Three widely accepted assumptions are based on telomere research in human cells: (i) telomere length is a determinant of replicative ageing; (ii) telomerase activity in somatic cells supports the proliferative capacity of the cells and thus contributes to their regenerative potential and is a determinant of organismal lifespan; and (iii) the lack of telomerase activity acts as a tumour suppression mechanism. However, from a broader view, the link between telomere biology and cellular and organismal ageing, as well as tumour development, remains of debate, as I demonstrate with numerous examples of invertebrate and vertebrate species. Consequently, I propose a novel hypothesis that telomere biology, via somatic telomerase activity, reflects ageing rate from the perspective of species reproduction strategy.
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http://dx.doi.org/10.1111/mec.16870 | DOI Listing |
Bioorg Chem
January 2025
Department of Medicinal Chemistry, Faculty of Pharmacy, Galala University, New Galala 43713, Egypt.
In this current work, we dedicated efforts to designing and synthesizing new 1,2,3-triazole-analogues (5a-d), (6a-d), and (7a-c) to act as dual VEGFR-2 and telomerase inhibitors with promising apoptotic potential. The synthesized analogues were examined against eleven diverse types of cancer cells and two normal cells to assess their ability to inhibit cell growth (GI%). Obviously, compound 7b showed the best average GI% (75.
View Article and Find Full Text PDFWorld J Gastrointest Oncol
January 2025
Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China.
Background: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high morbidity and mortality, and easy to develop resistance to chemotherapeutic agents. Telomeres are DNA-protein complexes located at the termini of chromosomes in eukaryotic cells, which are unreplaceable in maintaining the stability and integrity of genome. Telomerase, an RNA-dependent DNA polymerase, play vital role in telomere length maintain, targeting telomerase is a promising therapeutic strategy for cancer.
View Article and Find Full Text PDFBiol Direct
January 2025
Department of Clinical Laboratory, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
Thioredoxin1 (TRX1) and telomerase are both attractive oncology targets that are tightly implicated in tumor initiation and development. Here, we reported that the 6-dithio-2-deoxyguanosine analog thiotert exhibits an effective cytotoxic effect on myelodysplastic syndromes (MDS) cell SKM-1 and lymphoma cell U-937. Further studies confirmed that thiotert effectively disrupts cellular redox homeostasis, as evidenced by elevated intracellular reactive oxygen species (ROS) levels, increased MnSOD, accelerated DNA impairment, and activated apoptosis signal.
View Article and Find Full Text PDFMech Ageing Dev
January 2025
Department of Medicine, Divisions of Geriatric Medicine and Gerontology, the Department of Physiology and Biomedical Engineering, and the Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota. Electronic address:
Preclinical models of age-related osteoporosis have been developed based on the accumulation and clearance of senescent cells. The former include animal models based on telomere dysfunction and focal radiation; the latter based on genetic and pharmacological targeting (i.e.
View Article and Find Full Text PDFRegen Ther
March 2025
Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, China.
Background: Secreted frizzled-related protein 1 (SFRP1) inhibits Wnt signaling and is differentially expressed in human hair dermal papilla cells (DPCs). However, the specific effect of SFRP1 on cell function remains unclear. Telomerase reverse transcriptase (TERT) representing telomerase activity was found highly active around the hair dermal papilla.
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