Telomere dysfunction in ageing and age-related diseases. Nature cell biology Ageing organisms accumulate senescent cells that are thought to contribute to body dysfunction. Telomere shortening and damage are recognized causes of cellular senescence and ageing. Several human conditions associated with normal ageing are precipitated by accelerated telomere dysfunction. Here, we systematize a large body of evidence and propose a coherent perspective to recognize the broad contribution of telomeric dysfunction to human pathologies. 10.1038/s41556-022-00842-x

Regulation of Telomere Length and Atherosclerosis by Protection of Telomeres 1 Protein. Zhang Yanbo,Guo Yi,Zhou Gouqing,Li Shuang Journal of nanoscience and nanotechnology The aim of this study was to investigate the manifestation and significance of changes in both telomere length and the expression of human telomere protective protein (hPOT1) in the peripheral blood leukocytes of patients with atherosclerosis (AS). One hundred subjects-excluding those with acute or chronic inflammation, cancer, and autoimmune diseases-were enrolled in this study and divided into two groups: the atherosclerosis group (AS group) and control group. We extracted peripheral blood leukocyte DNA along with its peripheral proteins. After purity testing, a digoxigeninlabeled telomere probe was used for Southern blotting; the length of the telomeres was obtained by image scanning and software analysis. After extracting the peripheral proteins, hPOT1 expression was detected by western blotting and scanned with an image analysis software system. We found that the telomere lengths in the peripheral blood leukocytes of AS and control groups were 7.45 ± 1.15 kb versus 8.11 ± 0.69 kb, respectively, and that the difference between them was statistically significant ( < 0.005). The expression level of hPOT1 protein in the peripheral blood leukocytes of the AS group was significantly higher than that of the control group ( = 3.77, < 0.01). As can be determined from these results, telomere length in the peripheral blood leukocytes of AS patients was significantly shorter compared with that of the control group. The regulation of telomere length by hPOT1 by negative regulation may be one of the influencing factors in AS. Therefore, it is suggested that change in telomere length may play a role in the occurrence and development of AS. 10.1166/jnn.2019.16938

Telomere Length as Cardiovascular Aging Biomarker: JACC Review Topic of the Week. De Meyer Tim,Nawrot Tim,Bekaert Sofie,De Buyzere Marc L,Rietzschel Ernst R,Andrés Vicente Journal of the American College of Cardiology Telomeres shorten with age, the major risk factor for atherosclerotic cardiovascular disease (aCVD). The observation of shorter telomeres in aCVD patients thus suggested that critical telomere shortening may contribute to premature biological aging and aCVD. Therefore, telomere length often is suggested as a causal aCVD risk factor, a proposal supported by recent Mendelian randomization studies; however, epidemiological research has shown disappointingly low effect sizes. It therefore remains uncertain whether telomere shortening is a cause of aCVD or merely a consequence. The authors argue that elucidating the mechanistic foundation of these findings is essential for any possible translation of telomere biology to the clinic. Here, they critically evaluate evidence for causality in animal models and human studies, and review popular hypotheses and discuss their clinical implications. The authors identify 4 key questions that any successful mechanistic theory should address, and they discuss how atherosclerosis-associated local telomere attrition may provide the answers. 10.1016/j.jacc.2018.06.014

The Importance of Telomere Shortening for Atherosclerosis and Mortality. Herrmann Wolfgang,Herrmann Markus Journal of cardiovascular development and disease Telomeres are the protective end caps of chromosomes and shorten with every cell division. Short telomeres are associated with older age and adverse lifestyle factors. Leucocyte telomere length (LTL) has been proposed as a biomarker of biological age. The shortening of LTL with age is the result of the end-replication problem, environmental, and lifestyle-related factors. Epidemiologic studies have shown that LTL predicts cardiovascular disease, all-cause mortality, and death from vascular causes. Age appears to be an important co-variate that explains a substantial fraction of this effect. Although it has been proposed that short telomeres promote atherosclerosis and impair the repair of vascular lesions, existing results are inconsistent. Oxidative stress and chronic inflammation can both accelerate telomere shortening. Multiple factors, including homocysteine (HCY), vitamin B6, and vitamin B12 modulate oxidative stress and inflammation through direct and indirect mechanisms. This review provides a compact overview of telomere physiology and the utility of LTL measurements in atherosclerosis and cardiovascular disease. In addition, it summarizes existing knowledge regarding the impact of oxidative stress, inflammation, HCY, and B-vitamins on telomere function. 10.3390/jcdd7030029