Review article
Biochemical basis of lipofuscin, ceroid, and age pigment-like fluorophores

https://doi.org/10.1016/0891-5849(96)00175-XGet rights and content

Abstract

Serious studies of the formation mechanisms of age-related pigments and their possible cellular influence have been hampered for a long time by discrepancies and controversies over the definition, fluorescence emission, origin, and composition of these pigments. This review discusses several critical controversies in this field and lay special emphasis on the cellular and biochemical reactions related to the formation mechanisms of lipofuscin, ceroid, advanced glycation end-products (AGEs), and age pigment-like fluorophores (APFs). Various amino compounds and their reaction with secondary aldehydic products of oxygen free radical-induced oxidation, particularly lipid peroxidation, are important sources of the fluorophores of ceroid/lipofuscin, which progressively accumulate as a result of phagocytosis and autophagocytosis of modified biomaterials within secondary lysosomes of postmitotic and other cells. Lipofuscin is the classical age pigment of postmitotic cells, while ceroid accumulates due to pathologic and experimental processes. There are good reasons to consider both ceroid and lipofuscin as materials of the same principal origin. The age-related intracellular fluorophores of retinal pigment epithelium (RPE) seems to represent a special class of lipofuscin, which partly contains derivatives of retinoids and carotenoids. Saccharide-originated fluorophores, principally AGEs formed during glycation/Maillard reactions, may be mainly responsible for the extracellular fluorescence of long-lived proteins, such as collagen, elastin, and lens crystalline. Although lipofuscin, ceroid, AGEs, and APFs can be produced from different types of biological materials due to different side reactions of essential biology, the crosslinking of carbonyl-amino compounds is recognized as a common process during their formation.

References (187)

  • U. Brunk et al.

    Electron microscopical studies on rat brain neurons. Localization of acid phosphatase and mode of formation of lipofuscin bodies

    J. Ultrastruct. Res.

    (1972)
  • J. Alroy et al.

    Application of lectin histochemistry and carbohydrate analysis to the characterization of lysosomal storage diseases

    Carbohyd. Res.

    (1991)
  • A. Hervonen et al.

    Age related heterogeneity of lipopigments in human sympathetic ganglia

    Mech. Ageing Dev.

    (1986)
  • J. Koistinaho et al.

    The effect of bleaching on the lipopigments in the human sympathetic neurones

    Mech. Ageing Dev.

    (1986)
  • G.E. Eldred et al.

    Fluorophores of the human retinal pigment epithelium: Separation and spectral characterization

    Exp. Eye Res.

    (1988)
  • R.S. Sohal et al.

    Effect of ethanol on lipofuscin accumulation in the cultured rat cardiac myocytes

    Free Radic. Biol. Med.

    (1989)
  • T. Sato et al.

    Morphometrical and biochemical analysis on autofluorescent granules in various tissues and cells of the rats under several nutritional conditions

    Mech. Ageing Dev.

    (1988)
  • J.S. Ploem

    The microscopic differentiation of the colour of formaldehyde-induced fluorescence

    Prog. Brain Res.

    (1971)
  • S. Björkerud

    The isolation of lipofuscin granules from bovine cardiac muscle, with observations on the light and electron microscopic levers

    J. Ultrastruct. Res. Suppl.

    (1963)
  • A.N. Siakotos et al.

    Procedures for the isolation of lipopigments from brain, heart and liver, and their properties: A review

    Mech. Ageing Dev.

    (1973)
  • B.L. Fletcher et al.

    Measurement of fluorescent lipid peroxidation products in biological systems and tissues

    Anal. Biochem.

    (1973)
  • R. Maeba et al.

    Accumulation of ceroid-like pigments in macrophages cultured with phosphatidylcholine liposomes in vitro

    Biochim. Biophys. Acta

    (1990)
  • R.G. Bridges et al.

    Relationship between age-associated fluorescence and linoleic acid in the housefly Musca domestica

    Insect Biochem.

    (1980)
  • M. Tsuchida et al.

    Lipofuscin and lipofuscin-like substances

    Chem. Phys. Lipids

    (1987)
  • C. Hammer et al.

    Quantification of age pigments (lipofuscin)

    Comp. Biochem. Physiol.

    (1988)
  • A.N. Siakotos et al.

    Procedures for the isolation of two distinct lipopigments from human brain: Lipofuscin and ceroid

    Biochem. Med.

    (1970)
  • H. Shimasaki et al.

    Detection of age-related fluorescent substances in rat tissues

    Arch. Biochem. Biophys.

    (1977)
  • H. Donato et al.

    Age-related changes in lipofuscin-associated fluorescent substances in the adult male housefly, Musca domestica

    Exp. Gerontol.

    (1978)
  • K.D. Munkres et al.

    Ageing of neurospora crassa, VII. Accumulation of fluorescent pigment (lipofuscin) and inhibition of the accumulation by nordihydroguiaretic acid

    Mech. Ageing Dev.

    (1978)
  • J.F. Koster et al.

    Lipid peroxidation of rat liver microsomes

    Biochim. Biophys. Acta

    (1980)
  • R.S. Sohal et al.

    Relationship between fluorescent age pigment, physiological age and physical activity in the housefly, Musca domestica

    Mech. Ageing Dev.

    (1981)
  • D. Yin et al.

    Oxidized ascorbic acid and reaction products between ascorbic and amino acids might constitute part of age pigments

    Mech. Ageing Dev.

    (1991)
  • C. Giulivi et al.

    Dityrosine and tyrosine oxidation products are endogenous markers for the selective proteolysis of oxidatively modified red blood cell hemoglobin by (the 19 S) proteasome

    J. Biol. Chem.

    (1993)
  • G.E. Eldred et al.

    The autofluorescent products of lipid peroxidation may not be lipofuscin-like

    Free Radic. Biol. Med.

    (1989)
  • D. Yin et al.

    Microfluorometric and fluorometric lipofuscin spectral discrepancies: A concentration dependent metachromatic effect?

    Mech. Ageing Dev.

    (1991)
  • B.L. Strehler

    On the histochemistry and ultrastructure of age pigment

  • E.A. Porta et al.

    Lipid pigments in relation to aging and dietary factors

  • U.T. Brunk et al.

    Mechanisms of lipofuscin formation

  • W.M. Treff

    Das Involutionsmuster des Nucleus dentatus cerebelli

  • M. Elleder

    Chemical characterization of age pigment

  • L.S. Wolfe et al.

    Batten disease and related disorders: New findings on the chemistry of the storage material

  • G.E. Eldred et al.

    Retinal age pigments generated by self-assembling lysosomotropic detergents

    Nature

    (1993)
  • A. Hannover

    Mikroskopishe Undersogelser of Nevensystem

    Natturv. Math. Afh. Copenhagen

    (1842)
  • W. Hueck

    Pigmenstudien

    Beitr. Pathol. Anat. Allgem. Pathol.

    (1912)
  • L. Feeney

    Lipofuscin and melanin of human retinal pigment epithelium

    Invest. Ophthalmol. Visual Sci.

    (1978)
  • W.S. Hartroft et al.

    Choline in man

  • Cited by (365)

    View all citing articles on Scopus
    1

    Dr. Dazhong Yin received his B.S. degree in Chemistry in 1983 from Tongji University, Shanghai, People's Republic of China. He then served as a lecturer on the “Analysis of Food and Nutrition” at the Department of Food Science, Yangzhou University, P.R. China. From 1988–1989 he studied the mechanisms of lipid peroxidation as a visiting researcher at the Swedish Institute of Food Research, Gothenburg, Sweden. He then joined the Department of Pathology in Linköping University, Sweden, and received his Ph.D. degree in Medical Science in 1995. Dr. Yin has over 20 original publications. He was a runner-up for the 1993 Walter Nicolai Prize in Biomedical Gerontology and listed in “Who's Who in Science and Engineering 1996–1997.” He is a pioneer of the “Carbonyl-protein crosslinking theory of aging” and is currently seeking a research position in related fields. His research interests include oxygen free radicals, glycation reactions, aging mechanisms and aging-related diseases.

    View full text