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Inhibition of nucleotide synthesis promotes replicative senescence of human mammary epithelial cells.


ABSTRACT: Cellular senescence is a mechanism by which cells permanently withdraw from the cell cycle in response to stresses including telomere shortening, DNA damage, or oncogenic signaling. Senescent cells contribute to both age-related degeneration and hyperplastic pathologies, including cancer. In culture, normal human epithelial cells enter senescence after a limited number of cell divisions, known as replicative senescence. Here, to investigate how metabolic pathways regulate replicative senescence, we used LC-MS-based metabolomics to analyze senescent primary human mammary epithelial cells (HMECs). We did not observe significant changes in glucose uptake or lactate secretion in senescent HMECs. However, analysis of intracellular metabolite pool sizes indicated that senescent cells exhibit dep

SUBMITTER: Delfarah A 

PROVIDER: S-EPMC6615688 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature