Bibliographic Details
| Title: |
HDAC1/2 inhibitor therapy improves multiple organ systems in aged mice |
| Authors: |
Alessandra Tammaro, Eileen G. Daniels, Iman M. Hu, Kelly C. ‘t Hart, Kim Reid, Rio P. Juni, Loes M. Butter, Goutham Vasam, Rashmi Kamble, Aldo Jongejan, Richard I. Aviv, Joris J.T.H. Roelofs, Eleonora Aronica, Reinier A. Boon, Keir J. Menzies, Riekelt H. Houtkooper, Georges E. Janssens |
| Source: |
iScience, Vol 27, Iss 1, Pp 108681- (2024) |
| Publisher Information: |
Elsevier, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Science |
| Subject Terms: |
Drugs, Molecular biology, Epigenetics, Omics, Transcriptomics, Science |
| More Details: |
Summary: Aging increases the risk of age-related diseases, imposing substantial healthcare and personal costs. Targeting fundamental aging mechanisms pharmacologically can promote healthy aging and reduce this disease susceptibility. In this work, we employed transcriptome-based drug screening to identify compounds emulating transcriptional signatures of long-lived genetic interventions. We discovered compound 60 (Cmpd60), a selective histone deacetylase 1 and 2 (HDAC1/2) inhibitor, mimicking diverse longevity interventions. In extensive molecular, phenotypic, and bioinformatic assessments using various cell and aged mouse models, we found Cmpd60 treatment to improve age-related phenotypes in multiple organs. Cmpd60 reduces renal epithelial-mesenchymal transition and fibrosis in kidney, diminishes dementia-related gene expression in brain, and enhances cardiac contractility and relaxation for the heart. In sum, our two-week HDAC1/2 inhibitor treatment in aged mice establishes a multi-tissue, healthy aging intervention in mammals, holding promise for therapeutic translation to promote healthy aging in humans. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2589-0042 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S258900422302758X; https://doaj.org/toc/2589-0042 |
| DOI: |
10.1016/j.isci.2023.108681 |
| Access URL: |
https://doaj.org/article/42cc145abf8d478f88355c37c49e69d9 |
| Accession Number: |
edsdoj.42cc145abf8d478f88355c37c49e69d9 |
| Database: |
Directory of Open Access Journals |
