Hisayuki Amano, Arindam Chaudhury, Cristian Rodriguez-Aguayo, Lan Lu, Viktor Akhanov, Andre Catic, Yury V Popov, Eric Verdin, Hannah Johnson, Fabio Stossi, David A Sinclair, Eiko Nakamaru-Ogiso, Gabriel Lopez-Berestein, Jeffrey T Chang, Joel R Neilson, Alan Meeker, Milton Finegold, Joseph A Baur, Ergun Sahin
Telomere shortening is associated with stem cell decline, fibrotic disorders, and premature aging through mechanisms that are incompletely understood. Here, we show that telomere shortening in livers of telomerase knockout mice leads to a p53-dependent repression of all seven sirtuins. P53 regulates non-mitochondrial sirtuins (Sirt1, 2, 6, and 7) post-transcriptionally through microRNAs (miR-34a, 26a, and 145), while the mitochondrial sirtuins (Sirt3, 4, and 5) are regulated in a peroxisome proliferator-activated receptor gamma co-activator 1 alpha-/beta-dependent manner at the transcriptional level...
June 4, 2019: Cell Metabolism