| First Author | Tammaro A | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 1 | Pages | 108681 |
| PubMed ID | 38269100 | Mgi Jnum | J:351219 |
| Mgi Id | MGI:7578542 | Doi | 10.1016/j.isci.2023.108681 |
| Citation | Tammaro A, et al. (2024) HDAC1/2 inhibitor therapy improves multiple organ systems in aged mice. iScience 27(1):108681 |
| abstractText | 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. |
