A constraints-based theory of the primary cause of senescence: imbalance of epigenetic and non-epigenetic information in histone crosstalk

Cellular aging has been progressively elucidated by science. However, the fundamental cause of senescence—i.e., why organisms age at the multicellular-individual level—remains unclear. A recent theory of individuated multicellularity describes the emergence and growth of crucial information content for cell differentiation. This information is mostly conveyed in the non-epigenetic (i.e., transcription uncorrelated) histone crosstalk near transcription start sites. According to this theory, the non-epigenetic content emerges and grows at the expense of the information capacity for epigenetic content. If this “reassignment” of information capacity continues after adulthood, it may explain the senescence phenomenon. Here, I present a novel, falsifiable theory describing an uninterrupted growth of capacity for non-epigenetic information at the expense of that for epigenetic information not only during ontogeny but also throughout adulthood. As a byproduct, this continuous “reassignment” of capacity effectively creates an information imbalance in histone crosstalk, which in turn overregulates transcriptional levels. This overregulation is to be understood as transcriptional levels becoming more and more accurate but also less and less precise with respect to the needs of the multicellular individual—up to the point of dysfunctionality. This epigenetic/non-epigenetic information imbalance is proposed to be the primary reason why individuated multicellular organisms senesce.