Apolipoprotein E and its role in aging and survival

Francesca Bonomini , Francesca Filippini , Tony Hayek , Michael Aviram , Shlomo Keidar , Luigi F.Rodella , Raymond Coleman , Rita Rezzani

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) 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 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 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.

Mots clés: Apolipoprotein E

Francesca Bonomini, Francesca Filippini, Tony Hayek, Michael Aviram, Shlomo Keidar, et al.. Apolipoprotein E and its role in aging and survival. Experimental Gerontology, 2010, 45 (2), pp.149. ⟨10.1016/j.exger.2009.11.006⟩. ⟨hal-00559143⟩