Quantitative Approaches to Pathogenesis of Age-Related Metabolic Conditions

1990 ◽  
pp. 229-245
Author(s):  
Richard N. Bergman
Keyword(s):  
Age Related ◽  
Metabolic Conditions ◽  
Quantitative Approaches

scholarly journals An Overview of the Nrf2/ARE Pathway and Its Role in Neurodegenerative Diseases

2021 ◽  
Vol 22 (17) ◽  
pp. 9592
Author(s):  
Emilia Zgorzynska ◽  
Barbara Dziedzic ◽  
Anna Walczewska
Keyword(s):  
Leucine Zipper ◽  
Target Genes ◽  
Protective Efficacy ◽  
Antioxidant Response ◽  
Activation Mechanism ◽  
Age Related ◽  
Nrf2 Activation ◽  
Metabolic Conditions ◽  
Lateral Sclerosis

Nrf2 is a basic region leucine-zipper transcription factor that plays a pivotal role in the coordinated gene expression of antioxidant and detoxifying enzymes, promoting cell survival in adverse environmental or defective metabolic conditions. After synthesis, Nrf2 is arrested in the cytoplasm by the Kelch-like ECH-associated protein 1 suppressor (Keap1) leading Nrf2 to ubiquitin-dependent degradation. One Nrf2 activation mechanism relies on disconnection from the Keap1 homodimer through the oxidation of cysteine at specific sites of Keap1. Free Nrf2 enters the nucleus, dimerizes with small musculoaponeurotic fibrosarcoma proteins (sMafs), and binds to the antioxidant response element (ARE) sequence of the target genes. Since oxidative stress, next to neuroinflammation and mitochondrial dysfunction, is one of the hallmarks of neurodegenerative pathologies, a molecular intervention into Nrf2/ARE signaling and the enhancement of the transcriptional activity of particular genes are targets for prevention or delaying the onset of age-related and inherited neurogenerative diseases. In this study, we review evidence for the Nrf2/ARE-driven pathway dysfunctions leading to various neurological pathologies, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, as well as amyotrophic lateral sclerosis, and the beneficial role of natural and synthetic molecules that are able to interact with Nrf2 to enhance its protective efficacy.

scholarly journals Ocular disease mechanisms elucidated by genetics of human fetal retinal pigment epithelium gene expression

2018 ◽  
Author(s):  
Boxiang Liu ◽  
Melissa A. Calton ◽  
Nathan S. Abell ◽  
Gillie Benchorin ◽  
Michael J. Gloudemans ◽  
...  
Keyword(s):  
Gene Expression ◽  
Retinal Pigment Epithelium ◽  
Large Scale ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Lipid Synthesis ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Metabolic Conditions ◽  
Association Data

AbstractThe eye is an intricate organ with limited representation in large-scale functional genomics datasets. The retinal pigment epithelium (RPE) serves vital roles in ocular development and retinal homeostasis. We interrogated the genetics of gene expression of cultured human fetal RPE (fRPE) cells under two metabolic conditions. Genes with disproportionately high fRPE expression are enriched for genes related to inherited ocular diseases. Variants near these fRPE-selective genes explain a larger fraction of risk for both age-related macular degeneration (AMD) and myopia than variants near genes enriched in 53 other human tissues. Increased mitochondrial oxidation of glutamine by fRPE promoted expression of lipid synthesis genes implicated in AMD. Expression and splice quantitative trait loci (e/sQTL) analysis revealed shared and metabolic condition-specific loci of each type and several eQTL not previously described in any tissue. Fine mapping of fRPE e/sQTL across AMD and myopia genome-wide association data suggests new candidate genes, and mechanisms by which the same common variant of RDH5 contributes to both increased AMD risk and decreased myopia risk. Our study highlights the unique transcriptomic characteristics of fRPE and provides a resource to connect e/sQTL in a critical ocular cell type to monogenic and complex eye disorders.

scholarly journals The Dynamic Interplay Between Mast Cells, Aging/Cellular Senescence, and Liver Disease

2020 ◽  
Vol 20 (2) ◽  
pp. 77-88
Author(s):  
Debjyoti Kundu ◽  
Lindsey Kennedy ◽  
Vik Meadows ◽  
Leonardo Baiocchi ◽  
Gianfranco Alpini ◽  
...  
Keyword(s):  
Liver Disease ◽  
Mast Cells ◽  
Disease Progression ◽  
Cellular Senescence ◽  
Primary Biliary Cholangitis ◽  
Nonalcoholic Fatty Liver ◽  
Age Related ◽  
Metabolic Conditions ◽  
Age Related Changes

Mast cells are key players in acute immune responses that are evidenced by degranulation leading to a heightened allergic response. Activation of mast cells can trigger a number of different pathways contributing to metabolic conditions and disease progression. Aging results in irreversible physiological changes affecting all organs, including the liver. The liver undergoes senescence, changes in protein expression, and cell signaling phenotypes during aging, which regulate disease progression. Cellular senescence contributes to the age-related changes. Unsurprisingly, mast cells also undergo age-related changes in number, localization, and activation throughout their lifetime, which adversely affects the etiology and progression of many physiological conditions including liver diseases. In this review, we discuss the role of mast cells during aging, including features of aging (e.g., senescence) in the context of biliary diseases such as primary biliary cholangitis and primary sclerosing cholangitis and nonalcoholic fatty liver disease.

TP9.2.26Patients admitted onto an Emergency General Surgery unit with rib fractures are mostly elderly and frail and outcomes may be poor: results of a 12-month audit

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Elaine Lewis ◽  
Sarah Shamim ◽  
Richard Guy
Keyword(s):  
Flail Chest ◽  
The Elderly ◽  
Pulmonary Complications ◽  
Injury Mechanism ◽  
Rib Fracture ◽  
Emergency General Surgery ◽  
Age Related ◽  
Significant Difference ◽  
Chi Squared ◽  
Metabolic Conditions

Abstract Aim An audit of rib fracture (RF) patients admitted to an EGS unit to determine demographics, injury mechanisms & outcomes. Methods Retrospective analysis was undertaken of all RF patients admitted between 1st Jan & 31st Dec 2019. Patient demographics, injury mechanism, comorbidities, length of stay (LOS) & outcomes were recorded. Analysis of age-related differences was undertaken using Mann Whitney U & Chi Squared tests. Results There were 115 patients (67 males) with median age 74 (38 patients <65 yrs; 77 patients >65 yrs). Seventy-three patients (63.5%) sustained injury after a fall. Eighty (69%) patients had cardiorespiratory, cerebrovascular or metabolic conditions, of whom 62 (54%) were >65 yrs, & 31 (27%) were on antiplatelets or anticoagulants. Thirty-eight (33%) had a pneumothorax or haemothorax, 19 (5.4%) flail chest & 39 (34%) additional bony injuries. Some 107 (93%) were managed on a rib fracture pathway. Thirty-seven (32%) patients developed pulmonary complications (infection 27, effusion 5, contusion 5) & 8 (7%) died. Subgroup analysis revealed a significant difference in LOS (median 3 vs 6.5 days, p = 0.00144) for age <65 vs >65 years & gender (females 9.5 vs males 3.5 days, p = 0.00114), as well as for age <65 vs >65 & injury mechanism (no fall vs fall, p = 0.042). Conclusion RFs are commonly sustained in frail elderly patients following a fall & are associated with significant pulmonary consequences in around a third, with potentially long hospital stay. Close collaboration with Pain Teams and specialists in Medicine for the Elderly is essential.

Spindle shaped bodies in foveolar cones of the baboon retina

1989 ◽  
Vol 47 ◽  
pp. 960-961
Author(s):  
W. Krebs ◽  
I. Krebs
Keyword(s):  
Cross Sections ◽  
Inclusion Bodies ◽  
Photoreceptor Cells ◽  
Papio Anubis ◽  
Retinal Photoreceptor ◽  
Age Related ◽  
Cone Cells ◽  
Membrane Bound ◽  
Oriented Parallel ◽  
Shaped Inclusion

Various inclusion bodies occur in vertebrate retinal photoreceptor cells. Most of them are membrane bound and associated with phagocytosis or they are age related residual bodies. We found an additional inclusion body in foveal cone cells of the baboon (Papio anubis) retina.The eyes of a 15 year old baboon were fixed by immersion in cacodylate buffered glutaraldehyde (2%)/formaldehyde (2%) as described in detail elsewhere . Pieces of retina from various locations, including the fovea, were embedded in epoxy resin such that radial or tangential sections could be cut.Spindle shaped inclusion bodies were found in the cytoplasm of only foveal cones. They were abundant in the inner segments, close to the external limiting membrane (Fig. 1). But they also occurred in the outer fibers, the perikarya, and the inner fibers (Henle’s fibers) of the cone cells. The bodies were between 0.5 and 2 μm long. Their central diameter was 0.2 to 0. 3 μm. They always were oriented parallel to the long axis of the cone cells. In longitudinal sections (Figs. 2,3) they seemed to have a fibrous skeleton that, in cross sections, turned out to consist of plate-like (Fig.4) and tubular profiles (Fig. 5).

Autophagy and ageing: implications for age-related neurodegenerative diseases

2013 ◽  
Vol 55 ◽  
pp. 119-131 ◽  
Author(s):  
Bernadette Carroll ◽  
Graeme Hewitt ◽  
Viktor I. Korolchuk
Keyword(s):  
Neurodegenerative Diseases ◽  
Energy Availability ◽  
Future Studies ◽  
Intracellular Degradation ◽  
Age Related ◽  
Autophagy Induction ◽  
Social Importance ◽  
Cellular Dysfunction ◽  
Autophagy Activity ◽  
Intense Research

Autophagy is a process of lysosome-dependent intracellular degradation that participates in the liberation of resources including amino acids and energy to maintain homoeostasis. Autophagy is particularly important in stress conditions such as nutrient starvation and any perturbation in the ability of the cell to activate or regulate autophagy can lead to cellular dysfunction and disease. An area of intense research interest is the role and indeed the fate of autophagy during cellular and organismal ageing. Age-related disorders are associated with increased cellular stress and assault including DNA damage, reduced energy availability, protein aggregation and accumulation of damaged organelles. A reduction in autophagy activity has been observed in a number of ageing models and its up-regulation via pharmacological and genetic methods can alleviate age-related pathologies. In particular, autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Indeed, in certain situations, reduced autophagosome induction may actually provide benefits to ageing cells. Future studies will undoubtedly improve our understanding of exactly how the multiple signals that are integrated to control appropriate autophagy activity change during ageing, what affect this has on autophagy and to what extent autophagy contributes to age-associated pathologies. Identification of mechanisms that influence a healthy lifespan is of economic, medical and social importance in our ‘ageing’ world.

Differentiating Beyond Name Agreement for Picture Naming: Insight From Age-Related Selection Deficits

2019 ◽  
Vol 62 (5) ◽  
pp. 1373-1380
Author(s):  
Daniel L. Madden ◽  
Martin V. Sale ◽  
Gail A. Robinson
Keyword(s):  
Picture Naming ◽  
Name Agreement ◽  
Age Related

Oral and Oropharyngeal Sensory Function in Adults With Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 29 (2) ◽  
pp. 864-872
Author(s):  
Fernanda Borowsky da Rosa ◽  
Adriane Schmidt Pasqualoto ◽  
Catriona M. Steele ◽  
Renata Mancopes
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Oral Cavity ◽  
Pulmonary Disease ◽  
Thermal Sensation ◽  
Sensory Function ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Age Related ◽  
Copd Patients

Introduction The oral cavity and pharynx have a rich sensory system composed of specialized receptors. The integrity of oropharyngeal sensation is thought to be fundamental for safe and efficient swallowing. Chronic obstructive pulmonary disease (COPD) patients are at risk for oropharyngeal sensory impairment due to frequent use of inhaled medications and comorbidities including gastroesophageal reflux disease. Objective This study aimed to describe and compare oral and oropharyngeal sensory function measured using noninstrumental clinical methods in adults with COPD and healthy controls. Method Participants included 27 adults (18 men, nine women) with a diagnosis of COPD and a mean age of 66.56 years ( SD = 8.68). The control group comprised 11 healthy adults (five men, six women) with a mean age of 60.09 years ( SD = 11.57). Spirometry measures confirmed reduced functional expiratory volumes (% predicted) in the COPD patients compared to the control participants. All participants completed a case history interview and underwent clinical evaluation of oral and oropharyngeal sensation by a speech-language pathologist. The sensory evaluation explored the detection of tactile and temperature stimuli delivered by cotton swab to six locations in the oral cavity and two in the oropharynx as well as identification of the taste of stimuli administered in 5-ml boluses to the mouth. Analyses explored the frequencies of accurate responses regarding stimulus location, temperature and taste between groups, and between age groups (“≤ 65 years” and “> 65 years”) within the COPD cohort. Results We found significantly higher frequencies of reported use of inhaled medications ( p < .001) and xerostomia ( p = .003) in the COPD cohort. Oral cavity thermal sensation ( p = .009) was reduced in the COPD participants, and a significant age-related decline in gustatory sensation was found in the COPD group ( p = .018). Conclusion This study found that most of the measures of oral and oropharyngeal sensation remained intact in the COPD group. Oral thermal sensation was impaired in individuals with COPD, and reduced gustatory sensation was observed in the older COPD participants. Possible links between these results and the use of inhaled medication by individuals with COPD are discussed.

Age-Related Differences in Processing Dynamic Information to Identify Vowel Quality

1992 ◽  
Vol 35 (4) ◽  
pp. 892-902 ◽  
Author(s):  
Robert Allen Fox ◽  
Lida G. Wall ◽  
Jeanne Gokcen
Keyword(s):  
Older Adults ◽  
Vowel Quality ◽  
Perceptual Cues ◽  
Dynamic Information ◽  
Process Dynamic ◽  
Center Condition ◽  
Age Related ◽  
Control Version ◽  
Older Subjects ◽  
Whole Word

This study examined age-related differences in the use of dynamic acoustic information (in the form of formant transitions) to identify vowel quality in CVCs. Two versions of 61 naturally produced, commonly occurring, monosyllabic English words were created: a control version (the unmodified whole word) and a silent-center version (in which approximately 62% of the medial vowel was replaced by silence). A group of normal-hearing young adults (19–25 years old) and older adults (61–75 years old) identified these tokens. The older subjects were found to be significantly worse than the younger subjects at identifying the medial vowel and the initial and final consonants in the silent-center condition. These results support the hypothesis of an age-related decrement in the ability to process dynamic perceptual cues in the perception of vowel quality.

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