Shorter Leukocyte Telomere Length Is Associated with Worse Survival of Patients with Bladder Cancer and Renal Cell Carcinoma

Zheng, Xiao; Wezel, Felix; Azoitei, Anca; Meessen, Sabine; Wang, Wenya; Najjar, Gregoire; Wang, Xue; Kraus, Johann M.; Kestler, Hans A.; John, Axel; Zengerling, Friedemann; Bolenz, Christian; Güneş, Çagatay

doi:10.3390/cancers13153774

Cited by 8 publications

(7 citation statements)

References 102 publications

(140 reference statements)

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“…Several studies have clearly demonstrated that telomere length correlates with senescence, including in endothelial cells (48), but also with numerous aging-related diseases, including cardiovascular atherosclerotic and in ammatory disease, cancer, infections, stroke, mental pathologies, osteoporosis, and dementia (18,19,20,22,26,(49)(50)(51)(52).…”

Section: Discussionmentioning

confidence: 99%

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ASTCOQ02, a natural telomerase activator, lengthens telomeres in humans in a middle-aged population A randomized, double-blind, placebo-controlled study

Jaeger¹,

Kruiskamp²,

Voronska³

et al. 2022

Preprint

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Telomeres are ribonucleoprotein structures that form a protective buffer at the ends of chromosomes and thus maintain genomic integrity during the cell cycle. Replicative telomere erosion can be compensated by a telomerase. Average telomeres size decreases with age and associated with aging-related diseases such as cancer and cardio-vascular disease. We previously reported that ASTCOQ02 (an Astragalus extract that contains astragaloside IV and cycloastragenol), a telomerase activator showed benefit in an open prospective study on telomere size and cardiovascular impact in healthy volunteers. Here we performed a randomized, double-blind, controlled trial over 6 months comparing the effect of ASTCOQ02 versus placebo on telomere length (TL) in 40 healthy volunteers (mean age 56.1 ± 6.0 years). Twenty subjects received ASTCOQ02 and 20 received placebo capsules. All 40 subjects completed the study with no adverse side effects reported at 6 months. Subjects taking ASTCOQ02 had significantly longer median (P = 0.01) and short TL (P = 0.004) and a lower percentage of short telomeres over the 6 months period whereas placebo group TL remained unchanged. This randomized, double-blind, placebo-controlled trial confirmed that ASTCOQ02 significantly lengthens both median and short telomeres by increasing telomerase activity, and reduces the percentage of short telomere (< 3 Kbp) in a statistically and possibly clinically significant manner. The results of this study also converge with the previous open prospective trial that found zero toxicity associated with intake of ASTCOQ02. ASTCOQ02 warrants further human studies on health, longer life expectancy and healthy aging.

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Section: Discussionmentioning

confidence: 99%

“…Numerous studies show that telomere shortening in peripheral blood leukocytes is a risk factor for cardiovascular disease (atherosclerosis, early infarction, hypertension, vascular dementia), metabolic disorders (diabetes, obesity, insulin resistance), mental pathologies, infection and cancer (12,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

ASTCOQ02, a natural telomerase activator, lengthens telomeres in humans in a middle-aged population A randomized, double-blind, placebo-controlled study

Jaeger¹,

Kruiskamp²,

Voronska³

et al. 2022

Preprint

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show abstract

“…A multicenter clinical study showed that the overall mortality was slightly high and malignancies were prevalent in those with shorter leukocyte telomere lengths [5]. Telomeres with altered lengths and associated gene mutations are connected with tumorigenesis [6][7][8]. Some studies have reported the role of telomere-related genes in ccRCC [9].…”

Section: Introductionmentioning

confidence: 99%

Causal relationship between telomere length and renal cell carcinoma and prognostic modeling of ccRCC based on telomere- related lncRNAs

Chen,

Zeng,

2024

Preprint

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Background Telomeres have been demonstrated to be critical in the development of multiple tumors. However, the association of telomere-related lncRNAs with clear cell renal cell carcinoma (ccRCC) and their prognostic roles in ccRCC patients remain unknown. Methods Exposure data was obtained from GWAS database. Two-sample mendelian randomization (MR) was used to test for causal associations between telomere length and renal cell carcinoma. Expression matrix and clinicopathological data of ccRCC patients were extracted from The Cancer Genome Altas and UCSC Xena browser. The differentially expressed genes were identified and intersected with the telomere-related genes downloaded from the Telnet database. Telomere-related lncRNAs were screened by the univariate Cox regression analysis. Each patient's risk score was calculated to establish a nomogram based on eight telomere-related lncRNAs screened by the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression analysis. The correlation between telomere-related lncRNAs and immune cells was assessed by the CIBEERSORT algorithm. The immune and stromal infiltrations were quantified by the ESTIMATE algorithm. Gene set enrichment analysis (GSEA) was performed to explore the selected lncRNA functions. Result A causal relationship between telomere length and renal cell carcinoma was observed. We screened eight telomere-related lncRNAs and established a risk score model for predicting survival in ccRCC patients. A nomogram was developed to predict the survival outcomes of postoperative patients by integrating several clinical factors, and a well-predictive effect was observed. The correlation between selected lncRNAs and immune function was explored by the CIBEERSORT and ESTIMATE algorithms. Besides, GSEA showed that telomere-related lncRNAs could affect ccRCC prognosis through multiple pathways.

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“…Thus, the telomere has been referred to as a "mitotic clock" [12] and telomere length has been construed as a measure of "biological age" [13]. Consistent with these considerations, peripherally measured TL has been shown to be associated with a wide range of disease and health morbidities in adults [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] and children [29][30][31][32][33][34][35][36][37][38] and has become a popular biomarker for stress and accelerated biological aging [10,35,[39][40][41][42][43][44][45]. Thus, TL at birth and the course of TL shortening in blood or saliva may provide insight into associated between premature birth and future health trajectory.…”

Section: Introductionmentioning

confidence: 99%

Characteristics of salivary telomere length shortening in preterm infants

et al. 2023

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Objective To examine the association between gestational age, telomere length (TL) and rate of shortening in newborns. Study design Genomic DNA was isolated from buccal samples of 39 term infants at birth and one year and 32 preterm infants at birth, term-adjusted age (40 weeks post-conception) and age one-year corrected for gestational duration. Telomere length was measured by quantitative real-time PCR. Demographic and clinical data were collected during clinic or research visits and from hospital records. Socioeconomic status was estimated using the deprivation category (DEPCAT) scores derived from the Carstairs score of the subject’s postal code. Results At birth, preterm infants had longer telomeres than infants born at term. However, there was no difference in telomere length between preterm infants and term infants at one year of age, implying that the rate of telomere shortening was greater in pre-term than term infants. Interestingly, TL at age 40 weeks post-conception in preterm infants was significantly longer than term infant TL at birth, suggesting that time since conception is not the only factor that affects rate of shortening. Several factors, including sex, fetal growth restriction, maternal age, maternal booking body mass index (BMI), mother education level and DEPCAT score, also differed between the preterm and term groups. Conclusions Preterm infants have longer telomeres than term infants at birth. In the studied cohort, the rate of telomere shortening was greater in the premature group compared with the term infants. This finding agrees with previous studies using cord blood, suggesting that the longer TL in premature infants detected at birth do not persist and demonstrating that use of saliva DNA is acceptable for studies of telomere dynamics in infants. However, that the TL at age 40 weeks post-conception in preterm is longer than term infants at birth suggests that biological factors other than time since conception also affect rate of shortening.

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Shorter Leukocyte Telomere Length Is Associated with Worse Survival of Patients with Bladder Cancer and Renal Cell Carcinoma

Cited by 8 publications

References 102 publications

ASTCOQ02, a natural telomerase activator, lengthens telomeres in humans in a middle-aged population A randomized, double-blind, placebo-controlled study

ASTCOQ02, a natural telomerase activator, lengthens telomeres in humans in a middle-aged population A randomized, double-blind, placebo-controlled study

Causal relationship between telomere length and renal cell carcinoma and prognostic modeling of ccRCC based on telomere- related lncRNAs

Characteristics of salivary telomere length shortening in preterm infants

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