Amount Of Lipofuscin Research Articles

V1a Vasopressin Receptor Deficient Mice as a Model for Accelerated Aging

Deposition of age-related fluorescent pigment in tissues was initially discovered by A. Hanover in 1842 and the pigments were subsequently called lipofuscin by W. Hueck in 1912 and M. Borst in 1922. It has been known for decades that the lipofuscin is found in several aged organs such as the eyes, brain and adrenal cortex of humans and rodents. However, how these normal aging processes proceed is not known. In a preliminary study, we found that in the adrenal gland of V1a vasopressin receptor-deficient mice (V1aKO), more lipofuscin deposits were accumulated with age compared with wild-type (WT) mice. To quantitatively examine lipofuscin deposits, we have collected 60 adrenal glands from V1aKO and WT mice of both sexes at 2, 6 and 12 months of age. The sections were stained to visualize nucleus and plasma membrane and examined by using confocal microscope. We found lipofuscin fluorescent signals in the adrenal gland of both V1aKO and WT mice. However, the amount of lipofuscin in V1a-deficient adrenal gland was significantly increased compared with the adrenal gland of WT mice in both sexes at all ages. In particular, at 6 month of age, lipofuscin deposition in WT and V1aKO males occupied 3.9 and 5.6 % of entire adrenal cortex areas. Also, we found that lipofuscin accumulation started in the cytoplasm. The mechanism of an increase in this deposit formation, especially its relationship to the V1a receptor, needs to be further examined.

Idiosyncratic liver pigment alterations of five frog species in response to contrasting land use patterns in the Brazilian Cerrado.

BackgroundChanges in land use trigger environmental changes that can lead to decreased biodiversity and species loss. The liver is an essential detoxification organ that reflects systemic physiological responses to environmental changes. Here, we tested whether contrasting land use patterns influence the amount of substances from the hepatic cellular catabolism and melanomacrophages (MMs) of five anuran species in the Brazilian Cerrado.MethodsWe collected the same five species of pond-dwelling frogs in one protected area and in an area with intense agricultural activity. We used routine histological and histochemical techniques to quantify the area occupied by lipofuscin, melanin, and hemosiderin in the liver of two frogs Leptodactylus fuscus, Physalaemus cuvieri, and three tree-frogs Dendropsophus minutus, Scinax fuscomarginatus, and Boana albopunctata. We classified land use types in a buffer around each pond based on satellite images. We then used a double-constrained Correspondence Analysis, a recently developed ecological method to relate functional traits to environmental variables, to test the effect of each land use type on the area of each liver pigment.ResultsThere was an increase in the amount of melanin in environments with high proportion of agriculture, as well as variation in the amount of lipofuscin and hemosiderin. Liver pigments of P. cuvieri and B. albopunctata varied more strongly in response to land use types, suggesting they could be good indicator species. Therefore, the area of MMs in the liver and the metabolic products in their cytoplasm can be used as biomarkers of environmental changes in regions with intense agricultural activities. Our results add a new perspective to the influence of land use patterns on environmental health by highlighting the effect of environmental changes on internal morphological aspects of animals.

Mitochondrial Lipofuscin and Thermomitochondrial Lipofuscin in Homogenates of Rat Organs

Abstract—The amounts of lipofuscin (age pigment) were compared in four organs of rats: the liver, the kidney, the heart muscle, and the brain, as well as in a suspension of ghosts of hepatic mitochondria. It was shown that liver lipofuscin, which absorbs UV light at 360 nm and fluoresces at 460 nm, is predominantly formed due to mitochondrial processes. The lowest lipofuscin content was observed in the heart muscle; in the other organs studied, the levels of lipofuscin calculated per mg of protein were approximately the same. The spectral data and the lifetime of the excited state suggest that a considerable contribution to the fluorescence of lipofuscin in various organs belongs to mitochondrial lipofuscin. Along with lipofuscin, a fluorescent pigment, all organs were shown to contain non-fluorescent protein aggregates: their level was the highest in the heart muscle and the lowest in the liver. Among them, a significant portion were covalently cross-linked aggregates that were not destroyed by detergent treatment. Moderate heating of the organ homogenates caused the formation of thermolipofuscin. The level of thermolipofuscin production was the highest in the brain and the lowest in the heart. Apparently, a significant portion of the thermolipofuscin that formed in organ homogenates was thermomitochondrial lipofuscin from the membranes of damaged mitochondria. The formation of thermolipofuscin strongly involved aromatic residues: tyrosine and tryptophan.

Visible-light optical coherence tomography-based multimodal system for quantitative fundus autofluorescence imaging.

Quantitative fundus autofluorescence imaging with simultaneous visible-light optical coherence tomography-based multimodal technology has potential significant impact on the diagnosis and monitoring the progression of retinal diseases.

Identification of Atypical Peri-Nuclear Multivesicular Bodies in Oxidative and Glycolytic Skeletal Muscle of Aged and Pompe's Disease Mouse Models.

Muscle wasting that occurs during aging or from disease pathology presents with an accumulation of lipid species termed ceroid or lipofuscin. This unique species of lipid has been characterized in various cell types but its properties and organization in skeletal muscle remains unclear. Using immunofluorescence and transmission electron microscopy, we were able to visualize and characterize an atypical lipid storing organelle in skeletal muscle. White myofibers contain two organelles at each pole of the myonuclei and red myofibers contain many of these structures in and around the perinuclear space. These organelles contain markers for late endosomes, are morphologically similar to multivesicular bodies, store lipid, and hypertrophy in aged muscle and a model of muscle wasting with an accumulation of large amounts of lipofuscin. Rapamycin treatment reduces the multivesicular body hypertrophy, restores late endosomal protein markers, and also increases the number and intensity of lipofuscin deposits. Together, these data demonstrate for the first time a perinuclear organelle in skeletal muscle that hypertrophies in muscle wasting phenotypes and is involved in endocytic lipid storage.

Effects of chronic malnourishment and aging on the ultrastructure of pyramidal cells of the dorsal hippocampus

Objectives: Malnourishment (M) produces permanent alterations during the development of the CNS and might modify the aging process. In pyramidal neurons (PN) of the hippocampus, which are associated with learning and memory performance, few studies have focused on changes at the subcellular level under chronic malnutrition (ChM) in young (Y, 2 months old) and aged (A, 22 months old) rats. The present work evaluated the extent to which ChM disrupts organelles in PN of the dorsal hippocampus CA1 as compared to controls (C).Methods: Ultrastructural analysis was performed at 8000× and 20 000× magnification: Nucleus eccentricity and somatic, cytoplasmic, and nuclear areas were measured; and in the PN perikaryon, density indices (number of organelles/cytoplasmic area) of Golgi membrane systems (GMS, normal, and swollen), mitochondria (normal and abnormal), and vacuolated organelles (lysosomes, lipofuscin granules, and multivesicular bodies (MVB)) were determined.Results: The density of abnormal mitochondria, swollen GMS, and MVB increased significantly in the AChM group compared to the other groups. The amount of lipofuscin was significantly greater in the AChM than in the YChM groups – a sign of oxidative stress due to malnutrition and aging; however, in Y animals, ChM showed no effect on organelle density or the cytoplasmic area. An increased density of lysosomes as well as nucleus eccentricity was observed in the AC group, which also showed an increase in the cytoplasmic area.Discussion: Malnutrition produces subcellular alterations in vulnerable hippocampal pyramidal cells, and these alterations may provide an explanation for the previously reported deficient performance of malnourished animals in a spatial memory task in which aging and malnutrition were shown to impede the maintenance of long-term memory.

Lipofuscin Quantification as a Potential Tool for Age Estimation in Snow Crabs,Chionoecetes opilio (O. Fabricius, 1788) (Decapoda, Oregoniidae)

AbstractLipofuscin levels were investigated in snow crabs (Chionoecetes opilio) to assess the applicability of lipofuscin quantification as an age determining tool for this species. Localization and quantification of lipofuscin granules in the olfactory lobe cell mass (OLCM) of the brain were conducted by confocal microscopy and image analysis. The majority of immature crabs had no detectable lipofuscin. Crabs with a dirty carapace condition (an indication of greater age) had more lipofuscin (in terms of granule density, area fraction, and mean granule size) than crabs with a clean carapace condition; however, the amount of lipofuscin was much lower than that in more temperate species. Lipofuscin content was positively correlated with carapace size among crabs with a clean carapace but not among crabs with a dirty carapace. No correlation was observed between average lipofuscin granule fluorescent intensity and carapace width. OLCM neuron characteristics were also investigated. An inverse relationship was observed between neuron density and carapace width although it is unknown if this density reduction is due to a loss of neurons, an increase in size of the structures, or both. Furthermore, a positive relationship was observed between neuron size and carapace width. The range of neuron size also increased in larger crabs, suggesting the presence of mitotically active cells in the OLCM. Although lipofuscin levels were higher in dirty carapace condition (presumably older) crabs than in clean carapace crabs and increased with size (in mature, clean carapace snow crabs), the lack of detectable lipofuscin in most immature crabs, generally low levels of lipofuscin in mature crabs, and lack of increase with size in older (dirty carapace) crabs limits the applicability of this age estimation tool for this species.

Changes in fundus autofluorescence of choroidal melanomas following treatment

We have previously shown that fundus autofluorescence (FAF) associated with pigmented choroidal lesions can be attributed to mainly lipofuscin (orange pigment) but also to hyperpigmentation, drusen, or fibrous metaplasia. The purpose of this study is to describe the effects of treatment on FAF in choroidal melanomas after plaque radiotherapy alone or in combination with transpupillary thermotherapy (TTT). Retrospective chart review of eight consecutive patients with choroidal melanoma treated with plaque radiotherapy alone or in combination with TTT who underwent FAF photography before and after treatment. The correlation between FAF patterns and foci of orange pigment, hyperpigmentation, drusen, or fibrous metaplasia was evaluated. The median follow-up time was 4 (range 2-9) months. Foci of orange pigment and hyperpigmentation became larger and more numerous after treatment. Fibrous metaplasia was also increased. A complete correlation between increased FAF and orange pigment was found in all eight tumours (100%) before and after treatment. No correlation between hyperpigmentation and increased FAF was found before treatment but a partial correlation was found in all eyes after treatment. Before treatment, correlation between fibrous metaplasia was present in three eyes and increased FAF was partial in two eyes with no correlation in one case. After treatment, this correlation was partial in all presenting eyes (7). Following treatment, choroidal melanomas may show increased FAF, mainly due to an increase in the amount of lipofuscin (orange pigment) and hyperpigmentation.

Age-related structural and neurochemical changes of the human superior cervical ganglion

The aim of this study was to investigate age-related morphological and neurochemical changes in the human superior cervical ganglion (SCG). Thirty-seven superior sympathetic human cervical ganglia of young, adult, and aged subjects were examined using morphometric analysis, biotin-streptavidin immunohistochemistry for detecting neurofilament, myelin protein, protein gene product 9.5, nerve growth factor receptor p75 in sympathetic neurons and nerve fibers. Morphometric parameters of neurons (area, long and short axis, shape factor of the neuron body, nucleus, cytoplasm, and lipofuscin) were investigated in every sixth serial section of the ganglion. Seven hundred neurons with clearly visible nuclei were measured in each studied group. The present study showed that human SCG of older subjects had larger areas of neuron body, cytoplasm and nucleus, a lower shape factor, an increased amount of lipofuscin, and a greater number of large-size neurons, as compared to SCG obtained from young subjects. Neuronal cytoskeletal alterations manifested themselves through a decreased number of neurofilament-positive neurons were detected in old human SCG. The amount of myelinated fibers decreased with age, although the amount of myelinated fibers in the young and the adult subjects varied from few to a moderate number. PGP 9.5 immunoreactivity varied in different age groups. A marked reduction of nerve growth factor receptor p75 in old human sympathetic neurons was detected. In conclusion, the findings of this study confirm age-related morphological changes in the human SCG. Structural neuronal changes may influence the deterioration of neuronal functional capacity, neuronal plasticity, and regenerative characteristics.

Growing cells at 40% ambient oxygen conditions them to subsequent oxidative stress

Sirs, Although the influence of lipofuscin on cells and lysosomes is debated, it is considered to be either insignificant or damaging (reviewed in Terman et al. 2007; Kurz et al. in press; Brunk and Terman 2002). Recently, however, a paper (Stroikin et al. 2007) was published in Biogerontology that attributed to lipofuscin a new and stabilizing effect on lysosomes of starved fibroblasts. In that study it was concluded that lipofuscin in moderate amounts renders cells more, not less, resistant to starvation. Unfortunately, the experimental design does not seem to justify such conclusions. The cellular amount of lipofuscin was varied by growing cells for prolonged periods of time (months) at either 8% or 40% ambient oxygen, being an established method to restrict or enhance, respectively, lipofuscin formation (reviewed in Brunk and Terman 2002). The cellular response to oxidative stress, induced by starvation (Gaspar et al. 2006; Morales et al. 2004; Eisler et al. 2004), was then compared on the two groups of cells. However, growing cells at 40% oxygen also means exposing them to a condition of moderate oxidative stress and thereby preconditioning them to, and protecting them from, a later, more marked oxidative stress. This fact is described in relevant literature (Spitz et al. 1987; Tang et al. 2005; Fonager et al. 2002). In contrast, this is not the case for cells that have been grown at 8% oxygen before an ensuing oxidative stress. Therefore, the two groups in the study (Stroikin et al. 2007) were not directly comparable when they were exposed to starvation. Consequently, the observation that lipofuscinladen cells appeared more resistant to oxidative stress than non-lipofuscin-laden ones may not be attributable to the lipofuscin per se but, rather, to the fact that one of the groups had been conditioned by exposure to an elevated concentration of oxygen. No control experiments were done to rule out this objection, and in the absence of such controls it is not possible to draw the conclusions made in the paper (Stroikin et al. 2007). Given that the consequences of lipofuscin accumulation are potentially important for our understanding of the mechanisms behind postmitotic ageing, solid experimental data on these matters are needed. Therefore, it would be most interesting if the authors repeated their experiments with correctly matched controls. For example, cells moved from 8% to 40% oxygen for a few days before starvation would be preconditioned to the ensuing stress without becoming significantly more lipofuscin-laden. U. T. Brunk (&) Division of Pharmacology, Faculty of Health Sciences, Linkoping University, Linkoping 581 85, Sweden e-mail: ulf.brunk@imv.liu.se

A HISTOLOGICAL STUDY OF THE AGE-PIGMENT, LIPOFUSCIN, IN DENDROBRANCHIATE SHRIMP BRAINS

The presence, distribution, and histological features of lipofuscin granules were investigated in brains of the dendrobranchiate decapods Marsupenaeus japonicus Bate, 1888, Melicertus kerathurus (Forskal, 1775), Parapenaeus longirostris (Lucas, 1846) (family Penaeidae), and Aristeus antennatus (Risso, 1816) (family Aristeidae). Autofluorescent lipofuscin granules were prominent in wax sections of olfactory-lobe cell masses (OLCMs) of all the species but P. longirostris, in which the pigment granules could be distinctly identified only in histological sections of samples embedded in resin. Although quantification was not carried out in this study, the amount of lipofuscin was visibly higher in larger and older individuals. Lipofuscin granules are secondary lysosomes of heterogeneous content that derive from autophagic vacuoles. In samples treated for electron microscopy, cytoplasmic inclusions assumed to be lipofuscin granules stained positive with Sudan Black B, whereas all brains processed for light microscopy (embedded in either paraffin wax or resin) were Sudan Black B negative. No acid phosphatase activity was evidenced cytochemically in lipofuscin granules of M. japonicus OLCMs. The variable histochemical properties of lipofuscins suggest that, as has been shown previously for other decapods, the most accurate method for localization and quantification of the age-pigment in dendrobranchiates is the one based on autofluorescence. This technique is thought to be valuable in assessment of the age structure of shrimp natural stocks.

Lipofuscin accumulation in cultured retinal pigment epithelial cells reduces their phagocytic capacity

Purpose. Retinal pigment epithelial (RPE) cells slowly accumulate lipofuscin pigment within their acidic vacuolar apparatus as a result of extra- and/or intralysosomal oxidative alterations of phagocytosed photoreceptor outer segments (POS) with consequent imperfect degradation of these structures. In old age, lipofuscin accumulation may become quite substantial. It has been suggested that pronounced accumulation of lipofuscin is related to decreased RPE function and, possibly, to age-related macular degeneration. The aim of the present investigation was to study whether heavy loading with lipofuscin of RPE acidic lysosomes would affect the further phagocytic ability of the cells.Methods. In the first section of the investigation, cultures of rabbit RPE cells were exposed daily to bovine UV-irradiated POS (artificial lipofuscin) for 4 weeks, resulting in a pronounced lipofuscin accumulation of the cells. Fluorescent latex beads (labelled with a red fluorophore) were added to unloaded control cultures at 0 and 4 weeks after their establishment, and to lipofuscin loaded cells after 4 weeks of feeding with artificial lipofuscin. Cellular amounts of lipofuscin, and their phagocytotic activity, were quantified by static fluorometry measuring lipofuscin-specific and red bead-specific fluorescence, respectively. The intracellular location of the beads was verified by confocal laser scanning microscopy.Results. Unloaded, and thus almost lipofuscin-free, control cells exposed to latex beads showed numerous cytoplasmic particles emitting reddish fluorescence, while few particles were taken up by cells initially loaded with artificial, POS-derived, lipofuscin. Measurement of the latex bead-specific fluorescence showed significantly (p < 0.001) higher levels in unloaded control cells than in lipofuscin-loaded ones.In the second part of the investigation, unloaded control cultures and lipofuscin-loaded cultures were exposed to native bovine Texas Red-X-labelled POS 4 weeks after the establishment of the cultures. Unloaded control cells showed a large number of cytopiasmic POS emitting reddish fluorescence, while fewer POS were phagocytosed by cells loaded with artificial lipofuscin. Measurement of the Texas Red-X-specific fluorescence, thus quantifying the phagocytic ability of the cells, showed significantly (p < 0.001) higher levels in control cells than in lipofuscin-loaded ones.Conclusions. Severe lipofuscin accumulation of RPE cells appears to result in a greatly decreased phagocytic capacity. The resulting reduction in ability to cope with the needs of the overlying photoreceptor cells, in order to eliminate the obsolete tips of their POS, may well be of significance in the development of age-related macular degeneration. Curr. Eye Res. 17:851–857, 1998.

Reduced Intraneuronal Lipofuscin Content in Dementia with Lewy Bodies Compared with Alzheimer’s Disease and Controls

Lipofuscin has been of interest in dementia of Alzheimer’s type (DAT), because of the hypothesis that dementia is a kind of premature ageing. The results of studies on intraneuronal lipofuscin content in DAT are inconsistent. At present no data on intraneuronal lipofuscin in dementia with Lewy bodies (DLB) are available. The amount of lipofuscin in the neurons of the inferior olivary nucleus of 10 brains of DLB patients, 10 of age-matched DAT patients, and 10 of age-matched controls has been measured microfluorometrically. The intraneuronal lipofuscin content in the DLB patients was significantly lower than in the DAT patients and controls. This finding may indicate a general alteration of neuronal cell metabolism in DLB, e.g. a defect of mitochondrial DNA, not confined to neurons developing Lewy bodies.

Ultrastructural differences of hippocampal lipofuscin in human development

The lipofuscin of pyramidal cells in each hippocampal subfield of each of seven human autopsy cases without brain disease at the age of 3–12 months (infants) and of 17–23 years (young adults) was comparatively investigated at the electron microscopic level. In infant pyramidal neurons of the hippocampal subfields CA 1, CA 2, CA 3 and CA 4 O-2, very small lipofuscin particles were observed. The lipofuscin composition showed a slightly larger granular component compared to the vacuolar component with one or two small lipid droplets. No obvious ultrastructural variability of lipofuscin granules was observed. The CA 1 lipofuscin in young adults consists of larger particles than in infants, but no obvious difference in the composition of granular and vacuolar components from the infant lipofuscin was seen. The amount of lipofuscin in CA 1 strongly increased in young adults compared to infants and appeared in a perinuclear distribution. In young adults, in contrast to the infant group, the amount of lipofuscin in the subfields CA 2, CA 3 and CA 4 was significantly higher than in CA 1. In CA 2, CA 3 and CA 4 pyramidal neurons, the vacuolar component was significantly larger than the granular component. The similarity of infant hippocampal lipofuscin patterns in all subfields is discussed as a state of immaturity. To explain the observed differences between the CA 1 and the other subfields during neuronal development, as shown in the young adult group, several factors are discussed: the effects of cell specific metabolism, cellular functional activity, cytoprotective mechanisms and effects of efferent and afferent pathways connected with the subfields.

Changes in cathepsin B and lipofuscin during development and aging in rat brain and heart.

While results with inhibitors of thiol proteases have led to the suggestion that the progressive increase with age of lipofuscin in post-mitotic and some stable cells may be due to an age-related decline in the activity of these enzymes (Ivy et al., 1989), no direct evidence has been yet presented to support this hypothesis. In this study Wistar female rats were killed at age of 5, 14, and 24 months and the amounts of lipofuscin were histologically quantitated in neurons of the left cerebral parietal cortex and in cardiac myocytes of left ventricle. The sites of cathepsin B activity histochemically detected were quantitated in sections from left cerebral parietal cortex and left ventricle, and the activity of this enzyme was also measured biochemically in brain and heart homogenates. In line with previous findings, the amounts of lipofuscin in neurons and cardiac myocytes increased linearly during development and aging (from 5 to 14 and from 14 to 24 mo.). The sites of cathepsin B activity histochemically detected in sections from cerebral cortex significantly increased from 5 to 14 mo., but remained unchanged from 14 to 24 mo, while in sections from the left cardiac ventricle these sites of activity remained unchanged during development, and significantly increased during aging. On the other hand the biochemically determined activities of cathepsin B in brain and heart homogenates remained unchanged from 5 to 14 mo., but significantly decreased from 14 to 24 mo. These results suggest that the increase in lipofuscin with age may not be due to an age-wise decline in cathepsin B activity.

The lipofuscin content of nerve cells of the inferior olivary nucleus in Alzheimer's disease.

Lipofuscin, the age pigment, is of interest in Alzheimer's disease because of its property to accumulate in neurons and because of the hypothesis that Alzheimer's dementia is a kind of premature ageing. The amount of intraneuronal lipofuscin in the inferior olivary nucleus of 20 brains from patients with histologically confirmed Alzheimer's disease according to the CERAD protocol and of 20 controls has been measured microfluorometrically. Patients and controls were matched for age. The amount of lipofuscin in the neurons of the inferior olivary nucleus did not differ significantly between the cases of Alzheimer's disease and the controls. The result is discussed taking the findings of previous authors into account. We conclude that there is no evidence that lipofuscin plays an important role in the pathogenesis of Alzheimer's disease.

Ultrastructural morphometric analysis of lipofuscin in pyramidal cells of the human Ammon's horn

Lipofuscin is a waste product of autolysosomal metabolism. The amount of lipofuscin in the cytoplasm depends on cell type, cell function and age. In most studies, either the fluorescent or the stained component of lipofuscin was investigated. Quantitative morphological investigations of the lipofuscin composition separated into the vacuolar and granular component were missing. For the hippocampal pyramidal cells we have determined the lipofuscin quantity and, separately, the vacuolar and granular component at the ultrastructural level. The hippocampal subfields CA 1, CA 2, CA 3 and CA 4 were observed at the ages 20, 40, 60 and 80 years (±3 years). Quantitative determinations of the vacuolar and granular component of neuronal lipofuscin in pyramidal cells were performed with a semi-automatic image analysis system. In CA 1 pyramidal cells the lipofuscin content was significantly lower than in the other sectors, which did not differ significantly in their lipofuscin content. The amount of the granular component in relation to the vacuolar component in CA 1 was larger than in the other sectors. With advancing age the lipofuscin content per cell increased. The vacuolar component of all hippocampal subfields experienced a larger increase than the granular component. Consequently the relation of the vacuolar and granular component changed; the relative amount of the vacuolar component increased, while that of the granular component decreased with age. The differences between sector CA 1 and the other hippocampal subfields were discussed with reference to differences of metabolic and functional activity of the neurons. Cytoprotective factors like Calbindin D28k were discussed for CA 1.

Quantitative analysis of lipofuscin and neurofibrillary tangles in the hippocampal neurons of Alzheimer disease brains.

Using computer-enhanced image analysis, the amount of lipofuscin was measured in 500 hippocampal pyramidal neurons (regions CA2 and CA3) with and without neurofibrillary tangles (NFT), in brains of 10 patients with Alzheimer's disease (AD), as well as in 6 age-matched controls. The average content of lipofuscin in those cells from AD brains carrying NFT is only 10% of the total perikaryal area, whereas in the AD neurons free of NFT, and in age matched controls, lipofuscin amounted to 31 and 33% of cellular area, respectively. Measurements of lipofuscin's intrinsic autofluorescence confirmed this material to be three times more abundant in AD neurons without NFT and in controls. We propose that a breakdown in the capacity for making lipofuscin may result in the neuronal inability to store toxic waste. Such a defect could be responsible for the generation of NFT and ultimately may contribute to neuronal demise.

Unusual Pigmented Vesical Lesion in a Middle-Aged Woman

Excess lipofuscin deposition in tissues is a phenomenon observed in normal aging. The amount of lipofuscin in myocardium, liver, skeletal muscle, and adnexal skin structures varies considerably with age and increases in older individuals. In addition, lipofuscin deposition occurs in association with specific, non-age-related processes; these include melanosis coli, the so-called brown bowel syndrome, and the black thyroid. Localized lipofuscinosis has also been described in the gallbladder, esophagus, and fallopian tubes. The present article adds lipofuscinosis vesicalis to the list of entities characterized by focal lipofuscin deposition. All cases have a characteristic gross appearance that is somewhat variable from entity to entity and in some cases may suggest clinically an ominous pathologic process.

Ultrastructural features of neurons in the C57BL/6J mouse anteroventral cochlear nucleus: Young mice versus old mice with chronic presbycusis

Transmission electron microscopy was used to examine “bushy” and “multipolar” neurons in the anteroventral cochlear nucleus (AVCN) of young (2-month-old) and old (2-year-old) C57BL/6J mice, a strain that develops profound peripheral sensorineural auditory impairment during the second year of life. Two features differed with age irrespective of cell type or location within the AVCN: there was an increase in the incidence of neurons with heterochromatic nuclei and an increase in the percent of the neuron occupied by lipofuscin. Two features differed with age in multipolar cells only: there was a decrease in the roundness of nuclei and an increase in the number of nuclear invaginations. Some features differed with age to a greater extent in the dorsal portion of the AVCN: there were decreases in the length of terminals on bushy cells, and in the percentage of soma surface apposed by terminals, and increases in the incidence of neurons contacted by myelinated axons, in mean synaptic vesicle density, and in the amount of lipofuscin in bushy cells. Some features did not differ with age: the mean area of mitochondria, percentage of cytoplasm occupied by mitochondria, size of dense synaptic junctions, and for bushy cells only, nuclear shape and invaginations and width of perinuclear cisternae. Aging per se, chronic presbycusis, and neuronal type play roles in determining age-related changes in AVCN neurons.