Generation of fluorescent adducts of malondialdehyde and amino acids: toward an understanding of lipofuscin.

Lipofuscin is a yellow-brown, highly fluorescent pigment that undergoes an age-related progressive accumulation in animal cells, mainly in postmitotic cells. It is a heterogeneous, high-molecular weight material associated with proteins, lipids and nucleic acids. Lipofuscin is implicated in many aspects of human health, including aging, oxidative stress, macular degeneration, lipid peroxidation, atherosclerosis, dementia (Alzheimer's Disease) and diseases associated with prions. Although the fluorescent properties of lipofuscin have long been recognized, neither histologists nor chemists have yet isolated the pigments themselves or characterized their optical properties. We have prepared lipofuscinlike species by reacting malondialdehyde (MDA) with cysteine (Cys). MDA:Cys adducts 3:2 and 2:2 are two of those that have been identified among the many that were present in the reaction. Whereas previous attempts to synthesize lipofuscinlike species resulted in compounds that were either nonfluorescent or emitted principally in the blue, the MDA:Cys adducts reported in this study are not only fluorescent but also emit over a broader range.