Lipofuscin Research Articles

Sensitivity of histopathological and histochemical parameters in the digestive gland of the apple snail Pomacea canaliculata exposed to cypermethrin

The aim of this study was to evaluate the toxic effects of the pesticide cypermethrin (CYP) in the digestive gland of the apple snail, Pomacea canaliculata, analysing histological and histochemical alterations. Adult snails were exposed to sublethal CYP concentrations (10, 25, and 100 µg/L) under acute (1 day) and sub-chronic (14 days) conditions. Histological analyses of the morphology of the digestive gland were performed and a histopathological condition index (HI) was calculated. Also, both intracellular accumulation of lipofuscins (LF) and neutral lipids (NL) were evaluated. CYP exposure induced tissue damage to this organ, such as disorganisation of the connective tissue, fibrosis, haemocytic infiltration, atrophy, and necrosis under acute and sub-chronic conditions. These alterations, integrated into a single HI value, revealed notable CYP effects during both acute and sub-chronic exposures. Cell type replacement, measured as VvBAS, was only observed in the sub-chronic treatment. Under acute conditions, the pyrethroid affected NL accumulation at the highest concentration, while in sub-chronic conditions NL accumulation was only observed at the lowest concentrations. P. canaliculata also showed a dose-dependent response of LF under acute CYP exposure conditions. However, under sub-chronic conditions, this parameter was not sensitive to pesticide exposure. All these relevant structural lesions may affect the normal function of the digestive gland, even though the species presented additional mechanisms, as infiltration of hemocyte and basophilic cell hyperplasia, that help it to tolerate the exposure to pollutants. This study showed that some histological and histochemical parameters are sensitive in P. canaliculata at CYP concentrations to which the snail could be exposed in the environments it inhabits.

Paecilomyces variotii extract increases lifespan and protects against oxidative stress in Caenorhabditis elegans through SKN-1, but not DAF-16

A natural extract from Paecilomyces variotii ( P. variotii extract, PVE), an endophytic fungus, has been used widely to improve agricultural crop performance and control multiple plant pathogens. Most recent studies focused on its application as a plant growth promoter, while relatively few studies have been reported on the antioxidant potential in vivo and the underlying mechanism. The present study was designed to determine the antioxidant activities of PVE and its mechanisms using Caenorhabditis elegans . Results showed that, compared to the solvent control, PVE at 1.0, 10 and 100 ng/mL significantly extended the lifespan of C. elegans by 36.60%, 59.80% and 53.30%, respectively. PVE at 10 ng/mL consistently promoted nematodes growth, but all treatments did not influence nematode fecundity, locomotion behavior, and pharyngeal pumping. Furthermore, PVE at the three tested concentrations significantly reduced accumulation of reactive oxygen species (ROS), lipofuscin, lipid and malondialdehyde (MDA) content, meanwhile significantly promoted activities of superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) in the nematodes. Compared with the solvent control, PVE up-regulated gene expression of skn-1 , mev-1 , sod-3 , and daf-2 , but significantly down-regulated the expression of nhr-49 and daf-16 . Further evidence revealed that PVE at the three concentrations significantly promoted nuclear localization of SKN-1, but not affected that of DAF-16, indicating the complex roles of DAF-16 and SKN-1 in stress resistance and longevity regulation. Overall, our results demonstrated that SKN-1 played a critical role in increasing lifespan of C. elegans and protecting the nematodes from oxidative stress, independent of DAF-16.

Flavonol glycoside complanatoside A requires FOXO/DAF-16, NRF2/SKN-1, and HSF-1 to improve stress resistances and extend the life span of Caenorhabditis elegans.

Aging is associated with the increased risk of most age-related diseases in humans. Complanatoside A (CA) is a flavonoid compound isolated from the herbal medicine Semen Astragali Complanati. CA was reported to have potential anti-inflammatory and anti-oxidative activities. In this study, we investigated whether CA could increase the stress resistance capability and life span of Caenorhabditis elegans. Our results showed that CA could extend the longevity of C. elegans in a dosage-dependent manner, while 50 μM of CA has the best effect and increased the life span of C. elegans by about 16.87%. CA also improved the physiological functions in aging worms, such as enhanced locomotor capacity, and reduced the accumulation of the aging pigment. CA could also reduce the accumulation of toxic proteins (α-synuclein and β-amyloid) and delay the onset of neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease, in models of C. elegans. Further investigation has revealed that CA requires DAF-16/FOXO, SKN-1, and HSF-1 to extend the life span of C. elegans. CA could increase the antioxidation and detoxification activities regulated by transcription factor SKN-1 and the heat resistance by activating HSF-1 that mediated the expression of the chaperone heat shock proteins. Our results suggest that CA is a potential antiaging agent worth further research for its pharmacological mechanism and development for pharmaceutical applications.

TPC2 rescues lysosomal storage in mucolipidosis type IV, Niemann–Pick type C1, and Batten disease

Lysosomes are cell organelles that degrade macromolecules to recycle their components. If lysosomal degradative function is impaired, e.g., due to mutations in lysosomal enzymes or membrane proteins, lysosomal storage diseases (LSDs) can develop. LSDs manifest often with neurodegenerative symptoms, typically starting in early childhood, and going along with a strongly reduced life expectancy and quality of life. We show here that small molecule activation of the Ca2+‐permeable endolysosomal two‐pore channel 2 (TPC2) results in an amelioration of cellular phenotypes associated with LSDs such as cholesterol or lipofuscin accumulation, or the formation of abnormal vacuoles seen by electron microscopy. Rescue effects by TPC2 activation, which promotes lysosomal exocytosis and autophagy, were assessed in mucolipidosis type IV (MLIV), Niemann–Pick type C1, and Batten disease patient fibroblasts, and in neurons derived from newly generated isogenic human iPSC models for MLIV and Batten disease. For in vivo proof of concept, we tested TPC2 activation in the MLIV mouse model. In sum, our data suggest that TPC2 is a promising target for the treatment of different types of LSDs, both in vitro and in‐vivo.

Photobiology of lipofuscin granules in the retinal pigment epithelium cells of the eye: norm, pathology, age.

Lipofuscin granules (LGs) are accumulated in the retinal pigment epithelium (RPE) cells. The progressive LG accumulation can somehow lead to pathology and accelerate the aging process. The review examines composition, spectral properties and photoactivity of LGs isolated from the human cadaver eyes. By use of atomic force microscopy and near-field microscopy, we have revealed the fluorescent heterogeneity of LGs. We have discovered the generation of reactive oxygen species by LGs, and found that LGs and melanolipofuscin granules are capable of photoinduced oxidation of lipids. It was shown that A2E, as the main fluorophore (bisretinoid) of LGs, is much less active as an oxidation photosensitizer than other fluorophores (bisretinoids) of LGs. Photooxidized products of bisretinoids pose a much greater danger to the cell than non-oxidized one. Our studies of the fluorescent properties of LGs and their fluorophores (bisretinoids) showed for the first time that their spectral characteristics change (shift to the short-wavelength region) in pathology and after exposure to ionizing radiation. By recording the fluorescence spectra and fluorescence decay kinetics of oxidized products of LG fluorophores, it is possible to improve the methods of early diagnosis of degenerative diseases. Lipofuscin ("aging pigment") is not an inert "slag". The photoactivity of LGs can pose a significant danger to the RPE cells. Fluorescence characteristics of LGs are a tool to detect early stages of degeneration in the retina and RPE.

The effects of experimental temperature increase on gametogenesis and heat stress parameters in oysters: Comparison of a temperate-introduced species (Crassostrea gigas) and a native tropical species (Crassostrea corteziensis)

The effect of thermal stress during reproduction was experimentally evaluated in the oyster Crassostrea gigas, a temperate species, and in the tropical oyster Crassostrea corteziensis. The temperature was gradually increased (1 °C day−1) from 20 °C to 34 °C for two weeks. As expected, C. gigas was the species most affected by heat stress, with the highest mortality rate (P < 0.05) starting at 28 °C, while mortality in C. corteziensis was significant only at 34 °C. The reproductive effort at higher temperatures was reflected in C. gigas as the highest index of mature oocytes and the largest rate of atresic and degenerated oocytes. C. corteziensis showed significant increases in the proliferation of early-developing oocytes at maximum temperatures. Lipid peroxidation and lipofuscin accumulation significantly increased in both species at maximum temperatures, with levels in C. gigas being 8-fold higher than in C. corteziensis. A significant loss of biomass and glycogen reserves stored in gonads was found in C. gigas at 34 °C. The mRNA signal of Hsp70 was detected in gonadic tissues from both oysters after thermal stress for in situ hybridization (ISH), with a temperature increase in both species; the cover area of Hsp70 was significantly higher in C. gigas during the experiment. Hemocyte infiltration significantly increased with increasing temperature in both oyster species, and apoptosis was strongly correlated with Hsp70 in both species (r = 0.93; P < 0.05). These results could explain the high tolerance that C. corteziensis has to thermal stress compared to C. gigas and could be used to adapt aquaculture strategies to the use of native species in subtropical climates to reduce summer mortality events.

Cardioprotective Effect of Acetylsalicylic Acid in the Myocardial Ischemia-Reperfusion Model on Oxidative Stress Markers Levels in Heart Muscle and Serum.

Heart failure occurs in increased oxidative stress conditions, which contribute to the progression of pathological changes. Orally or intravenously administered acetylsalicylic acid (ASA, aspirin) is typically used in human patients with acute myocardial ischemia. The study used an experimental porcine ischemia-reperfusion model to evaluate the potential cardioprotective effect of intracoronary administered ASA on myocardial ischemia-reperfusion injury. The cardioprotective effect of ASA was evaluated by measuring selected oxidative stress markers levels in infarcted and non-infarcted myocardium 14 days after the procedure, and three times in serum, before the procedure, during the reperfusion process, and after 14-day recovery. The results showed that intracoronary administrated ASA reduced the oxidative stress. The level of oxidative stress, measured with the non-enzymatic markers total antioxidant capacity (TAC), total oxidative status (TOS), and malondialdehyde (MDA), and the enzymatic markers glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST), in heart tissue was significantly higher in a control group injected with saline. The level of oxidative stress in serum, measured with TAC, TOS, oxidative stress index (OSI), and lipofuscin (LF), was also higher in the control group than in animals injected with ASA. The confirmed cardioprotective effect of intracoronary administered ASA provides the foundation for further studies on ASA intracoronary application, which may lead to the development of a new therapy for the treatment of ischemia-reperfusion complications in humans.

Oligosaccharides from agar extends lifespan through activation of unfolded protein response via SIR-2.1 in Caenorhabditis elegans.

Agaro-oligosaccharides (AGO), hydrolysis products of agarose, is known to have antioxidant and anti-inflammatory properties. Speculating that AGO is effective for preventing aging, we investigated the longevity-supporting effects of AGO and their mechanisms using Caenorhabditis elegans. Caenorhabditis elegans were fed AGO from young adulthood. The lifespan, locomotory activity, lipofuscin accumulation, and heat stress resistance of the worms were examined. To elucidate mechanisms of AGO-mediated longevity, we conducted comprehensive expression analysis using microarrays. Moreover, we used quantitative real-time PCR (qRT-PCR) to verify the genes showing differential expression levels. Furthermore, we measured the lifespan of loss-of-function mutants to determine the genes related to AGO-mediated longevity. AGO extended the lifespan of C. elegans, reduced lipofuscin accumulation, and maintained vigorous locomotion. The microarray analysis revealed that the endoplasmic reticulum-unfolded protein response (ER-UPR) and insulin/insulin-like growth factor-1-mediated signaling (IIS) pathway were activated in AGO-fed worms. The qRT-PCR analysis showed that AGO treatment suppressed sir-2.1 expression, which is a negative regulator of ER-UPR. In loss-of-function mutant of sir-2.1, AGO-induced longevity and heat stress resistance were decreased or cancelled completely. Furthermore, the pro-longevity effect of AGO was decreased in loss-of-function mutants of abnormal Dauer formation (daf) -2 and daf-16, which are IIS pathway-related genes. AGO delays the C. elegans aging process and extends their lifespan through the activations of ER-UPR and the IIS pathway.

Vitamin A, systemic T-cells, and the eye: Focus on degenerative retinal disease.

The first discovered vitamin, vitamin A, exists in a range of forms, primarily retinoids and provitamin carotenoids. The bioactive forms of vitamin A, retinol and retinoic acid, have many critical functions in body systems including the eye and immune system. Vitamin A deficiency is associated with dysfunctional immunity, and presents clinically as a characteristic ocular syndrome, xerophthalmia. The immune functions of vitamin A extend to the gut, where microbiome interactions and nutritional retinoids and carotenoids contribute to the balance of T cell differentiation, thereby determining immune status and contributing to inflammatory disease around the whole body. In the eye, degenerative conditions affecting the retina and uvea are influenced by vitamin A. Stargardt’s disease (STGD1; MIM 248200) is characterised by bisretinoid deposits such as lipofuscin, produced by retinal photoreceptors as they use and recycle a vitamin A-derived chromophore. Age-related macular degeneration features comparable retinal deposits, such as drusen featuring lipofuscin accumulation; and is characterised by parainflammatory processes. We hypothesise that local parainflammatory processes secondary to lipofuscin deposition in the retina are mediated by T cells interacting with dietary vitamin A derivatives and the gut microbiome, and outline the current evidence for this. No cures exist for Stargardt’s or age-related macular degeneration, but many vitamin A-based therapeutic approaches have been or are being trialled. The relationship between vitamin A’s functions in systemic immunology and the eye could be further exploited, and further research may seek to leverage the interactions of the gut-eye immunological axis.

Exposure to fluopimomide at sublethal doses causes oxidative stress in Caenorhabditis elegans regulated by insulin/insulin-like growth factor 1-like signaling pathway.

Fluopimomide is an innovative pesticide, widely used for agricultural pest management; however, little is known about its effect on non-target organisms. This study was designed to assess the potential risk of fluopimomide and the molecular mechanisms using Caenorhabditis elegans, a common model animal. The oxidative stress-related indicators were analyzed in C. elegans after exposure to fluopimomide for 24 h at three sublethal doses (0.2, 1.0, and 5.0mg/L). The results demonstrated that sublethal exposure to fluopimomide adversely affected the nematodes growth, locomotive behaviors, reproduction, and lifespan, accompanying with enhanced of reactive oxygen species (ROS) generation, lipid and lipofuscin accumulation, and malondialdehyde content. In addition, exposure to fluopimomide significantly inhibited antioxidant systems including superoxide dismutase, catalase, glutathione S-transferase, and glutathione in the nematodes. Moreover, the expression of oxidative stress-related genes of sod-3, hsp-16.1, gst-4, ctl-2, daf-16, and daf-2 were significantly down-regulated, while the expression of skn-1 was significantly up-regulated. Further evidence revealed that daf-16 and skn-1 mutant strains of C. elegans significantly decreased ROS production upon fluopimomide exposure compared with the wild-type nematodes. Overall, our findings indicated that exposure to fluopimomide at sublethal doses caused oxidative damage, mainly associated with insulin/IGF-1-like signaling pathway in C. elegans. This is the first report of potential toxic effects of fluopimomide even at low concentrations, providing a new insight into the mechanisms of toxicity to C. elegans by fluopimomide.

Administration of krill oil extends lifespan of fish Nothobranchius guentheri via enhancement of antioxidant system and suppression of NF-κB pathway.

Krill oil (KO) extracted from Antarctic krill (Euphausia superba) mainly comprises phospholipids and triglycerides. KO has been shown to prolong the median lifespan of the nematode Caenorhabditis elegans, but to shorten the lifespan of long-lived F1 mice; therefore, it remains controversial over the life-extending property of KO. In this study, we clearly demonstrated that dietary intake of KO extended both the mean and maximum lifespans of aged male Nothobranchius guentheri (p < 0.05), reduced the accumulation of lipofuscin (LF) (p < 0.05) in the gills and senescence-associated β-galactosidase (SA-β-Gal) (p < 0.05) in the caudal fins, and lowered the levels of protein oxidation (p < 0.05), lipid peroxidation (p < 0.01), and reactive oxygen species (ROS) (p < 0.01) in the muscles and livers, indicating that KO possesses rejuvenation and anti-aging activity. We also showed that KO enhanced the activities of antioxidant enzymes catalase (CAT) (p < 0.05), superoxide dismutase (SOD) (p < 0.05), and glutathione peroxidase (GPX) (p < 0.05) in aged male N. guentheri. In addition, KO administration effectively reversed histological lesions including inflammatory cell infiltration and structural collapse in the muscles and livers of aged N. guentheri and suppressed the nuclear factor kappa-B (NF-κB) signaling pathway (p < 0.05), a master regulator of inflammation. Altogether, our study indicates that KO has anti-aging and rejuvenation property. It also suggests that KO exerts its anti-aging and rejuvenation effects via enhancement of the antioxidant system and suppression of the NF-κB signaling pathway.

Vitexin and Isovitexin Act through Inhibition of Insulin Receptor to Promote Longevity and Fitness in Caenorhabditis elegans

Vitexin and isovitexin are natural plant nutraceuticals for human health and longevity. This research investigates the underlying mechanisms of vitexin and isovitexin on aging and health. The vital role of DAF-2/insulin-like growth factor-1 receptor (IGFR) is illustrated in the insulin/insulin-like growth signaling pathway (IIS) modulated by vitexin and isovitexin. In vitro, in vivo models and molecular docking methods are performed to explore the antiaging mechanism of vitexin and isovitexin. Vitexin and isovitexin (50 and 100µM) extended the lifespan of Caenorhabditis elegans. The declines of pharyngeal pumping and body bending rates, and the increase of intestinal lipofuscin accumulation, three markers of aging, are postponed by these compounds. They inhibit IIS pathway in a daf-16-dependent manner, subsequently increasing the expressions of DAF-16 downstream protein and gene in nematodes. Molecular docking studies demonstrate that these compounds mightinhibit insulin signal by binding to the crucial amino acid residue ARG1003 in the pocket of IGFR. Western blot indicates that IGFR, PI3K, and AKT kinase expressions in senescent cells are decreased after vitexin and isovitexin treatment. Vitexin and isovitexin may inhibit IIS pathway by occupying adenosine-triphosphate binding site pocket of IGFR, subsequently decreasing IGFR expression, thereby promoting longevity and fitness.

Lack of Cathepsin D in the central nervous system results in microglia and astrocyte activation and the accumulation of proteinopathy-related proteins

Neuronal ceroid lipofuscinosis is one of many neurodegenerative storage diseases characterized by excessive accumulation of lipofuscins. CLN10 disease, an early infantile neuronal ceroid lipofuscinosis, is associated with a gene that encodes cathepsin D (CtsD), one of the major lysosomal proteases. Whole body CtsD-knockout mice show neurodegenerative phenotypes with the accumulation of lipofuscins in the brain and also show defects in other tissues including intestinal necrosis. To clarify the precise role of CtsD in the central nervous system (CNS), we generated a CNS-specific CtsD-knockout mouse (CtsD-CKO). CtsD-CKO mice were born normally but developed seizures and their growth stunted at around postnatal day 23 ± 1. CtsD-CKO did not exhibit apparent intestinal symptoms as those observed in whole body knockout. Histologically, autofluorescent materials were detected in several areas of the CtsD-CKO mouse’s brain, including: thalamus, cerebral cortex, hippocampus, and cerebellum. Expression of ubiquitin and autophagy-associated proteins was also increased, suggesting that the autophagy-lysosome system was impaired. Microglia and astrocytes were activated in the CtsD-CKO thalamus, and inducible nitric oxide synthase (iNOS), an inflammation marker, was increased in the microglia. Interestingly, deposits of proteinopathy-related proteins, phosphorylated α-synuclein, and Tau protein were also increased in the thalamus of CtsD-CKO infant mice. Considering these results, we propose thatt the CtsD-CKO mouse is a useful mouse model to investigate the contribution of cathepsin D to the early phases of neurodegenerative diseases in relation to lipofuscins, proteinopathy-related proteins and activation of microglia and astrocytes.

Structure and function of ABCA4 and its role in the visual cycle and Stargardt macular degeneration.

ABCA4 is a member of the superfamily of ATP-binding cassette (ABC) transporters that is preferentially localized along the rim region of rod and cone photoreceptor outer segment disc membranes. It uses the energy from ATP binding and hydrolysis to transport N-retinylidene-phosphatidylethanolamine (N-Ret-PE), the Schiff base adduct of retinal and phosphatidylethanolamine, from the lumen to the cytoplasmic leaflet of disc membranes. This ensures that all-trans-retinal and excess 11-cis-retinal are efficiently cleared from photoreceptor cells thereby preventing the accumulation of toxic retinoid compounds. Loss-of-function mutations in the gene encoding ABCA4 cause autosomal recessive Stargardt macular degeneration, also known as Stargardt disease (STGD1), and related autosomal recessive retinopathies characterized by impaired central vision and an accumulation of lipofuscin and bis-retinoid compounds. High resolution structures of ABCA4 in its substrate and nucleotide free state and containing bound N-Ret-PE or ATP have been determined by cryo-electron microscopy providing insight into the molecular architecture of ABCA4 and mechanisms underlying substrate recognition and conformational changes induced by ATP binding. The expression and functional characterization of a large number of disease-causing missense ABCA4 variants have been determined. These studies have shed light into the molecular mechanisms underlying Stargardt disease and a classification that reliably predicts the effect of a specific missense mutation on the severity of the disease. They also provide a framework for developing rational therapeutic treatments for ABCA4-associated diseases.

Epi-fluorescence imaging of the human brain through a multimode fiber

Visualization of the subcellular structures deep into the living brain is a major challenge in life science. Miniaturized microendoscopes allow for imaging of deep brain structures in vivo. Conventional approaches use gradient index (GRIN) microlenses, which unfortunately suffer from greater aberrations and restricted fields of view if they become smaller and less invasive. Multimode fiber based endoscopes offer minimal invasive access to deep tissue, and when combined with advanced wavefront engineering techniques, they provide high-resolution imaging. Here, we report auto-fluorescence human brain imaging through a single 50 μm-core multimode fiber probe with a numerical aperture of 0.22 via two approaches: raster-scan imaging by active wavefront shaping and speckle-based compressive imaging enabled by computational image recovery. The compressive imaging approach significantly decreases the acquisition time for an up to three times bigger area of interest while maintaining a high spatial resolution. Accumulation of age-related pigment lipofuscin in Alzheimer’s disease human brain has been visualized with sub-Nyquist–Shannon speed with an improvement of up to 18 times. The proposed technique offers fast, sensitive, and high-resolution endoscopic imaging through a single hair-thin fiber, which would be of broader interest in the fields of neuroimaging and (pre-)clinical research.

Women’s health update: A literature review impacting primary care

The authors review studies on key issues in women's health with potential impact on internal medicine practice. The reviewed articles discuss cardiovascular disease risks, bone health, breast cancer genetics, cervical cancer prevention, depression in the peripartum period, pelvic pain, and emergency contraception.

Brain Cell Senescence: A New Therapeutic Target for the Acute Treatment of Ischemic Stroke.

Aging is a major risk factor for cerebral infarction. Since cellular senescence is intrinsic to aging, we postulated that stroke-induced cellular senescence might contribute to neural dysfunction. Adult male Wistar rats underwent 60-minute middle cerebral artery occlusion and were grouped according to 3 reperfusion times: 24 hours, 3, and 7 days. The major biomarkers of senescence: 1) accumulation of the lysosomal pigment, lipofuscin; 2) expression of the cell cycle arrest markers p21, p53, and p16INK4a; and 3) expression of the senescence-associated secretory phenotype cytokines interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) were investigated in brain samples. Lipofuscin accumulation was scarce at the initial stage of brain damage (24 hours), but progressively increased until it reached massive distribution at 7 days post-ischemia. Lipofuscin granules (aggresomes) were mainly confined to the infarcted areas, that is parietal cortex and adjacent caudate-putamen, which were equally affected. The expression of p21, p53, and p16INK4a, and that of IL-6, TNF-α, and IL-1β, was significantly higher in the ischemic hemisphere than in the non-ischemic hemisphere. These data indicate that brain cell senescence develops during acute ischemic infarction and suggest that the acute treatment of ischemic stroke might be enhanced using senolytic drugs.

A Brief Overview to Ageing-Related Organ Damage: A Light and Electron Microscopic Approach to Several Systems

Ageing is thought to be a degenerative process caused by accumulated damage leading to cellular dysfunction, tissue, and organ failure, and eventually death. Although aging-related skin changes are considered the most important indicator of ageing, morphological and functional changes occur in all of the internal organs. Most of those changes are directly or indirectly associated with age-related decline of life quality. Histopathological features of the organs of old people are examined in postmortem tissues which are probably affected by diseases alongside ageing itself. Recent studies principally report the cellular changes obtained from rodents. The most commonly reported ageing-related ultrastructural changes are mitochondrial damage, lysosome and lipofuscin accumulation and dilatation or proliferation of endoplasmic reticulum. Here I summarize ageing-related changes in various organs such as skin, brain, heart, kidney, intestines etc. that have been revealed by light and electron microscopic examinations so far. Understanding ageing-related cell and tissue-based changes and related molecular mechanisms will contribute to the development of new strategies to prevent or eliminate age-related organ damage.

Caenorhabditis elegans DAF-16 regulates lifespan and immune responses to Cryptococcus neoformans and Cryptococcus gattii infections

BackgroundCryptococcosis is a life-threatening infection is primarily caused by two sibling species Cryptococcus neoformans and Cryptococcus gattii. Several virulence-related factors of these cryptococci have been widely investigated in Caenorhabditis elegans, representing a facile in vivo model of host–pathogen interaction. While recent studies elucidated cryptococcal virulence factors, intrinsic host factors that affect susceptibility to infections by cryptococci remain unclear and poorly investigated.ResultsHere, we showed that defects in C. elegans insulin/insulin-like growth factor-1 (IGF-1) signaling (IIS) pathway influenced animal lifespan and mechanisms of host resistance in cryptococcal infections, which required the activation of aging regulator DAF-16/Forkhead box O transcription factor. Moreover, accumulation of lipofuscin, DAF-16 nuclear localization, and expression of superoxide dismutase (SOD-3) were elevated in C. elegans due to host defenses during cryptococcal infections.ConclusionThe present study demonstrated the relationship between longevity and immunity, which may provide a possibility for novel therapeutic intervention to improve host resistance against cryptococcal infections.

Impacts of engineered iron nanoparticles on oxidative stress, fatty acid composition, and histo-architecture of the smooth scallop Flexopecten glaber.

Engineered iron nanoparticles are widely used in environmental remediation, yet their potential toxic effects on marine biota remain poorly elucidated. This study aimed to gain insight into the nanoscale zero-valent iron (NZVI) toxicity mechanisms for marine invertebrates. Aside from the effect on oxidative status and histopathology, the effect of NZVI on lipid metabolism in bivalves was studied for the first time. To this end, specimens of Flexopecten glaber were exposed to ascending concentrations (0.5, 1, and 1.5 mg/L) of NZVI for 96 h. Results illustrate differential patterns of iron accumulation in the gills and the digestive gland. By increasing NZVI concentrations, the total iron level tended to markedly increase in the gills and decrease in the digestive gland, reaching 132 and 37.6 μg/g DW, respectively, in the specimens exposed to 1.5 mg/L. Biochemical and cellular biomarkers highlighted that NZVI caused oxidative stress (measured as hydrogen peroxide, malondialdehyde, and advanced oxidation protein product levels) and alterations of antioxidant defense systems, including reduced glutathione, non-protein thiol, glutathione peroxidase, superoxide dismutase, and catalase. Modulation of lipid metabolism with changed fatty acid compositions (mainly an increase in the saturation and a decrease in unsaturation levels) was also observed in both gills and digestive gland. Moreover, several histological damages, including lipofuscin accumulation, infiltrative inflammations, and digestive tubule alterations, were observed in the two studied organs, providing supplementary evidence regarding the toxic effect of NZVI. This study adds to the growing body of evidence pointing to the hazardous impacts of iron NPs on aquatic ecosystems.