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    Cellular stress responses of long-lived and cancer-resistant naked mole-rats
    (WALTER DE GRUYTER GMBH, 2021-01-01) Bozaykut, Perinur
    Objectives: Some organisms are long-lived and naturally resistant to cancer such as naked mole-rats (NMRs). Studies have shown that these animals can better tolerate stress due to mechanisms, such as upregulation of antioxidant pathways and improved proteostasis. In the present study, we aimed to analyze the tolerance against stress and the cellular mechanisms related to the stress response in NMR cells comparative to mouse cells. Materials and methods: NMR and mouse fibroblasts were exposed to cellular stresses including H2O2 and/or NaNO3 and the viability of the cells were analyzed. In addition messanger RNA (mRNA) expression of antioxidant transcription factor Nuclear factor erythroid-derived 2-like 2 (Nrf2) and its target gene NAD(P)H quinone dehydrogenase 1 (NQO1) were determined by qRT-PCR and comprehensive analysis of stress-related gene expression was performed by RNA-Sequencing in fibroblasts and induced pluripotent stem cells (iPSC). Results: Surprisingly, NMR fibroblasts were found to be more sensitive than mouse cells to H2O2 and NaNO3. Furthermore, it was shown that fibroblasts and iPSCs mainly aren't identical in the expression pattern of cellular defense signaling and several factors are mainly downregulated in NMR iPSCs. Conclusions: Collectively, the data gained from the present study help to improve the understanding of evolved mechanisms that contribute to stress resistance, aging and cancer.
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    Transcriptomics and Proteomics Analyses Reveal JAK Signaling and Inflammatory Phenotypes during Cellular Senescence in Blind Mole Rats: The Reflections of Superior Biology
    (MDPI, 2022-01-01) Inci, Nurcan; Akyildiz, Erdogan Oguzhan; Bulbul, Abdullah Alper; Turanli, Eda Tahir; Akgun, Emel; Baykal, Ahmet Tarik; Colak, Faruk; Bozaykut, Perinur
    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.
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    Age-Related Changes in Corneal Epithelial Thickness Measured with an Ultrasound Pachymeter
    (DOVE MEDICAL PRESS LTD, 2022-01-01) Colakoglu, Ahmet; Cosar, Cemile Banu
    Background: There is increasing research on the aging process of the cornea and its effect on the corneal parameters measured objectively. Nevertheless, the association of corneal epithelial thickness (CET) with age has yet to be fully illustrated.Purpose: We aimed to measure CET in healthy subjects to determine its age-related variation by using an ultrasound device. Patients and Methods: A total of one hundred and three subjects were enrolled in this study and grouped according to age: Group < 30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years, and > 71 years. The CET and total central corneal thickness (CCT) of each subject were measured by the Sonogage Corneo-Gage Plus 2 (Cleveland, Ohio) ultrasound pachymeter. The relationships between thickness values, laterality, age groups, and gender were analyzed using the Jonckheere-Terpstra test. The Partial correlation test was employed to assess the effect of age on the CET and CCT. Results: The mean CET was 47.88 +/- 1.15 mu m, with no statistically significant gender-related difference between right and left eyes. In addition, the CCT difference detected between female and male eyes was insignificant. The difference in mean CET across age groups was statistically significant (p =0.029). The difference in mean CET of left eyes across age groups was statistically significant (p=0.031). The mean CET and left CET of the oldest group were significantly thinner than the younger groups.Conclusion: Ultrasound pachymeter of the corneal epithelium demonstrated that there was no correlation between age and CCT, or gender. The CET becomes thinner with age in the central zone in both genders and there is no difference between males and females. Based on these results, age has a negative effect on CET. These findings could offer further insight into age-related changes in the cornea.