Insights into DNA Damage in Regenerating Young and Aged Mouse Livers

نویسندگان

چکیده

Abstract Background The maintenance of genome stability is a key process to slow aging. One the mechanisms ensuring this correct coordination origins replication (ORI), resulting in successful transmission DNA. Previously, we mapped and compared ORI firing between young aged mice vivo, using regenerating liver mouse model. We confirmed decreased hepatocyte efficiency mice, known have impaired regeneration. proved be fully rescued when blocking mice's ATR serine/threonine-protein kinase, suggesting that DNA checkpoint actively mediates impairment upon damage detection. Aims To explore differences livers. Methods induce proliferation, were subjected partial hepatectomy (PH) sections harvested at different timepoints. Immunohistochemistry staining (IHC) used address proliferation damage, Ki67 serine 139 phosphorylated histone H2AX (g-H2AX) as markers, respectively. Results lack signal prior PH. takes off 24-28h post-PH reaches its peak 36-48h, which significantly lower mice. After 48h post-PH, hepatocytes’ basal level 120h post-PH. However, maintained low levels overtime. Next, kinetics Both groups present an increase g-H2AX PH, higher decreases hepatocytes after until disappearing post Aged maintain rates overtime Conclusions Our data suggests develop able resolved but remains livers, ultimately leading

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ژورنال

عنوان ژورنال: British Journal of Surgery

سال: 2023

ISSN: ['1365-2168', '0007-1323']

DOI: https://doi.org/10.1093/bjs/znad178.007