Longevity-dependent organ-specific accumulation of DNA damage in two closely related murine species.

To measure directly the accumulation of DNA damage with age, and to understand better the effect of modulators of DNA damage in vivo, the DNA of brain, liver, and kidney of two mice from different families, Mus musculus and Peromyscus leucopus, have been examined for age-dependent accumulation of single-strand breaks plus alkali-labile bonds, by the alkaline sucrose sedimentation method. These two species of small rodents are closely related taxonomically, yet differ significantly in maximum achievable lifespan. Using the reciprocal of the number average molecular weight for estimation of DNA size, these analyses indicate that: (a) DNA damage does not measurably accumulate in brain tissue; (b) the accumulation of DNA damage was more pronounced in hepatic DNA than other tissue DNA; and (c) the rate of accumulation of DNA damage in liver and kidney cells with age was greater in the shorter-lived species (M. musculus) and was inversely proportional to maximum achievable lifespan. There are suggestions that a similar threshold might exist for tolerance of DNA damage in the two species in specific organs, and that these species differ in the rate at which this threshold is reached as a function of maximum achievable lifespan.