Epigenome Changes Due to Aging and Reconstitution to a Youthful State Using Targeted and Generic Means

Abstract

The inescapable burden of aging more and more for each passing year often feels like a sinister payment owed for experiencing ever more life. A slow march towards guaranteed frailty and dysfunction, each additional year of old age brings our tissues and cells further away from the optimal function they experienced in youth. We may, however, be at the precipice of a new revolution in humankind, where aging is no longer measured in additional years survived, but by changes in one’s epigenetic profile. Furthermore, this profile may very well be reprogrammable, enabling a return to the proper form and function experienced in more youthful years. The goal of this research was to better understand epigenetic changes due to aging, followed by attempting to reverse those changes in a tightly targeted manner. The first aim of the study was to evaluate genomic regions most affected by epigenetic drift over time, to better understand if the epigenome truly changes with age and to what degree. The second aim was to understand how global cellular reprogramming with OSK, a promising candidate for some types of aging reversal, changes the epigenetic profiles of young and old cells. The third and most ambitious aim was to perform a tightly targeted remapping of an old epigenome to a more youthful epigenome, and vice versa, showing the ability to both reverse and advance epigenetic age in a precise fashion. This is the first demonstration of this ability as known to the author and suggests the feasibility of highly controllable age reversal. This study covers H3K27 tri-methylation, H3K4 mono-methylation, and R-loops, as discussed shortly.