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| Status |
Public on Mar 01, 2017 |
| Title |
Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The accumulation of irreparable cellular damage restricts healthy lifespan after acute stress or natural aging. Senescent cells are thought to impair tissue function and their genetic clearance can successfully delay features of aging. Identifying how senescent cells avoid apoptosis would allow for the prospective design of anti-senescence compounds to address whether homeostasis can be restored. Here, we identify FOXO4 as a pivot in the maintenance of senescent cell viability. We designed a FOXO4-based peptide which selectively competes for interaction of FOXO4 with p53. In senescent cells, this results in p53 nuclear exclusion and cell-intrinsic apoptosis. Importantly, under conditions where it was well tolerated, the FOXO4 peptide restored liver function after Doxorubicin-induced chemotoxicity. Moreover, in fast aging XpdTTD/TTD, as well as in naturally aged mice the FOXO4 peptide could counteract the loss of fitness, fur density and renal function. Thus, it is possible to therapeutically target senescent cells and thereby effectively counteract senescence-associated loss of tissue homeostasis.
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| Overall design |
mRNA expression levels are compared between IR-induced senescent and proliferating IMR90 cells in triplicate
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| Contributor(s) |
de Keizer PL, Baar MP, Derks KW, van IJcken WF |
| Citation(s) |
28340339 |
| |
| Submission date |
Feb 01, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Peter L.J. de Keizer |
| E-mail(s) |
p.dekeizer@erasmusmc.nl
|
| Organization name |
Erasmus University Medical Center
|
| Department |
Molecular Genetics
|
| Lab |
Senescence in Cancer and Aging
|
| Street address |
Wytemaweg 80
|
| City |
Rotterdam |
| ZIP/Postal code |
3015CN |
| Country |
Netherlands |
| |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA369561 |
| SRA |
SRP098713 |
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