Biochemical Significance of Age Pigment in Neurones

Abstract

The progressive intracellular accumulation of age pigment or lipofuscin granules in non-dividing cells is generally taken as one hallmark of cellular aging. The relationships of the intracellular lipofuscin concentration with the reduction of cellular efficiency in senescent tissues is not clear. In fact, there has been very little speculation, let alone solid evidence, on how these accumulating lipofuscin bodies interfere with and/or alter the metabolic economy of the aging cell. The presence of lipofuscin granules in the central nervous system of very young children or newborn infants has been, at times, in dispute. The reason for this uncertainty is not clear. It may on the one hand be due to the lack of specificity of histological techniques employed to detect lipofuscin or, on the other, to the extraction of the early lipid-rich precursors of age pigment by the solvents used for the dehydration of tissue specimens. Although the observations on the presence of lipofuscin in brains of children within the first year of life are very few, some authors have observed lipofuscin granules in the spinal cord of human fetuses (Humphrey, 1944 and Chu, 1954). Brody (1960) first reported the absence of lipofuscin in newborn to two month old human brain, but later (Brody, 1974) observed lipofuscin in the inferior olive of a three-month-old child. In his earlier study, Brody (1970) used dioxane dehydration and paraffin embedding in his tissue preparations. As will be pointed out later in this report, the extraction and concentration of trace quantities of lipofuscin by subcellular fractionation techniques is a more efficient technique for the detection of low concentrations of lipofuscin granules and lipofuscin-like particles from large samples of human brain. In any event, the relative paucity of lipofuscin granules in normal human infant brains is apparent in an electron micrograph of cortical biopsy of a 5 year old brain shown in Figure 1. In contrast, two electron micrographs (Figures 2 and 3) of an autopsy specimen of normal human brain of 53 years of age reveals many lipofuscin granules. In Figure 3, the massive intraneuronal accumulation of lipofuscin appears to have displaced normal cellular organelles such as the mitochondria, to the periphery of the cell. In addition, Figure 3 reveals extensive clumping of the rough endoplasmic reticulum. The age-related accumulation of intraneuronal lipofuscin has been well documented in animal studies (Brizzee et al., 1974). In man, large amounts of lipofuscin may accumulate in some neuropathologic conditions, especially Huntington’s Chorea (Telez-Nagel et al., 1973), and Alzheimer’s disease (Wisniewski and Terry, 1973). Similar accumulations may be seen in the brains of patients with long-term epilepsy, possibly secondary to drugs or anoxia, and also in patients with chronic alcoholism (Siakotos, unpublished data).