Gut-specific telomerase expression counteracts systemic aging in telomerase-deficient zebrafish

Area of Science:

• Gerontology
• Molecular Biology
• Zebrafish Model Organisms

Background:

• Telomere shortening is a key aging indicator, particularly rapid in the zebrafish gut.
• Gut aging contributes to tissue dysfunction and systemic aging, but its causal role is unclear.
• Telomerase counteracts telomere shortening, but its tissue-specific role in aging is understudied.

Purpose of the Study:

• To investigate if gut-specific telomerase expression can prevent telomere shortening and rescue aging.
• To determine if averting gut aging impacts systemic aging and lifespan in zebrafish.
• To explore the effects of gut telomerase induction on gut health and distant organ function.

Main Methods:

• Utilized zebrafish (tert-/-) models with premature aging due to telomerase deficiency.
• Induced tissue-specific telomerase expression in the gut of aging zebrafish.
• Assessed telomere length, gut senescence, proliferation, tissue integrity, microbiota, and aging in distant organs.

Main Results:

• Gut-specific telomerase expression prevented telomere shortening and rescued premature aging phenotypes in tert-/- zebrafish.
• Induction of gut telomerase restored gut tissue integrity, reduced inflammation, and corrected microbiota dysbiosis.
• Averting gut aging led to systemic benefits, improving reproductive and hematopoietic system aging and extending lifespan by 40%.

Conclusions:

• Gut aging significantly contributes to systemic aging in zebrafish.
• Tissue-specific telomerase expression in the gut is sufficient to counteract aging systemically.
• Targeting gut telomere maintenance offers a promising strategy for aging interventions.