Immune abnormality in relation to nonimmune diseases in SAM mice

A series of related strains of senescence-accelerated mouse (SAM) shows strain-unique age-related diseases, such as amyloidosis, deficit in learning and memory, osteoporosis, and brain atrophy, while many of these disease-prone mouse (SAMP) strains have impaired immune activity as young adults, and have a short life span, probably not due directly to the diseases. Because the mean life span was prolonged and the time of the disease onset was delayed by a low-calorie dietary condition or a specific pathogen-free environment, both of which ameliorate the impaired immune activity, the enhancement of immune activity may help decrease the deteriorative process of aging, to that seen in ordinary strains of mice. Studies using the SAMP model may help elucidate the role of immunity in the aging process. Herein, we review the cellular and genetic basis of the immune abnormality in SAMP mice, then discuss the relationship between immune abnormality and development of the age-related disease, senile amyloidosis, findings obtained on SAMP hybrid mice and congenic mice for disease-related genes. Activation of the gene(s) for senile amyloid per se shortened the life span, and the early development of the immune dysfunction primarily seems to be both genetically and physiologically independent of amyloidosis, although the disease may be indirectly modified in the aged with depressed immune activity.