p18 (Ink4c) deletion prolongs lifespan of telomere dysfunctional mice by improving stem cell self-renewal independent of DNA damage checkpoint activation
FacultiesFakultät für Naturwissenschaften
Cyclin dependent kinase (CDK) inhibitors (CKIs) have a critical role in inhibiting cell cycle progression. A variety of molecular stress factors induce the expression of CKIs including DNA damage, cytokines, and oxidative stress. p18 (INK4c) is one of the cyclin dependant kinase inhibitor which belongs to INK4 family. p18 has a role in regulation of cell cycle and it also restricts the self-renewal of hematopoietic stem cells. p18 (INK4c) has not been implicated to be involved in DNA damage signaling or aging. Here, we crossed p18 (Ink4c) knockout mice with late generation of telomerase knockout mice (G4 mTerc-/-) with dysfunctional telomeres. G4 mTerc-/- mice show a premature aging phenotype predominantly affecting organ proliferative organs, such as the hematopoietic system and the small intestine. The study shows that p18 gene status does not affect the induction of DNA damage checkpoints in telomere dysfunctional tissues. In addition, activation of DNA damage signals is not associated with an induction of p18 expression. Nevertheless, p18 deletion improves stem cell maintenance, organ homeostasis, and lifespan rescue of aged telomere dysfunctional mice. Taken together these results indicate that deletion of p18 can improve maintenance of telomere dysfunctional tissue by improving stem cell self-renewal independent of activated DNA damage signaling. Die Online-Version wurde zurückgezogen. Bitte verwenden Sie die publizierte gedruckte Version, die sich im Bestand des kiz befindet und auch via Fernleihe zugänglich ist.
Subject HeadingsAging [MeSH]
Cyclin-dependent kinase inhibitor p18 [MeSH]
Receptors, Notch [MeSH]
Stem cells [MeSH]