Maintaining integrity of germline DNA: individuals age, species do not

2015 ◽  
Vol 27 (6) ◽  
pp. 865 ◽  
Author(s):  
G. E. Seidel, Jr
Keyword(s):  
Genetic Material ◽  
Life Forms ◽  
Oxygen Species ◽  
Radiation Chemical ◽  
Older Parents ◽  
Disease States ◽  
Accumulation Of Damage ◽  
Germline Cells ◽  
Best Fit ◽  
Maintenance Methylation

All life forms are under constant assault, resulting in an accumulation of damage within each individual, in both somatic and germline cells. The obvious causes are: (1) mutations from radiation, chemical reactions like peroxidation and errors in replicating genetic material; (2) injury due to environmental insults, such as chemical alteration of proteins by reactive oxygen species; (3) epigenetic errors, such as failure of appropriate maintenance methylation of cytosines of DNA; and (4) numerous other problems, including retroviral invasions, inflammation and unhealthy microbiomes. Collectively, these phenomena constitute aging and/or certain disease states. Nature has developed numerous mechanisms to counteract these problems, such as proofreading enzymes, ubiquitous antioxidants and apoptotic death of unfit cells. However, none of these is completely effective. Although individuals accumulate damage, species usually do not become increasingly damaged; however, this could be one of the mechanisms for eventual extinction or evolution to a different species, the apparent fate of essentially all species. Nevertheless, germline DNA appears to remain sufficiently pristine to maintain fairly stable phenotypes over many generations. How do species avoid accumulating damage when composed of individuals that do? One broad answer seems to be reproductive redundancy followed by elimination of defects through the death of gametes, embryos, fetuses, neonates and postpubertal individuals, with the culling pressure increasing as potential parents age. Another major force appears to be evolutionary pressure; individuals that best fit the environment out-reproduce those that fit less well. What is impressive is that older and older parents continue to have offspring that are nearly as pristine as those of younger parents, even though their germline cells have continued to age. Although the offspring of old parents are not as fit, on average, as those of young parents, differences are small and, in some species, compensated for by superior parenting with accumulated experience. To conclude, it appears that species do not age, even though they are composed of individuals whose somatic and germline cells have aged.

scholarly journals Metabolic Control of m6A RNA Modification

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 80
Author(s):  
Joohwan Kim ◽  
Gina Lee
Keyword(s):  
Cell Fate ◽  
Metabolic Pathways ◽  
Epigenetic Modification ◽  
Genetic Material ◽  
Rna Modification ◽  
Cell Fate Decisions ◽  
Disease States ◽  
Evolutionarily Conserved ◽  
Regulate Cell Growth ◽  
Epigenetic Processes

Nutrients and metabolic pathways regulate cell growth and cell fate decisions via epigenetic modification of DNA and histones. Another key genetic material, RNA, also contains diverse chemical modifications. Among these, N6-methyladenosine (m6A) is the most prevalent and evolutionarily conserved RNA modification. It functions in various aspects of developmental and disease states, by controlling RNA metabolism, such as stability and translation. Similar to other epigenetic processes, m6A modification is regulated by specific enzymes, including writers (methyltransferases), erasers (demethylases), and readers (m6A-binding proteins). As this is a reversible enzymatic process, metabolites can directly influence the flux of this reaction by serving as substrates and/or allosteric regulators. In this review, we will discuss recent understanding of the regulation of m6A RNA modification by metabolites, nutrients, and cellular metabolic pathways.

scholarly journals Isoprostanes: an overview and putative roles in pulmonary pathophysiology

2001 ◽  
Vol 280 (6) ◽  
pp. L1067-L1082 ◽  
Author(s):  
L. J. Janssen
Keyword(s):  
Oxidative Stress ◽  
Membrane Lipids ◽  
Cell Types ◽  
Oxygen Species ◽  
Cell Type ◽  
Experimental Conditions ◽  
The Past ◽  
Disease States ◽  
Biological Responses ◽  
Markers Of Oxidative Stress

Isoprostanes are produced during peroxidation of membrane lipids by free radicals and reactive oxygen species. Initially, they were recognized as being valuable markers of oxidative stress, and in the past 10 years, dozens of disease states and experimental conditions with diverse etiologies have been shown to be associated with marked increases in urinary, plasma, and tissue levels of isoprostanes. However, they are not just mere markers; they evoke important biological responses on virtually every cell type found within the lung, and these responses exhibit compound-, tissue-, and species-related variations. In fact, the isoprostanes may mediate many of the features of the disease states for which they are used as indicators. In this review, I describe the chemistry, metabolism, and pharmacology of isoprostanes, with a particular emphasis on pulmonary cell types, and the possible roles of isoprostanes in pulmonary pathophysiology.

scholarly journals The Exacerbation of Aging and Oxidative Stress in the Epididymis of Sod1 Null Mice

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 151 ◽  
Author(s):  
Anaīs Noblanc ◽  
Alicia Klaassen ◽  
Bernard Robaire
Keyword(s):  
Oxidative Damage ◽  
Oxygen Species ◽  
Superoxide Dismutase 1 ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Theory Of Aging ◽  
Accumulation Of Damage ◽  
Effects Of Aging ◽  
And Oxidative Stress

There is growing evidence that the quality of spermatozoa decreases with age and that children of older fathers have a higher incidence of birth defects and genetic mutations. The free radical theory of aging proposes that changes with aging are due to the accumulation of damage induced by exposure to excess reactive oxygen species. We showed previously that absence of the superoxide dismutase 1 (Sod1) antioxidant gene results in impaired mechanisms of repairing DNA damage in the testis in young Sod1−/− mice. In this study, we examined the effects of aging and the Sod−/− mutation on mice epididymal histology and the expression of markers of oxidative damage. We found that both oxidative nucleic acid damage (via 8-hydroxyguanosine) and lipid peroxidation (via 4-hydroxynonenal) increased with age and in Sod1−/− mice. These findings indicate that lack of SOD1 results in an exacerbation of the oxidative damage accumulation-related aging phenotype.

Article Commentary: Regulation of Protein Function by Residue Oxidation

2010 ◽  
Vol 3 ◽  
pp. PRI.S3327 ◽  
Author(s):  
Xing-Hai Zhang
Keyword(s):  
Protein Function ◽  
Regulatory Mechanism ◽  
Cellular Metabolism ◽  
Life Forms ◽  
Biological Macromolecules ◽  
Oxygen Species ◽  
Cellular Processes ◽  
Methionine Residues ◽  
Living Organisms ◽  
Face Generation

A majority of extant life forms require O2 to survive and thrive. Oxidation is inevitably one of the most active cellular processes and one constant challenge that living organisms must face. Generation of oxidants including reactive oxygen species is a natural consequence of cellular metabolism of all biological systems during normal life cycle under different environments. These oxidants oxidize many biological macromolecules such as proteins and affect their functions. Oxidation of specific amino acids in proteins may cause damage to protein structure and impair function, or may also activate protein activities and promote cellular metabolism. As an example, the reversible oxidation of cysteine and methionine residues has a profound impact on protein function and cellular process. A recent study that examines the effect of Met oxidation on Ser phosphorylation in a mitochondrial enzyme, pyruvate dehydrogenase, provides another demonstration that protein oxidation is an important regulatory mechanism for organisms to deal with developmental and environmental challenges throughout life processes.

scholarly journals Recurrent losses and rapid evolution of the condensin II complex in insectsg

2018 ◽  
Author(s):  
T. King ◽  
C.J. Leonard ◽  
J.C. Cooper ◽  
S. Nguyen ◽  
E. Joyce ◽  
...  
Keyword(s):  
Genome Organization ◽  
Molecular Mechanisms ◽  
Somatic Cells ◽  
Rapid Evolution ◽  
Genetic Material ◽  
Life Forms ◽  
Model Organisms ◽  
Homologous Chromosomes ◽  
Homologous Chromosome Pairing ◽  
Key Aspects

AbstractCondensins play a crucial role in the organization of genetic material by compacting and disentangling chromosomes. The condensin I and condensin II complexes are widely considered to have distinct functions based on studies in a few model organisms, although the specific functions of each complex are yet to be fully understood. The condensin II complex is critical for genome organization in Drosophila, and is a key anti-pairing factor that separates homologous chromosomes in somatic cells. Intriguingly, the Cap-G2 subunit of condensin II is absent in Drosophila melanogaster, and this loss may be related to the high levels of homologous chromosome pairing in somatic cells seen in flies. Here, we find that this Cap-G2 loss predates the origin of Dipterans, and other CapG2 losses have occurred independently in multiple insect lineages. Furthermore, the Cap-H2 and Cap-D3 subunits have also been repeatedly and independently lost in several insect orders, and some taxa lack condensin II-specific subunits entirely. We used Oligopaint DNA-FISH to quantify pairing levels in ten species across seven orders, representing several different configurations of the condensin II complex. We find that all non-Dipteran insects display near-uniform low pairing levels, suggesting that some key aspects of genome organization are robust to condensin II subunit losses. Finally, we observe consistent signatures of positive selection in condensin II subunits across flies and mammals. These findings suggest that these ancient complexes are far more evolutionarily labile than previously suspected, and are at the crossroads of several forms of genomic conflicts. Our results raise fundamental questions about the specific functions of the two condensin complexes and the interplay between them in taxa that have experienced subunit losses, and open the door to further investigations to elucidate the diversity of molecular mechanisms that underlie genome organization across various life forms.

scholarly journals An improved CRISPR/dCas9 interference tool for neuronal gene suppression

2020 ◽  
Author(s):  
Corey G. Duke ◽  
Svitlana V. Bach ◽  
Jasmin S. Revanna ◽  
Faraz A. Sultan ◽  
Nicholas T. Southern ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Repression ◽  
Expression System ◽  
Genetic Material ◽  
Gene Promoters ◽  
Disease States ◽  
Transcriptional Inhibition ◽  
Health And Disease ◽  
Neuronal Systems ◽  
And Function

The expression of genetic material governs brain development, differentiation, and function, and targeted manipulation of gene expression is required to understand contributions of gene function to health and disease states. Although recent improvements in CRISPR/dCas9 interference (CRISPRi) technology have enabled targeted transcriptional repression at selected genomic sites, integrating these techniques for use in non-dividing neuronal systems remains challenging. Previously, we optimized a dual lentivirus expression system to express CRISPR-based activation machinery in post-mitotic neurons. Here we used a similar strategy to adapt an improved dCas9-KRAB-MeCP2 repression system for robust transcriptional inhibition in neurons. We find that lentiviral delivery of a dCas9-KRAB-MeCP2 construct driven by the neuron-selective promoter human synapsin 1 enabled transgene expression in primary rat neurons. Next, we demonstrate transcriptional repression using CRISPR sgRNAs targeting diverse gene promoters, and show superiority of this system in neurons compared to existing RNA interference methods for robust transcript specific manipulation at the complex Brain-derived neurotrophic factor (Bdnf) gene. Our findings advance this improved CRISPRi technology for use in neuronal systems for the first time, potentially enabling improved ability to manipulate gene expression states in the nervous system.

scholarly journals Reactive Oxygen Species as Potential Drivers of the Seed Aging Process

Plants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 174 ◽  
Author(s):  
Katarzyna Kurek ◽  
Beata Plitta-Michalak ◽  
Ewelina Ratajczak
Keyword(s):  
Reactive Oxygen Species ◽  
Genetic Material ◽  
Seed Viability ◽  
Reactive Oxygen ◽  
Life Cycle Stage ◽  
Storage Conditions ◽  
Oxygen Species ◽  
Membrane Phospholipids ◽  
Seed Aging ◽  
Long Term Storage

Seeds are an important life cycle stage because they guarantee plant survival in unfavorable environmental conditions and the transfer of genetic information from parents to offspring. However, similar to every organ, seeds undergo aging processes that limit their viability and ultimately cause the loss of their basic property, i.e., the ability to germinate. Seed aging is a vital economic and scientific issue that is related to seed resistance to an array of factors, both internal (genetic, structural, and physiological) and external (mainly storage conditions: temperature and humidity). Reactive oxygen species (ROS) are believed to initiate seed aging via the degradation of cell membrane phospholipids and the structural and functional deterioration of proteins and genetic material. Researchers investigating seed aging claim that the effective protection of genetic resources requires an understanding of the reasons for senescence of seeds with variable sensitivity to drying and long-term storage. Genomic integrity considerably affects seed viability and vigor. The deterioration of nucleic acids inhibits transcription and translation and exacerbates reductions in the activity of antioxidant system enzymes. All of these factors significantly limit seed viability.

scholarly journals The Ryanodine Receptor as a Sensor for Cellular Environments in Muscles

2021 ◽  
Author(s):  
Takuya Kobayashi ◽  
Nagomi Kurebayashi ◽  
Takashi Murayama
Keyword(s):  
Ryanodine Receptor ◽  
Divalent Cations ◽  
Oxygen Species ◽  
Channel Activity ◽  
Release Channel ◽  
Disease States ◽  
Cellular Environment ◽  
Associated Proteins ◽  
Cardiac Muscles ◽  
Exercise Fatigue

The ryanodine receptor (RyR) is a Ca2+ release channel in the sarcoplasmic reticulum of skeletal and cardiac muscles and plays a key role in excitation-contraction coupling. The activity of the RyR is regulated by many intracellular factors such as divalent cations (Ca2+ and Mg2+), nucleotides, associated proteins, and reactive oxygen species. Since these intracellular factors change depending on the condition of the muscle, e.g., exercise, fatigue, or disease states, the RyR channel activity will be altered accordingly. In this review, we describe how the RyR channel is regulated under various conditions and discuss the possibility that the RyR acts as a sensor for change in the cellular environment of muscles.

scholarly journals From Ashes to Diamonds

2021 ◽  
Vol 26 ◽  
pp. 122-138
Author(s):  
Filipe Calvão ◽  
Lindsay Bell
Keyword(s):  
United States ◽  
Human Body ◽  
Genetic Material ◽  
The United States ◽  
Life Forms ◽  
Life And Death ◽  
Synthetic Diamonds ◽  
Artificial Memory ◽  
Emotional Value ◽  
Living Objects

This article examines the making and makers of “memorial diamonds.” These are “natural” diamonds identical to gemstones found in nature but produced in laboratories with carbon sourced from genetic material (cremation ashes) or other objects of symbolic and emotional value. Threading corporality and objectified life forms, we examine the transformation from ashes to the “afterlife” of these “living” objects that are at once synthetic and organic. We ask, first, what material and affective properties distinguish synthetic diamonds from those extracted from nature? Second, how are these living and memorialized representations of inert substances – in continuity with bodily elements of the deceased – valued and mediated through “real” human, though artificially grown, natural objects? Drawing from research with the leading companies in the memorial diamond business in Switzerland and the United States, this article suggests that these diamonds’ singular connection to the human body offer a window into the transmutations between nature and the artificial, memory and material likeness, life and death.

scholarly journals Transplanting a Microbial Organ: the Good, the Bad, and the Unknown

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Dionysios A. Antonopoulos ◽  
Eugene B. Chang
Keyword(s):  
Inflammatory Bowel Disease ◽  
Complex Disease ◽  
Fecal Microbiota Transplantation ◽  
Genetic Material ◽  
Fecal Microbiota ◽  
Unintended Consequences ◽  
State Of Health ◽  
Disease States ◽  
Intestinal Dysbiosis ◽  
Inflammatory Bowel

ABSTRACT Fecal microbiota transplantation (FMT) has received increased attention as a therapy for correcting intestinal dysbiosis and restoring a state of health in patients suffering from either recalcitrant infection by Clostridium difficile or more complex disease states, such as inflammatory bowel disease (IBD). The “gut microbial organ” from the donor that is used in these transplants may serve to transfer genetic material between donor and recipient via virus-like particles, specifically bacteriophages, that infect the bacterial component of the microbiota. The recently published study by Chehoud et al. provides evidence for not only the transfer of bacteriophages during FMT but also the transfer of multiple populations of bacteriophages to recipients from the donor microbiota used (C. Chehoud et al., mBio 7:e00322-16, 2016, http://dx.doi.org/10.1128/mBio.00322-16 ). While the clinical significance of these findings remains unclear, nothing short of a diligent and persistent effort is needed to define the intended and unintended consequences of FMT.

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