Implications of increased intercellular variability of lipofuscin content with age in dentate gyrus granule cells in the mouse

The purpose of this study was to further characterize lipofuscin (LF) accumulation with aging in brain cells, with a specific focus on the amount of intercellular variability of lipofuscin content within an apparently a homogenous population of dentate gyrus granule cells in the hippocampus of mice, as a function of age and caloric restriction (CR). Three age groups of CR and control mice including groups at maximum lifespan were studied. This study demonstrated that the intercellular variability of lipofuscin content was significantly greater in older mice and was significantly less in mice calorically restricted. Increased variability of metabolic function among cells with age, as measured by increased intercellular variability of lipofuscin content, may represent a definitive mechanism underlying the overall decreased efficiency of tissue and organ functioning that occurs with age. That this is so, is supported by the fact that CR, which has been shown to maintain the "youthful" state of many physiological functions, has been shown in this study to maintain the "youthful" state of low intercellular variability of lipofuscin content within a population of cells. LF accumulation may be a marker for the intrusion of entropy into cell metabolism.