Cardiac telomere length in heart development, function, and disease
- Booth, Scott, Charchar, Fadi
- Authors: Booth, Scott , Charchar, Fadi
- Date: 2017
- Type: Text , Journal article , Review
- Relation: Physiological Genomics Vol. 49, no. 7 (2017), p. 368-384
- Relation: http://purl.org/au-research/grants/nhmrc/1034371
- Full Text: false
- Reviewed:
- Description: 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. © 2017 the American Physiological Society.
- Gielen, Marij, Hageman, Geja, Antoniou, Evangelia, Nordfjall, Katarina, Mangino, Massimo, Balasubramanyam, Muthuswamy, De Meyer, Tim de, Hendricks, Audrey, Giltay, Erik, Hunt, Steven, Nettleton, Jennifer, Salpea, Klelia, Diaz, Vanessa, Farzaneh-Far, Ramin, Atzmon, Gil, Harris, Sarah, Hou, Lifang, Gilley, David, Hovatta, Iiris, Kark, Jeremy, Nassar, Hisham, Kurz, David, Mather, Karen, Willeit, Peter, Zheng, Yun-Ling, Pavanello, Sofia, Demerath, Ellen, Rode, Line, Bunout, Daniel, Steptoe, Andrew, Boardman, Lisa, Marti, Amelia, Needham, Belinda, Zheng, Wei, Ramsey-Goldman, Rosalind, Pellatt, Andrew, Kaprio, Jaakko, Hofmann, Jonathan, Gieger, Christian, Paolisso, Giuseppe, Hjelmborg, Jacob, Mirabello, Lisa, Seeman, Teresa, Wong, Jason, Van Der Harst, Pim, Broer, Linda, Kronenberg, Florian, Kollerits, Barbara, Strandberg, Timo, Eisenberg, Dan, Duggan, Catherine, Verhoeven, Josine, Schaakxs, Roxanne, Zannolli, Raffaela, Dos Reis, Rosana, Charchar, Fadi, Tomaszewski, Maciej, Mons, Ute, Demuth, Ilja, Molli, Andrea, Cheng, Guo, Krasnienkov, Dmytro, D'Antono, Bianca, Kasielski, Marek, McDonnell, Barry, Ebstein, Richard, Sundquist, Kristina, Pare, Guillaume, Chong, Michael, Zeegers, Maurice
- Authors: Gielen, Marij , Hageman, Geja , Antoniou, Evangelia , Nordfjall, Katarina , Mangino, Massimo , Balasubramanyam, Muthuswamy , De Meyer, Tim de , Hendricks, Audrey , Giltay, Erik , Hunt, Steven , Nettleton, Jennifer , Salpea, Klelia , Diaz, Vanessa , Farzaneh-Far, Ramin , Atzmon, Gil , Harris, Sarah , Hou, Lifang , Gilley, David , Hovatta, Iiris , Kark, Jeremy , Nassar, Hisham , Kurz, David , Mather, Karen , Willeit, Peter , Zheng, Yun-Ling , Pavanello, Sofia , Demerath, Ellen , Rode, Line , Bunout, Daniel , Steptoe, Andrew , Boardman, Lisa , Marti, Amelia , Needham, Belinda , Zheng, Wei , Ramsey-Goldman, Rosalind , Pellatt, Andrew , Kaprio, Jaakko , Hofmann, Jonathan , Gieger, Christian , Paolisso, Giuseppe , Hjelmborg, Jacob , Mirabello, Lisa , Seeman, Teresa , Wong, Jason , Van Der Harst, Pim , Broer, Linda , Kronenberg, Florian , Kollerits, Barbara , Strandberg, Timo , Eisenberg, Dan , Duggan, Catherine , Verhoeven, Josine , Schaakxs, Roxanne , Zannolli, Raffaela , Dos Reis, Rosana , Charchar, Fadi , Tomaszewski, Maciej , Mons, Ute , Demuth, Ilja , Molli, Andrea , Cheng, Guo , Krasnienkov, Dmytro , D'Antono, Bianca , Kasielski, Marek , McDonnell, Barry , Ebstein, Richard , Sundquist, Kristina , Pare, Guillaume , Chong, Michael , Zeegers, Maurice
- Date: 2018
- Type: Text , Journal article
- Relation: American Journal of Clinical Nutrition Vol. 108, no. 3 (2018), p. 453-475
- Relation: http://purl.org/au-research/grants/nhmrc/1123472
- Full Text: false
- Reviewed:
- Description: Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectionalmeta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Studyspecific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a-3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI:-10.03,-5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10-3 unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10-3, -1.01 × 10-3) difference in ageand sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10-3 unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10-3, -1.25 × 10-3). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL arewarranted.
Telomere therapy for chronic kidney disease
- Akinnibosun, Olutope, Maier, Michelle, Eales, James, Tomaszewski, Maciej, Charchar, Fadi
- Authors: Akinnibosun, Olutope , Maier, Michelle , Eales, James , Tomaszewski, Maciej , Charchar, Fadi
- Date: 2022
- Type: Text , Journal article
- Relation: Epigenomics Vol. 14, no. 17 (2022), p. 1039-1054
- Full Text: false
- Reviewed:
- Description: Chronic kidney disease (CKD) is estimated to affect almost 10% of individuals worldwide and is one of the leading causes of morbidity and mortality. Renal fibrosis, a central pathway in CKD progression (irrespective of etiology), is associated with shortened or dysfunctional telomeres in animal studies. Telomeres are specialized nucleoprotein structures located at the chromosome end that maintain genomic integrity. The mechanisms of associations between telomere length and CKD have not yet been fully elucidated, however, CKD patients with shorter telomere length may have decreased renal function and a higher mortality rate. A plethora of ongoing research has focused on possible therapeutic applications of telomeres with the overall goal to preserve telomere length as a therapy to treat CKD. Chronic kidney disease or CKD is one of the leading causes of illness and death worldwide. Scarring of the kidney tissue that occurs in CKD has been associated with shorter telomeres in studies using rats. Telomeres, said to act as the cellular ‘shoelace caps’, maintain the structure of chromosomes, allowing for genetic material inside cells to divide correctly. The length of telomeres (TL) is influenced by diverse factors such as genetics and lifestyle. The underlying processes for the associations between TL and CKD are still not understood, however, patients with CKD and shorter TL have reduced kidney function and an increased death rate. Therefore, research is focused on possible ways to preserve TL and treat CKD. Preserving telomere length may reduce rates of chronic kidney disease, thereby decreasing morbidity & mortality worldwide.
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