Male-specific age estimation based on Y-chromosomal DNA methylation

Area of Science:

• Epigenetics
• Genomics
• Aging Research

Background:

• DNA methylation on autosomal CpGs offers reliable age prediction.
• No male-specific age predictor currently exists utilizing Y-CpGs (CpG sites on the Y chromosome).
• Sex chromosomes are crucial in aging processes, highlighting the need for male-specific aging markers.

Purpose of the Study:

• To develop and validate a male-specific epigenetic age predictor based on Y-CpGs.
• To investigate the utility of Y-CpG methylation for forensic applications.
• To explore potential differences in age prediction accuracy compared to autosomal CpG-based methods.

Main Methods:

• Analysis of blood-based DNA methylation microarray data from 1,057 males aged 15-87 across six cohorts.
• Identification of 75 Y-CpGs with significant age-related methylation changes (hyper- and hypomethylation).
• Application of machine learning algorithms, specifically support vector machines with a radial kernel, for age prediction.

Main Results:

• A male-specific epigenetic clock was developed using 75 Y-CpGs, achieving a mean absolute deviation (MAD) of 7.54 years with a correlation of 0.81 in validation.
• A refined model using 19 key Y-CpGs yielded a MAD of 8.46 years (cor=0.73).
• Age predictor accuracy remained consistent across age groups, unlike autosomal predictors that decline in accuracy for older individuals.

Conclusions:

• The study presents the first Y-chromosome-based epigenetic age predictor for males.
• This novel predictor demonstrates robust performance and potential for forensic science and studying male-specific aging.
• The findings underscore the importance of sex chromosomes in epigenetic aging patterns.