International Journal of Hematology and Oncology 2023, Vol 33, Num 4 Page(s): 066-074
Harbinger of Trouble; Fingerprints in the Pre-Senile Stage of NK Cell’s Dysfunction

Seyhan TURK1, Ayriana Safari BAESMAT2, Aysegul YILMAZ2, Umit Yavuz MALKAN3, Can TURK2, Ibrahim Celalettin HAZNEDAROGLU3, Gulberk UCAR1

1Hacettepe University, Faculty of Pharmacy, Department of Biochemistry, Ankara, Turkey
2Lokman Hekim University, Faculty of Medicine, Department of Medical Microbiology, Ankara, Turkey
3Hacettepe University, Faculty of Medicine, Department of Hematology, Ankara, Turkey

Keywords: Natural killer, Gene biomarkers, Aging
Natural killer (NK) cells are the predominant innate lymphocyte subsets that mediate anti-tumor and anti-viral responses. The importance of NK cells in the immune system remains significant during old age. Age-associated changes in natural killer (NK) cell population, phenotype, and functions are directly attributed to the risk of several diseases and infections. This in silico study aimed to discover the potential age-related gene biomarkers in NK cells isolated from pre-elderly individuals and investigate their role in the cytotoxicity capacity of NK cells. Transcription profile data of human NK cell lines isolated from 13-62 years old individuals (GSE19067), were obtained from the gene expression omnibus database. We used a series of computational methods including GEO2R analysis,
hierarchical clustering, functional pathway analysis, and Gene set enrichment analysis to identify the transcriptome alterations on age related NK cells. The impacts of nine genes (COL21A1, CYB5A, LIF, MEIS2, PTPRM, RASEF, RBMS3, TCF4, ZNF827) with substantially altered expression were assessed in relation to the age related NK cells. These nine genes have two important features, firstly, when we compare the under-40 age (group A) and over-40 age (group B) groups, they are expressed highly differently (adj-p< 0.05, log FC> 3), and secondly, the expression rates alter with age (Pearson p< 0.05, r > 0.6). All of these genes were discovered to be downregulated in over 40 years old NK samples. In this study, we investigated the transcriptional changes of NK cell lines in the pre-senile period and how these changes may affect the cytotoxicity functions of NK cells. Hope to identify early signs of alteration in NK’s genome that lead to dysfunction or malfunction of these important immune cells in old age.