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

Area of Science:

• Genetics
• Cell Biology
• Molecular Biology

Background:

• Telomeres safeguard chromosome ends, shortening with cell division without telomerase.
• Critically short or damaged telomeres trigger DNA damage responses, leading to cellular senescence or death.
• Telomere shortening and dysfunction are linked to aging and various diseases, including cancer and developmental disorders, collectively termed telomere biology disorders.

Purpose of the Study:

• To review telomere protection, maintenance, and damage mechanisms.
• To highlight critical differences between human and mouse telomere biology.
• To discuss the development of humanized mouse models for studying telomere biology disorders.

Main Methods:

• Literature review of telomere biology research.
• Comparative analysis of human and mouse telomere mechanisms.
• Discussion of advancements in creating humanized mouse models.

Main Results:

• Telomere dysfunction, not just shortening, is implicated in various human diseases (telomeropathies).
• Existing mouse models often fail to fully recapitulate human telomere-related diseases due to species-specific differences.
• New humanized mouse models are being developed to better reflect human telomere biology.

Conclusions:

• Understanding limitations in current mouse models is crucial for advancing telomere research.
• Improved humanized models will enhance the study of telomere biology disorders.
• Further research into telomere biology holds promise for developing novel therapeutic strategies.