An investigation of the age-dependency of chromosome abnormalities in human populations exposed to low-dose ionising radiation

Vorobtsova, I.E.; Семенов, А. В.; Timofeyeva, Natalia; Kanayeva, A; Зверева, И. В.

doi:10.1016/s0047-6374(01)00275-5

Cited by 23 publications

(6 citation statements)

References 40 publications

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“…The geometric mean frequency increased from 0.71x10 -5 in neonates to 6.53x10 -5 in the elderly (Grist et al, 1992). Similarly, stable chromosome aberrations that increased in frequency with increasing age were observed in human peripheral lymphocytes (Vorobtsova et al, 2001). All these studies demonstrate an accumulation of cells that have undergone loss-of-function mutations and/or LOH in mammals of advanced age.…”

Section: The Experimental Datamentioning

confidence: 68%

Does age influence loss of heterozygosity?

Carr

Gottschling

2008

Experimental Gerontology

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The striking correlation between advanced age and an increased incidence of cancer has led investigators to examine the influence of aging on genome maintenance.Because loss of heterozygosity (LOH) can lead to the inactivation of tumor suppressor genes, and thus carcinogenesis, understanding the affect of aging on this type of mutation event is particularly important. Several factors may affect the rate of LOH, including an increase in the amount of DNA damage, specifically double-strand breaks (DSB), and the ability to efficiently repair this damage via pathways that minimize the loss of genetic information. Because of experimental constraints, there is only suggestive evidence for a change in the rate of DNA damage as humans age. However, recent studies in model organisms find that there are increased rates of LOH with age, and that repair of DNA damage occurs via a different pathway in old cells versus young cells. We speculate that the age-dependent change in DNA repair may explain why there is increased LOH, and that the findings from these model organisms may extend to humans.

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Section: The Experimental Datamentioning

confidence: 68%

Does age influence loss of heterozygosity?

Carr

Gottschling

2008

Experimental Gerontology

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“…clonal expansion). Previous work has shown that the occurrence of chromosomal anomalies (rearrangements and aneuploidies) during cell division increases with age in cultured lymphocytes and fibroblasts 30,31 , that DNA damage accumulates with age in mouse hematopoietic stem cells 32 , and that mitotic recombination (leading to uniparental disomy) increases with replicative age in yeast 33 . This apparent increase in somatic mutation may result from age-related decline in genomic maintenance mechanisms (such as telomere attrition 34 ).…”

Section: Discussionmentioning

confidence: 99%

Detectable clonal mosaicism from birth to old age and its relationship to cancer

Laurie¹,

Laurie²,

Rice³

et al. 2012

Nat Genet

528

498

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Clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) was detected using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells (>5–10%) with the same abnormal karyotype (presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rises rapidly to 2–3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions that pinpoint the locations of genes previously associated with hematological cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer prior to DNA sampling, those without a prior diagnosis have an estimated 10-fold higher risk of a subsequent hematological cancer (95% confidence interval = 6–18).

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“…Spontaneous, somatic gene mutations such as in the HPRT locus increase exponentially with age in human kidney epithelia [71]. Vorobtsova et al [72] studied a control group and two irradiated populations from aged 3 to 72 years old. Individuals exposed to low doses of IR, derived from the Chernobyl accident and atomic bomb testing, exhibited acceleration of the age-related increase of stable-chromosome aberrations, but not unstable-chromosome aberrations, in cultured lymphocytes.…”

Section: Comparison Of Aging and Radiation Effectsmentioning

confidence: 99%

Ionizing radiation and aging: rejuvenating an old idea

Richardson

2009

Aging

118

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This paper reviews the contemporary evidence that radiation can accelerate aging, degenerative health effects and mortality. Around the 1960s, the idea that ionizing radiation caused premature aging was dismissed as the radiation-induced health effects appeared to be virtually confined to neoplasms. More recently, radiation has become associated with a much wider spectrum of age-related diseases, including cardiovascular disease; although some diseases of old age, such as diabetes, are notably absent as a radiation risk. On the basis of recent research, is there a stronger case today to be made linking radiation and aging? Comparison is made between the now-known biological mechanisms of aging and those of radiation, including oxidative stress, chromosomal damage, apoptosis, stem cell exhaustion and inflammation. The association between radiation effects and the free-radical theory of aging as the causative hypothesis seems to be more compelling than that between radiation and the nutrient-sensing TOR pathway. Premature aging has been assessed by biomarkers in calorie restriction studies; yet, biomarkers such as telomere erosion and p16INK4a are ambiguous for radiation-induced aging. Some animal studies suggest low dose radiation may even demonstrate hormesis health benefits. Regardless, there is virtually no support for a life span extending hypothesis for A-bomb survivors and other exposed subjects.

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An investigation of the age-dependency of chromosome abnormalities in human populations exposed to low-dose ionising radiation

Cited by 23 publications

References 40 publications

Does age influence loss of heterozygosity?

Does age influence loss of heterozygosity?

Detectable clonal mosaicism from birth to old age and its relationship to cancer

Ionizing radiation and aging: rejuvenating an old idea

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