Telomere function and regulation from mouse models to human ageing and disease.

Autor: Jones-Weinert C; The Salk Institute for Biological Studies, La Jolla, CA, USA., Mainz L; The Salk Institute for Biological Studies, La Jolla, CA, USA., Karlseder J; The Salk Institute for Biological Studies, La Jolla, CA, USA. karlseder@salk.edu.
Jazyk: angličtina
Zdroj: Nature reviews. Molecular cell biology [Nat Rev Mol Cell Biol] 2024 Nov 29. Date of Electronic Publication: 2024 Nov 29.
DOI: 10.1038/s41580-024-00800-5
Abstrakt: Telomeres protect the ends of chromosomes but shorten following cell division in the absence of telomerase activity. When telomeres become critically short or damaged, a DNA damage response is activated. Telomeres then become dysfunctional and trigger cellular senescence or death. Telomere shortening occurs with ageing and may contribute to associated maladies such as infertility, neurodegeneration, cancer, lung dysfunction and haematopoiesis disorders. Telomere dysfunction (sometimes without shortening) is associated with various diseases, known as telomere biology disorders (also known as telomeropathies). Telomere biology disorders include dyskeratosis congenita, Høyeraal-Hreidarsson syndrome, Coats plus syndrome and Revesz syndrome. Although mouse models have been invaluable in advancing telomere research, full recapitulation of human telomere-related diseases in mice has been challenging, owing to key differences between the species. In this Review, we discuss telomere protection, maintenance and damage. We highlight the differences between human and mouse telomere biology that may contribute to discrepancies between human diseases and mouse models. Finally, we discuss recent efforts to generate new 'humanized' mouse models to better model human telomere biology. A better understanding of the limitations of mouse telomere models will pave the road for more human-like models and further our understanding of telomere biology disorders, which will contribute towards the development of new therapies.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. Springer Nature Limited.)
Databáze: MEDLINE
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