Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.devcel.2018.09.001
Title: Drug Synergy Slows Aging and Improves Healthspan through IGF and SREBP Lipid Signaling
Authors: Admasu, Tesfahun Dessale
Batchu, Krishna Chaithanya 
Barardo, Diogo
Ng, Li Fang 
Lam, Vanessa Yuk Man 
Xiao, Linfan
Cazenave-Gassiot, Amaury 
Wenk, Markus R 
Tolwinski, Nicholas S 
Gruber, Jan 
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
Developmental Biology
LIFE-SPAN EXTENSION
CALORIC RESTRICTION MIMETICS
CAENORHABDITIS-ELEGANS
C-ELEGANS
MODEL ORGANISMS
DROSOPHILA-MELANOGASTER
REGULATES LONGEVITY
DIETARY RESTRICTION
GENE
METFORMIN
Issue Date: 2018
Publisher: CELL PRESS
Citation: Admasu, Tesfahun Dessale, Batchu, Krishna Chaithanya, Barardo, Diogo, Ng, Li Fang, Lam, Vanessa Yuk Man, Xiao, Linfan, Cazenave-Gassiot, Amaury, Wenk, Markus R, Tolwinski, Nicholas S, Gruber, Jan (2018). Drug Synergy Slows Aging and Improves Healthspan through IGF and SREBP Lipid Signaling. DEVELOPMENTAL CELL 47 (1) : 67-+. ScholarBank@NUS Repository. https://doi.org/10.1016/j.devcel.2018.09.001
Abstract: © 2018 Elsevier Inc. 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. Admasu et al. used drug combinations to test whether lifespan extension in C. elegans may be enhanced by simultaneous targeting of multiple aging pathways. They found that synergistic drug combinations can modulate pathways, such as IGF and SREBP lipid signaling, not impacted by the individual drugs, resulting in significant lifespan extension.
Source Title: DEVELOPMENTAL CELL
URI: https://scholarbank.nus.edu.sg/handle/10635/170491
ISSN: 15345807
18781551
DOI: 10.1016/j.devcel.2018.09.001
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
47. Drug Synergy Slows Aging and Improves Healthspan.pdfPublished version4.32 MBAdobe PDF

OPEN

PublishedView/Download

SCOPUSTM   
Citations

14
checked on Jul 31, 2020

Page view(s)

23
checked on Jul 30, 2020

Download(s)

1
checked on Jul 30, 2020

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.