Telomere shortening has been linked to a variety of neurodegenerative diseases. Recent evidence suggests that reduced telomerase expression results in shorter telomeres in leukocytes from sporadic patients with amyotrophic lateral sclerosis (ALS) compared with healthy controls. Here, we have characterized telomere length in microglia, astroglia and neurons in human post mortem brain tissue from ALS patients and healthy controls. Moreover, we studied the consequences of telomerase deletion in a genetic mouse model for ALS. We found a trend towards longer telomeres in microglia in the brains of ALS patients compared to non-neurologic controls. Knockout of telomerase leading to telomere shortening accelerated the ALS phenotype inSOD1G93A-transgenic mice. Our results suggest that telomerase dysfunction might contribute to the age-related risk for ALS.
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http://dx.doi.org/10.18632/aging.100904 | DOI Listing |
Eur J Med Chem
January 2025
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, People's Republic of China. Electronic address:
Telomere repeat-binding factor 2 (TRF2) is a crucial component of the shelterin complex, commonly overexpressed in osteosarcoma (OS) and positively correlated with its progression. To date, effective TRF2 inhibitors for in vivo applications remain limited. In this study, a series of Flavokavain B derivatives were designed and synthesized, and their TRF2 inhibition and antitumor activity were evaluated.
View Article and Find Full Text PDFExp Hematol Oncol
January 2025
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Telomeres and telomerase play crucial roles in the initiation and progression of cancer. As biomarkers, they aid in distinguishing benign from malignant tissues. Despite the promising therapeutic potential of targeting telomeres and telomerase for therapy, translating this concept from the laboratory to the clinic remains challenging.
View Article and Find Full Text PDFNat Commun
January 2025
Sorbonne Université, CNRS, Laboratory of Computational and Quantitative Biology, LCQB, Paris, France.
Telomere shortening ultimately causes replicative senescence. However, identifying the mechanisms driving replicative senescence in cell populations is challenging due to the heterogeneity of telomere lengths and the asynchrony of senescence onset. Here, we present a mathematical model of telomere shortening and replicative senescence in Saccharomyces cerevisiae which is quantitatively calibrated and validated using data of telomerase-deficient single cells.
View Article and Find Full Text PDFNutrients
January 2025
Department of Nutrition, Food Sciences and Physiology, Center for Nutrition and Research, University of Navarra, 31008 Pamplona, Spain.
Background And Aim: Telomere length (TL) is a key biomarker of cellular aging, with shorter telomeres associated with age-related diseases. Lifestyle interventions mitigating telomere shortening are essential for preventing such conditions. This study aimed to examine the effects of two weight loss dietary strategies, based on a moderately high-protein (MHP) diet and a low-fat (LF) diet on TL in individuals with overweight or obesity.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Department of Molecular Biosciences, University of South Florida, 4202 East Fowler Avenue, ISA2015, Tampa, FL 33620, USA.
Background/objectives: As cells divide, telomeres shorten through a phenomenon known as telomere attrition, which leads to unavoidable senescence of cells. Unprotected DNA exponentially increases the odds of mutations, which can evolve into premature aging disorders and tumorigenesis. There has been growing academic and clinical interest in exploring this duality and developing optimal therapeutic strategies to combat telomere attrition in aging and cellular immortality in cancer.
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