Apolipoprotein E and its role in aging and survival

Abstract

The study of biological aging has seen spectacular progress in the last decade and markers are increasingly employed for understanding physiological processes that change with age. Recently, it has been demonstrated that apolipoprotein E (apoE) has a major impact on longevity, but its mechanisms are still not fully understood. ApoE-deficient (E o ) mice have proved to be a very popular model for studying spontaneous hypercholesterolemia and the subsequent development of atherosclerotic lesions, but only limited data are available with regard to aging and aging changes.We used this murine model to better characterize the involvement of apoE in aging and to evaluate its role in the maintenance of normal organ morphology. Our results show that E 0 mice at different ages (6, 12, 20 weeks old) developed age-dependent morphological and biochemical alterations, including fibrosis (newly formed collagen), pro-inflammatory cytokine (IL-6 and iNOS), lipofuscin accumulation, and decrease of antioxidant enzymes (superoxide dismutase and catalase) in several organs (kidney, liver and heart). It is significant that the observed degenerative findings in E 0 mice at different ages (6, 12, 20 weeks old) were not identified in control mice (C57BL), at 6, 12 and 20 weeks of age. Consequently, since these mice showed enzymatic and structural alterations, normally linked to the age, such as increase of lipofuscin, pro-inflammatory cytokines and decrease of antioxidant enzymes, we can conclude that apoE is a useful player in studies of longevity and age-related diseases, such as inflammatory status and atherosclerosis that are known risk factors for functional decline and early mortality. Moreover, it is possible that apoE may also play a role in other pathological conditions including, for example, cancer, rheumatoid arthritis and macular degeneration.

Recent progress in histochemistry and cell biology

“…The severe hyperlipidemia observed is similar to human type III hyperlipidemia (Ghiselli et al 1981). Recently, glomerular inflammation, mesangial expansion, foam cell formation and endothelial activation have been observed in the kidney of apoE null mice (Bonomini et al 2011a;Bruneval et al 2002;Vaziri et al 2010;Wen et al 2002). In this context and the fact that only limited data are available for the role of apoE in kidney disease Bonomini et al (2011b) focused on the question as to how apoE inactivation induces kidney disease.…”

The Role of Mitochondrial Function in Glutamate-Dependent Metabolism in Neuronal Cells

“…These processes alter the speed of the electron transport chain (ETC) as a result of the increasing ROS production. Alterations in mitochondrial processes are more remarkable in aging cells than in cells from young specimens [129]. Neuronal mitochondria have a high Ca 2+ ion storage capacity and can therefore protect neurons from transient elevations in intracellular Ca 2+ concentrations during neuronal hyperactivity.…”

Role of apolipoprotein E in renal damage protection

“…Recently, glomerular inflammation, mesangial expansion, foam cell formation and endothelial activation have been found to occur in the kidney of apoE null mice (Bruneval et al 2002;Wen et al 2002;Bonomini et al 2010;Vaziri et al 2010). Therefore, apoE null mice provide an animal model suitable to study the effects of hyperlipidaemia on kidney disease.…”