Cancer and exercise
Adam P. Sharples, James P. Morton, Henning Wackerhage in Molecular Exercise Physiology, 2022
Currently, there is little evidence to suggest whether this is caused by an effect of exercise on mutagenesis. However, as almost 2/3 of all cancers are caused by mutations whose frequency is determined primarily by the rate of cell proliferation, any exercise-induced change of cell proliferation may affect how likely it is that a cancer develops. Another cause of mutations is genomic instability which might be linked to telomere length. Telomeres are the caps at the ends of our chromosomes, and these become shorter each time a cell divides ultimately meaning cells become senescent and stop dividing. There are a few studies that suggest exercise training affects telomere length. For example, Puterman et al (2010) demonstrated that exercise might inhibit telomere shortening (41), and later Sjögren et al demonstrated that less sedentary behaviour was associated with telomere lengthening (42). However, causality between lower incidence of cancer and increased telomere length in exercisers remains to be established (43).
Nucleic Acids as Therapeutic Targets and Agents
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
Telomerase is the ribonucleoprotein enzyme that maintains the telomeric DNA that extends for many kilobases at the ends of chromosomes and, in humans, consists of hexameric 5′-TTAGGG-3′ tandem repeats (Figure 5.81A). It was discovered by Carol Greider and Elizabeth Blackburn in 1984 in the ciliate Tetrahymena, and together with Jack Szostak, they were awarded the 2009 Nobel Prize in Physiology or Medicine. The enzyme is crucial for cellular immortality and is thus a key component of most cancer cells, although it is rarely expressed to significant levels in normal cells. However, embryonic stem cells express telomerase which allows them to divide repeatedly to form an individual organism, and in adults telomerase is highly expressed in cells that need to divide regularly (e.g., in the immune system), whereas most somatic cells express it only at very low levels in a cell-cycle-dependent manner. Therefore, inhibition of telomerase has gained interest as a potential anticancer strategy, although there are a number of caveats. For example, cells are thought to have alternative methods of telomere maintenance such as the “ALT” pathway of telomere maintenance and DNA storage known to exist in cancer stem cells, and this pathway can be activated if the telomerase mechanism is inhibited.
Nanomaterials for Theranostics: Recent Advances and Future Challenges *
Valerio Voliani in Nanomaterials and Neoplasms, 2021
Drugs such as cisplatin, the antibiotics daunorubicin and DOX, and etoposide disrupt the replication of the DNA and cause formation of nonsense DNA or RNA by inhibiting telomerase activity or eliminating telomeric DNA. Telomerase as the natural enzyme for elongating telomeres enables cancer cells to divide virtually forever. Immortalization of cancer cells is considered to stem from their activity [354, 360]. Therefore, DOX, which is effective in treatments of acute leukemia, malignant lymphoma, and a variety of solid tumors, acts by intercalating between nucleic acid bases. It also inhibits the action of the enzyme topoisomerase II, thereby interfering with DNA and RNA biosynthesis. The four planar rings of the drug intercalate into DNA, whereas the hydroxyl group on the side chain interacts with topoisomerases II, which causes cleavage of DNA to stop the replication process [372, 373]. However, because it induces common toxicities, including cardiotoxicity [38], attempts to reduce its toxicity have been made by introducing novel carrier systems such as PEGylated liposomes [374–380]. Etoposide does not intercalate into DNA but forms a ternary complex with DNA and topoisomerase II enzyme, thereby preventing religation of the DNA strands, inducing errors in DNA synthesis and apoptosis of cancer cells [372–373].
First-trimester maternal renin-angiotensin-aldosterone system activation and the association with maternal telomere length after natural and IVF/ICSI conceived pregnancies: the Rotterdam periconception cohort
Published in Hypertension in Pregnancy, 2023
D. Aoulad Fares, R.E. Wiegel, A.J. Eggink, J.B.J. van Meurs, S.P. Willemsen, A.H.J. Danser, R.P.M. Steegers-Theunissen
TL is suggested to be a long-term biomarker of chronic oxidative stress, as it shows the cumulative burden of oxidative stress (23). Short telomeres and telomere dysfunction, independently of age have been linked to numerous age-related diseases. Large population-based studies identify that subjects with shorter telomeres were characterized by a significantly higher hazard ratio for all-cause mortality compared to those with higher TL (36). Recently, it has been hypothesized that periconceptional long-term exposure to excessive oxidative stress and inflammation accelerates maternal TL shortening, and thereby increasing the underlying risk of neural tube defects in offspring (21). In this manner, shorter maternal TL were also associated with an increased risk of having a child with a ventricular septal defect (22). As the vulnerability of telomeres for oxidative stress and inflammation is well known, the RAAS is suggested to contribute to the acceleration of TL shortening. RAAS contributes to the pathogenesis of several human diseases that have a clear association with accelerated TL shortening, including cardiovascular diseases, stroke, and diabetes (37). By this means, several studies confirmed that Ang II induces the shorting of TL, in particular accelerated the rate of telomere loss (>2-fold versus control) in a dose-dependent manner (17,18,38). This is consistent with our findings that a higher level of renin is associated with significant shorter TL due to excessive exposure to oxidative stress.
The impact of childhood maltreatment on telomere length in cocaine use disorder
Published in Journal of Substance Use, 2023
Chiara Pesca, Luisa Lo Iacono, Valeria Carola
As discussed, the experience of CM has been clearly related with telomere shortening, as well as with negative long-term health outcomes (X. Chen et al., 2019; Epel & Prather, 2018; Li et al., 2022; Navarro-Mateu et al., 2019; Wade et al., 2020). In addition, telomere shortenings are associated with several age-related diseases (D’Mello et al., 2015; Shay, 2016; Wang et al., 2016). However, less is known about the function of TL erosion in predicting the risk of various psychopathologies. In this study, we challenged this triadic relationship in patients who have been diagnosed with cocaine use disorder (CUD). Whereas the association between CM and the development of CUD is well established (Cicchetti & Handley, 2019; Halpern et al., 2018; Yoon et al., 2020), few studies have determined the influence of TL on this relationship. In a murine model (Lo Iacono et al., 2017, 2018), exposure to early-life social stress altered several genes that are implicated in telomere elongation during cocaine withdrawal. In humans, TL was lower in crack cocaine-dependent women who reported early-life adversity exposure (Levandowski et al., 2016). This study implicates TL as an emerging biomarker that captures exposure to CM and heralds future risk of CUD.
Inhibition of Posterior Capsule Opacification by Adenovirus-Mediated Delivery of Short Hairpin RNAs Targeting TERT in a Rabbit Model
Published in Current Eye Research, 2023
Na He, Xiangxiang Zhang, Peiling Xie, Jialing He, Zhigang Lv
Telomerase is a ribonucleoprotein complex that maintains telomere length, prevents chromosomes from degradation and recombination, and repairs DNA strand breaks.11 Telomerase is active in germline and stem cells and in the majority of human cancers but absent in most normal somatic cells.11,12 Recent studies have shown telomerase activity was not present in all ocular tissues except LECs.13 Heather et al. found high telomerase activity, which may increase the proliferative capability of LECs and lead to lens epithelial cell EMT, in human lens capsules with PCO formation.14 We previously found telomerase activity in the LECs of rabbits with PCO.15 Thus, we hypothesized that the inhibition of telomerase activity may prevent or eliminate PCO.
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