Analysis of age- and sex-related SIRT6 gene expression levels in saliva

Cell senescence is a process that occurs due to telomere shortening during DNA replication and can be induced by various stressors. Senescent cells stop dividing but remain viable, metabolically active and able to secrete many molecules. Some of the hallmarks of aging are cell enlargement, increased granularity, induction of SA-β-galactosidase activity, and an increase in cyclin-dependent kinase inhibitors, p16, and p21. One of the new players associated with cell aging is Sirtuins. Sirtuins (SIRTs) form a class of proteins with mono-ADP ribosyltransferase or NAD+ dependent deacetylase activity. SIRTs are NAD-dependent histone deacetylases that epigenetically regulate the expression of genes and cell metabolism and play an important role in maintaining homeostasis. Sirtuins have been reported to play a key role during cell response to various stresses such as oxidative or genotoxic stress and are crucial for cell metabolism. SIRT6 is a chromatin-associated protein that stabilizes genomes and telomeres. SIRT6 is a critical regulator of genome transcription, telomere integrity, DNA repair and metabolic homeostasis. A stable and positive linear correlation of SIRT6 and telomerase emerged. Thus, SIRT6 prevents premature aging of cells, and its deficiency accelerates replicative senescence. Finding a reliable biomarker for age estimation of biological samples is one of the important tasks in forensic DNA phenotyping. In this thesis, age and sex related SIRT6 gene expression levels in saliva will be analyzed. Generally, based on our findings, while comparing to the 4-9 age group as the reference, we observed a roughly 2-fold decline in sirtuin 6 (sirt 6) expression among the 14-19 age group. Conversely, in the 24-29 age group, there was an approximately 1.75-fold increase, followed by another 2-fold decrease in the 30years and older group. These results indicate the possibility of age and gender-related variations in SIRT6 expression. Additional research is necessary to fully grasp the consequences of these discrepancies and their potential impacts on both health and the aging process. Keywords: Aging, Biomarker, Saliva, SIRT6, Telomerase, Histone deacetylase, Forensic age estimation, Forensic epigenetics, RNA extraction, RT-PCR; Real-Time Polymerase Chain Reaction