The age-related changes and differences in energy metabolism and glutamate-glutamine recycling in the d-gal-induced and naturally occurring senescent astrocytes in vitro

Cerium oxide nanoparticles (nanoceria) are generally known for their recyclable antioxidative properties making them an appealing biomaterial for protecting against physiological and pathological age-related changes that are caused by reactive oxygen species (ROS). Cataract is one such pathology that has been associated with oxidation and glycation of the lens proteins (crystallins) leading to aggregation and opacification. A novel coated nanoceria formulation has been previously shown to enter the human lens epithelial cells (HLECs) and protect them from oxidative stress induced by hydrogen peroxide (H2O2). In this work, the mechanism of nanoceria uptake in HLECs is studied and multiple anti-cataractogenic properties are assessed in vitro. Our results show that the nanoceria provide multiple beneficial actions to delay cataract progression by (1) acting as a catalase mimetic in cells with inhibited catalase, (2) improving reduced to oxidised glutathione ratio (GSH/GSSG) in HLECs, and (3) inhibiting the non-enzymatic glucose-induced glycation of the chaperone lens protein α-crystallin. Given the multifactorial nature of cataract progression, the varied actions of nanoceria render them promising candidates for potential non-surgical therapeutic treatment.

Download Full-text

Age-related changes in in vitro and in vivo survival of murine CFU-S and CFU-c

Mechanisms of Ageing and Development ◽

10.1016/0047-6374(82)90060-4 ◽

1982 ◽

Vol 19 (3) ◽

pp. 279-287 ◽

Cited By ~ 5

Author(s):

Marvin L. Tyan

Keyword(s):

Age Related ◽

Age Related Changes

Download Full-text

Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression

Genetika ◽

10.2298/gensr1401287b ◽

2014 ◽

Vol 46 (1) ◽

pp. 287-301 ◽

Cited By ~ 6

Author(s):

Biljana Bufan ◽

Jasmina Djikic ◽

Mirjana Nacka-Aleksic ◽

Zorica Stojic-Vukanic ◽

Mirjana Dimitrijevic ◽

...

Keyword(s):

Dendritic Cell ◽

Rt Pcr ◽

Autoimmune Encephalomyelitis ◽

Expression Of Genes ◽

Age Related ◽

Genes Encoding ◽

Immunosuppressive Cytokines ◽

Age Related Changes ◽

Experimental Autoimmune

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis, a prototype of Th1/Th17-mediated organ-specific autoimmune disease. In the rat, susceptibility to development of these diseases is shown to be strain-and age-dependent. In adult rats of distinct strains, it correlates with splenic dendritic cell (DC) subset composition, which also exhibit age-related changes. The aim of this study was to examine influence of aging on: i) Albino Oxford (relatively resistant to EAE) and Dark Agouti (susceptible to EAE) rat development of EAE and ii) their splenic conventional (OX62+) DC population in respect to its subset composition and expression of mRNAs for proinflammatory and immunosuppressive cytokines. We used 3month-old (young) and 26-month-old (aged) rats of AO and DA strain. The rats were immunized for EAE with rat spinal cord homogenate in complete Freund?s adjuvant and clinical course of the disease was followed. Fresh OX62+DCs were examined for the expression of CD4 (using flow cytometry) and genes encoding cytokines influencing DC activation/maturation (TNF-? and IL-6) using RT-PCR. Additionally, in vitro lipopolysaccharide (LPS) activated/matured DCs were examined for the expression of genes encoding cytokines controlling Th1/Th17 cell polarization using RT-PCR. With aging, AO rats became more susceptible, whereas DA rats largely lose their susceptibility to the induction of EAE. In AO rats aging shifted CD4+:CD4DC ratio towards CD4-cells, producing large amount of proinflammatory cytokines, whereas in DA rats CD4+:CD4-DC ratio remained stable with aging. In fresh DCs from rats of both the strains the expression of TNF-? mRNA increased with aging, whereas that of IL-6 mRNA decreased and increased in DCs from AO and DA rats, respectively. Following in vitro LPS stimulation OX62+ DCs from aged AO rats up-regulated the expression of mRNA for IL-23p19 (specific subunit of IL-23; crucial for sustained IL-17 production) and IL-1? (positive IL-17 regulator), whereas down-regulated the expression of IL-10 (negative IL-17 regulator) when compared with young strain-matched rats. In DA rats aging incresed IL-23p19 mRNA expression in LPS-stimulated DCs, whereas exerted the opposing effects on the expression of mRNAs for IL-10 and IL-1? compared to AO rats. Irrespective of the rat strain, aging did not influence mRNA expression for IL-12p35 (driving Th1 polarization) in DCs. Overall, results suggest role of changes in the expression of genes encoding proinflammatory and immunosuppressive cytokines in development of age-related alterations in rat susceptibility to EAE induction.

Download Full-text

Age-related changes in the secretion of LH in vivo and in vitro in infantile and prepubertal Holstein bull calves

Reproduction ◽

10.1530/jrf.0.1010453 ◽

1994 ◽

Vol 101 (2) ◽

pp. 453-458 ◽

Cited By ~ 3

Author(s):

J. M. McAndrews ◽

J. L. Peters ◽

D. R. Deaver

Keyword(s):

Holstein Bull ◽

Age Related ◽

Bull Calves ◽

Age Related Changes

Download Full-text

The Diverse Roles of TIMP-3: Insights into Degenerative Diseases of the Senescent Retina and Brain

Cells ◽

10.3390/cells9010039 ◽

2019 ◽

Vol 9 (1) ◽

pp. 39 ◽

Cited By ~ 3

Author(s):

Dewing ◽

Carare ◽

Lotery ◽

Ratnayaka

Keyword(s):

Stem Cell ◽

Age Related Macular Degeneration ◽

Tissue Inhibitor Of Metalloproteinase ◽

Degenerative Diseases ◽

Risk Alleles ◽

Age Related ◽

New Treatments ◽

Extracellular Environment ◽

Age Related Changes

Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a component of the extracellular environment, where it mediates diverse processes including matrix regulation/turnover, inflammation and angiogenesis. Rare TIMP-3 risk alleles and mutations are directly linked with retinopathies such as age-related macular degeneration (AMD) and Sorsby fundus dystrophy, and potentially, through indirect mechanisms, with Alzheimer’s disease. Insights into TIMP-3 activities may be gleaned from studying Sorsby-linked mutations. However, recent findings do not fully support the prevailing hypothesis that a gain of function through the dimerisation of mutated TIMP-3 is responsible for retinopathy. Findings from Alzheimer’s patients suggest a hitherto poorly studied relationship between TIMP-3 and the Alzheimer’s-linked amyloid-beta (A) proteins that warrant further scrutiny. This may also have implications for understanding AMD as aged/diseased retinae contain high levels of A. Findings from TIMP-3 knockout and mutant knock-in mice have not led to new treatments, particularly as the latter does not satisfactorily recapitulate the Sorsby phenotype. However, recent advances in stem cell and in vitro approaches offer novel insights into understanding TIMP-3 pathology in the retina-brain axis, which has so far not been collectively examined. We propose that TIMP-3 activities could extend beyond its hitherto supposed functions to cause age-related changes and disease in these organs.

Download Full-text