PUBLICATION
cGAS-STING are responsible for premature aging of telomerase-deficient zebrafish
- Authors
- Şerifoğlu, N., Allavena, G., Lopes-Bastos, B., Marzullo, M., Marques, A., Colibert, P., Bousounis, P., Trompouki, E., Ferreira, M.G.
- ID
- ZDB-PUB-250610-21
- Date
- 2025
- Source
- The EMBO journal : (Journal)
- Registered Authors
- Ferreira, Miguel Godinho
- Keywords
- Aging, Inflammation, Telomerase, Zebrafish, cGAS-STING
- MeSH Terms
-
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Animals
- Membrane Proteins*/genetics
- Membrane Proteins*/metabolism
- Nucleotidyltransferases*/genetics
- Nucleotidyltransferases*/metabolism
- DNA Damage
- Aging, Premature*/genetics
- Aging, Premature*/metabolism
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism
- Telomerase*/deficiency
- Telomerase*/genetics
- Telomerase*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 40490553 Full text @ EMBO J.
Citation
Şerifoğlu, N., Allavena, G., Lopes-Bastos, B., Marzullo, M., Marques, A., Colibert, P., Bousounis, P., Trompouki, E., Ferreira, M.G. (2025) cGAS-STING are responsible for premature aging of telomerase-deficient zebrafish. The EMBO journal. :.
Abstract
Telomere shortening occurs in multiple tissues throughout aging. When telomeres become critically short, they trigger DNA-damage responses and p53 stabilization, leading to apoptosis or replicative senescence. In vitro, cells with short telomeres activate the cGAS-STING innate immune pathway resulting in type-I interferon-based inflammation and senescence. However, the consequences of these events for the organism are not yet understood. Here, we show that sting is responsible for premature aging of telomerase-deficient zebrafish. We generated sting-/- tert-/- double-mutant animals and observed a thorough rescue of tert-/- phenotypes. At the cellular level, lack of cGAS-STING in tert mutants resulted in reduced senescence, increased cell proliferation, and decreased inflammation despite similarly short telomeres. Critically, absence of sting function resulted in dampening of the DNA damage response and reduced p53 levels. At the organism level, sting-/- tert-/- zebrafish regained fertility, showed delayed cachexia, and decreased cancer incidence, resulting in increased healthspan and lifespan of telomerase mutant animals.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping