Aging clock based on nucleosome reorganisation derived from cell‐free DNA

Abstract

Aging induces systematic changes in the distribution of nucleosomes, which affect gene expression programs. Here we reconstructed nucleosome maps based on cell‐free DNA (cfDNA) extracted from blood plasma using four cohorts of people of different ages. We show that nucleosomes tend to be separated by larger genomic distances in older people, and age correlates with the nucleosome repeat length (NRL). Furthermore, we developed the first aging clock based on cfDNA nucleosomics. Machine learning based on cfDNA distance distributions allowed predicting person's age with the median absolute error of 3–3.5 years.

DNA-Binding Proteins and Passenger Proteins in Plasma DNA–Protein Complexes: Imprint of Parental Cells or Key Mediators of Carcinogenesis Processes?

“…Cell-free DNA is protected from hydrolysis by endogenous nucleases by packaging into membrane structures (such as apoptotic bodies [5][6][7]) and by binding to proteins [8][9][10], including histones [11]. It should be noted that the resulting nucleoprotein complexes (NPCs) can either circulate freely [12,13] or bind to the surface of blood cells [14,15] and exosomes [16] by interacting with protein [17,18] and DNA [19,20] receptors. At the same time, it is still not entirely clear what cellular processes (apoptosis [21][22][23], necrosis [23][24][25][26], active secretion [23,[25][26][27], NETosis [23,28]) lead to the entry of cell-free DNA into the bloodstream, and the contributions of these processes to the generation of extracellular DNA in normal and pathological conditions.…”