The senescence-accelerated mouse (SAM), consisting of 14 senescence-prone inbred strains (SAMP) and 4 senescence-resistant inbred strains (SAMR) have been under development since 1970 through selective inbreeding of the AKR/J strain of mice donated by the Jackson Laboratory in 1968, based on the data of the grading score of senescence, life span and pathologic phenotypes. Data from survival curves, the Gompertzian function and the grading score of senescence, together with growth patterns of body weight of SAMP and SAMR mice revealed that the characteristic feature of aging common to all SAMP mice is“accelerated senescence”: early onset and irreversible advance of senescence manifested by several signs and gross lesions such as the loss of normal behavior, various skin lesions, and increased lordoky-phosis, after a period of normal development. SAMP and SAMR strains were found to manifest various pathobiological phenotypes which were often unique enough to differentiate the strains. These features included senile amyloidosis, contracted kidney, impaired immune response, hyperinflation of the lungs, hearing impairment, cataracts, degenerative joint disease, senile osteoporosis, deficits in learning and memory, emotional disorder, brain atrophy, and ovarian cysts.
Judging from reports regarding the underlying mechanisms of accelerated senescence in SAMP, it is reasonable to assume that accelerated oxidative damages to biological components such as lipids, proteins, nucleic acids and chromosomes play an important role in the manifestation of accelerated senescence in SAMP. Mitochondrial deficiency in antioxidant enzyme, CuZn-SOD and/or mitochondrial failure in electron transport system have been proposed as causal factors of oxidative stress in SAMP. The genetic background of the SAM model and the significance of SAM development were also discussed.

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