of drugs that selectively clear senescent cells (SC). The first senolytic drugs Dasatinib, Quercetin, Fisetin, and Navitoclax were discovered using a hypothesis-driven approach. SC accumulate with aging and at causal sites of multiple chronic disorders, including diseases accounting for the bulk of morbidity, mortality, and health expenditures. The most deleterious SC are resistant to apoptosis and have up-regulation of anti-apoptotic pathways which defend SC against their...
#1Vivian W. Tang(UIUC: University of Illinois at Urbana–Champaign)H-Index: 7
The emergence of collagen I in vertebrates resulted in a dramatic increase in the stiffness of the extracellular environment, supporting long-range force propagation and the development of low-comp...
Abstract The 1-dimensional information of genomic DNA is hierarchically packed inside the eukaryotic cell nucleus and organized in 3-dimensional (3D) space. Genome-wide chromosome conformation capture (Hi-C) methods have uncovered the 3D genome organization and revealed multi-scale chromatin domains of compartments and topologically associating domains (TADs). Moreover, single-nucleosome live-cell imaging experiments have revealed the dynamic organization of chromatin domains caused by stochasti...
Last. Youngjo Kim(SCH: Soonchunhyang University)H-Index: 10
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Aging is characterized by the gradual loss of tissue function and integrity. Activation of inflammatory responses accelerates the deterioration of cells and tissues. Many studies have shown that alteration of the components of the nuclear lamina is associated with inflammation, both in vivo and in vitro. However, the mechanism by which the nuclear lamina regulates inflammation is largely unknown. Recent studies have suggested that the nuclear lamina regulates both organization of the three-dimen...
The heart is par excellence the ‘in-motion’ organ in the human body. Compelling evidence shows that, besides generating forces to ensure continuous blood supply (e.g., myocardial contractility) or withstanding passive forces generated by flow (e.g., shear stress on endocardium, myocardial wall strain, and compression strain at the level of cardiac valves), cells resident in the heart respond to mechanical cues with the activation of mechanically dependent molecular pathways. Cardiac stromal cell...
With the term ‘mechanotransduction’, it is intended the ability of cells to sense and respond to mechanical forces by activating intracellular signal transduction pathways and the relative phenotypic adaptation. While a known role of mechanical stimuli has been acknowledged for developmental biology processes and morphogenesis in various organs, the response of cells to mechanical cues is now also emerging as a major pathophysiology determinant. Cells of the cardiovascular system are typically e...
Cardiomyocytes are large (∼40,000 µm3), rod-shaped muscle cells that provide the working force behind each heartbeat. These highly structured cells are packed with dense cytoskeletal networks that ...