Age-associated epigenetic modifications in human DNA increase its immunogenicity.

Abstract:

:Chronic inflammation, increased reactivity to self-antigens and incidences of cancer are hallmarks of aging. However, the underlying mechanisms are not well understood. Age-associated alterations in the DNA either due to oxidative damage, defects in DNA repair or epigenetic modifications such as methylation that lead to mutations and changes in the expression of genes are thought to be partially responsible. Here we report that epigenetic modifications in aged DNA also increase its immunogenicity rendering it more reactive to innate immune system cells such as the dendritic cells. We observed increased upregulation of costimulatory molecules as well as enhanced secretion of IFN-alpha from dendritic cells in response to DNA from aged donors as compared to DNA from young donors when it was delivered intracellularly via Lipofectamine. Investigations into the mechanisms revealed that DNA from aged subjects is not degraded, neither is it more damaged compared to DNA from young subjects. However, there is significantly decreased global level of methylation suggesting that age-associated hypomethylation of the DNA may be the cause of its increased immunogenicity. Increased immunogenicity of self DNA may thus be another mechanism that may contribute to the increase in age-associated chronic inflammation, autoimmunity and cancer.

journal_name

Aging (Albany NY)

journal_title

Aging

authors

Agrawal A,Tay J,Yang GE,Agrawal S,Gupta S

doi

10.18632/aging.100121

subject

Has Abstract

pub_date

2010-03-20 00:00:00

pages

93-100

issue

2

issn

1945-4589

pii

v2/n2/full/100121.html

journal_volume

2

pub_type

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