Aging lipofuscin

The age pigments (lipofuscin), which accumulate with age, aie largely made up of these precipitated Hpid-proteia complexes resultiag from such cross-linking. Vitamin E may function to help prevent formation of these complexes. The metaboHc role of antioxidants (qv) such as vitamin E in animal tissues, however, remains quite controversial. 

Katz, ML, 2002. Potential role of retinal pigment epithelial lipofuscin accumulation in age-related macular degeneration. Arch Gerontol Geriatr 34, 359-370. 

Mata, NL, Tzekov, RT, Liu, XR, Weng, J, Birch, DG, and Travis, GH, 2001. Delayed, dark-adaptation and lipofuscin accumulation in abcr+/- mice Implications for involvement of ABCR in age-related macular degeneration. Invest Ophthalmol Vis Sci 42, 1685-1690. 

Rozanowska, M, Korytowski, W, Rozanowski, B, Skumatz, C, Boulton, ME, Burke, JM, and Sarna, T, 2002. Photoreactivity of aged human RPE melanosomes A comparison with lipofuscin. Invest Ophthalmol Vis Sci 43, 2088-2096. 

Rdzanowska, M and Rozanowski, B, 2008. Visual transduction and age-related changes in lipofuscin. In Tombran-Tink, J and Barnstable, CJ (Eds.), Ophthalmology Research The Visual Transduction Cascade. The Humana Press Inc., Totowa, NJ, pp. 405 146. 

Kikugawa, K., Beppu, M., Sato, A. and Kasai, H. (1997). Separation of multiple yellow fluorescent lipofuscin components in rat kidney and their characterization. Mech. Ageing Dev. 97, 93-107. 

Autofluorescence of cells often complicates the studies with fluorescence microscopy (especially the application of green fluorescent substances). There are different reasons for the occurrence of this phenomenon (157) (i) the fluorescent pigment lipofuscin, which settles with rising age in the cytoplasm of cells (ii) cell culture medium, which often contains phenol red that increases autofluorescence (iii) endogen substances such as flavin coenzymes [flavin-adenine dinucleotide (FDA), flavin mononucleotide (FMN) absorp-tion/emission 450/515nm], pyridine nucleotides [reduced nicotinamide adenine dinucleotide (NADH) absorption/emission 340/460nm] or porphyrine (iv) substances taken up by cells (as mentioned above filipin) and (v) preparation of the cells fixation with glutaraldehyde increases autofluorescence. 

Any indigestible material within the lysosome is normally expelled through the plasma membrane, but as cells grow older, this process functions less effectively so that cells become loaded with unwanted Upid and protein, which is oxidised to produce a complex known as lipofuscin (an age pigment). Over many years, this can accumulate and impair... 

The malonaldehyde-amine reaction has been extensively studied by Tappel and co-workers (2), by Csallany et al. (3), by Privett and co-workers (4), Knook et al. (5), Buttkus and Bose (6 ), as well as many others. As shown in Figure 1, malonaldehyde may react with a primary amine to produce an initial ene-amine Schiff base ( 7 ), then by further condensation with another amine, an amino-imino-propene compound. Heat and acid are required in the usual model reaction. The model compounds (lysine with malonaldehyde, for example) fluoresce between 430 and 470 nm when excited between 350 and 360 nm (8). These are typical of the "aging" pigments, the organic solvent-soluble lipofuscin in oxidizing tissue. 

Figure 5.4 The levels of the autofluorescence pigment lipofuscin as a function of age. Lipo-fuscin accumulates within the retinal pigment epithelium as a result of oxidative damage to lipid membranes within the retina and is often regarded as a marker of the health of the retinal/RPE complex. (Data derived from Wing, G.L. et al., Invest. Ophthalmol. Vis. Sci., 17(7), 601-607, 1978.)...

Tokutake S. 1997. Accumulation of aluminum and silicon in lipofuscin granules suggests retardation of blood-brain barrier function by aging. Ann N Y Acad Sci 826 510-512. 

Browning due to interaction of oxidised lipids and proteins occurs in vivo, the brown pigment deposited in tissues being termed lipofuscin or ceroid. The appearance of brown discoloration in the adipose tissues of, inter alia, pig, mink, and chicken, has been called the yellow fat disease . Ceroid accumulates slowly and has therefore been described as the age pigment . 

In spite of the increased activities of SOD-1 and GPx and normal catalase activity, increased lipid peroxides in the blood plasma of DS patients have been reported (K10), as has as an increased accumulation rate of age pigments (i.e., lipofuscin and ceroid, known products of lipid peroxidation) (K9). In addition, an early study showed increased lipid peroxides in the cerebral cortex of DS fetal brains (B15). More recently, cortical neurons from fetal DS and age-matched normal brains were shown to differentiate normally early in cell cultures. However, DS neurons subsequently degenerated and underwent apoptosis, whereas the normal cells remained viable (B18). In addition, the DS neurons exhibited a three- to fourfold increase in reactive oxygen species and increased lipid peroxidation that preceded cell death. Importantly, DS neuron degeneration could be prevented by treatment with the free radical spin trap A-ferf-butyl-2-sulphophenylnitrone, the... 

K5. Kato, Y., Maruyama, W., Naoi, M., Hashizume, Y., and Osawa, T., Immunohistochemical detection of dityrosine in lipofuscin pigments in the aged human brain. FEBS Lett. 439, 231-234 (1998). 

Y8. Yin, D., Biochemical basis of lipofuscin, ceroid, and age pigment-like fluorophores. Free Radicals Biol. Med. 21, 871-888 (1996). 

Moreover, the occurrence of fluorescing pigments in the form of lipofuscin, ceroid and porphyrin (as found in Wilson s disease, haemochromatosis, Dubin-Johnson-Sprinz syndrome, porphyria cutanea tarda and abuse of analgesics - as well as pigmentation in old age) is a reliable sign of excessive free-radical formation in the cell. 

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