Cardiac telomere length in heart development, function, and disease

Abstract

Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury.

Aging: Molecular Pathways and Implications on the Cardiovascular System

“…Cardiac telomerase activity is detectable at the earliest stages of life and is downregulated in an adult rat myocardium [ 52 , 53 ]. Recently, Richardson and colleagues showed a natural expression of telomerase functionally important in adult mammalian hearts [ 54 ], which could be targeted for cardiovascular regeneration.…”

Short telomeres — A hallmark of heritable cardiomyopathies

“…Telomeres are non-coding TTAGGG DNA repeats at chromosomal ends that shorten with cell division and aging (Blackburn et al, 2015; Booth and Charchar, 2017a). Telomeres are bound by shelterin protein complexes which act as protective caps to prevent genomic instability (de Lange, 2005; Palm and de Lange, 2008).…”

Telomere shortening is a hallmark of genetic cardiomyopathies

“…Genetic cardiomyopathy—hypertrophic and dilated—affects 1 in 500–2,500 people worldwide and is the leading indication for heart transplantation. Genetic hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are caused by mutations in proteins with a diverse range of functions ( 1 , 2 ). Genetic HCM is characterized by ventricular wall thickening, whereas DCM is characterized by dilation of the ventricular chamber.…”