Lityum klorür ve dairesel RNA delesyonlarının caenorhabditis elegans yaşam ömrüne etkisinin araştırılması

Aging is defined as the defects that occur over time in the tissues and cells of the organism. These defects constitute the primary risk for neurodegenerative and cardiovascular diseases, cancer, diabetes, and many other diseases. Even though some common hallmarks are defined in aging organisms such as genomic instability, loss of proteostasis, cellular senescence and more, the reason behind aging is not completely understood. The aging field, therefore, research how and why do organisms age, and tries to delay or possibly revert this process. This is mostly done on model organisms, and the roundworm Caenorhabditis elegans (C. elegans) is one of the best models for aging research due to its short life cycle. In the first part of this study, the correlation between aging and lithium chloride treatment was aimed to be understood. This substance is commonly used as a drug in bipolar disorder, and an extension of lifespan upon lithium chloride treatment has been explored in multiple studies on different models. A pathway analysis was performed to determine what could be an unknown regulator of this process, and the worm ortholog of the human protein Rev-erb-α, NHR-85, was identified as a possible contributor. A loss-of-function mutation of this protein was found to extend lifespan in C. elegans when compared to its wild type, and lifespan was further extended by treatment with lithium chloride. A decay in brood size and locomotion functions was also observed upon treatment, but it is suggested that this may contribute to the extension of lifespan. Furthermore, it is suggested that this extension in lifespan could be caused by a developmental delay. In the second part of this study, it was aimed to understand whether some age-accumulated circular RNAs of C. elegans could be contributing to the aging process. Circular RNAs are covalently linked single-stranded RNA molecules joined at their ends, resulting in a loop shape. This covalent link is considered to contribute significantly to their stability, as most RNA-degrading enzymes require an open end to initiate degradation. Upon analysis of a circular RNA–specific RNA-seq study that sequenced RNA across different life stages until aging, four circular RNAs of two different genes were identified to accumulate extensively during aging. CRISPR/Cas9 was then utilized to specifically silence selected circular RNAs by targeting their circularization, and the effects of these deletions on C. elegans longevity were investigated.