Characterization of the Age Changes in Brain and Liver Enzymes of Senescence-Accelerated Mice (SAM)

Abstract

Editor's Note: The SAM (senescence accelerated mouse) model has been used in various aspects of aging research and JAAM has published work on this area previously (see HosoL·wa et al., l:l;[27][28][29][30][31][32][33][34][35][36][37]. The current study attempts to clarify some of the changes which occur in aging cells with the brain and liver of such a model. The particular approach here is to understand how enzymes which affect free radical metabolism alter over the lifespan of the aging animal. ABSTRACTThe comparative neurochemical characteristics of brain and liver membranes of senescenceaccelerated mice, prone (SAMPl) and senescence-accelerated mice, resistant (SAMR1) strains were evaluated using males and females of several ages. Abnormal N-methyl-D-aspartic acid (NMDA) binding and monoamine oxidase b activity in SAMP brain membranes may pro¬ mote increased accumulation of reactive oxygen species (ROS) in neurons. Na/K-adinosine triphosphatase (ATPase) and liver cytochrome P450 activities are greater in SAMPl neurons than in SAMR1 neurons, which may reflect an adaptive tissue response to ROS accumula¬ tion.Age changes in animal tissues are highly lar ROS generation remain obscure. Nonethecorrelated with an increased generation of less, we suggest that senescence-dependent reactive oxygen species (ROS).1'2 Senescence-ac-metabolic defects are induced by noncompencelerated mice (SAM), selected from the sis-sated intracellular ROS generation.2'4 We can¬ ter-brother mating of AKR/J strain mice,3 are not exclude such defects resulting from seccharacterized by ROS-induced accelerated ondary features of aging (i.e., resulting from senescence at earlier steps of normal develop-tissue adaptation.7 To elucidate the metabolic ment.4 These animals have aging changes in reactions providing the intracellular source of their tissues by 4 to 6 weeks after birth that are ROS and the primary targets for oxidative modaccompanied by increased ROS levels.5 This ification during aging, we studied the activity may be the major reason for accelerated senes-of specific brain and liver membrane systems in cence,5'6 although the precise sources of cellu-SAM animals at different developmental stages.

Aging and cancer in transgenic and mutant mice

“…There are several senescence-prone strains (SAMP), which live 12-15 months, and several senescence-resistant (SAMR) strains, which are normal controls for accelerated aging and have a life span of 24-30 months. It has been shown that SAMP mice develop normally until the age of 4 months and then they reveal signs of accelerated aging (such as loss of hair, skin ulceration, decrease of locomotor activity, deficiency in learning and memory, emotional disorders, abnormal circadian rhythms, brain atrophy, hearing impairment, cataracts, increased production of reactive oxidation specimens (ROS) and 8-hydroxyguanine levels in all organs (40)(41)(42)(43)(44)). The amount of Cu, Zn-SOD in the mitochondria fraction of the SAMP-1 was only half that of the SAMR-1 (45).…”