The RNA-Seq data analysis shows how the ontogenesis defines aging

Abstract

This paper presents a global statistical analysis of the RNA-Seq results of the entire Mus musculus genome. We explain aging by a gradual redistribution of limited resources between two major tasks of the organism: its self-sustenance based on the function of the housekeeping gene group (HG) and functional differentiation provided by the integrative gene group (IntG). All known disorders associated with aging are the result of a deficiency in the repair processes provided by the cellular infrastructure. Understanding exactly how this deficiency arises is our primary goal. Analysis of RNA production data of 35,630 genes, from which 5,101 were identified as HG genes, showed that RNA production levels in the HG and IntG genes had statistically significant differences (p-value <0.0001) throughout the entire observation period. In the reproductive period of life, which has the lowest actual mortality risk for Mus musculus, changes in the age dynamics of RNA production occur. The statistically significant dynamics of the decrease of RNA production in the HG group in contrast to the IntG group was determined (p-value = 0.0045). The trend toward significant shift in the HG/IntG ratio occurs after the end of the reproductive period, coinciding with the beginning of the mortality rate increase in Mus musculus indirectly supports our hypothesis. The results demonstrate a different orientation of the impact of ontogenesis regulatory mechanisms on the groups of genes representing cell infrastructures and their organismal functions, making the chosen direction promising for further research and understanding the mechanisms of aging.

Relation of Known Hallmarks of Aging to the Ontogenesis Program

“…Our confirmation of the differences in RNA production in the studied functional groups of the genome suggests that there is a global mechanism of ontogenesis that affects the activity of these groups and, most importantly, their correlation. As was shown in our recent work [36], the implementation of the ontogenesis program naturally leads to an imbalance of activity between HG and IntG groups. In turn, such imbalance leads to insufficient provision of cellular functions with their infrastructure represented in the genome by the HG functional group and, as a result, to aging of the organism.…”

The RNA Genome Sequencing Demonstrates Increased Production of Metabolic Genes in Late Ages in Highly Differentiated Tissues

“…Analyzing the results obtained in the previous paper 21 we noticed a tendency to some increase in RNA production of HG genes after 21 months of age. This result somewhat contradicts our aging model and we assumed that an explanation can be found for this fact, which is the purpose of this paper.…”

“…To analyze the results of RNA sequencing of Mus musculus genome production, we used the same material as in our previous article 21 (HRT Atlas v1.0, (www.housekeeping.unicamp.br). When the HG list was compiled, all variants of genes from those already listed, were additionally included.…”