Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 19;85(12):2390-2408.e6.
doi: 10.1016/j.molcel.2025.05.025. Epub 2025 Jun 12.

SIRT7 regulates NUCKS1 chromatin binding to elicit metabolic and inflammatory gene expression in senescence and liver aging

Khoa A Tran  1 , Michael Gilbert  2 , Berta N Vazquez  3 , Alessandro Ianni  4 , Benjamin A Garcia  5 , Alejandro Vaquero  6 , Shelley L Berger  7
Affiliations

SIRT7 regulates NUCKS1 chromatin binding to elicit metabolic and inflammatory gene expression in senescence and liver aging

Khoa A Tran et al. Mol Cell. .

Abstract

Sirtuin enzymes are deeply associated with senescence and aging. Sirtuin proteins are tightly regulated, but how their levels are governed during aging and how they elicit tissue-specific cellular changes are unclear. Here, we demonstrate that SIRT7 undergoes proteasomal degradation during senescence via targeting by the E3 ligase TRIP12. We identified the transcription factor nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) as an interactor of SIRT7 and found NUCKS1 recruitment onto chromatin during senescence mediated by SIRT7 loss, correlating with increased NUCKS1 acetylation. NUCKS1 depletion delayed senescence, leading to reduced inflammatory gene expression associated with transcription factors RELA and CEBPβ. In Sirt7 knockout and aged mouse livers, NUCKS1 was bound at the promoters and enhancers of age-related genes, and these regulatory regions gained accessibility during aging. Overall, our results uncover NUCKS1 as an interactor of SIRT7 and indicate that proteasomal loss of SIRT7 during senescence and liver aging promotes NUCKS1 acetylation and chromatin binding to induce metabolic and inflammatory genes.

Keywords: NUCKS1; SIRT7; acetylation; aging; post-translation modification; protein regulation; senescence; sirtuins.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Update of

References

    1. López-Otín C, Blasco MA, Partridge L, Serrano M, and Kroemer G (2013). The Hallmarks of Aging. Cell 153, 1194–1217. 10.1016/j.cell.2013.05.039. - DOI - PMC - PubMed
    1. Kennedy BK, Berger SL, Brunet A, Campisi J, Cuervo AM, Epel ES, Franceschi C, Lithgow GJ, Morimoto RI, Pessin JE, et al. (2014). Geroscience: Linking Aging to Chronic Disease. Cell 159, 709– 713. 10.1016/j.cell.2014.10.039. - DOI - PMC - PubMed
    1. Childs BG, Durik M, Baker DJ, and van Deursen JM (2015). Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat. Med 21, 1424–1435. 10.1038/nm.4000. - DOI - PMC - PubMed
    1. Finkel T, Deng C-X, and Mostoslavsky R (2009). Recent progress in the biology and physiology of sirtuins. Nature 460, 587–591. 10.1038/nature08197. - DOI - PMC - PubMed
    1. Houtkooper RH, Pirinen E, and Auwerx J (2012). Sirtuins as regulators of metabolism and healthspan. Nat. Rev. Mol. Cell Biol 13, 225–238. 10.1038/nrm3293. - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources