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

Ana Maria Garcia, Rita A. Busuttil, R. Brent Calder, Martijn E.T. Dollé, Vivian Diaz, C. Alex McMahan, Andrzej Bartke, James Nelson, Robert Reddick, Jan Vijg

Producción científica: Articlerevisión exhaustiva

57 Citas (Scopus)

Resumen

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 reduce 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 Escherichia 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/6J 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.

Idioma originalEnglish (US)
Páginas (desde-hasta)528-533
Número de páginas6
PublicaciónMechanisms of Ageing and Development
Volumen129
N.º9
DOI
EstadoPublished - sept 2008

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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