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| Status |
Public on Sep 09, 2016 |
| Title |
Lifespan extension by diet restriction in DNA repair deficient progeroid Ercc1Δ/- mice [mRNA] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
DNA repair-deficient Ercc1Δ/- mice show premature cell death, senescence and numerous accelerated aging features limiting lifespan to 4-6 month. Simultaneously they exhibit a ‘survival response’, which suppresses growth and enhances maintenance, resembling the anti-aging response induced by dietary restriction (DR). Here we report that subjecting these progeroid, dwarf mutants to actual dietary restriction (DR) resulted in the largest lifespan increase recorded in mammals. Thirty percent DR tripled median and maximal remaining lifespan, and drastically retarded numerous aspects of accelerated aging, e.g. DR animals retained 50% more neurons and maintained full motoric function. The DR response in Ercc1Δ/- mice resembled DR in wild type animals including reduced insulin signaling. Interestingly, ad libitum Ercc1Δ/- liver expression profiles showed preferential extinction of expression of long genes, consistent with genome-wide accumulation of stochastic, transcription-blocking lesions, which affect long genes more than short ones. DR largely prevented this decline of transcriptional output, indicating that DR prolongs genome function. Our findings strengthen the link between DNA damage and aging, establish Ercc1Δ/- mice as powerful model for identifying interventions to promote healthy aging, reveal untapped potential for reducing endogenous damage, provide new venues for understanding the molecular mechanism of DR, and suggest a counterintuitive DR-like therapy for human progeroid genome instability syndromes and DR-like interventions for preventing neurodegenerative diseases.
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| Overall design |
20 samples (4 groups with 5 replicates each) analyzed on Affymetrix genechips
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| Contributor(s) |
Pennings J, Dollé M, Gyenis A, Vermeij W |
| Citation(s) |
27556946 |
| Submission date |
Jan 27, 2016 |
| Last update date |
Apr 21, 2020 |
| Contact name |
Jeroen Pennings |
| E-mail(s) |
Jeroen.Pennings@rivm.nl
|
| Phone |
+31 88 689 2214
|
| Organization name |
Natl. Inst. Public Health & Environment
|
| Street address |
A. van Leeuwenhoeklaan 9
|
| City |
Bilthoven |
| ZIP/Postal code |
3721MA |
| Country |
Netherlands |
| |
|
| Platforms (1) |
| GPL11180 |
[HT_MG-430_PM] Affymetrix HT MG-430 PM Array Plate |
|
| Samples (20)
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| This SubSeries is part of SuperSeries: |
| GSE77495 |
Unprecedented life- and healthspan extension and genome preservation by diet restriction in DNA repair deficient progeroid Ercc1 Δ/- mice |
|
| Relations |
| BioProject |
PRJNA310020 |
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