Age-dependent DNA methylation patterns on the Y chromosome in elderly males

Aging Cell
Jesper Beltoft LundQihua Tan

Abstract

The Y chromosome, a sex chromosome that only exists in males, has been ignored in traditional epigenetic association studies for multiple reasons. However, sex differences in aging-related phenotypes and mortality could suggest a critical role of the sex chromosomes in the aging process. We obtained blood-based DNA methylation data on the Y chromosome for 624 men from four cohorts and performed a chromosome-wide epigenetic association analysis to detect Y-linked CpGs differentially methylated over age and cross-validated the significant CpGs in the four cohorts. We identified 40-219 significant CpG sites (false discovery rate <0.05) with >82% of them hypermethylated with increasing age, which is in strong contrast to the patterns reported on the autosomal chromosomes. Comparing the rate of change in the Y-linked DNA methylation across cohorts that represent different age intervals revealed a trend of acceleration in DNA methylation with increasing age. The age-dependent DNA methylation patterns on the Y chromosome were further examined for their association with all-cause mortality with results suggesting that the predominant pattern of age-related hypermethylation on the Y chromosome is associated with reduced risk of death.

References

Jun 10, 2000·Journal of Aging and Health·K ChristensenJ W Vaupel
Feb 6, 2002·Genome Research·UNKNOWN Y Chromosome Consortium
Aug 5, 2003·Nature Reviews. Genetics·Mark A Jobling, Chris Tyler-Smith
Jul 1, 2005·Demography·Anne Case, Christina Paxson
Apr 25, 2006·Biostatistics·W Evan JohnsonAriel Rabinovic
Jan 19, 2012·International Journal of Epidemiology·Ian J DearyJohn M Starr
May 10, 2012·BMC Bioinformatics·Eugene Andres HousemanKarl T Kelsey
Jan 15, 2013·Epigenetics : Official Journal of the DNA Methylation Society·Yi-an ChenRosanna Weksberg
May 7, 2013·American Journal of Human Genetics·Anastasia L WiseTeri A Manolio
Jul 5, 2013·PloS One·Asa JohanssonUlf Gyllensten
Dec 3, 2014·Current Biology : CB·Damian K Dowling
Jul 7, 2015·Journal of Proteome Research·Haghighat VakilianGhasem Hosseini Salekdeh
Mar 19, 2016·Lancet Neurology·Carolyn M Mazure, Joel Swendsen
Apr 12, 2016·Nature Genetics·Weiyin ZhouStephen J Chanock
Jun 16, 2016·Cell Metabolism·Steven N Austad, Kathleen E Fischer
May 31, 2017·Nature Reviews. Genetics·Mark A Jobling, Chris Tyler-Smith
Aug 31, 2017·Journal of Proteome Research·Anna MeyfourGhasem Hosseini Salekdeh
Nov 1, 2017·Molecular Psychiatry·R Karlsson LinnérD J Benjamin
Nov 9, 2017·Nature Medicine
Dec 26, 2018·Nature Reviews. Genetics·Ekaterina A KhramtsovaBarbara E Stranger

❮ Previous
Next ❯

Citations

Jul 20, 2019·Biochemical Society Transactions·Huiming ZhangJian-Kang Zhu
Mar 11, 2020·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Jesper B LundQihua Tan
Feb 6, 2020·Human Genetics·Xihan GuoXu Wang
Sep 2, 2020·Aging·Qihua Tan
Mar 22, 2021·Aging·Athina VidakiManfred Kayser
Jul 31, 2021·Human Molecular Genetics·Melissa A Wilson

❮ Previous
Next ❯

Methods Mentioned

BETA
methylation sequencing

Software Mentioned

minfi R package )
R package celltypes450
LOESS
sva R
R package minfi

Related Concepts

Related Feeds

Cell Aging

This feed focuses on cellular aging with emphasis on mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Genetics & Epigenetics of Aging

Dozens of genes are implicated in lifespan, and epigenetic changes during aging affect cell function. This feed focuses on the genetics and epigenetics of aging.

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.