Age-associated changes in methylation of the insulin-like growth factor II (IGF-II) gene


Hoffman, Elizabeth G., Day, Ian N. M. and Ganderton, Rosalind H. (2002) Age-associated changes in methylation of the insulin-like growth factor II (IGF-II) gene. Mechanisms of Ageing and Development, 123, (4), 442-443. (doi:10.1016/S0047-6374(01)00381-5).

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Description/Abstract

During normal human ageing, changes in DNA
methylation are seen, with global hypomethylation occurring
in tandem with gene and tissue specific hypermethylation.
This epigenetic change is thought to be
one of the mechanisms by which genes may become
dysregulated during normal ageing, with affected tissues
becoming increasingly susceptible to
carcinogenesis.

In 1996, Issa et al. demonstrated, using normal and
tumour derived colonic tissue, age-associated hypermethylation
in the human IGF II gene using a Southern
blotting based methodology. We have investigated the
change in methylation status of three regulatory regions of the human IGF II gene. These regions were the
biallelically expressed promoter (P) 1, imprinted promoter
(P) 3 and the downstream differentially methylated
region (DMR) 2. The two cohorts were ‘Young’s’
30 years and ‘Elderly’ 75 years. In order to increase
sensitivity and throughput of the methylation
detection, a methylation-sensitive/bisulphite sequencing
protocol was applied to human peripheral blood
lymphocyte derived, bisulphite modified genomic DNA.

Promoter 1 and the downstream DMR2 showed
neither hyper- nor hypo-methylation during ageing in
peripheral blood lymphocytes. However, the distal region
of the imprinted promoter 3 showed significant
hypermethylation with increasing age. The P3 result is
in concordance with the report of Issa et al. 1996. This
validates the use of peripheral blood lymphocyte
derived DNA as a proxy for the methylation status of
less easily available tissue and removes one of the
barriers to high throughput studies of population
methylation.

Item Type: Article
ISSNs: 0047-6374 (print)
Related URLs:
Keywords: time, methylation,england, insulin-like growth factor ii, gene, growth, ireland
Subjects: R Medicine
R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
Divisions: University Structure - Pre August 2011 > School of Medicine > Developmental Origins of Health and Disease
University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair
University Structure - Pre August 2011 > School of Medicine
University Structure - Pre August 2011 > School of Medicine > Human Genetics
ePrint ID: 59832
Date Deposited: 04 Sep 2008
Last Modified: 27 Mar 2014 18:41
URI: http://eprints.soton.ac.uk/id/eprint/59832

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