Analysis of lipid composition and hydroxyl radicals in brain membranes of senescence-accelerated mice

This study demonstrates that brain membrane and lipid peroxidation alterations readily occur in senescence-accelerated mice (SAM); when comparing two substrains, senescence-prone (SAM P1) with senescence-resistant (SAM R1), results indicate that age-related changes are more pronounced in the SAM P1 than in the SAM R1. For example, one age-related change observed in mice is elevated cholesterol in tissue. Experiments found that cholesterol-levels, as well as cholesterol/phospholipid ratios, are significantly higher in brain mitochondria and microsomes in SAM P1 than those in SAM R1. Another indicator of age-related change in the P1 substrain, oxidative status, is shown by higher levels of peroxidizable fatty-acids, Results show the peroxidizability index, derived from the mitochondrial fatty acid profile, is consistently higher in SAM P1 than in SAM R1, indicating its increased vulnerability to oxidative damage. This vulnerability was confirmed by a higher malondialdehyde content in brain microsomes and significantly higher amounts of hydroxyl radicals in the brain membrane than those in SAM R1. Similar differences were noted in the ratios of arachidonic/linoleic acid in the brain microsomes of SAM P1. Taken together, these results indicate an elevated oxidative status in the senescence-prone strain, SAM Pi, and leads to the proposal that increased oxidative stress may play an important role in this substrain's susceptibility to the senescence process. This study also shows these mice substrains can be useful for the study of free radical metabolism because it has characteristics that are consistent with the predictions made by the oxidative stress hypothesis of aging.