Pigments in Aging: An Overview

Abstract

Although during the normal aging process there are numerous pigmentary changes, the best recognized are those of melanin and lipofuscin. Melanin may increase (e.g., age spots, senile lentigo, or melanosis coli) or decrease (e.g., graying of hair or ocular melanin) with age, while lipofuscin (also called age pigment) always increases with age. In fact, the time-dependent accumulation of lipofuscin in lysosomes of postmitotic cells and some stable cells is the most consistent and phylogenetically constant morphologic change of aging. This pigment displays a typical autofluorescence (Ex: approximately 440; Em: approximately 600 nm), sudanophilia, argyrophilia, PAS positiveness, and acid fastness. Advances on its biogenesis, composition, evolution, and lysosomal degradation have been hampered by the persistent confusion between lipofuscin and the large family of ceroid pigments found in a variety of pathological conditions, as evidenced by the frequent use of the hybrid term lipofuscin/ceroid by investigators mainly working with in vitro systems of disputable relevance to in vivo lipofuscinogenesis. While lipofuscin and ceroid pigments may share some of their physicochemical properties at one moment or another in their evolutions, these pigments have different tissue distribution, rates of accumulation, origin of their precursors, and lectin binding affinities. Although it is widely believed that lipofuscin is a marker of oxidative stress, and that it can be, therefore, modified by antioxidants and prooxidants, these assumptions are mainly based on in vitro experiments and are not generally supported by in vivo studies. Another common misconception is the belief that lipofuscin can be extracted from tissues by lipid solvents and measured spectrofluorometrically. These and other disturbing problems are reviewed and discussed in this presentation.

Autophagy, organelles and ageing

“…Such disease-related lipofuscin pigment is occasionally called 'ceroid'. Attempts have been made to distinguish between lipofuscin and ceroid, based on their morphological and physicochemical properties [86,87]. However, due to the variable composition of lysosomal pigment in ageing and different diseases, as well as in different tissues, these attempts seem to have a low practical value, and the distinction between lipofuscin and ceroid is reasonable only from an aetiological viewpoint.…”

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

“…Weak, punctate TR-like autofluorescence (or aldehyde-induced fluorescence) was detected in the bullfrog saccule at elevated laser intensity settings, and in apical coils of 21−28 day old murine cochleae after the vehicle alone was administered (data not shown). This auto-fluorescence was attributed to age-related pigments (lipofuscin) that accumulate in post-mitotic cells, with an emission peak at 600 nm (Porta, 2002).…”

“…Intensity differences between basal and apical cochlear surface preparations of 21−28 day mice were obscured by autofluorescence in apical OHCs, which is attributed to age-related pigments (lipofuscin; emission peak at ∼600 nm) that accumulate in post-mitotic cells (Porta, 2002), close to that of Texas Red. At later time points (>24 h), intensity differences between apical and basal coils were not distinguishable, as with guinea pig cochleae using GTTR or immunoenzymatic methods (Imamura and Adams, 2003a).…”

Lysosome-targeted stress reveals increased stability of lipofuscin-containing lysosomes

“…Such material is collectively called lipofuscin, when age-related, and ceroid when its accumulation is caused by pathological conditions (Porta 2002;Seehafer and Pearce 2006). According to the free-radical theory of ageing (Harman 1956), formation of oxidatively damaged intracellular structures is an inevitable side effect of aerobic life.…”