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Drug Synergy Slows Aging and Improves Healthspan through IGF and SREBP Lipid Signaling.
- Source :
-
Developmental cell [Dev Cell] 2018 Oct 08; Vol. 47 (1), pp. 67-79.e5. Date of Electronic Publication: 2018 Sep 27. - Publication Year :
- 2018
-
Abstract
- There is growing interest in pharmacological interventions directly targeting the aging process. Pharmacological interventions against aging should be efficacious when started in adults and, ideally, repurpose existing drugs. We show that dramatic lifespan extension can be achieved by targeting multiple, evolutionarily conserved aging pathways and mechanisms using drug combinations. Using this approach in C. elegans, we were able to slow aging and significantly extend healthy lifespan. To identify the mechanism of these drug synergies, we applied transcriptomics and lipidomics analysis. We found that drug interactions involved the TGF-β pathway and recruited genes related with IGF signaling. daf-2, daf-7, and sbp-1 interact upstream of changes in lipid metabolism, resulting in increased monounsaturated fatty acid content and this is required for healthy lifespan extension. These data suggest that combinations of drugs targeting distinct subsets of the aging gene regulatory network can be leveraged to cause synergistic lifespan benefits.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Allantoin
Animals
Caenorhabditis elegans metabolism
Caenorhabditis elegans Proteins metabolism
Drosophila melanogaster drug effects
Drug Synergism
Ficusin
Gene Expression Regulation drug effects
Gene Expression Regulation genetics
Gene Regulatory Networks drug effects
Insulin-Like Growth Factor I metabolism
Lipid Metabolism
Lipids
Longevity genetics
Metformin
Rifampin
Signal Transduction drug effects
Signal Transduction genetics
Sirolimus
Sterol Regulatory Element Binding Protein 1 metabolism
Transcriptome
Transforming Growth Factor beta metabolism
Aging drug effects
Longevity drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1551
- Volume :
- 47
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 30269951
- Full Text :
- https://doi.org/10.1016/j.devcel.2018.09.001