Calorie restriction modulates chemically induced in vivo somatic mutation frequency

Casciano, Daniel A.; Chou, Ming W.; Lyn‐Cook, Lascelles E.; Aidoo, Anane

doi:10.1002/(sici)1098-2280(1996)27:2<162::aid-em10>3.0.co;2-d

Cited by 24 publications

(7 citation statements)

References 19 publications

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“…81,82 Spontaneous-and induced-mutation frequencies are also reduced. 83,84 In addition, CR completely reverses the age-related decline in base excision repair capacity. 85,86 In brief, CR delays aging, decreases the level of oxidative stress, and decreases cancer incidence; this is the exact inverse of progeria syndromes where aging occurs prematurely and is associated with numerous DNA alterations and mutations and increased cancer incidence.…”

Section: Senescence-associated Oxidative Damage Is Mutagenic and Possmentioning

confidence: 96%

“…Long‐term CR decreases the rate of mitochondria H 2 O 2 production 80 and mitochondrial and nuclear accumulation of 8oxoG, 34 as well as mitochondrial DNA deletions and rearrangements 81,82 . Spontaneous‐ and induced‐mutation frequencies are also reduced 83,84 . In addition, CR completely reverses the age‐related decline in base excision repair capacity 85,86 .…”

Section: Senescence‐associated Oxidative Damage Is Mutagenic and Possmentioning

confidence: 99%

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Acquisition of Oxidative DNA Damage during Senescence

Martien

Abbadie

2007

Annals of the New York Academy of Sciences

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As a result of time and cumulative divisions in vitro and in vivo, normal cells enter an irreversible nonproliferative state termed replicative or cellular senescence that is thought to contribute to organism aging. Both telomere shortening and cumulative oxidative damage were shown to contribute to senescence, probably acting at different degrees according to proliferation index, cell type, or environment. Because of its associated cohort of damages and irreversible cell-cycle arrest induced by shortened telomeres, senescence is commonly considered as a tumor-suppressor mechanism that stops the proliferation of genetically altered cells (i.e., potentially cancerous). However, the incidence of the most frequent cancers in humans, carcinomas, exponentially increases with age; the phenotypes of progeroid syndromes are often associated with an increase in tumor incidence, and inversely when aging is delayed by caloric restriction, the cancer incidence decreases. How can this positive link between aging and tumorigenesis be explained if senescence is a tumor-suppressor mechanism? The present article considers data and arguments supporting a protumoral role of senescence. We focus on the importance of the oxidative damage that targets DNA during senescence. Indeed, because of its mutagenic effects, oxidative damage could affect oncogenes and/or tumor-suppressor genes in some senescent cells, hence promoting their evolution toward initiated cancer cells. This mechanism could be particularly relevant for age-associated carcinomas because senescence in epithelial cells is driven more by oxidative stress than by telomere shortening.

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Section: Senescence-associated Oxidative Damage Is Mutagenic and Possmentioning

confidence: 96%

Section: Senescence‐associated Oxidative Damage Is Mutagenic and Possmentioning

confidence: 99%

Acquisition of Oxidative DNA Damage during Senescence

Martien

Abbadie

2007

Annals of the New York Academy of Sciences

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“…There is evidence that CR reduces spontaneous mutation frequency at the Hprt locus in T lymphocytes in mice (Dempsey et al, 1993) and rats (Aidoo et al, 2003). Evidence has also been obtained that CR reduces the number of mutations in T lymphocytes of rats induced by environmental mutagens (Casciano et al, 1996). However, the Hprt assay does not allow the direct analysis of different organs and tissues.…”

Section: Introductionmentioning

confidence: 99%

Effect of Ames dwarfism and caloric restriction on spontaneous DNA mutation frequency in different mouse tissues

Garcı́a

Busuttil

Calder

et al. 2008

Mechanisms of Ageing and Development

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Genetic instability has been implicated as a causal factor in cancer and aging. Caloric restriction (CR) and suppression of the somatotroph axis significantly increase life span in the mouse and reduces multiple symptoms of aging, including cancer. To test if in vivo spontaneous mutation frequency is reduced by such mechanisms, we crossed long-lived Ames dwarf mice with a C57BL/6J line harboring multiple copies of the lacZ mutation reporter gene as part of a plasmid that can be recovered from tissues and organs into E. coli to measure mutant frequencies. Four cohorts were studied: (1) ad lib wild-type; (2) CR wild-type; (3) ad lib dwarf; and (4) CR dwarf. While both CR wild-type and ad lib dwarf mice lived significantly longer than the ad lib wild-type mice, under CR conditions dwarf mice did not live any longer than ad lib wild-type mice. While this may be due to an as yet unknown adverse effect of the C57Bl/6 background, it did not prevent an effect on spontaneous mutation frequencies at the lacZ locus, which were assessed in liver, kidney and small intestine of 7-and 15-month old mice of all four cohorts. A lower mutant frequency in the ad lib dwarf background was observed in liver and kidney at 7 and 15 months of age and in small intestine at 15 months of age as compared to the ad lib wild-type. CR also significantly reduced spontaneous mutant frequency in kidney and small intestine, but not in liver. In a separate cohort of lacZ-C57BL/6J mice CR was also found to significantly reduce spontaneous mutant frequency in liver and small intestine, across three age levels. These results indicate that two major pro-longevity interventions in the mouse are associated with a reduced mutation frequency. This could be responsible, at least in part, for the enhanced longevity associated with Ames dwarfism and CR.

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“…However, the results of studies examining the spontaneous mutant frequency have not been as conclusive. Although Casciano et al (1996) did not find a significant decrease in the spontaneous mutant frequency in lymphocytes of calorically restricted animals as compared with those in animals fed ad libitum, they did find lower spontaneous mutant frequencies in restricted mice. Similarly, Shima et al (2000) observed that restriction of the caloric intake of dams before birth and during lactation and of their pups after weaning did not significantly reduce the spontaneous mutant frequency of the pups.…”

Section: Introductionmentioning

confidence: 71%

“…Previous studies have shown that a reduction in the diet of mice can lower the induced mutant frequency as compared with mice fed ad libitum (Casciano et al, 1996;Shima et al, 2000). However, the results of studies examining the spontaneous mutant frequency have not been as conclusive.…”

Section: Introductionmentioning

confidence: 96%

The effect of dietary restriction during development in utero on the frequency of spontaneous somatic mutations

Newell

Heddle

2002

Mutagenesis

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Caloric or dietary restriction is known to be protective against cancer in humans and in mice but the mechanism is uncertain. Given that somatic mutations are important in carcinogenesis, dietary restriction may act by changing mutation rates. Indeed, previous studies have shown that reductions in caloric intake during development or in adult life make mice less susceptible to high doses of mutagens. In these studies there have been hints that the spontaneous mutant frequency may also be reduced, but no significant decrease has been observed save in one study of very old mice. Since the spontaneous mutant frequency is already low, reductions from this level require the use of much larger sample sizes than usual and larger than those used in the previous studies. As pre-existing mutations cannot be eliminated, it is necessary to reduce the dietary intake over a period of time when a substantial proportion of spontaneous mutations arise in order to see an effect. To overcome such problems, the dietary restriction in this study was applied during the time of the highest mutation rate, early development, and many more than the usual number of animals were studied. SWR female mice were crossed with Muta(TM)Mouse males to obtain F(1) progeny for analysis of mutant frequency. At conception, the dams were put into two groups, one that was fed ad libitum and another which was fed 80% of the ad libitum diet. Pups were killed at birth, DNA was extracted from the whole animal and used to measure the mutant frequencies of the mice at the cII locus. Although the weights of the pups from dams whose diet was restricted were significantly less than those of the ad libitum mice (P = 0.003), the litter sizes in the two groups were approximately the same and did not differ significantly (P = 0.13). There was no significant difference in the mutant frequencies in the dietarily restricted and ad libitum groups (P = 0.43). In addition, there was no significant correlation between the weights of the pups and their mutant frequency in either the ad libitum or dietarily restricted groups (r(2) = 0.14 and r(2) = 0.024). No difference was observed in mutant frequency between the ad libitum and dietarily restricted mice from litters of the same size (P = 0.61). These results indicate that the protective effect of dietary restriction on cancer rates is not mediated by an alteration in the spontaneous rate of mutation but rather by another mechanism, such as its effect on induced mutation.

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Calorie restriction modulates chemically induced in vivo somatic mutation frequency

Cited by 24 publications

References 19 publications

Acquisition of Oxidative DNA Damage during Senescence

Acquisition of Oxidative DNA Damage during Senescence

Effect of Ames dwarfism and caloric restriction on spontaneous DNA mutation frequency in different mouse tissues

The effect of dietary restriction during development in utero on the frequency of spontaneous somatic mutations

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