Disruption of mitochondrial unfolded protein response results in telomere shortening in mouse oocytes and somatic cells.
Aging (Albany NY)
; 16(3): 2047-2060, 2024 02 12.
Article
em En
| MEDLINE
| ID: mdl-38349865
ABSTRACT
Caseinolytic peptidase P (CLPP) plays a central role in mitochondrial unfolded protein response (mtUPR) by promoting the breakdown of misfolded proteins and setting in motion a cascade of reactions to re-establish protein homeostasis. Global germline deletion of Clpp in mice results in female infertility and accelerated follicular depletion. Telomeres are tandem repeats of 5'-TTAGGG-3' sequences found at the ends of the chromosomes. Telomeres are essential for maintaining chromosome stability during somatic cell division and their shortening is associated with cellular senescence and aging. In this study, we asked whether the infertility and ovarian aging phenotype caused by global germline deletion of Clpp is associated with somatic aging, and tested telomere length in tissues of young and aging mice. We found that impaired mtUPR caused by the lack of CLPP is associated with accelerated telomere shortening in both oocytes and somatic cells of aging mice. In addition, expression of several genes that maintain telomere integrity was decreased, and double-strand DNA breaks were increased in telomeric regions. Our results highlight how impaired mtUPR can affect telomere integrity and demonstrate a link between loss of mitochondrial protein hemostasis, infertility, and somatic aging.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Telomerase
/
Infertilidade Feminina
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Aging (Albany NY)
/
Aging (Albany, N.Y. Online)
Assunto da revista:
GERIATRIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos