Telomere length measurement as a clinical biomarker of aging and disease

Fasching, Clare L.

doi:10.1080/10408363.2018.1504274

Cited by 119 publications

(84 citation statements)

References 158 publications

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“…Thus it is crucial to be aware that some of the methods would benefit only as screening methods but very accurate. The methods for telomere length assessment were revised elsewhere with all the advantages and disadvantages discussed thoroughly [41]. Briefly, there are two basic approaches used in telomere length assessment, i.e.…”

Section: Telomere Length Profilingmentioning

confidence: 99%

Telomere length: how the length makes a difference

et al. 2020

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Telomerase is perceived as an immortality enzyme that might provide longevity to cells and whole organisms. Importantly, it is generally inactive in most somatic cells of healthy, adult men. Consequently, its substrates, i.e. telomeres, get shorter in most human cells with time. Noteworthy, cell life limitation due to telomere attrition during cell divisions, may not be as bad as it looks since longer cell life means longer exposition to harmful factors. Consequently, telomere length (attrition rate) becomes a factor that is responsible for inducing the signaling that leads to the elimination of cells that lived long enough to acquire severe damage. It seems that telomere length that depends on many different factors (including telomerase activity but also genetic factors, a hormonal profile that reflects sex, etc.) might become a useful marker of aging and exposition to stress. Thus in the current paper, we review the factors that affect telomere length in human cells focusing on sex that all together with different environmental and hormonal regulations as well as parental aspect affect telomere attrition rate. We also raise some limitations in the assessment of telomere length that hinders a trustworthy meta-analysis that might lead to acknowledgment of the real value of this parameter.

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Section: Telomere Length Profilingmentioning

confidence: 99%

Telomere length: how the length makes a difference

et al. 2020

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“…Very short telomeres have relatively low cancer risk (due to cell senescence blocking cell division), but could be associated with 708 L. Fani et al / Telomere Length and Alzheimer's Disease increased DNA damage [5]. Given the tight link with cell death, short telomere length has been linked to poorer survival [6,7] and other age-related diseases, including dementia as has been shown in a recent meta-analysis [8]. Conversely, there is evidence that over-elongated telomeres represent pathological cell function with decreased DNA repair and increased cancer risk [9], which has also been shown in human embryonic stem cells [10], while "normally" long telomeres are protective, including against DNA damage.…”

Section: Introductionmentioning

confidence: 99%

Telomere Length and the Risk of Alzheimer’s Disease: The Rotterdam Study

Fani

Hilal

Sedaghat

et al. 2020

JAD

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There is a wide interest in biomarkers that capture the burden of detrimental factors as these accumulate with the passage of time, i.e., increasing age. Telomere length has received considerable attention as such a marker, because it is easily quantified and it may aid in disentangling the etiology of dementia or serve as predictive marker. We determined the association of telomere length with risk of Alzheimer's disease and all-cause dementia in a population-based setting. Within the Rotterdam Study, we performed quantitative PCR to measure mean leukocyte telomere length in blood. We determined the association of telomere length with risk of Alzheimer's disease until 2016, using Cox regression models. Of 1,961 participants (mean age 71.4 ± 9.3 years, 57.1% women) with a median follow-up of 8.3 years, 237 individuals were diagnosed with Alzheimer's disease. We found a U-shaped association between telomere length and risk of Alzheimer's disease: compared to the middle tertile the adjusted hazard ratio was 1.59 (95% confidence interval (CI), 1.13-2.23) for the lowest tertile and 1.47 (1.03-2.10) for the highest tertile. Results were similarly U-shaped but slightly attenuated for all-cause dementia. In conclusion, shorter and longer telomere length are both associated with an increased risk of Alzheimer's disease in the general population.

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“…This relationship might reflect the impact of biological aging, particularly, in regards to the accumulation of endothelial and vascular damage over time [4]. Telomeres are specialized DNA-protein complexes at linear chromosome ends in eukaryotes, and have been considered as a marker of biological aging at both the cellular and organism level [5,6]. They safeguard genome stability by preventing DNA degradation and fusion at chromosomal termini [7].…”

Section: Introductionmentioning

confidence: 99%

Association between telomere length in peripheral blood leukocytes and risk of ischemic stroke in a Han Chinese population: a linear and non-linear Mendelian randomization analysis

et al. 2020

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Background Many contradictory conclusions pertaining to the telomere length in peripheral leukocyte chromosomes as a potential biomarker for ischemic stroke (IS) risk have been reported by the various observational studies in previous years. This study aims to investigate whether the leukocyte telomere length is associated with an increased IS risk or not, based on the Mendelian randomization (MR) approach. Methods Based on the NHGRI-EBI GWAS Catalog database, the Chinese online genetic database as well as the previous published studies, twelve single nucleotide polymorphisms (SNPs) with minor allele frequency ≥ 0.05 were selected and the leukocyte telomere length was measured in 431 first-ever IS patients and 304 healthy controls (quantitative polymerase chain reaction). To explore linear and non-linear effect of telomere length on the IS risk, we preformed the linear MR analysis (the inverse-variance weighted method, the maximum likelihood method, and the mode-based estimation method), and the non-linear MR analysis (semiparametric method with three tests for non-linearity, including the quadratic test, Cochran’s Q test, and the fractional polynomial test). Results Two verified SNPs (rs11125529 and rs412658) were chosen as instrumental variables. In linear MR analysis, the adjusted odds ratios and 95% confidence intervals of IS for genetically predicted telomere lengths, based on the two SNPs, were 1.312 (0.979 to 1.759), 1.326 (0.932 to 1.888) and 1.226 (0.844 to 1.781) for the inverse-variance weighted method, the maximum likelihood method, and the mode-based estimation method, respectively. Three tests for nonlinearity failed to reject the null exactly, indicating that the relationship between telomere length and IS risk is unlikely to be non-linear. Conclusion This MR study based on individual data does not provide strong evidence for a positive linear or non-linear effect of telomere length on the IS risk.

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Telomere length measurement as a clinical biomarker of aging and disease

Cited by 119 publications

References 158 publications

Telomere length: how the length makes a difference

Telomere length: how the length makes a difference

Telomere Length and the Risk of Alzheimer’s Disease: The Rotterdam Study

Association between telomere length in peripheral blood leukocytes and risk of ischemic stroke in a Han Chinese population: a linear and non-linear Mendelian randomization analysis

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