Cardiac aging and heart disease in humans

Steenman, Marja; Lande, Gilles

doi:10.1007/s12551-017-0255-9

Cited by 195 publications

(178 citation statements)

References 63 publications

Supporting

Mentioning

154

Contrasting

Order By: Relevance

“…Ageing is a primary risk factor for cardiac disease [56]. Cardiac ageing manifests as a decline in structure and function of the heart, leading to cardiac disease [57,58]. At the cellular level, ageing entails a decline in mitochondrial function and dysregulation of cellular processes, such as oxidative stress, autophagy, and metabolic imbalance, in cardiomyocytes [57].…”

Section: Alterations Of Interactions Between the Er And Mitochondria mentioning

confidence: 99%

Imbalance of ER and Mitochondria Interactions: Prelude to Cardiac Ageing and Disease?

Jin

Zhang

Brundel

et al. 2019

Cells

View full text Add to dashboard Cite

Cardiac disease is still the leading cause of morbidity and mortality worldwide, despite some exciting and innovative improvements in clinical management. In particular, atrial fibrillation (AF) and heart failure show a steep increase in incidence and healthcare costs due to the ageing population. Although research revealed novel insights in pathways driving cardiac disease, the exact underlying mechanisms have not been uncovered so far. Emerging evidence indicates that derailed proteostasis (i.e., the homeostasis of protein expression, function and clearance) is a central component driving cardiac disease. Within proteostasis derailment, key roles for endoplasmic reticulum (ER) and mitochondrial stress have been uncovered. Here, we describe the concept of ER and mitochondrial stress and the role of interactions between the ER and mitochondria, discuss how imbalance in the interactions fuels cardiac ageing and cardiac disease (including AF), and finally assess the potential of drugs directed at conserving the interaction as an innovative therapeutic target to improve cardiac function. of 15including the ubiquitin-proteasomal system (UPS) and autophagy [9]. In general, cellular stress, including stress caused by cardiac disease, activates multiple stress pathways, including the cytosolic heat shock response, the endoplasmic reticulum (ER) unfolded protein response (UPR ER ), and the mitochondrial UPR (UPR mt ) [10][11][12].Within the PQC, the ER and mitochondria play a critical role in the regulation of protein homeostasis and the maintenance of normal cellular function. The ER is an essential organelle involved in protein synthesis, folding, and trafficking. As protein folding is an error-prone process, the PQC system of the ER is specialized in optimizing this process, thereby preserving cardiac protein quality and homeostasis [13]. As approximately 30% of the cardiomyocyte volume is comprised of mitochondria, the maintenance of a healthy and functional mitochondrial PQC system, which includes molecular chaperones (e.g., HSP60 and HSP10) and proteases (e.g., ClpP), is critical to conserve the energy balance and cardiomyocyte function. The PQC system in mitochondria activates, upon stress, protein folding assistance mechanisms and promotes clearance of misfolded proteins to preserve mitochondrial function [14,15].Thus, a healthy proteostasis in cardiomyocytes safeguards the proper contractile function in the heart. The ER and mitochondria are essential organelles for regulating protein homeostasis, thereby guaranteeing cardiomyocyte function and survival. Therefore, a deeper understanding of ER and mitochondrial function during health and cardiac disease is required to ultimately develop novel therapeutic strategies. Role of the ER in Cardiac HealthThe ER is an essential organelle supporting multiple cellular processes such as protein synthesis, protein folding, regulation of Ca 2+ homeostasis, and contribution to the generation of autophagosomes and peroxisomes [16]. The ER lumen constitutes of a specialized fol...

show abstract

Section: Alterations Of Interactions Between the Er And Mitochondria mentioning

confidence: 99%

Imbalance of ER and Mitochondria Interactions: Prelude to Cardiac Ageing and Disease?

Jin

Zhang

Brundel

et al. 2019

Cells

View full text Add to dashboard Cite

show abstract

“…In addition, aging hampers psychosocial well-being by adding new developmental tasks or situations (e.g., isolation; Steptoe et al, 2015). In particular, the prevalence of Alzheimer's disease, cancer, chronic obstructive pulmonary disease, maculopathy, osteoarthritis, osteopenia, Parkinson's disease, periodontitis, rheumatoid arthritis, sarcopenia, cardiovascular diseases, and type 2 diabetes increases with age (Tolosa et al, 2006;Dubois et al, 2010;Marengoni et al, 2011;Edwards et al, 2015;Steenman and Lande, 2017;Yakaryilmaz and Öztürk, 2017;Franceschi et al, 2018). Additionally, several clinical conditions may jeopardize the well-being of older people, such as mild cognitive impairment, frailty, or metabolic syndrome (Fried et al, 2001;Petersen, 2004;Portet et al, 2006;Huang, 2009;Xue, 2011;Fedarko, 2012).…”

Section: Introductionmentioning

confidence: 99%

Usability Issues of Clinical and Research Applications of Virtual Reality in Older People: A Systematic Review

Tuena

Pedroli

Trimarchi

et al. 2020

Front. Hum. Neurosci.

124

View full text Add to dashboard Cite

Aging is a condition that may be characterized by a decline in physical, sensory, and mental capacities, while increased morbidity and multimorbidity may be associated with disability. A wide range of clinical conditions (e.g., frailty, mild cognitive impairment, metabolic syndrome) and age-related diseases (e.g., Alzheimer's and Parkinson's disease, cancer, sarcopenia, cardiovascular and respiratory diseases) affect older people. Virtual reality (VR) is a novel and promising tool for assessment and rehabilitation in older people. Usability is a crucial factor that must be considered when designing virtual systems for medicine. We conducted a systematic review with Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines concerning the usability of VR clinical systems in aging and provided suggestions to structure usability piloting. Findings show that different populations of older people have been recruited to mainly assess usability of non-immersive VR, with particular attention paid to motor/physical rehabilitation. Mixed approach (qualitative and quantitative tools together) is the preferred methodology; technology acceptance models are the most applied theoretical frameworks, however senior adapted models are the best within this context. Despite minor interaction issues and bugs, virtual systems are rated as usable and feasible. We encourage usability and user experience pilot studies to ameliorate interaction and improve acceptance and use of VR clinical applications in older people with the aid of suggestions (VR-USOP) provided by our analysis.

show abstract

“…In this study, we developed a new simulation-based approach to predict the consequences of age-related cellular remodelling. A large number of ageing-related myocardial changes are already known, including ionic remodelling associated with changes in biophysical/biochemical mechanisms affecting the function of cardiomyocytes [21,30,31].…”

Section: Discussionmentioning

confidence: 99%

A Population Modelling Approach to Studying Age-Related Effects on Excitation-Contraction Coupling in Human Cardiomyocytes

Dokuchaev

Khamzin

Solovyova

2019

Preprint

View full text Add to dashboard Cite

Ageing is the dominant risk factor for cardiovascular diseases. A great body of experimental data has been gathered on cellular remodelling in the Ageing myocardium from animals. Very few experimental data are available on age-related changes in the human cardiomyocyte. We have used our combined electromechanical model of the human cardiomyocyte and the population modelling approach to investigate the variability in the response of cardiomyocytes to age-related changes in the model parameters. To generate the model population, we varied nine model parameters and excluded model samples with biomarkers falling outside of the physiological ranges. We evaluated the response to age-related changes in four electrophysiological model parameters reported in the literature: reduction in the density of the K + transient outward current, maximal velocity of SERCA, and an increase in the density of NaCa exchange current and CaL-type current. The sensitivity of the action potential biomarkers to individual parameter variations was assessed. Each parameter modulation caused an increase in APD, while the sensitivity of the model to changes in G CaL and V max_up was much higher than to those in the effects of G to and K NaCa . Then 60 age-related sets of the four parameters were randomly generated and each set was applied to every model in the control population. We calculated the frequency of model samples with repolarisation anomalies (RA) and the shortening of the electro-mechanical window in the ageing model populations as an arrhythmogenic ageing score. The linear dependence of the score on the deviation of the parameters showed a high determination coefficient with the most significant impact due to the age-related change in the CaL current. The population-based approach allowed us to classify models with low and high risk of age-related RA and to predict risks based on the control biomarkers.

show abstract

Cardiac aging and heart disease in humans

Cited by 195 publications

References 63 publications

Imbalance of ER and Mitochondria Interactions: Prelude to Cardiac Ageing and Disease?

Imbalance of ER and Mitochondria Interactions: Prelude to Cardiac Ageing and Disease?

Usability Issues of Clinical and Research Applications of Virtual Reality in Older People: A Systematic Review

A Population Modelling Approach to Studying Age-Related Effects on Excitation-Contraction Coupling in Human Cardiomyocytes

Contact Info

Product

Resources

About