Universal Markers of Cellular and Replicative Senescence
Authors: Arbatskiy M. S. , Balandin D. E. 
Published: November 2024

The investigation into cellular and replicative aging is crucial for both biology and medicine, particularly in light of the increasing percentage of the older 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 aging, researchers can reveal both common and distinct molecular mechanisms, thus opening innovative approaches for diagnosing and treating age-related diseases. The identified aging markers can contribute to personalized medicine, improving the diagnosis and treatment of aging cells. Thus, these studies enhance developing methods for combating age-related diseases.

AIM. The study aims to analyze cellular and replicative aging 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. Specific objectives include identifying aspects of aging and identifying 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 management of age-related conditions, thereby improving overall population health.

MATERIALS AND METHODS. The public datasets E-MTAB-4879 (cellular senescence) and GSE130727 (replicative senescence) were analysed. Quality control was carried out using the FastQC program. Adapter removal was performed by sequencing using the cutadapt 2.3 and Trimmomatic-0.38 programs. Mapping was done using the bowtie2-2.4.0 program. Re-verification of the mapping results was performed using the kallisto-v0.45.0 pseudo-alignment algorithm. Quantification was done using featureCounts. RPKM (Read Per Kilobase per Million) normalization was applied (to the average total reads, coverage depth, and gene length). The mirnet.ca online service was used to search for regulatory miRNAs.

RESULTS. For groups of genes that showed decreased (7,275) and increased (5,059) expression levels in the E-MTAB-4879 and GSE130727 datasets after filtering, we identified the biological processes they are involved in. For lists of the top 15 genes, we provided information on their role in the aging process. Additionally, for a group of commonly expressed genes, functional groups were determined using GO. The study compared two aging-related gene datasets and identified a total of 7,275 genes with decreased expression. Of these, 1,342 showed 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. Further analyses identified 143 non-coding RNAs associated with aging and cancer. In a separate group, 1,673 genes exhibited increased expression, involving processes such as glycerolipid biosynthesis and actin filament regulation, as well as wound healing. Among these, 194 non-coding RNAs were linked to oncogenesis and osteogenesis.

CONCLUSION. In conclusion, our study has identified key differences and similarities between cellular and replicative aging. This has allowed us to gain a deeper understanding of these aging processes and their roles in age-related changes. The analysis revealed that common molecular mechanisms such as decreased gene expression related to G-protein signaling and cholesterol metabolism significantly influence both forms of aging. Additionally, unique features have been identified, including differences in gene and non-coding 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 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 illnesses by emphasizing the significance of investigating both the common and distinctive features of cellular and replicative aging processes.