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

Area of Science:

• Genomics
• Epigenetics
• Molecular Biology

Background:

• Aging is associated with systematic changes in nucleosome distribution.
• Nucleosome organization influences gene expression programs.
• Cell-free DNA (cfDNA) in blood plasma reflects in vivo chromatin states.

Purpose of the Study:

• To investigate age-related changes in nucleosome distribution using cfDNA.
• To develop and validate the first aging clock based on cfDNA nucleosomics.
• To correlate cfDNA nucleosome spacing with chronological age.

Main Methods:

• Reconstruction of nucleosome maps from cfDNA extracted from blood plasma across four age cohorts.
• Analysis of nucleosome spacing and nucleosome repeat length (NRL).
• Development of a machine learning model utilizing cfDNA distance distributions for age prediction.

Main Results:

• Nucleosomes exhibit larger genomic separation in older individuals.
• Age significantly correlates with nucleosome repeat length (NRL).
• The developed cfDNA nucleosomics aging clock achieved a median absolute error of 3-3.5 years in age prediction.

Conclusions:

• cfDNA nucleosome mapping provides insights into age-related epigenetic alterations.
• Nucleosome organization dynamics in cfDNA can serve as a biomarker for biological aging.
• This novel cfDNA nucleosomics approach offers a non-invasive method for age estimation.