Extra-telomeric impact of telomeres: Emerging molecular connections in pluripotency or stemness

Vinayagamurthy, Soujanya; Ganguly, Akansha; Chowdhury, Shantanu

doi:10.1074/jbc.rev119.009710

Cited by 12 publications

(16 citation statements)

References 125 publications

(139 reference statements)

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“…Although further work will be required to test this, based on our findings here, it is possible that establishment of a telomeretelomerase crosstalk through TRF2 (telomeric along with non-telomeric binding at the hTERT promoter) is key to how telomeres are managed in cancer cells. In addition, relatively enhanced levels of telomerase and long telomeres are crucial for maintenance/survival of pluripotent stem cells (Aguado et al, 2017;Vinayagamurthy et al, 2020;Zou et al, 2017) It is possible, therefore, that TRF2-mediated hTERT regulation, linked to telomeres, is of significance in pluripotency. Kim et al (2016) showed looping of the 5p chromosome telomere to a region $1.2 Mb away and 100 kb downstream of hTERT.…”

Section: Discussionmentioning

confidence: 99%

Human telomerase is directly regulated by non-telomeric TRF2-G-quadruplex interaction

et al. 2021

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Human telomerase is directly regulated by nontelomeric TRF2-G-quadruplex interactionGraphical abstract Highlights d Non-telomeric TRF2 suppresses re-activated human telomerase in glioblastoma cells d PRC2 recruitment depends on the TRF2 hTERT-Gquadruplex interaction d Clinically deleterious hTERT promoter mutations disrupt G4-TRF2 association d G4 stabilization reinstates TRF2-induced hTERT repression in patient glioblastoma

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Section: Discussionmentioning

confidence: 99%

Human telomerase is directly regulated by non-telomeric TRF2-G-quadruplex interaction

et al. 2021

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“…When gene silencing occurs over long-distances of DNA via long telomeres looping back in the chromatin, the phenomenon is referred to as TPE-over long distances or TPE-OLD. The expression of hTERT is thought to be regulated by a TPE-OLD [ 155 , 156 ]. Both TTP1 and POT1 are involved in regulating telomerase by promoting processivity.…”

Section: Discussionmentioning

confidence: 99%

Physical Activity on Telomere Length as a Biomarker for Aging: A Systematic Review

et al. 2022

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Background Overall life expectancy continues to rise, approaching 80 years of age in several developed countries. However, healthy life expectancy lags far behind, which has, in turn, contributed to increasing costs in healthcare. One way to improve health and attenuate the socio-economic impact of an aging population is to increase overall fitness through physical activity. Telomere attrition or shortening is a well-known molecular marker in aging. As such, several studies have focused on whether exercise influences health and aging through telomere biology. This systematic review examines the recent literature on the effect of physical activity on telomere length (TL) and/or telomerase activity as molecular markers of aging. Methods A focused search was performed in the databases PubMed and Web of Science for retrieving relevant articles over the past ten years. The search contained the following keywords: exercise, sport, physical activity, fitness, sedentary, physical inactivity, telomere, telomere length, t/s ratio, and telomerase. PRISMA guidelines for systematic reviews were observed. Results A total of 43 articles were identified and categorized into randomized controlled trials (RCT), observational or interventional studies. RCTs (n = 8) showed inconsistent findings of increased TL length with physical activity in, e.g. obese, post-menopausal women. In comparison with a predominantly sedentary lifestyle, observational studies (n = 27) showed significantly longer TL with exercise of moderate to vigorous intensity; however, there was no consensus on the duration and type of physical activity and training modality. Interventional studies (n = 8) also showed similar findings of significantly longer TL prior to exercise intervention; however, these studies had smaller numbers of enrolled participants (mostly of high-performance athletes), and the physical activities covered a range of exercise intensities and duration. Amongst the selected studies, aerobic training of moderate to vigorous intensity is most prevalent. For telomere biology analysis, TL was determined mainly from leukocytes using qPCR. In some cases, especially in RCT and interventional studies, different sample types such as saliva, sperm, and muscle biopsies were analyzed; different leukocyte cell types and potential genetic markers in regulating telomere biology were also investigated. Conclusions Taken together, physical activity with regular aerobic training of moderate to vigorous intensity appears to help preserve TL. However, the optimal intensity, duration of physical activity, as well as type of exercise still need to be further elucidated. Along with TL or telomerase activity, participants’ fitness level, the type of physical activity, and training modality should be assessed at different time points in future studies, with the plan for long-term follow-up. Reducing the amount of sedentary behavior may have a positive effect of preserving and increasing TL. Further molecular characterization of telomere biology in different cell types and tissues is required in order to draw definitive causal conclusions on how physical activity affects TL and aging.

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“…This phenomenon is known as telomere positioning effect (TPE). Telomere looping does also occur over long distances so that TPEs can influence the expression of distant genes (TP-OLD) [6,7]. Short telomeres are no longer able to maintain their complex three-dimensional structure, which abolishes TPE and TPE-OLD.…”

Section: Introductionmentioning

confidence: 99%

Telomere length in leucocytes and solid tissues of young and aged rats

Semeraro

Almer

Renner

et al. 2022

Aging

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Background: Telomeres are protective nucleoprotein structures at the end of chromosomes that shorten with age. Telomere length (TL) in peripheral blood mononuclear cells (PBMCs) has been proposed as surrogate marker for TL in the entire organism. Solid evidence that supports this concept is lacking. Methods: Relative TL (RTL) was measured in PBMCS and multiple solid tissues from 24 young (4 months) and 24 aged (14 months) Sprague-Dawley (SD) rats. The mRNA expression of telomerase (TERT) and shelterin proteins TERF-1 and TERF-2 was also measured. Results: Mean RTL in PBMCs and solid tissues of young rats ranged from 0.64 ± 0.26 in large intestine to 1.07 ± 0.22 in skeletal muscle. RTL in PBMCs correlated with that in kidney (r = 0.315, p = 0.008), skeletal muscle (r = 0.276, p = 0.022), liver (r = 0.269, p = 0.033), large intestine (r = −0.463, p = 7.035E-5) and aorta (r = −0.273, p = 0.028). A significant difference of RTL between young and aged animals was only observed in aorta (0.98 ± 0.15 vs. 0.76 ± 0.11, p = 1.987E-6), lung (0.76 ± 0.14 vs. 0.85 ± 0.14, p = 0.024) and visceral fat (0.83 ± 0.14 vs. 0.92 ± 0.15, p = 0.44). The expression of TERT significantly differed between the tested organs with highest levels in liver and kidney. Age-related differences in TERT expression were found in PBMCs, skeletal muscle, and visceral fat. mRNA expression of TERF-1 and TERF-2 was tissue-specific with the highest levels in liver. Age-related differences in TERF-1 and TERF-2 expression were inconsistent. Conclusions: The present study questions the utility of RTL in PBMCs as a biomarker for the individual assessment of aging.

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Extra-telomeric impact of telomeres: Emerging molecular connections in pluripotency or stemness

Cited by 12 publications

References 125 publications

Human telomerase is directly regulated by non-telomeric TRF2-G-quadruplex interaction

Human telomerase is directly regulated by non-telomeric TRF2-G-quadruplex interaction

Physical Activity on Telomere Length as a Biomarker for Aging: A Systematic Review

Telomere length in leucocytes and solid tissues of young and aged rats

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