scholarly journals Epigenetics of Aging and Aging-Associated Diseases

2021 ◽  
Vol 22 (1) ◽  
pp. 401
Author(s):  
Dominik Saul ◽  
Robyn Laura Kosinsky
Keyword(s):  
Neurodegenerative Disorders ◽  
Physiological Function ◽  
Living Organism ◽  
Histone Variants ◽  
Chromatin Accessibility ◽  
Epigenetic Changes ◽  
Cellular Processes ◽  
The Past ◽  
Epigenetic Events ◽  
Expression Activity

Aging represents the multifactorial decline in physiological function of every living organism. Over the past decades, several hallmarks of aging have been defined, including epigenetic deregulation. Indeed, multiple epigenetic events were found altered across different species during aging. Epigenetic changes directly contributing to aging and aging-related diseases include the accumulation of histone variants, changes in chromatin accessibility, loss of histones and heterochromatin, aberrant histone modifications, and deregulated expression/activity of miRNAs. As a consequence, cellular processes are affected, which results in the development or progression of several human pathologies, including cancer, diabetes, osteoporosis, and neurodegenerative disorders. In this review, we focus on epigenetic mechanisms underlying aging-related processes in various species and describe how these deregulations contribute to human diseases.

scholarly journals Uncovering the Invisible: Mono-ADP-ribosylation Moved into the Spotlight

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 680
Author(s):  
Ann-Katrin Hopp ◽  
Michael O. Hottiger
Keyword(s):  
Nucleic Acids ◽  
Nicotinamide Adenine Dinucleotide ◽  
Physiological Function ◽  
Adenosine Diphosphate ◽  
Current Understanding ◽  
Post Translational Modification ◽  
Adp Ribosylation ◽  
Cellular Processes ◽  
The Past ◽  
Technological Advances

Adenosine diphosphate (ADP)-ribosylation is a nicotinamide adenine dinucleotide (NAD+)-dependent post-translational modification that is found on proteins as well as on nucleic acids. While ARTD1/PARP1-mediated poly-ADP-ribosylation has extensively been studied in the past 60 years, comparably little is known about the physiological function of mono-ADP-ribosylation and the enzymes involved in its turnover. Promising technological advances have enabled the development of innovative tools to detect NAD+ and NAD+/NADH (H for hydrogen) ratios as well as ADP-ribosylation. These tools have significantly enhanced our current understanding of how intracellular NAD dynamics contribute to the regulation of ADP-ribosylation as well as to how mono-ADP-ribosylation integrates into various cellular processes. Here, we discuss the recent technological advances, as well as associated new biological findings and concepts.

The nucleosome: a little variation goes a long wayThis paper is one of a selection of papers published in this Special Issue, entitled 27th International West Coast Chromatin and Chromosome Conference, and has undergone the Journal's usual peer review process.

2006 ◽  
Vol 84 (4) ◽  
pp. 505-507 ◽  
Author(s):  
Emily Bernstein ◽  
Sandra B. Hake
Keyword(s):  
Peer Review Process ◽  
Gene Activation ◽  
Epigenetic Inheritance ◽  
Histone Variants ◽  
Post Translational Modifications ◽  
Chromatin Compaction ◽  
Cellular Processes ◽  
Chromatin Template ◽  
Mitosis And Meiosis ◽  
Selection Of

Changes in the overall structure of chromatin are essential for the proper regulation of cellular processes, including gene activation and silencing, DNA repair, chromosome segregation during mitosis and meiosis, X chromosome inactivation in female mammals, and chromatin compaction during apoptosis. Such alterations of the chromatin template occur through at least 3 interrelated mechanisms: post-translational modifications of histones, ATP-dependent chromatin remodeling, and the incorporation (or replacement) of specialized histone variants into chromatin. Of these mechanisms, the exchange of variants into and out of chromatin is the least well understood. However, the exchange of conventional histones for variant histones has distinct and profound consequences within the cell. This review focuses on the growing number of mammalian histone variants, their particular biological functions and unique features, and how they may affect the structure of the nucleosome. We propose that a given nucleosome might not consist of heterotypic variants, but rather, that only specific histone variants come together to form a homotypic nucleosome, a hypothesis that we refer to as the nucleosome code. Such nucleosomes might in turn participate in marking specific chromatin domains that may contribute to epigenetic inheritance.

scholarly journals Cell Tracking for Organoids: Lessons From Developmental Biology

2021 ◽  
Vol 9 ◽  
Author(s):  
Max A. Betjes ◽  
Xuan Zheng ◽  
Rutger N. U. Kok ◽  
Jeroen S. van Zon ◽  
Sander J. Tans
Keyword(s):  
Cell Tracking ◽  
Cellular Level ◽  
Model Systems ◽  
Great Promise ◽  
Cellular Processes ◽  
The Past ◽  
Fluorescent Markers ◽  
Lineage Trees ◽  
Microscopy Techniques ◽  
Organizational Principles

Organoids have emerged as powerful model systems to study organ development and regeneration at the cellular level. Recently developed microscopy techniques that track individual cells through space and time hold great promise to elucidate the organizational principles of organs and organoids. Applied extensively in the past decade to embryo development and 2D cell cultures, cell tracking can reveal the cellular lineage trees, proliferation rates, and their spatial distributions, while fluorescent markers indicate differentiation events and other cellular processes. Here, we review a number of recent studies that exemplify the power of this approach, and illustrate its potential to organoid research. We will discuss promising future routes, and the key technical challenges that need to be overcome to apply cell tracking techniques to organoid biology.

scholarly journals A genome-wide screen in the mouse liver reveals sex-specific and cell non-autonomous regulation of cell fitness

2021 ◽  
Author(s):  
Heather R. Keys ◽  
Kristin A. Knouse
Keyword(s):  
Functional Genomics ◽  
High Throughput ◽  
Mouse Liver ◽  
Ex Vivo ◽  
Screening Method ◽  
Living Organism ◽  
Cellular Processes ◽  
Autonomous Regulation ◽  
Genome Wide ◽  
A Genome

ABSTRACTOur ability to understand and modulate mammalian physiology and disease requires knowing how all genes contribute to any given phenotype in the organism. Genome-wide screening using CRISPR-Cas9 has emerged as a powerful method for the genetic dissection of cellular processes1,2, but the need to stably deliver single guide RNAs to millions of cells has restricted its implementation to ex vivo systems. These ex vivo systems cannot reproduce all of the cellular phenotypes observed in vivo nor can they recapitulate all of the factors that influence these phenotypes. There thus remains a pressing need for high-throughput functional genomics in a living organism. Here, we establish accessible genome-wide screening in the mouse liver and use this approach to uncover the complete regulation of cellular fitness in a living organism. We discover novel sex-specific and cell non-autonomous regulation of cell growth and viability. In particular, we find that the class I major histocompatibility complex is essential for preventing immune-mediated clearance of hepatocytes. Our approach provides the first comprehensive picture of cell fitness in a living organism and highlights the importance of investigating cellular phenomena in their native context. Our screening method is robust, scalable, and easily adapted to examine diverse cellular processes using any CRISPR application. We have hereby established a foundation for high-throughput functional genomics in a living mammal, enabling unprecedented insight into mammalian physiology and disease.

Proteasome-Independent Functions of Ubiquitin in Endocytosis and Signaling

Science ◽  
2007 ◽  
Vol 315 (5809) ◽  
pp. 201-205 ◽  
Author(s):  
Debdyuti Mukhopadhyay ◽  
Howard Riezman
Keyword(s):  
Neurodegenerative Disorders ◽  
Posttranslational Modification ◽  
Protein Trafficking ◽  
Cellular Proteins ◽  
Cellular Processes ◽  
Signal Transduction Protein ◽  
Major Player ◽  
Independent Functions ◽  
Inflammatory Immune Response ◽  
Ubiquitination System

Ubiquitination is a reversible posttranslational modification of cellular proteins, in which a 76–amino acid polypeptide, ubiquitin, is primarily attached to the ϵ-amino group of lysines in target proteins. Ubiquitination is a major player in regulating a broad host of cellular processes, including cell division, differentiation, signal transduction, protein trafficking, and quality control. Aberrations in the ubiquitination system are implicated in pathogenesis of some diseases, certain malignancies, neurodegenerative disorders, and pathologies of the inflammatory immune response. Here, we discuss the proteasome-independent roles of ubiquitination in signaling and endocytosis.

‘Language of the past’ - Exploring past tense disruption during autobiographical narration in neurodegenerative disorders

2015 ◽  
Vol 10 (2) ◽  
pp. 295-316 ◽  
Author(s):  
Muireann Irish ◽  
Jody Kamminga ◽  
Donna Rose Addis ◽  
Stephen Crain ◽  
Rosalind Thornton ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Past Tense ◽  
The Past

scholarly journals Dynamically remembered present: Virtual memory as a basis for the stories we live

2013 ◽  
Vol 69 (1) ◽  
Author(s):  
Cornelius W. Du Toit
Keyword(s):  
Literary History ◽  
Life Stories ◽  
Human Life ◽  
Living Organism ◽  
Virtual Memory ◽  
Historical Research ◽  
Human Consciousness ◽  
The Past ◽  
The Universe

In this article memory was viewed as a crucial key to the discovery of reality. It is the basis of historical research at all levels, hence it is not confined to a function of human consciousness (brain operations): its physical vestiges are discernible in the universe, in fossils, in the DNA of species. Memory inscribes information in various ways. On a human level it is not recalled computer-wise: imagination, emotion and tacit motives play a role in how we remember. The article investigated the way in which memory underlies the operation of every cell in any living organism. Against this background the role of memory in humans and its decisive influence on every level of human life are examined. Gerald Edelman’s work in this regard was considered. Marcel Proust’s focus on memory is an underlying thread running through his novels, unrivalled in literary history. Some prominent examples were analysed in this article. In light of the foregoing the role of memory in religious experience was then discussed. The virtuality of memory is encapsulated in the statement that we remember the present whilst reliving the past. Memory characterised by virtuality is basic to our autobiographic narratives. The nature of memory determines our life stories, hence our perception of the human self as dynamically variable and open to the future.

scholarly journals Active enhancer and chromatin accessibility landscapes chart the regulatory network of primary multiple myeloma

Blood ◽  
2018 ◽  
Vol 131 (19) ◽  
pp. 2138-2150 ◽  
Author(s):  
Yi Jin ◽  
Kenian Chen ◽  
Ayla De Paepe ◽  
Eva Hellqvist ◽  
Aleksandra D. Krstic ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Regulatory Network ◽  
Chromatin Accessibility ◽  
Epigenetic Changes ◽  
Active Enhancer ◽  
Key Points ◽  
Gene Regulatory

Key Points Gene regulatory features in MM patients reveal a key regulatory network and epigenetic changes that underpin the disease.

scholarly journals Epigenetic reprogramming and chromatin accessibility in pediatric diffuse intrinsic pontine gliomas: a neural developmental disease

2019 ◽  
Vol 22 (2) ◽  
pp. 195-206 ◽  
Author(s):  
Flor M Mendez ◽  
Felipe J Núñez ◽  
Maria B Garcia-Fabiani ◽  
Santiago Haase ◽  
Stephen Carney ◽  
...  
Keyword(s):  
Histone Variants ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Chromatin Accessibility ◽  
Therapeutic Implications ◽  
Polycomb Repressive Complex 2 ◽  
K27m Mutation ◽  
Histone 3 ◽  
Epigenetic Programming ◽  
Genes Encoding ◽  
Diffuse Intrinsic Pontine Gliomas

Abstract Diffuse intrinsic pontine glioma (DIPG) is a rare but deadly pediatric brainstem tumor. To date, there is no effective therapy for DIPG. Transcriptomic analyses have revealed DIPGs have a distinct profile from other pediatric high-grade gliomas occurring in the cerebral hemispheres. These unique genomic characteristics coupled with the younger median age group suggest that DIPG has a developmental origin. The most frequent mutation in DIPG is a lysine to methionine (K27M) mutation that occurs on H3F3A and HIST1H3B/C, genes encoding histone variants. The K27M mutation disrupts methylation by polycomb repressive complex 2 on histone H3 at lysine 27, leading to global hypomethylation. Histone 3 lysine 27 trimethylation is an important developmental regulator controlling gene expression. This review discusses the developmental and epigenetic mechanisms driving disease progression in DIPG, as well as the profound therapeutic implications of epigenetic programming.

scholarly journals Pharmaceutical Applications of Molecular Tweezers, Clefts and Clips

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1803 ◽  
Author(s):  
Amira Mbarek ◽  
Ghina Moussa ◽  
Jeanne Leblond Chain
Keyword(s):  
Cardiovascular Disease ◽  
Neurodegenerative Disorders ◽  
Therapeutic Agents ◽  
Mechanistic Studies ◽  
Molecular Tweezers ◽  
The Past ◽  
Pharmaceutical Applications ◽  
Controlled Motion

Synthetic acyclic receptors, composed of two arms connected with a spacer enabling molecular recognition, have been intensively explored in host-guest chemistry in the past decades. They fall into the categories of molecular tweezers, clefts and clips, depending on the geometry allowing the recognition of various guests. The advances in synthesis and mechanistic studies have pushed them forward to pharmaceutical applications, such as neurodegenerative disorders, infectious diseases, cancer, cardiovascular disease, diabetes, etc. In this review, we provide a summary of the synthetic molecular tweezers, clefts and clips that have been reported for pharmaceutical applications. Their structures, mechanism of action as well as in vitro and in vivo results are described. Such receptors were found to selectively bind biological guests, namely, nucleic acids, sugars, amino acids and proteins enabling their use as biosensors or therapeutics. Particularly interesting are dynamic molecular tweezers which are capable of controlled motion in response to an external stimulus. They proved their utility as imaging agents or in the design of controlled release systems. Despite some issues, such as stability, cytotoxicity or biocompatibility that still need to be addressed, it is obvious that molecular tweezers, clefts and clips are promising candidates for several incurable diseases as therapeutic agents, diagnostic or delivery tools.

Sign in / Sign up

Export Citation Format

Share Document