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Replicative and radiation-induced aging: a comparison of gene expression profiles
Alexander M Aliper1, Marine E Bozdaganyan1, Philipp S Orekhov1,2
1Inсilico Medicine, Inc., Baltimore, MD 21218, USA.
Aging
|April 20, 2019
Summary
Ionizing radiation and cellular aging share similar molecular signaling pathways. Replicatively aged cells resemble those exposed to higher radiation doses, suggesting potential targets for gero- and radioprotectors.
Area of Science:
- Cell Biology
- Molecular Biology
- Gerontology
Background:
- Aging is a universal biological process affecting all organisms.
- Ionizing radiation exposure is known to accelerate aging.
- A comprehensive comparative analysis of the signaling pathways involved in both processes is lacking.
Purpose of the Study:
- To conduct a comparative signaling pathway analysis of transcriptomes from fibroblasts.
- To investigate similarities and differences between radiation-induced and replicative senescence.
- To identify shared signaling pathways for potential therapeutic targeting.
Main Methods:
- Comparative transcriptomic analysis of fibroblasts.
- Fibroblasts were subjected to varying doses of ionizing radiation.
- Fibroblasts were analyzed based on replicative age and patient age (young, middle, old).
Main Results:
- Significant concordance was found between irradiation-induced and replicative senescence signalome signatures.
- Transcriptional responses differed significantly between high and low-dose irradiated fibroblasts.
- Replicatively aged fibroblasts showed greater transcriptome similarity to cells irradiated with 2 Gy than 5 cGy.
Conclusions:
- Shared signaling pathways exist between cellular senescence and ionizing radiation exposure.
- These pathways represent potential targets for novel gero- and radioprotective agents.
- The findings provide insights into the molecular mechanisms underlying aging and radiation response.
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