Transcriptomics and Proteomics Analyses Reveal JAK Signaling and Inflammatory Phenotypes during Cellular Senescence in Blind Mole Rats: The Reflections of Superior Biology.
Inci Kavum, Nurcan; Akyildiz, Erdogan Oguzhan; Bulbul, Abdullah Alperet al.
JAK–STAT; MMP; NF-κB; SASP; aging; anticancer; cancer; cellular senescence; inflammation; Biochemistry, Genetics and Molecular Biology (all); Immunology and Microbiology (all); Agricultural and Biological Sciences (all); General Agricultural and Biological Sciences; General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology
Abstract :
[en] The blind mole rat (BMR), a long-living subterranean rodent, is an exceptional model for both aging and cancer research since they do not display age-related phenotypes or tumor formation. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is a cytokine-stimulated pathway that has a crucial role in immune regulation, proliferation, and cytokine production. Therefore, the pathway has recently attracted interest in cellular senescence studies. Here, by using publicly available data, we report that JAK-STAT signaling was suppressed in the BMR in comparison to the mouse. Interestingly, our experimental results showed upregulated Jak1/2 expressions in BMR fibroblasts during the replicative senescence process. The transcriptomic analysis using publicly available data also demonstrated that various cytokines related to JAK-STAT signaling were upregulated in the late passage cells, while some other cytokines such as MMPs and SERPINs were downregulated, representing a possible balance of senescence-associated secretory phenotypes (SASPs) in the BMR. Finally, our proteomics data also confirmed cytokine-mediated signaling activation in senescent BMR fibroblasts. Together, our findings suggest the critical role of JAK-STAT and cytokine-mediated signaling pathways during cellular senescence, pointing to the possible contribution of divergent inflammatory factors to the superior resistance of aging and cancer in BMRs.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Inci Kavum, Nurcan ✱; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Akyildiz, Erdogan Oguzhan ✱; Department of Molecular and Translational Biomedicine, Institute of Natural and Applied Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey
Bulbul, Abdullah Alper ; Department of Biostatistics and Bioinformatics, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey
Turanli, Eda Tahir; Department of Molecular and Translational Biomedicine, Institute of Natural and Applied Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey ; Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey
Akgun, Emel; Department of Medical Biochemistry, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey
Baykal, Ahmet Tarik ; Department of Medical Biochemistry, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey
Colak, Faruk; Department of Biology, Faculty of Arts and Science, Zonguldak Bulent Ecevit University, Zonguldak 67100, Turkey
Bozaykut, Perinur ; Department of Molecular and Translational Biomedicine, Institute of Natural and Applied Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey ; Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey
✱ These authors have contributed equally to this work.
Language :
English
Title :
Transcriptomics and Proteomics Analyses Reveal JAK Signaling and Inflammatory Phenotypes during Cellular Senescence in Blind Mole Rats: The Reflections of Superior Biology.
Scientific and Technological Research Council of Turkey ACU - Acıbadem University
Funding text :
The experimental parts of this research were funded by The Scientific and Technological Research Council of Turkey (TUBITAK), Grant Nos. 121N467 and 121Z564, and the Acibadem University Scientific Research Project Commission, Grant No. 2020/02/01, which were awarded to Perinur Bozaykut. BMR capture was supported by a grant from the Zonguldak Bülent Ecevit University Research Project Commission, Grant No. 2019-84906727-01, and was awarded to Faruk Colak.
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