Loss of H3K9 trimethylation leads to premature aging
Author Information
Author(s): Mrabti Calida, Yang Na, Desdín-Micó Gabriela, Alonso-Calleja Alejandro, Vílchez-Acosta Alba, Pico Sara, Parras Alberto, Piao Yulan, Schoenfeldt Lucas, Luo Siyuan, Haghani Amin, Brooke Robert T., Maza María del Carmen, Branchina Clémence, Bignon Yohan, Maroun Céline Yacoub, von Meyenn Ferdinand, Naveiras Olaia, Horvath Steve, Sen Payel, Ocampo Alejandro
Primary Institution: University of Lausanne
Hypothesis
The loss of H3K9me3 in adulthood contributes to the aging process in mammals.
Conclusion
The study demonstrates that the loss of H3K9me3 leads to premature aging in mice, characterized by reduced lifespan and various age-related phenotypes.
Supporting Evidence
- TKOc mice exhibited reduced lifespan and increased frailty index.
- Loss of H3K9me3 was associated with multi-organ degeneration.
- Significant upregulation of transposable elements was observed in TKOc mice.
- TKOc mice showed accelerated epigenetic age compared to controls.
- Behavioral assessments indicated hypoactivity and increased anxiety in TKOc mice.
- Histological analyses revealed significant tissue remodeling in TKOc mice.
- Blood parameters indicated signs of anemia in TKOc mice.
- Overall, the findings support the role of H3K9me3 loss in driving aging.
Takeaway
When a specific chemical mark on DNA called H3K9me3 is removed in adult mice, they start to age faster and show signs of getting old much sooner.
Methodology
The study used a novel mouse strain with a triple knockout of methyltransferases to induce the loss of H3K9me3 and assessed various aging-related phenotypes.
Potential Biases
Potential bias in interpreting results due to the specific genetic modifications used in the study.
Limitations
The study primarily focuses on a specific genetic model and may not fully represent the complexity of aging in all mammals.
Participant Demographics
Mice used in the study were of a hybrid C57BL/6J, B6C3F1 background.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website