Aging-dependent DNA hypermethylation and gene expression of GSTM1 involved in T cell differentiation

Shu Hui Yeh, Cheng Ling Liu, Ren Chieh Chang, Chih Chiang Wu, Chia Hsueh Lin, Kuender D. Yang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

7 Scopus citations


This study investigated whether aging was associated with epigenetic changes of DNA hypermethylation on immune gene expression and lymphocyte differentiation. We screened CG sites of methylation in blood leukocytes from different age populations, picked up genes with age-related increase of CG methylation content more than 15%, and validated immune related genes with CG hypermethylation involved in lymphocyte differentiation in the aged population. We found that 12 genes (EXHX1, IL-10, TSP50, GSTM1, SLC5A5, SPI1, F2R, LMO2, PTPN6, FGFR2, MMP9, MET) were associated with promoter or exon one DNA hypermethylation in the aged group. Two immune related genes, GSTM1 and LMO2, were chosen to validate its aging-related CG hypermethylation in different leukocytes. We are the first to validate that GSTM1_P266 and LMO2_E128 CG methylation contents in T lymphocytes but not polymorphonuclear cells (PMNs) or mononuclear cells (MNCs) were significantly increased in the aged population. The GSTM1 mRNA expression in T lymphocytes but not PMNs or MNCs was inversely associated with the GSTM1 CG hypermethylation levels in the aged population studied. Further studies showed that lower GSTM1 CG methylation content led to the higher GSTM1 mRNA expression in T cells and knockdown of GSTM1 mRNA expression decreased type 1 T helper cell (Th1) differentiation in Jurkat T cells and normal adult CD4 T cells. The GSTM1_P266 hypermethylation in the aged population associated with lower GSTM1 mRNA expression was involved in Th1 differentiation, highlighting that modulation of aging-associated GSTM1 methylation may be able to enhance T helper cell immunity in the elders.

Original languageEnglish
Pages (from-to)48591-48602
Number of pages12
Issue number30
StatePublished - 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© Yeh et al.


  • Aging
  • DNA hypermethylation
  • Epigenetic
  • GSTM1
  • Gerotarget
  • T cell differentiation


Dive into the research topics of 'Aging-dependent DNA hypermethylation and gene expression of GSTM1 involved in T cell differentiation'. Together they form a unique fingerprint.

Cite this