Age-associated hydroxymethylation in human bone-marrow mesenchymal stem cells

Area of Science:

• Epigenetics
• Genomics
• Stem Cell Biology

Background:

• Genomic DNA methylation changes with age are primarily linked to 5-methylcytosine (5mC).
• 5-hydroxymethylcytosine (5hmC) is an epigenetic mark increasingly recognized for its potential role in aging processes.

Purpose of the Study:

• To investigate the genome-wide profile of 5hmC in mesenchymal stem cells (MSCs) across a wide age range.
• To identify age-associated changes in 5hmC patterns within MSCs.

Main Methods:

• Genome-wide analysis of 5hmC in bone-marrow-derived MSCs from donors aged 2 to 89 years.
• Identification and characterization of frequently hydroxymethylated CpG sites and their association with genomic features and histone modifications.

Main Results:

• 10,685 frequently hydroxymethylated CpG sites were identified in MSCs, associated with CpG density, introns, H3k4me1, and enhancers.
• Age-associated changes revealed 785 hyper- and 846 hypo-hydroxymethylated CpG sites in older individuals' MSCs.

Conclusions:

• DNA hyper-hydroxymethylation in older MSCs is associated with a loss of 5mC, suggesting 5hmC's role in lifetime DNA methylation dynamics.
• Age-related epigenomic alterations in MSCs may have functional consequences, emphasizing the importance of donor age in clinical applications.