scholarly journals Lifelong Cytomegalovirus and Early-Life Irradiation Synergistically Potentiate Age-Related Defects in Response to Vaccination and Infection

2021 ◽  
Author(s):  
Jason L. Pugh ◽  
Christopher P. Coplen ◽  
Alona S. Sukhina ◽  
Jennifer L. Uhrlaub ◽  
Jose Padilla-Torres ◽  
...  
Keyword(s):  
Dna Damage ◽  
Early Life ◽  
Acute Infection ◽  
Late Life ◽  
Whole Body ◽  
Murine Cytomegalovirus ◽  
Live Attenuated Vaccine ◽  
Age Related ◽  
Theory Of Aging ◽  
High Level

ABSTRACTA popular “DNA-damage theory” of aging posits that unrepaired DNA damage leads to cellular (and organismal) senescence. Indeed, some hallmarks of immune aging are more prevalent in individuals exposed to Whole-Body Irradiation (WBI). To test this hypothesis in a model relevant to human immune aging, we examined separate and joint effects of lifelong latent Murine Cytomegalovirus (MCMV) and early-life WBI (i) over the course of the lifespan; (ii) in response to a West Nile virus (WNV) live attenuated vaccine; and (iii) following lethal WNV challenge subsequent to vaccination. We recently published that a single dose of non-lethal WBI in youth, on its own, was not sufficient to accelerate aging of the murine immune system despite causing widespread DNA damage and repopulation stress in hematopoietic cells. However, 4Gy sub-lethal WBI caused manifest reactivation of MCMV. Following vaccination and challenge with WNV in the old age, MCMV-infected animals experiencing 4Gy, but not lower, dose of sub-lethal WBI in youth had reduced survival. By contrast, old irradiated mice lacking MCMV and MCMV-infected, but not irradiated, mice were both protected to the same high level as the old non-irradiated, uninfected controls. Analysis of the quality and quantity of anti-WNV immunity showed that higher mortality in MCMV-positive WBI mice correlated with increased levels of MCMV-specific immune activation during WNV challenge. Moreover, we demonstrate that infection, including that by WNV, led to MCMV reactivation. Our data suggest that MCMV reactivation may be an important determinant of increased late-life mortality following early-life irradiation and late-life acute infection.

scholarly journals Variety of Enriching Early-Life Activities Linked to Late-Life Cognitive Functioning in Urban Community-Dwelling African Americans

2018 ◽  
Vol 74 (8) ◽  
pp. 1345-1355 ◽  
Author(s):  
Thomas Chan ◽  
Jeanine M Parisi ◽  
Kyle D Moored ◽  
Michelle C Carlson
Keyword(s):  
Health Disparities ◽  
African Americans ◽  
Cognitive Functioning ◽  
Early Life ◽  
Late Life ◽  
Community Dwelling ◽  
Cognitive Outcomes ◽  
Positive Role ◽  
Childhood Experiences ◽  
Age Related

Abstract Objectives The early environment is thought to be a critical period in understanding the cognitive health disparities African Americans face today. Much is known about the positive role enriching environments have in mid- and late-life and the negative function adverse experiences have in childhood; however, little is known about the relationship between enriching childhood experiences and late-life cognition. The current study examines the link between a variety of enriching early-life activities and late-life cognitive functioning in a sample of sociodemographic at-risk older adults. Method This study used data from African Americans from the Brain and Health Substudy of the Baltimore Experience Corps Trial (M = 67.2, SD = 5.9; N = 93). Participants completed a battery of neuropsychological assessments and a seven-item retrospective inventory of enriching activities before age 13. Results Findings revealed that a greater enriching early-life activity score was linked to favorable outcomes in educational attainment, processing speed, and executive functioning. Discussion Results provide promising evidence that enriching early environments are associated with late-life educational and cognitive outcomes. Findings support the cognitive reserve and engagement frameworks, and have implications to extend life-span prevention approaches when tackling age-related cognitive declines, diseases, and health disparities.

Nuclear Genomic Instability and Aging

2018 ◽  
Vol 87 (1) ◽  
pp. 295-322 ◽  
Author(s):  
Laura J. Niedernhofer ◽  
Aditi U. Gurkar ◽  
Yinsheng Wang ◽  
Jan Vijg ◽  
Jan H.J. Hoeijmakers ◽  
...  
Keyword(s):  
Dna Damage ◽  
Genomic Instability ◽  
Nuclear Dna ◽  
Nuclear Genome ◽  
Accelerated Aging ◽  
Genotoxic Stress ◽  
Dna Lesions ◽  
Age Related ◽  
Damage Accrual ◽  
Theory Of Aging

The nuclear genome decays as organisms age. Numerous studies demonstrate that the burden of several classes of DNA lesions is greater in older mammals than in young mammals. More challenging is proving this is a cause rather than a consequence of aging. The DNA damage theory of aging, which argues that genomic instability plays a causal role in aging, has recently gained momentum. Support for this theory stems partly from progeroid syndromes in which inherited defects in DNA repair increase the burden of DNA damage leading to accelerated aging of one or more organs. Additionally, growing evidence shows that DNA damage accrual triggers cellular senescence and metabolic changes that promote a decline in tissue function and increased susceptibility to age-related diseases. Here, we examine multiple lines of evidence correlating nuclear DNA damage with aging. We then consider how, mechanistically, nuclear genotoxic stress could promote aging. We conclude that the evidence, in toto, supports a role for DNA damage as a nidus of aging.

scholarly journals Age-specific reproduction in female pied flycatchers: evidence for asynchronous aging

Oecologia ◽  
2021 ◽  
Author(s):  
Rémi Fay ◽  
Pierre-Alain Ravussin ◽  
Daniel Arrigo ◽  
Jan A. C. von Rönn ◽  
Michael Schaub
Keyword(s):  
Early Life ◽  
Success Probability ◽  
Reproductive Traits ◽  
Late Life ◽  
Peak Performance ◽  
Laying Date ◽  
Vital Rates ◽  
Related Variation ◽  
Age Related ◽  
Life Improvement

AbstractAge-related variation in reproductive performance is central for the understanding of population dynamics and evolutionary processes. Our understanding of age trajectories in vital rates has long been limited by the lack of distinction between patterns occurring within- and among-individuals, and by the lack of comparative studies of age trajectories among traits. Thus, it is poorly understood how sets of demographic traits change within individuals according to their age. Based on 40 years of monitoring, we investigated age-related variation in five reproductive traits in female pied flycatchers (Ficedula hypoleuca) including laying date, clutch size, brood size, nest success (probability that a nest produces at least one chick) and egg success of successful nests (proportion of eggs resulting in a chick). We disentangled within- from among-individual processes and assessed the relative contribution of within-individual age-specific changes and selective appearance and disappearance. Finally, we compared the aging pattern among these five reproductive traits. We found strong evidence for age-specific performance including both early-life improvement and late-life decline in all reproductive traits but the egg success. Furthermore, the aging patterns varied substantially among reproductive traits both for the age of peak performance and for the rates of early-life improvement and late-life decline. The results show that age trajectories observed at the population level (cross-sectional analysis) may substantially differ from those occurring at the individual level and illustrate the complexity of variation in aging patterns across traits.

Age- and sex-related bone uptake of Tc-99m-HDP measured by whole-body bone scanning

2000 ◽  
Vol 39 (05) ◽  
pp. 127-132 ◽  
Author(s):  
Nicole Sieweke ◽  
K. H. Bohuslavizki ◽  
W. U. Kampen ◽  
M. Zuhayra ◽  
M. Clausen ◽  
...  
Keyword(s):  
Whole Body ◽  
Bone Lesions ◽  
Men And Women ◽  
Bone Uptake ◽  
Normal Bone ◽  
Age Related ◽  
Number Of Patients ◽  
Wide Range ◽  
Bone Scans ◽  
Body Bone

Summary Aim of this study was to validate a recently introduced new and easy-to-perform method for quantifying bone uptake of Tc-99m-labelled diphosphonate in a routine clinical setting and to establish a normal data base for bone uptake depending on age and gender. Methods: In 49 women (14-79 years) and 47 men (6-89 years) with normal bone scans as well as in 49 women (33-81 years) and 37 men (27-88 years) with metastatic bone disease whole-body bone scans were acquired at 3 min and 3-4 hours p.i. to calculate bone uptake after correction for both urinary excretion and soft tissue retention. Results: Bone uptake values of various age-related subgroups showed no significant differences between men and women (p >0.05 ). Furthermore, no differences could be proven between age-matched subgroups of normals and patients with less than 10 metastatic bone lesions, while patients with wide-spread bone metastases revealed significantly increased uptake values. In both men and women highest bone uptake was obtained (p <0.05 ) in subjects younger than 20 years with active epiphyseal growth plates. In men, bone uptake slowly decreased with age up to 60 years and then showed a tendency towards increasing uptake values. In women, the mean uptake reached a minimun in the decade 20-29 years and then slowly increased with a positive linear correlation of age and uptake in subjects older than 55 years (r = 0.57). Conclusion: Since the results proposed in this study are in good agreement with data from literature, the new method used for quantification could be validated in a large number of patients. Furthermore, age- and sexrelated normal bone uptake values of Tc-99m-HDP covering a wide range of age could be presented for this method as a basis for further studies on bone uptake.

Serum of 8-OHdG as a potential biomarker of oxidative DNA damage in workers exposed to harmful working environments

2020 ◽  
pp. 783-783
Author(s):  
I. A. Umnyagina ◽  
L. A. Strakhova ◽  
T. V. Blinova
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Blood Serum ◽  
Oxidative Dna Damage ◽  
Working Environment ◽  
Working Environments ◽  
Potential Biomarker ◽  
High Level ◽  
Damage Marker

In the blood serum of 70% individuals exposed to harmful factors of the working environment, a high level of oxidative stress and the DNA damage marker 8-Hydroxy-2’-Deoxyguanosine (8-OHdG) were detected.

Oxidative Stress, Ocular Disease and Diabetes Retinopathy

2019 ◽  
Vol 24 (40) ◽  
pp. 4726-4741 ◽  
Author(s):  
Orathai Tangvarasittichai ◽  
Surapon Tangvarasittichai
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Death ◽  
Protein Modification ◽  
Morphological Changes ◽  
Corneal Dystrophy ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Retinal Light Damage ◽  
Age Related

Background: Oxidative stress is caused by free radicals or oxidant productions, including lipid peroxidation, protein modification, DNA damage and apoptosis or cell death and results in cellular degeneration and neurodegeneration from damage to macromolecules. Results: Accumulation of the DNA damage (8HOdG) products and the end products of LPO (including aldehyde, diene, triene conjugates and Schiff’s bases) were noted in the research studies. Significantly higher levels of these products in comparison with the controls were observed. Oxidative stress induced changes to ocular cells and tissues. Typical changes include ECM accumulation, cell dysfunction, cell death, advanced senescence, disarrangement or rearrangement of the cytoskeleton and released inflammatory cytokines. It is involved in ocular diseases, including keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, cataract, age-related macular degeneration, primary open-angle glaucoma, retinal light damage, and retinopathy of prematurity. These ocular diseases are the cause of irreversible blindness worldwide. Conclusions: Oxidative stress, inflammation and autophagy are implicated in biochemical and morphological changes in these ocular tissues. The development of therapy is a major target for the management care of these ocular diseases.

Language and Aging

2019 ◽  
pp. 294-316
Author(s):  
Jonathan E. Peelle
Keyword(s):  
Language Processing ◽  
Brain Function ◽  
Neural Systems ◽  
Language Abilities ◽  
Physiological Mechanisms ◽  
Cognitive Changes ◽  
Older Adulthood ◽  
Neural Organization ◽  
Age Related ◽  
High Level

Language processing in older adulthood is a model of balance between preservation and decline. Despite widespread changes to physiological mechanisms supporting perception and cognition, older adults’ language abilities are frequently well preserved. At the same time, the neural systems engaged to achieve this high level of success change, and individual differences in neural organization appear to differentiate between more and less successful performers. This chapter reviews anatomical and cognitive changes that occur in aging and popular frameworks for age-related changes in brain function, followed by an examination of how these principles play out in the context of language comprehension and production.

scholarly journals Corticobasal Degeneration Misdiagnosed As Musculoskeletal Disease: A Challenging Diagnosis of Higher-Level Gait Disease

2020 ◽  
Vol 11 (04) ◽  
pp. 640-642
Author(s):  
Halil Onder
Keyword(s):  
Corticobasal Degeneration ◽  
The Elderly ◽  
Gait Disorders ◽  
Physiological Changes ◽  
Gait Abnormality ◽  
Age Related ◽  
Musculoskeletal Problems ◽  
Neurological Exam ◽  
Long Time ◽  
High Level

AbstractGait disorders are common in the elderly as there are various causes of neurological and non-neurological conditions. On the other hand, most of the gait parameters do change with advancing age which is identified as age-related physiological changes in gait. At this point, the discrimination between age-related physiological changes and gait disorders may be strictly challenging. After identifying gait as an abnormal pattern, classification of it and making the responsible pathophysiology also require high-level expertise in this regard. Herein, we present a rare patient with corticobasal degeneration (CBD) who had admitted initially due to complaints of gait problems. Over a long time, the patient had received the misdiagnosis of gait abnormality due to musculoskeletal problems by multiple physicians. However, the detailed neurological exam showed a higher level gait disorder (HLGD). Further investigations at this point yielded the diagnosis of CBD.

scholarly journals The m15 Locus of Murine Cytomegalovirus Modulates Natural Killer Cell Responses to Promote Dissemination to the Salivary Glands and Viral Shedding

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 866
Author(s):  
Baca Chan ◽  
Maja Arapović ◽  
Laura Masters ◽  
Francois Rwandamuiye ◽  
Stipan Jonjić ◽  
...  
Keyword(s):  
Nk Cells ◽  
Salivary Glands ◽  
Natural Killer ◽  
Nk Cell ◽  
Acute Infection ◽  
Killer Cell ◽  
Viral Escape ◽  
Murine Cytomegalovirus ◽  
Viral Shedding ◽  
Cell Responses

As the largest herpesviruses, the 230 kb genomes of cytomegaloviruses (CMVs) have increased our understanding of host immunity and viral escape mechanisms, although many of the annotated genes remain as yet uncharacterised. Here we identify the m15 locus of murine CMV (MCMV) as a viral modulator of natural killer (NK) cell immunity. We show that, rather than discrete transcripts from the m14, m15 and m16 genes as annotated, there are five 3′-coterminal transcripts expressed over this region, all utilising a consensus polyA tail at the end of the m16 gene. Functional inactivation of any one of these genes had no measurable impact on viral replication. However, disruption of all five transcripts led to significantly attenuated dissemination to, and replication in, the salivary glands of multiple strains of mice, but normal growth during acute infection. Disruption of the m15 locus was associated with heightened NK cell responses, including enhanced proliferation and IFNγ production. Depletion of NK cells, but not T cells, rescued salivary gland replication and viral shedding. These data demonstrate the identification of multiple transcripts expressed by a single locus which modulate, perhaps in a concerted fashion, the function of anti-viral NK cells.

scholarly journals Systemic exposure following intravitreal administration of therapeutic agents: an integrated pharmacokinetic approach. 2. THR-687

2021 ◽  
Author(s):  
Marc Vanhove ◽  
Jean-Marc Wagner ◽  
Bernard Noppen ◽  
Bart Jonckx ◽  
Elke Vermassen ◽  
...  
Keyword(s):  
General Circulation ◽  
Pharmacokinetic Model ◽  
Systemic Exposure ◽  
Age Related Macular Degeneration ◽  
Whole Body ◽  
Pharmacological Agents ◽  
Age Related ◽  
Pharmacokinetic Properties ◽  
High Concentrations ◽  
Systemic Compartment

AbstractIntravitreal (IVT) injection remains the preferred administration route of pharmacological agents intended for the treatment of back of the eye diseases such as diabetic macular edema (DME) and neovascular age-related macular degeneration (nvAMD). The procedure enables drugs to be delivered locally at high concentrations whilst limiting whole body exposure and associated risk of systemic adverse events. Nevertheless, intravitreally-delivered drugs do enter the general circulation and achieving an accurate understanding of systemic exposure is pivotal for the evaluation and development of drugs administered in the eye. We report here the full pharmacokinetic properties of THR-687, a pan RGD integrin antagonist currently in clinical development for the treatment of DME, in both rabbit and minipig. Pharmacokinetic characterization included description of vitreal elimination, of systemic pharmacokinetics, and of systemic exposure following IVT administration. For the latter, we present a novel pharmacokinetic model that assumes clear partition between the vitreous humor compartment itself where the drug is administered and the central systemic compartment. We also propose an analytical solution to the system of differential equations that represent the pharmacokinetic model, thereby allowing data analysis with standard nonlinear regression analysis. The model accurately describes circulating levels of THR-687 following IVT administration in relevant animal models, and we suggest that this approach is relevant to a range of drugs and analysis of subsequent systemic exposure.

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