Universal Markers of Cellular and Replicative Senescence

Abstract

The investigation into cellular and replicative senescence is crucial for both biology and medicine, particularly in light of the increasing percentage of the elderly population. Gaining a deeper understanding of the mechanisms of these forms of aging can help develop strategies aimed at prolonging active longevity. By comparing the processes of cellular and replicative senescence, researchers can reveal both common and distinct molecular mechanisms, thus opening up innovative approaches to diagnosing and treating age-related diseases. The identified aging markers can contribute to personalized medicine and improving the diagnosis and treatment of aging cells. Thus, these studies greatly facilitate the development of methods for combating age-related diseases. The study aims to analyze cellular and replicative senescence in order to identify common mechanisms underlying the aging process. The goal is to understand the relationship between these processes and their influence on age-related changes. The specific objectives of this work include identifying aspects of aging and molecular markers that can be used for the diagnosis and monitoring of age-related disorders. The findings from this study will contribute to the prevention and treatment of age-related conditions, thereby improving overall population health. The public datasets E-MTAB-4879 (cellular senescence) and GSE130727 (replicative senescence) are analyzed. Quality control is carried out using the FastQC program. Adapter removal is performed by sequencing using the cutadapt 2.3 and Trimmomatic-0.38 programs. Mapping is carried out using the bowtie2-2.4.0 program. Reverification of the mapping results is performed using the kallisto-v0.45.0 pseudo-alignment algorithm. Quantification is carried out using featureCounts. RPKM (Read Per Kilobase per Million) normalization is applied (to average the total reads, coverage depth, and gene length). The mirnet.ca online service is used to search for regulatory miRNAs. For groups of genes that showed decreased (7275) and increased (5059) expression levels in the E-MTAB-4879 and GSE130727 datasets after filtering, we identify the biological processes they are involved in. For lists of the top 15 genes, we provide information on their role in the aging process. Additionally, for a group of commonly expressed genes, functional groups are determined using GO. The study compares two aging-related gene datasets and a total of 7275 genes with decreased expression are identified. Of these, 1342 show significant decreases in expression, with processes related to G-protein signaling, cholesterol metabolism, and cytokine signaling standing out. Some genes affect aging through inflammatory responses, membrane potential control, neurodegeneration, and cell differentiation. 143 noncoding RNAs associated with aging and cancer are identified upon further analysis. In a separate group, 1673 genes exhibit increased expression, involving processes such as glycerolipid biosynthesis and actin filament regulation, as well as wound healing. Among these, 194 noncoding RNAs are linked to oncogenesis and osteogenesis. In conclusion, our study has identified key differences and similarities between cellular and replicative senescence. This has allowed us to gain a deeper understanding of these aging processes and their roles in age-related changes. The analysis has revealed that common molecular mechanisms such as decreased gene expression related to G-protein signaling and cholesterol metabolism significantly influence both forms of senescence. Additionally, unique features have been identified, including differences in gene and noncoding RNA expression, which opens up possibilities for the development of personalized diagnostic and treatment strategies. These identified markers and mechanisms have the potential to contribute not only to diagnosis but also to the monitoring of age-related changes and improving approaches to age-associated disease treatment. Therefore, our research significantly contributes to the development of techniques to combat age-associated diseases by emphasizing the significance of investigating both the common and distinctive features of cellular and replicative senescence.