Age-related development of a refractive index plateau in the human lens: evidence for a distinct nucleus

Background/Objective:: The aim of this systematic review is to identify all the available data on human lens proteomics with a critical role to age-related cataract formation in order to elucidate the physiopathology of the aging lens. Materials and Methods:: We searched on Medline and Cochrane databases. The search generated 328 manuscripts. We included nine original proteomic studies that investigated human cataractous lenses. Results:: Deamidation was the major age-related post-translational modification. There was a significant increase in the amount of αA-crystallin D-isoAsp58 present at all ages, while an increase in the extent of Trp oxidation was apparent in cataract lenses when compared to aged normal lenses. During aging, enzymes with oxidized cysteine at critical sites included GAPDH, glutathione synthase, aldehyde dehydrogenase, sorbitol dehydrogenase, and PARK7. Conclusion:: D-isoAsp in αA crystallin could be associated with the development of age-related cataract in human, by contributing to the denaturation of a crystallin, and decreasing its ability to act as a chaperone. Oxidation of Trp may be associated with nuclear cataract formation in human, while the role of oxidant stress in age-related cataract formation is dominant.

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Nanoceria Prevents Glucose-Induced Protein Glycation in Eye Lens Cells

Nanomaterials ◽

10.3390/nano11061473 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1473

Author(s):

Belal I. Hanafy ◽

Gareth W. V. Cave ◽

Yvonne Barnett ◽

Barbara K. Pierscionek

Keyword(s):

Protein Glycation ◽

Human Lens ◽

Lens Epithelial Cells ◽

Oxide Nanoparticles ◽

Lens Protein ◽

Oxygen Species ◽

Human Lens Epithelial Cells ◽

Age Related ◽

Age Related Changes

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.

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Change by challenge: A common genetic basis behind childhood cognitive development and cognitive training

npj Science of Learning ◽

10.1038/s41539-021-00096-6 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Bruno Sauce ◽

John Wiedenhoeft ◽

Nicholas Judd ◽

Torkel Klingberg

Keyword(s):

Cognitive Development ◽

Brain Plasticity ◽

Training Sample ◽

Age Related ◽

Central Piece ◽

Gene Environment ◽

Related Development ◽

Explained Variation ◽

Genetic And Environmental Factors ◽

Cognitive Challenges

AbstractThe interplay of genetic and environmental factors behind cognitive development has preoccupied multiple fields of science and sparked heated debates over the decades. Here we tested the hypothesis that developmental genes rely heavily on cognitive challenges—as opposed to natural maturation. Starting with a polygenic score (cogPGS) that previously explained variation in cognitive performance in adults, we estimated its effect in 344 children and adolescents (mean age of 12 years old, ranging from 6 to 25) who showed changes in working memory (WM) in two distinct samples: (1) a developmental sample showing significant WM gains after 2 years of typical, age-related development, and (2) a training sample showing significant, experimentally-induced WM gains after 25 days of an intense WM training. We found that the same genetic factor, cogPGS, significantly explained the amount of WM gain in both samples. And there was no interaction of cogPGS with sample, suggesting that those genetic factors are neutral to whether the WM gains came from development or training. These results represent evidence that cognitive challenges are a central piece in the gene-environment interplay during cognitive development. We believe our study sheds new light on previous findings of interindividual differences in education (rich-get-richer and compensation effects), brain plasticity in children, and the heritability increase of intelligence across the lifespan.

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Age-Related Changes in Normal and Cataractous Human Lens Crystallins, Separated by Fast-Performance Liquid Chromatography

Ophthalmic Research ◽

10.1159/000267406 ◽

1994 ◽

Vol 26 (3) ◽

pp. 149-157 ◽

Cited By ~ 3

Author(s):

P.C. Pereira ◽

J.S. Ramalho ◽

C.J. Faro ◽

M.C. Mota

Keyword(s):

Liquid Chromatography ◽

Human Lens ◽

Lens Crystallins ◽

Age Related Changes

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Age-Related Changes in Human Lens Crystallins Identified by HPLC and Mass Spectrometry

Experimental Eye Research ◽

10.1006/exer.1998.0482 ◽

1998 ◽

Vol 67 (1) ◽

pp. 21-30 ◽

Cited By ~ 117

Author(s):

ZHIXIANG MA ◽

STACY R.A. HANSON ◽

KIRSTEN J. LAMPI ◽

LARRY L. DAVID ◽

DAVID L. SMITH ◽

...

Keyword(s):

Mass Spectrometry ◽

Human Lens ◽

Lens Crystallins ◽

Age Related ◽

Age Related Changes

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Increased Association of Deamidated αA-N101D with Lens Membrane of Transgenic αAN101D vs. Wild Type αA Mice: Potential Effects on Intracellular Ionic Imbalance and Membrane Disorganization

10.21203/rs.2.17769/v4 ◽

2020 ◽

Author(s):

Om Srivast ◽

Kiran Srivast ◽

Roy Joseph ◽

Landon Wilson

Keyword(s):

Epithelial Cells ◽

Western Blot ◽

Immunogold Labeling ◽

Human Lens ◽

Membrane Association ◽

Related Protein ◽

Wild Type ◽

Age Related ◽

Ionic Imbalance

Abstract We have generated two mouse models, in one by inserting the human lens αAN101D transgene in CRYαAN101D mice, and in the other by inserting human wild-type αA-transgene in CRYαAWT mice. The CRYαAN101D mice developed cortical cataract at about 7-months of age relative to CRYαAWT mice. The objective of the study was to determine the following relative changes in the lenses of CRYαAN101D- vs. CRYαAWT mice: age-related changes with specific emphasis on protein insolubilization, relative membrane-association of αAN101D vs. WTαA proteins, and changes in intracellular ionic imbalance and membrane organization. Methods: Lenses of varying ages from CRYαAWT and CRYαAN101D mice were compared for an age-related protein insolubilization. The relative lens membrane-association of the αAN101D- and WTαA proteins in the two types of mice was determined by immunohistochemical-, immunogold-labeling-, and western blot analyses. The relative levels of membrane-binding of recombinant αAN101D- and WTαA proteins was determined by an in vitro assay, and the levels of intracellular Ca2+ uptake and Na, K-ATPase mRNA were determined in the cultured epithelial cells from lenses of the two types of mice.Results: Compared to the lenses of CRYαAWT, the lenses of CRYαAN101D mice exhibited: (A) An increase in age-related protein insolubilization beginning at about 4-months of age. (B) A greater lens membrane-association of αAN101D- relative to WTαA protein during immunogold-labeling- and western blot analyses, including relatively a greater membrane swelling in the CRYαAN101D lenses. (C) During in vitro assay, the greater levels of binding αAN101D- relative to WTαA protein to membranes was observed. (D) The 75% lower level of Na, K-ATPase mRNA but 1.5X greater Ca2+ uptake were observed in cultured lens epithelial cells of CRYαAN101D- than those of CRYαAWT mice. Conclusions: The results show that an increased lens membrane association of αAN101D--relative WTαA protein in CRYαAN101D mice than CRYαAWT mice occurs, which causes intracellular ionic imbalance, and in turn, membrane swelling that potentially leads to cortical opacity.

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Attitudes Toward Animals: Age-Related Development among Children

Advances in Animal Welfare Science 1984 ◽

10.1007/978-94-009-4998-0_3 ◽

1985 ◽

pp. 43-60 ◽

Cited By ~ 5

Author(s):

Stephen R. Kellert

Keyword(s):

Age Related ◽

Attitudes Toward Animals ◽

Related Development

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Bifidobacterial Succession and Correlation Networks in a Large Unselected Cohort of Mothers and Their Children

Applied and Environmental Microbiology ◽

10.1128/aem.02359-12 ◽

2012 ◽

Vol 79 (2) ◽

pp. 497-507 ◽

Cited By ~ 47

Author(s):

E. Avershina ◽

O. Storrø ◽

T. Øien ◽

R. Johnsen ◽

R. Wilson ◽

...

Keyword(s):

Human Populations ◽

Bifidobacterium Adolescentis ◽

Content Type ◽

Individual Level ◽

Correlation Networks ◽

Age Related ◽

Related Development ◽

Healthy Cohort ◽

Stool Samples ◽

The Individual

ABSTRACTBifidobacteria are a major microbial component of infant gut microbiota, which is believed to promote health benefits for the host and stimulate maturation of the immune system. Despite their perceived importance, very little is known about the natural development of and possible correlations between bifidobacteria in human populations. To address this knowledge gap, we analyzed stool samples from a randomly selected healthy cohort of 87 infants and their mothers with >90% of vaginal delivery and nearly 100% breast-feeding at 4 months. Fecal material was sampled during pregnancy, at 3 and 10 days, at 4 months, and at 1 and 2 years after birth. Stool samples were predicted to be rich in the speciesBifidobacterium adolescentis,B. bifidum,B. dentium,B. breve, andB. longum. Due to high variation, we did not identify a clear age-related structure at the individual level. Within the population as a whole, however, there were clear age-related successions. Negative correlations between theB. longumgroup andB. adolescentiswere detected in adults and in 1- and 2-year-old children, whereas negative correlations betweenB. longumandB. brevewere characteristic for newborns and 4-month-old infants. The highly structured age-related development of and correlation networks between bifidobacterial species during the first 2 years of life mirrors their different or competing nutritional requirements, which in turn may be associated with specific biological functions in the development of healthy gut.

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