scholarly journals The Matrisome during Aging and Longevity: A Systems-Level Approach towards Defining Matreotypes Promoting Healthy Aging

2019 ◽  
Author(s):  
Collin Ewald
Keyword(s):  
Healthy Aging ◽  
Physiological State ◽  
Cell Types ◽  
Physiological Status ◽  
Ecm Proteins ◽  
Age Related ◽  
Accumulation Of Damage ◽  
Cellular Identity ◽  
Multicellular Organisms ◽  
Cellular Components

Accumulation of damage is generally considered the cause of aging. Interventions that delay aging mobilize mechanisms that protect and repair cellular components. Consequently, research has been focused on studying the protective and homeostatic mechanisms within cells. However, in humans and other multicellular organisms, cells are surrounded by extracellular matrices (ECM), which are important for tissue structure, function and intercellular communication. During aging, components of the ECM become damaged through fragmentation, glycation, crosslinking, and accumulation of protein aggregation, all of which contribute to age-related pathologies. Interestingly, placing senescent cells into a young ECM rejuvenates them and we found that many longevity-assurances pathways re-activate de-novosynthesis of ECM proteins during aging. This raises the question of what constitutes a young ECM to reverse aging or maintain health? In order to make inroads to answering this question, I suggest a systems-level approach of quantifying the matrisome or ECM compositions reflecting health, pathology, or phenotype and propose a novel term, the “matreotype”, to describe this. The matreotype is defined as the composition and modification of ECM or matrisome proteins associated with or caused by a phenotype, such as longevity, or a distinct and acute physiological state, as observed during aging or disease. Every cell type produces its unique ECM. Interestingly, cancer-cell types can even be identified based on their unique ECM composition. Thus, the matreotype reflects cellular identity and physiological status. Defined matreotypes could be used as biomarkers or prognostic factors for disease or health status during aging with potential relevance for personalized medicine. Treatment with biologics that alter ECM-to-cell mechanotransduction might be a strategy to reverse age-associated pathologies. An understanding of how to reverse from an old to a young matreotype might point towards novel strategies to rejuvenate cells and help maintain tissue homeostasis to promote health during aging.

Aging of the Retina: Molecular and Metabolic Turbulences and Potential Interventions

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Laura Campello ◽  
Nivedita Singh ◽  
Jayshree Advani ◽  
Anupam K. Mondal ◽  
Ximena Corso-Diaz ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Cell Types ◽  
Lifestyle Changes ◽  
Annual Review ◽  
Past Century ◽  
Publication Date ◽  
Vision Science ◽  
Human Lifespan ◽  
Cellular Events ◽  
Age Related

Multifaceted and divergent manifestations across tissues and cell types have curtailed advances in deciphering the cellular events that accompany advanced age and contribute to morbidities and mortalities. Increase in human lifespan during the past century has heightened awareness of the need to prevent age-associated frailty of neuronal and sensory systems to allow a healthy and productive life. In this review, we discuss molecular and physiological attributes of aging of the retina, with a goal of understanding age-related impairment of visual function. We highlight the epigenome–metabolism nexus and proteostasis as key contributors to retinal aging and discuss lifestyle changes as potential modulators of retinal function. Finally, we deliberate promising intervention strategies for promoting healthy aging of the retina for improved vision. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Common diseases alter the physiological age-related blood microRNA profile

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Tobias Fehlmann ◽  
Benoit Lehallier ◽  
Nicholas Schaum ◽  
Oliver Hahn ◽  
Mustafa Kahraman ◽  
...  
Keyword(s):  
Whole Blood ◽  
Healthy Aging ◽  
The Elderly ◽  
Cell Types ◽  
Physiological Age ◽  
Transcriptional Gene Silencing ◽  
Old Patients ◽  
Post Transcriptional Gene Silencing ◽  
Age Related ◽  
Microrna Profile

AbstractAging is a key risk factor for chronic diseases of the elderly. MicroRNAs regulate post-transcriptional gene silencing through base-pair binding on their target mRNAs. We identified nonlinear changes in age-related microRNAs by analyzing whole blood from 1334 healthy individuals. We observed a larger influence of the age as compared to the sex and provide evidence for a shift to the 5’ mature form of miRNAs in healthy aging. The addition of 3059 diseased patients uncovered pan-disease and disease-specific alterations in aging profiles. Disease biomarker sets for all diseases were different between young and old patients. Computational deconvolution of whole-blood miRNAs into blood cell types suggests that cell intrinsic gene expression changes may impart greater significance than cell abundance changes to the whole blood miRNA profile. Altogether, these data provide a foundation for understanding the relationship between healthy aging and disease, and for the development of age-specific disease biomarkers.

scholarly journals Genome instability: a conserved mechanism of ageing?

2017 ◽  
Vol 61 (3) ◽  
pp. 305-315 ◽  
Author(s):  
Jan Vijg ◽  
Xiao Dong ◽  
Brandon Milholland ◽  
Lei Zhang
Keyword(s):  
Mutation Rate ◽  
Genome Instability ◽  
Single Cells ◽  
Somatic Cells ◽  
Cell Types ◽  
Base Substitution ◽  
Age Related ◽  
First Results ◽  
Substitution Mutations ◽  
Multicellular Organisms

DNA is the carrier of genetic information and the primary template from which all cellular information is ultimately derived. Changes in the DNA information content through mutation generate diversity for evolution through natural selection but are also a source of deleterious effects. It has since long been hypothesized that mutation accumulation in somatic cells of multicellular organisms could causally contribute to age-related cellular degeneration and death. Assays to detect different types of mutations, from base substitutions to large chromosomal aberrations, have been developed and show unequivocally that mutations accumulate in different tissues and cell types of ageing humans and animals. More recently, next-generation sequencing-based methods have been developed to accurately determine the complete landscape of base substitution mutations in single cells. The first results show that the somatic mutation rate is much higher than the germline mutation rate and that base substitution loads in somatic cells are high enough to potentially affect cellular function.

Role of Transcriptional Read-Through in PRE Activity in Drosophila melanogaster

Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 79-86 ◽  
Author(s):  
P. V. Elizar’ev ◽  
D. V. Lomaev ◽  
D. A. Chetverina ◽  
P. G. Georgiev ◽  
M. M. Erokhin
Keyword(s):  
Dna Sequences ◽  
Cell Types ◽  
Transcription Terminator ◽  
Response Elements ◽  
Polycomb Response Elements ◽  
The Individual ◽  
Multicellular Organisms ◽  
Different Cell Types ◽  
Main Factor

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.

ABOUT SOME PECULIARITIES OF THE PHYSIOLOGICAL HETEROGENEITY OF THE POPULATION OF SCENEDESMUS QUADRICAUDA (TURP.) BREB. IN THE PRESENCE OF LOW CONCENTRATIONS OF METALS

2018 ◽  
pp. 34-43
Author(s):  
V. I. Ipatova ◽  
A. G. Dmitrieva ◽  
О. F. Filenko ◽  
T. V. Drozdenko
Keyword(s):  
Cell Division ◽  
Toxic Effect ◽  
Copper Chloride ◽  
Single Cells ◽  
Physiological State ◽  
Scenedesmus Quadricauda ◽  
Physiological Status ◽  
Lag Phase ◽  
Protective Mechanism ◽  
Low Concentrations

The structure of the laboratory population of green microalgae Scenedesmus quadricauda (Turp.) Breb (=Desmodesmus communis E. Hegew.) was studied at different stages of its growth (lag-phase, log-phase and stationary phase) at low concentrations of copper chloride and silver nitrate by the method microculture, allowing to monitor the state and development of single cells having different physiological status. The response of the culture of S. quadricauda - the change in the number of cells and the fractional composition (the fraction of dividing, «dormant» and dying cells) depended not only on the concentration of the toxicant in the medium, but also on the physiological state of the culture: the level of synchronization and the growth phase. Silver ions at low concentrations had a more pronounced toxic effect on the culture than copper ions at different phases of its development, especially at a concentration of 0.001 mg/l (10-9 M). The main mechanism of the toxic effect of metals is to inhibit the process of cell division. At low concentrations of toxicants, especially at a concentration of 0.001 mg/l, a «paradoxical» effect expressed in the predominance of the fraction of «dormant» cells was revealed. The temporary inhibition of the process of cell division can be regarded as a protective mechanism that allows preserving the integrity of the population and its ability to survive in a changing environment. The obtained data explain the effect of action of low concentrations of substances due to their inclusion in the cell, the subsequent accumulation in the cell and their low excretion.

Efficacy of prayer in inducing immediate physiological changes: a systematic analysis of objective experiments

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Felix Chin ◽  
Ryan Chou ◽  
Muhammad Waqas ◽  
Kunal Vakharia ◽  
Hamid Rai ◽  
...  
Keyword(s):  
Physiological State ◽  
Experimental Studies ◽  
Peripheral Resistance ◽  
Pain Tolerance ◽  
Physiological Status ◽  
Physiological Changes ◽  
Mental Functioning ◽  
Baroreceptor Sensitivity ◽  
Systematic Analysis ◽  
Blood Marker

Abstract Objectives To assess the immediate impact of prayer on physiological state by systematically reviewing objective, controlled experimental studies in the literature. Content Experimental studies measuring objective physiological changes induced by prayer. Studies containing the keyword, “Prayer” anywhere in the title or abstract were curated from the following databases: Public/Publisher Medline (PubMed), Excerpta Medica Database (EMBASE) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) in May 2019. Titles and abstracts were screened with the remaining 30 articles analyzed for inclusion. Only experimental studies were included. Summary Eight experimental studies were identified of which five investigated neurocognitive changes and three investigated systemic physiological changes during prayer. The five studies focusing on neuroactivity used functional MRI (fMRI), electroencephalography or SPECT imaging to obtain measurements. The remaining three studies analyzed an array of systemic physiological metrics, including blood pressure, heart rate, respiratory rate, peripheral resistance, baroreceptor sensitivity and/or cardiovascular rhythm variability during prayer. All studies aside from one saw objective changes during prayer. Neurocognitive changes were mainly associated with improved mental functioning, control and pain tolerance. Prayer was found to slow down physiological functions in two of the three vital-based studies, with the third reporting no change in physiological status. None of the studies measured blood marker changes. Outlook Experimental studies show prayer to induce healthy neurocognitive and physiological changes. Additional studies exploring objective measures from prayer are encouraged to provide practitioners with a more nuanced, scientific perspective when it comes to prescribing prayer as a complementary and alternative medicine (CAM) therapy.

scholarly journals Scotopic thresholds on dark-adapted chromatic perimetry in healthy aging and age-related macular degeneration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manjot Kaur Grewal ◽  
Shruti Chandra ◽  
Alan Bird ◽  
Glen Jeffery ◽  
Sobha Sivaprasad
Keyword(s):  
Macular Degeneration ◽  
Healthy Aging ◽  
Intraclass Correlation ◽  
Age Related Macular Degeneration ◽  
Healthy Individuals ◽  
Age Related ◽  
Rod Function ◽  
The Mean ◽  
Highly Correlated ◽  
Effect Of Age

AbstractTo evaluate the effect of aging, intra- and intersession repeatability and regional scotopic sensitivities in healthy and age-related macular degeneration (AMD) eyes. Intra- and intersession agreement and effect of age was measured in healthy individuals. The mean sensitivity (MS) and pointwise retinal sensitivities (PWS) within the central 24° with 505 nm (cyan) and 625 nm (red) stimuli were evaluated in 50 individuals (11 healthy and 39 AMD eyes). The overall intra- and intersession had excellent reliability (intraclass correlation coefficient, ICC > 0.90) and tests were highly correlated (Spearman rs = 0.75–0.86). Eyes with subretinal drusenoid deposit (SDD) had reduced PWS centrally, particularly at inferior and nasal retinal locations compared with controls and intermediate AMD (iAMD) without SDD. There was no difference in MS or PWS at any retinal location between iAMD without SDD and healthy individuals nor between iAMD with SDD and non-foveal atrophic AMD groups. Eyes with SDD have reduced rod function compared to iAMD without SDD and healthy eyes, but similar to eyes with non-foveal atrophy. Our results highlight rod dysfunction is not directly correlated with drusen load and SDD location.

scholarly journals A generalization of t-SNE and UMAP to single-cell multimodal omics

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Van Hoan Do ◽  
Stefan Canzar
Keyword(s):  
Dimensionality Reduction ◽  
Single Cell ◽  
Cell Types ◽  
High Dimensional ◽  
Omics Data ◽  
Relative Contribution ◽  
Reduction Techniques ◽  
Dimensionality Reduction Techniques ◽  
Concise Representation ◽  
Cellular Identity

AbstractEmerging single-cell technologies profile multiple types of molecules within individual cells. A fundamental step in the analysis of the produced high-dimensional data is their visualization using dimensionality reduction techniques such as t-SNE and UMAP. We introduce j-SNE and j-UMAP as their natural generalizations to the joint visualization of multimodal omics data. Our approach automatically learns the relative contribution of each modality to a concise representation of cellular identity that promotes discriminative features but suppresses noise. On eight datasets, j-SNE and j-UMAP produce unified embeddings that better agree with known cell types and that harmonize RNA and protein velocity landscapes.

Monkey Model for IgE-Mediated Otitis Media with Effusion

1983 ◽  
Vol 92 (6_suppl) ◽  
pp. 30-30
Author(s):  
R. A. Friedman ◽  
W. J. Doyle ◽  
J. Fagin ◽  
C. D. Bluestone ◽  
P. Fireman
Keyword(s):  
Otitis Media With Effusion ◽  
Challenge Test ◽  
Complement C3 ◽  
Monkey Model ◽  
Age Related ◽  
Additional Funding ◽  
Adults And Children ◽  
Total Complement ◽  
Invasive Techniques ◽  
Cellular Components

Allergic and other immune mechanisms have been suggested as important in the etiology and pathogenesis of OME, and both humoral and cellular components of the immune response have been identified in MEEs obtained from patients with OME. Yet, specific and direct documentation of an immune basis for OME has not been forthcoming. To establish a causal relationship between an immune hypersensitivity and middle ear pathophysiology, a provocative intranasal antigen challenge test has been designed using the nine-step inflation-deflation tympanometric test for ET dysfunction. These initial studies were undertaken by OMRC personnel in association with the allergy and immunology service. Subsequently, on the basis of the preliminary observations additional funding was obtained (NIAID AI 19262) to confirm and extend these studies to document antigen-induced ET dysfunction in allergic adults and children, and to establish a clinical relevance for antigen-induced ET dysfunction. Because questions concerning the etiology and pathogenesis required invasive techniques and are not suitable in humans, a monkey animal model has also been developed. Our future plans will be to further develop the monkey model of OME employing IgE and other immune reactions in monkeys with normal ET function, or with compromised, surgically created ET function. The experimental MEE will be assayed for immune components, including IgA and its secretory piece; IgG, IgM, and IgE, total complement; C3, C4, and cells including polymorphonuclear leukocytes, eosinophils, and lymphocytes (both T and B cells). Since OME is mainly a disease of the young child, it is essential that age-related differences be explored in each aspect of our experimental model. The reversal and prevention of ET dysfunction and/or OME with several drugs, including cromolyn, steroids, and antihistamines, will be studied in humans and in the monkey model.

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