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Measuring Genome Instability in Aging - a Mini-review

Overview
Journal Gerontology
Specialty Geriatrics
Date 2011 Dec 14
PMID 22156741
Citations 16
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Abstract

Background: There is mounting evidence for an age-dependent accumulation of somatic mutations as a result of the inherent imperfection of DNA replication and repair. A possible age-related decline in genome maintenance systems may exacerbate this age-related loss of genome integrity. A review of the current methods of mutation detection is timely in view of the lack of insight as to the magnitude of somatic mutation accumulation, the types of mutations that accumulate, and their functional consequences.

Objective: In this paper we review the current methods for measuring genome instability in organisms during aging or in relation to life span.

Methods: The review is based on established and novel concepts from the existing literature, with some examples from our own laboratory.

Results: Studies using cytogenetic assays and endogenous or transgenic mutation reporter assays provide strong evidence for age-related increases of different types of mutations in animals and humans during aging. This increase in DNA mutations is tissue-specific and also differs between species.

Conclusion: Today, our knowledge of somatic mutation profiles in aging is mainly derived from cytogenetics and the use of endogenous and transgenic mutation reporter assays. The emergence of new approaches, most notably massively parallel sequencing, will give us deeper insight into the nature of spontaneous genome instability and its possible causal relationship to aging and age-related disease.

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References
1.
Pellestor F, Anahory T, Hamamah S . Effect of maternal age on the frequency of cytogenetic abnormalities in human oocytes. Cytogenet Genome Res. 2005; 111(3-4):206-12. DOI: 10.1159/000086891. View

2.
Suh Y, Lee K, Kim W, Han B, Vijg J, Park S . Aging alters the apoptotic response to genotoxic stress. Nat Med. 2002; 8(1):3-4. DOI: 10.1038/nm0102-3. View

3.
Vicencio J, Galluzzi L, Tajeddine N, Ortiz C, Criollo A, Tasdemir E . Senescence, apoptosis or autophagy? When a damaged cell must decide its path--a mini-review. Gerontology. 2008; 54(2):92-9. DOI: 10.1159/000129697. View

4.
Cole J, Skopek T . International Commission for Protection Against Environmental Mutagens and Carcinogens. Working paper no. 3. Somatic mutant frequency, mutation rates and mutational spectra in the human population in vivo. Mutat Res. 1994; 304(1):33-105. DOI: 10.1016/0027-5107(94)90320-4. View

5.
Dolle M, Snyder W, Gossen J, Lohman P, Vijg J . Distinct spectra of somatic mutations accumulated with age in mouse heart and small intestine. Proc Natl Acad Sci U S A. 2000; 97(15):8403-8. PMC: 26960. DOI: 10.1073/pnas.97.15.8403. View