Mitochondrial Unfolded Protein Response and Telomere Shortening | Aging-US



February 20, 2024

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  • Aging-US published this trending research paper on February 12, 2024, in Volume 16, Issue 3, entitled, “Disruption of mitochondrial unfolded protein response results in telomere shortening in mouse oocytes and somatic cells" by researchers from the Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT; IVIRMA Global Research Alliance, IVIRMA Roma, Rome, Italy; IVIRMA Global Research Alliance, Fundacion IVI-IIS la Fe, Valencia, Spain; IVIRMA Global Research Alliance, IVIRMA New Jersey, Basking Ridge, NJ; IVIRMA Global Research Alliance, IVIRMA New Jersey, Marlton, NJ; Department of Genetics, Yale School of Medicine, New Haven, CT; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom. DOI - Corresponding author - Emre Seli - 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. Sign up for free Altmetric alerts about this article - Subscribe for free publication alerts from Aging - Keywords - aging, telomere length, Clpp, mitochondrial dysfunction, unfolded protein response About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at​​ and connect with us: Facebook - X - Instagram - YouTube - LinkedIn - Pinterest - Spotify - Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

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