scholarly journals Cardiac Aging: From Basic Research to Therapeutics

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Mingjing Yan ◽  
Shenghui Sun ◽  
Kun Xu ◽  
Xiuqing Huang ◽  
Lin Dou ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Clinical Medicine ◽  
Basic Research ◽  
Left Ventricular ◽  
Research Progress ◽  
Cardiac Aging ◽  
New Era ◽  
Age Related ◽  
Systolic And Diastolic Function ◽  
And Function

With research progress on longevity, we have gradually recognized that cardiac aging causes changes in heart structure and function, including progressive myocardial remodeling, left ventricular hypertrophy, and decreases in systolic and diastolic function. Elucidating the regulatory mechanisms of cardiac aging is a great challenge for biologists and physicians worldwide. In this review, we discuss several key molecular mechanisms of cardiac aging and possible prevention and treatment methods developed in recent years. Insights into the process and mechanism of cardiac aging are necessary to protect against age-related diseases, extend lifespan, and reduce the increasing burden of cardiovascular disease in elderly individuals. We believe that research on cardiac aging is entering a new era of unique significance for the progress of clinical medicine and social welfare.

scholarly journals The Expression and Function of Circadian Rhythm Genes in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yanan Jiang ◽  
Xiuyun Shen ◽  
Moyondafoluwa Blessing Fasae ◽  
Fengnan Zhi ◽  
Lu Chai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Pathogenic Mechanism ◽  
Research Progress ◽  
Biological Processes ◽  
And Function ◽  
Novel Therapeutic

Hepatocellular carcinoma (HCC) is among the most common and lethal form of cancer worldwide. However, its diagnosis and treatment are still dissatisfactory, due to limitations in the understanding of its pathogenic mechanism. Therefore, it is important to elucidate the molecular mechanisms and identify novel therapeutic targets for HCC. Circadian rhythm-related genes control a variety of biological processes. These genes play pivotal roles in the initiation and progression of HCC and are potential diagnostic markers and therapeutic targets. This review gives an update on the research progress of circadian rhythms, their effects on the initiation, progression, and prognosis of HCC, in a bid to provide new insights for the research and treatment of HCC.

scholarly journals Targeting Age-Related Pathways in Heart Failure

2020 ◽  
Vol 126 (4) ◽  
pp. 533-551 ◽  
Author(s):  
Haobo Li ◽  
Margaret H. Hastings ◽  
James Rhee ◽  
Lena E. Trager ◽  
Jason D. Roh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Elderly Population ◽  
Molecular Mechanisms ◽  
The Elderly ◽  
Structure And Function ◽  
Experimental Platform ◽  
Age Related ◽  
Cardiac Structure And Function ◽  
And Function ◽  
Increased Susceptibility

During aging, deterioration in cardiac structure and function leads to increased susceptibility to heart failure. The need for interventions to combat this age-related cardiac decline is becoming increasingly urgent as the elderly population continues to grow. Our understanding of cardiac aging, and aging in general, is limited. However, recent studies of age-related decline and its prevention through interventions like exercise have revealed novel pathological and cardioprotective pathways. In this review, we summarize recent findings concerning the molecular mechanisms of age-related heart failure and highlight exercise as a valuable experimental platform for the discovery of much-needed novel therapeutic targets in this chronic disease.

scholarly journals Metabolic reprogramming of human CD8+ memory T cells through loss of SIRT1

2017 ◽  
Vol 215 (1) ◽  
pp. 51-62 ◽  
Author(s):  
Mark Y. Jeng ◽  
Philip A. Hull ◽  
Mingjian Fei ◽  
Hye-Sook Kwon ◽  
Chia-Lin Tsou ◽  
...  
Keyword(s):  
T Cells ◽  
Molecular Mechanisms ◽  
Memory T Cells ◽  
Cell Metabolism ◽  
Global Gene Expression ◽  
Metabolic Reprogramming ◽  
Transcriptional Reprogramming ◽  
Age Related ◽  
Global Gene Expression Profiling ◽  
And Function

The expansion of CD8+CD28– T cells, a population of terminally differentiated memory T cells, is one of the most consistent immunological changes in humans during aging. CD8+CD28– T cells are highly cytotoxic, and their frequency is linked to many age-related diseases. As they do not accumulate in mice, many of the molecular mechanisms regulating their fate and function remain unclear. In this paper, we find that human CD8+CD28– T cells, under resting conditions, have an enhanced capacity to use glycolysis, a function linked to decreased expression of the NAD+-dependent protein deacetylase SIRT1. Global gene expression profiling identified the transcription factor FoxO1 as a SIRT1 target involved in transcriptional reprogramming of CD8+CD28– T cells. FoxO1 is proteasomally degraded in SIRT1-deficient CD8+CD28– T cells, and inhibiting its activity in resting CD8+CD28+ T cells enhanced glycolytic capacity and granzyme B production as in CD8+CD28– T cells. These data identify the evolutionarily conserved SIRT1–FoxO1 axis as a regulator of resting CD8+ memory T cell metabolism and activity in humans.

scholarly journals Atrial Electrophysiological Remodeling and Fibrillation in Heart Failure

2016 ◽  
Vol 10s1 ◽  
pp. CMC.S39713 ◽  
Author(s):  
Sandeep V. Pandit ◽  
Antony J. Workman
Keyword(s):  
Heart Failure ◽  
Molecular Mechanisms ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Calcium Handling ◽  
Ion Currents ◽  
Multiple Variables ◽  
The Individual ◽  
And Function

Heart failure (HF) causes complex, chronic changes in atrial structure and function, which can cause substantial electrophysiological remodeling and predispose the individual to atrial fibrillation (AF). Pharmacological treatments for preventing AF in patients with HF are limited. Improved understanding of the atrial electrical and ionic/molecular mechanisms that promote AF in these patients could lead to the identification of novel therapeutic targets. Animal models of HF have identified numerous changes in atrial ion currents, intracellular calcium handling, action potential waveform and conduction, as well as expression and signaling of associated proteins. These studies have shown that the pattern of electrophysiological remodeling likely depends on the duration of HF, the underlying cardiac pathology, and the species studied. In atrial myocytes and tissues obtained from patients with HF or left ventricular systolic dysfunction, the data on changes in ion currents and action potentials are largely equivocal, probably owing mainly to difficulties in controlling for the confounding influences of multiple variables, such as patient's age, sex, disease history, and drug treatments, as well as the technical challenges in obtaining such data. In this review, we provide a summary and comparison of the main animal and human electrophysiological studies to date, with the aim of highlighting the consistencies in some of the remodeling patterns, as well as identifying areas of contention and gaps in the knowledge, which warrant further investigation.

scholarly journals Mitochondria and Calcium Homeostasis: Cisd2 as a Big Player in Cardiac Ageing

2020 ◽  
Vol 21 (23) ◽  
pp. 9238
Author(s):  
Chi-Hsiao Yeh ◽  
Yi-Ju Chou ◽  
Cheng-Heng Kao ◽  
Ting-Fen Tsai
Keyword(s):  
Energy Metabolism ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Dynamic Control ◽  
Basic Research ◽  
Human Populations ◽  
Age Related ◽  
Novel Target ◽  
High Level ◽  
New Evidence

The ageing of human populations has become a problem throughout the world. In this context, increasing the healthy lifespan of individuals has become an important target for medical research and governments. Cardiac disease remains the leading cause of morbidity and mortality in ageing populations and results in significant increases in healthcare costs. Although clinical and basic research have revealed many novel insights into the pathways that drive heart failure, the molecular mechanisms underlying cardiac ageing and age-related cardiac dysfunction are still not fully understood. In this review we summarize the most updated publications and discuss the central components that drive cardiac ageing. The following characters of mitochondria-related dysfunction have been identified during cardiac ageing: (a) disruption of the integrity of mitochondria-associated membrane (MAM) contact sites; (b) dysregulation of energy metabolism and dynamic flexibility; (c) dyshomeostasis of Ca2+ control; (d) disturbance to mitochondria–lysosomal crosstalk. Furthermore, Cisd2, a pro-longevity gene, is known to be mainly located in the endoplasmic reticulum (ER), mitochondria, and MAM. The expression level of Cisd2 decreases during cardiac ageing. Remarkably, a high level of Cisd2 delays cardiac ageing and ameliorates age-related cardiac dysfunction; this occurs by maintaining correct regulation of energy metabolism and allowing dynamic control of metabolic flexibility. Together, our previous studies and new evidence provided here highlight Cisd2 as a novel target for developing therapies to promote healthy ageing

scholarly journals Review of Single-Cell RNA Sequencing in the Heart

2020 ◽  
Vol 21 (21) ◽  
pp. 8345
Author(s):  
Shintaro Yamada ◽  
Seitaro Nomura
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Clinical Medicine ◽  
Basic Research ◽  
Cellular Level ◽  
Cardiovascular Development ◽  
Biological Mechanisms ◽  
Technological Advances ◽  
Single Cell Rna Sequencing

Single-cell RNA sequencing (scRNA-seq) technology is a powerful, rapidly developing tool for characterizing individual cells and elucidating biological mechanisms at the cellular level. Cardiovascular disease is one of the major causes of death worldwide and its precise pathology remains unclear. scRNA-seq has provided many novel insights into both healthy and pathological hearts. In this review, we summarize the various scRNA-seq platforms and describe the molecular mechanisms of cardiovascular development and disease revealed by scRNA-seq analysis. We then describe the latest technological advances in scRNA-seq. Finally, we discuss how to translate basic research into clinical medicine using scRNA-seq technology.

scholarly journals Establishment of a novel probe-based RT-qPCR approach for detection and quantification of tight junctions reveals age-related changes in the gut barriers of broiler chickens

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248165
Author(s):  
J. Sophia von Buchholz ◽  
Ivana Bilic ◽  
Jörg R. Aschenbach ◽  
Michael Hess ◽  
Taniya Mitra ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Tight Junctions ◽  
Broiler Chickens ◽  
Molecular Mechanisms ◽  
Dominant Role ◽  
Molecular Composition ◽  
Gut Health ◽  
Age Related ◽  
And Function ◽  
Detection And Quantification

Tight junctions (TJs) play a dominant role in gut barrier formation, therefore, resolving the structures of TJs in any animal species is crucial but of major importance in fast growing broilers. They are regulated in molecular composition, ultrastructure and function by intracellular proteins and the cytoskeleton. TJ proteins are classified according to their function into barrier-forming, scaffolding and pore-forming types with deductible consequences for permeability. In spite of their importance for gut health and its integrity limited studies have investigated the TJs in chickens, including the comprehensive evaluation of TJs molecular composition and function in the chicken gut. In the actual study sequence-specific probes to target different TJ genes (claudin 1, 3, 5, 7, 10, 19, zonula occludens 1 (ZO1), occludin (OCLN) and tricellulin (MD2)) were designed and probe-based RT-qPCRs were newly developed. Claudin (CLDN) 1, 5, ZO1 and CLDN 3, 7, MD2 were engulfed in multiplex RT-qPCRs, minimizing the number of separate reactions and enabling robust testing of many samples. All RT-qPCRs were standardized for chicken jejunum and caecum samples, which enabled specific detection and quantification of the gene expression. Furthermore, the newly established protocols were used to investigate the age developmental changes in the TJs of broiler chickens from 1–35 days of age in the same organ samples. Results revealed a significant increase in mRNA expression between 14 and 21days of age of all tested TJs in jejunum. However, in caecum, mRNA expression of some TJs decreased after 1 day of age whereas some TJs mRNA remained constant till 35 days of age. Taken together, determining the segment-specific changes in the expression of TJ- proteins by RT-qPCR provides a deeper understanding of the molecular mechanisms underpinning pathophysiological changes in the gut of broiler chickens with various etiologies.

Environment and Brain Plasticity: Towards an Endogenous Pharmacotherapy

2014 ◽  
Vol 94 (1) ◽  
pp. 189-234 ◽  
Author(s):  
Alessandro Sale ◽  
Nicoletta Berardi ◽  
Lamberto Maffei
Keyword(s):  
Environmental Enrichment ◽  
Molecular Mechanisms ◽  
Brain Plasticity ◽  
System Development ◽  
Basic Research ◽  
Nervous System Development ◽  
Adult Brain ◽  
Aging Brain ◽  
Cerebral Neurons ◽  
And Function

Brain plasticity refers to the remarkable property of cerebral neurons to change their structure and function in response to experience, a fundamental theoretical theme in the field of basic research and a major focus for neural rehabilitation following brain disease. While much of the early work on this topic was based on deprivation approaches relying on sensory experience reduction procedures, major advances have been recently obtained using the conceptually opposite paradigm of environmental enrichment, whereby an enhanced stimulation is provided at multiple cognitive, sensory, social, and motor levels. In this survey, we aim to review past and recent work concerning the influence exerted by the environment on brain plasticity processes, with special emphasis on the underlying cellular and molecular mechanisms and starting from experimental work on animal models to move to highly relevant work performed in humans. We will initiate introducing the concept of brain plasticity and describing classic paradigmatic examples to illustrate how changes at the level of neuronal properties can ultimately affect and direct key perceptual and behavioral outputs. Then, we describe the remarkable effects elicited by early stressful conditions, maternal care, and preweaning enrichment on central nervous system development, with a separate section focusing on neurodevelopmental disorders. A specific section is dedicated to the striking ability of environmental enrichment and physical exercise to empower adult brain plasticity. Finally, we analyze in the last section the ever-increasing available knowledge on the effects elicited by enriched living conditions on physiological and pathological aging brain processes.

Atrial fibrillation, cardiogenic embolism, and tumors

ESC CardioMed ◽  
2018 ◽  
pp. 493-496
Author(s):  
Bogdan A. Popescu ◽  
Maria-Magdalena Gurzun ◽  
Carmen Ginghina
Keyword(s):  
Atrial Fibrillation ◽  
Transthoracic Echocardiography ◽  
Left Atrial ◽  
Transoesophageal Echocardiography ◽  
Left Ventricular ◽  
Functional Changes ◽  
Atrial Size ◽  
Valvular Function ◽  
Systolic And Diastolic Function ◽  
And Function

Transthoracic echocardiography is recommended in patients with atrial fibrillation (class IC indication). It can identify cardiac structural and functional changes responsible for or related to atrial fibrillation. Echocardiography is used in patients with atrial fibrillation to assess left and right atrial size and function, left ventricular systolic and diastolic function, left ventricular filling pressures, valvular function, right ventricular function, and the pericardium. The data obtained by echocardiography is used to predict the risk of atrial fibrillation, the embolic risk in patients with atrial fibrillation, the feasibility of cardioversion, and the maintenance of sinus rhythm after cardioversion. While for left atrial size and function assessment transthoracic echocardiography is the modality most often used, the accurate evaluation of the left atrial appendage requires transoesophageal echocardiography.

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