Lipofuscin

The histopathological features of cutaneous hyperpigmentation in Addison disease have very occasionally been reported, and they include acanthosis, hyperkeratosis, focal parakeratosis, spongiosis, superficial perivascular lymphocytic infiltrate, basal melanin hyperpigmentation, and superficial dermal melanophages. We present a study on 2 biopsies from the arm and the thigh in a 77-year-old woman with a long clinical history of Addison disease as well as senile purpura and alopecia of female pattern. The patient presented diffuse hyperpigmentation of the skin, more pronounced on her face, and left upper forehead...

Romanowsky-Giemsa (RG) stains were devised during the 19th century for identifying plasmodia parasites in blood smears. Later, RG stains became standard procedures for hematology and cytology. Numerous attempts have been made to apply RG staining to formalin-fixed paraffin-embedded tissue sections, with varied success. Most published work on this topic described RG staining methods in which sections were overstained, then subjected to acid differentiation; unfortunately, the differentiation step often caused inconsistent staining outcomes...

A variety of tissue biomolecules and intracellular structures are known to be autofluorescent. However, autofluorescent signals in brain tissues often confound analysis of the fluorescent markers used for immunohistochemistry. While investigating tissue and cellular pathologies induced by 3-nitropropionic acid, a mitochondrial toxin selective for striatal neurons, we encountered many autofluorescent signals confined to the lesion core. These structures were excited by blue (wavelength = 488 nm) and yellow-orange (555 nm), but not by red (639 nm) or violet (405 nm) lasers, indicating that this autofluorescence overlaps with the emission spectra of commonly used fluorophores...

The review considers various aspects of myocardium aging in normal and dilated cardiomyopathy (DC). There is a partial fibrosis of the heart tissue due to accumulation of collagen type 1, and accumulation of amyloid during normal aging. Men myocardial aging is accompanied by loss of cardiomyocytes and increased volume of the remaining cells, whereas in women this effect is absent. There is an expression of nuclear proteins decrease (lamin A and C), the accumulation of lipofuscin, increased content of reactive oxygen species, reduction of protein synthesis Sirt1 in cardiomyocytes with aging...

Purpose: Microaneurysms are present in healthy old-age human retinas. However, to date, no age-related pathogenic mechanism has been implicated in their formation. Here, cellular senescence, a hallmark of aging and several age-related diseases, has been analyzed in the old-age human retina and in the retina of a progeric mouse. Methods: Retinas were obtained from 17 nondiabetic donors and from mice deficient in Bmi1. Cellular senescence was analyzed by immunohistochemistry, senescent-associated β-galactosidase activity assay, Sudan black B staining, conventional transmission electron microscopy, and immunoelectronmicroscopy...

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Age-related macular degeneration (AMD), the most important cause of vision loss in elderly people, is a degenerative disorder of the central retina with a multifactorial etiopathology. AMD is classified in dry AMD (d-AMD) or neovascular AMD depending on the presence of choroidal neovascularization. Currently, no therapy is approved for geographic atrophy, the late form of d-AMD, because no treatment can restore the damage of retinal pigment epithelium (RPE) or photoreceptors. For this reason, all treatment approaches in d-AMD are only likely to prevent and slow down the progression of existing atrophy...

Oxidative stress causes significant increases in both cholesterol uptake and intracellular accumulation of the aging biomarker lipofuscin. Here we show that HPβCD addition mitigates these adverse effects in human fibroblasts by significantly reducing LDLr and SREBP1 gene expression. In the absence of oxidative stress, HPβCD addition induces a paradoxical response, increasing cholesterol accumulation (but not lipofuscin) via upregulation of cholesterol biosynthesis. These two distinct, but opposite effects highlight a previously overlooked therapeutic consideration: the cholesterol content of the treated cell determines which cholesterol pathways, either beneficial or harmful, are responsive to HPβCD...

Retinal pigment epithelium (RPE) cells take part in retinal preservation, such as phagocytizing the shed photoreceptor outer segments (POS), every day. The incomplete phagocytic function accelerates RPE degeneration and formation of the toxic by-product lipofuscin. Excessive lipofuscin accumulation is characteristic of various blinding diseases in the human eye. Progranulin is a cysteine-rich protein that has multiple biological activities, and it has a high presence in the retina. Progranulin has been recognized to be involved in macrophage phagocytosis in the brain...

Discoloration are symptoms of skin aging. They are connected with presence of melanin and lipofuscin, whose excess and abnormal distribution in the skin cause dark spots to appear. Melanin is formed under the influence of tyrosinase during melanogenesis. Its content changes with age, which may be a result of menopause. Lipofuscin is another example of the age pigment. It is composed of proteins, lipids and carbohydrates. It is described as an age pigment because its content increases with age. The formation and accumulation of lipofuscin is inevitable and leads to cell and homeostasis dysfunction because it reduces the proteasome activity...

Age-related macular degeneration (AMD) is the major cause of blindness in developed nations. AMD is characterized by retinal pigmented epithelial (RPE) cell dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate important contributions of dietary patterns to the risk for AMD, but the mechanisms relating diet to disease remain unclear. Here we investigate the effect on AMD of isocaloric diets that differ only in the type of dietary carbohydrate in a wild-type aged-mouse model. The consumption of a high-glycemia (HG) diet resulted in many AMD features (AMDf), including RPE hypopigmentation and atrophy, lipofuscin accumulation, and photoreceptor degeneration, whereas consumption of the lower-glycemia (LG) diet did not...

Convallatoxin is widely used as a cardiac glycoside in acute and chronic congestive heart-failure and paroxysmal tachycardia, with many effects and underlying protective mechanisms on inflammation and cellular proliferation. However, convallatoxin has not been investigated in its antioxidant effects and lifespan extension in Caenorhabditis elegans. In this study, we found that convallatoxin (20 μM) could significantly prolong the lifespan of wild-type C. elegans up to 16.3% through daf-16, but not sir-2.1 signaling and increased thermotolerance and resistance to paraquat-induced oxidative stress...

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. The two types of AMD are: dry and wet AMD. While laser-induced choroidal neovascularization has been used extensively in the studies of wet AMD, there is no established mouse model that fully recapitulates the cardinal features of dry AMD. A lack of appropriate mouse model for dry AMD has hampered the translational research on the pathogenesis of the disease and the development of therapeutic agents. We hypothesized that 5XFAD mice, an animal model for the study of Alzheimer's disease, can be used as a mouse model for dry AMD with regard to the amyloid beta (Aβ) related pathology...

The impact of dispersed crude oil and dispersant on adult Pacific oysters, Crassostrea gigas, was evaluated through an integrative biomarker approach including (1) biochemical (plasma catecholase- and laccase-type phenoloxidase and superoxide dismutase), (2) histological (digestive cell lysosomal responses, digestive gland histopathology) and (3) physiological (flesh condition index) endpoints in the haemolymph and digestive gland. Adult oysters were exposed to non-contaminated water (control), chemically-dispersed oil (Brut Arabian Light), mechanically-dispersed oil and dispersant (FINASOL®) alone for 2days, and further depurated in non-contaminated water for 4weeks...

Pollution with heavy metals may influence the immune system of fish, leading to impairment of their health or even increase their mortality. The fish kidney is one of the first fish organs to be affected by water contamination. Amounts of kidney macrophages (MACs), which are involved in fish immune response, as well as the qualitative and quantitative changes in the pigmented MACs in fish kidney, are used as biomarkers of pollution. Therefore, in this study, we have evaluated relative and total volumes of trunk kidney pigmented MACs, and analyzed the pigments accumulated within them...

Studies show that a decrease in protein kinase CK2 (CK2) activity is associated with cellular senescence. However, the role of CK2 in organism aging is still poorly understood. Here, we investigated whether protein kinase CK2 (CK2) modulated longevity in Caenorhabditis elegans. CK2 activity decreased with advancing age in the worms. Knockdown of kin-10 (the ortholog of CK2β) led to a short lifespan phenotype and induced age-related biomarkers, including retardation of locomotion, decreased pharyngeal pumping rate, increased lipofuscin accumulation, and reduced resistance to heat and oxidative stress...

Gangliosides (sialylated glycolipids) play an essential role in the CNS by regulating recognition and signaling in neurons. Metabolic blocks in processing and catabolism of gangliosides result in the development of severe neurologic disorders, including gangliosidoses manifesting with neurodegeneration and neuroinflammation. We demonstrate that 2 mammalian enzymes, neuraminidases 3 and 4, play important roles in catabolic processing of brain gangliosides by cleaving terminal sialic acid residues in their glycan chains...

This study aimed at evaluating the environmental quality of a coastal lagoon (Pialassa Piomboni, NW-Adriatic, Italy) by combining analyses of biomarkers of environmental stress and bioaccumulation of contaminants in marine mussels (Mytilus galloprovincialis) transplanted for 28days to six selected sites. Assessed biomarkers encompassed lysosomal endpoints, oxidative stress and detoxification parameters, specific responses to metals, neuro- and genotoxic substances; chemical analyses focused on PAHs, metals, pesticide and pharmaceuticals...

Age-related macular degeneration (AMD) leads to progressive loss of central vision in the elderly. At a cellular level, there is aging of the retinal pigment epithelial (RPE) cells, and accumulation of lipofuscin that interferes with the proper functioning of RPE which eventually leads to apoptosis. Treatment depends on the stage of the disease. Wet AMD which has neovascularization is managed by local therapies such as laser photocoagulation and photodynamic therapy and is managed with injections of antivascular endothelial growth factor-based therapy...

Two of the most studied and widely accepted conjectures on possible aging mechanisms are the oxidative stress hypothesis and the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway. Intermittent fasting (IF) is known to modulate aging and to prolong lifespan in a variety of organisms, but the mechanisms are still under debate. In this study, we first demonstrated that late-onset two consecutive days a week fasting, a form of IF, termed intermittent food restriction (IFR), exhibited a time-dependent effect, and long-term late-onset IFR extended the mean lifespan and maximum lifespan by approximately 3...