scholarly journals Comparison of the transcriptome in circulating leukocytes in early lactation between primiparous and multiparous cows provides evidence for age-related changes

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Laura Buggiotti ◽  
Zhangrui Cheng ◽  
Mazdak Salavati ◽  
Claire D. Wathes ◽  
Alan Fahey ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Cell Function ◽  
Energy Utilization ◽  
Model Organisms ◽  
Early Lactation ◽  
Functional Annotation Cluster ◽  
Age Related ◽  
Genes Encoding ◽  
Dna Replication And Repair ◽  
Defence Proteins

Abstract Background Previous studies have identified many immune pathways which are consistently altered in humans and model organisms as they age. Dairy cows are often culled at quite young ages due to an inability to cope adequately with metabolic and infectious diseases, resulting in reduced milk production and infertility. Improved longevity is therefore a desirable trait which would benefit both farmers and their cows. This study analysed the transcriptome derived from RNA-seq data of leukocytes obtained from Holstein cows in early lactation with respect to lactation number. Results Samples were divided into three lactation groups for analysis: i) primiparous (PP, n = 53), ii) multiparous in lactations 2–3 (MP 2–3, n = 121), and iii) MP in lactations 4–7 (MP > 3, n = 55). Leukocyte expression was compared between PP vs MP > 3 cows with MP 2–3 as background using DESeq2 followed by weighted gene co-expression network analysis (WGCNA). Seven modules were significantly correlated (r ≥ 0.25) to the trait lactation number. Genes from the modules which were more highly expressed in either the PP or MP > 3 cows were pooled, and the gene lists subjected to David functional annotation cluster analysis. The top three clusters from modules more highly expressed in the PP cows all involved regulation of gene transcription, particularly zinc fingers. Another cluster included genes encoding enzymes in the mitochondrial beta-oxidation pathway. Top clusters up-regulated in MP > 3 cows included the terms Glycolysis/Gluconeogenesis, C-type lectin, and Immunity. Differentially expressed candidate genes for ageing previously identified in the human blood transcriptome up-regulated in PP cows were mainly associated with T-cell function (CCR7, CD27, IL7R, CAMK4, CD28), mitochondrial ribosomal proteins (MRPS27, MRPS9, MRPS31), and DNA replication and repair (WRN). Those up-regulated in MP > 3 cows encoded immune defence proteins (LYZ, CTSZ, SREBF1, GRN, ANXA5, ADARB1). Conclusions Genes and pathways associated with lactation number in cows were identified for the first time to date, and we found that many were comparable to those known to be associated with ageing in humans and model organisms. We also detected changes in energy utilization and immune responses in leukocytes from older cows.

scholarly journals Age Related Changes in the Circulating Leukocyte Transcriptome in Dairy Cows

2020 ◽  
Author(s):  
Laura Buggiotti ◽  
Zhangrui Cheng ◽  
Mazdak Salavati ◽  
Claire D. Wathes
Keyword(s):  
Dairy Cows ◽  
Ribosomal Proteins ◽  
Cell Function ◽  
Age Groups ◽  
Energy Utilization ◽  
Model Organisms ◽  
Functional Annotation Cluster ◽  
Age Related ◽  
Genes Encoding ◽  
Defence Proteins

Abstract Background: Previous studies of ageing have identified many pathways which are consistently altered in humans and model organisms. Dairy cows are often culled at quite young ages due to an inability to cope adequately with metabolic and infectious diseases, resulting in reduced milk production and infertility. Improved longevity is therefore a desirable trait which would benefit both farmers and their cows. This study analysed the transcriptome derived from RNA-seq data of leukocytes obtained from Holstein cows in early lactation with respect to lactation number. Results: Samples were divided into three age groups for analysis: i) primiparous (PP, n = 53), ii) multiparous in lactations 2-3 (MP 2-3, n = 121), and iii) MP in lactations 4-7 (MP>3, n = 55). Leukocyte expression was compared between PP vs MP>3 cows with MP 2-3 as background using DESeq2 followed by weighted gene co-expression network analysis (WGCNA). Seven modules were significantly correlated (r ≥ 0.25) to the trait age. Genes from the modules which were more highly expressed in either the PP or MP>3 cows were pooled, and the gene lists subjected to David functional annotation cluster analysis. The top three clusters from modules more highly expressed in the PP cows all involved regulation of gene transcription, particularly zinc fingers. Another cluster included genes encoding enzymes in the mitochondrial beta-oxidation pathway. Top clusters up-regulated in MP>3 cows included the terms Glycolysis/Gluconeogenesis, C-type lectin, and Immunity. Differentially expressed candidate genes for ageing previously identified in the human blood transcriptome up-regulated in PP cows were mainly associated with T-cell function (CCR7, CD27, IL7R, CAMK4, CD28), mitochondrial ribosomal proteins (MRPS27, MRPS9, MRPS31), and DNA replication and repair (WRN). Those up-regulated in MP>3 cows encoded immune defence proteins (LYZ, CTSZ, SREBF1, GRN, ANXA5, ADARB1). Conclusions: Genes and pathways associated with age in cows were identified for the first time to date, and we found that many were comparable to those known to be associated with ageing in humans and model organisms. We also detected changes in energy utilization and immune responses in leukocytes with age.

Ribosomal protein gene regulation: what about plants?

2006 ◽  
Vol 84 (3) ◽  
pp. 342-362 ◽  
Author(s):  
Kerri B. McIntosh ◽  
Peta C. Bonham-Smith
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Ribosomal Proteins ◽  
Protein Gene ◽  
Current Knowledge ◽  
Ribosomal Protein Gene ◽  
Regulatory Mechanisms ◽  
Model Organisms ◽  
Functional Genes ◽  
Genes Encoding

The ribosome is an intricate ribonucleoprotein complex with a multitude of protein constituents present in equimolar amounts. Coordination of the synthesis of these ribosomal proteins (r-proteins) presents a major challenge to the cell. Although most r-proteins are highly conserved, the mechanisms by which r-protein gene expression is regulated often differ widely among species. While the primary regulatory mechanisms coordinating r-protein synthesis in bacteria, yeast, and animals have been identified, the mechanisms governing the coordination of plant r-protein expression remain largely unexplored. In addition, plants are unique among eukaryotes in carrying multiple (often more than two) functional genes encoding each r-protein, which substantially complicates coordinate expression. A survey of the current knowledge regarding coordinated systems of r-protein gene expression in different model organisms suggests that vertebrate r-protein gene regulation provides a valuable comparison for plants.

scholarly journals Molecular and phenotypic analysis of rodent models reveals conserved and species-specific modulators of human sarcopenia

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Anastasiya Börsch ◽  
Daniel J. Ham ◽  
Nitish Mittal ◽  
Lionel A. Tintignac ◽  
Eugenia Migliavacca ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Inflammatory Responses ◽  
Molecular Data ◽  
Model Organisms ◽  
Sequencing Data ◽  
Phenotypic Analysis ◽  
Age Related ◽  
Analogous Data ◽  
Species Specific ◽  
And Function

AbstractSarcopenia, the age-related loss of skeletal muscle mass and function, affects 5–13% of individuals aged over 60 years. While rodents are widely-used model organisms, which aspects of sarcopenia are recapitulated in different animal models is unknown. Here we generated a time series of phenotypic measurements and RNA sequencing data in mouse gastrocnemius muscle and analyzed them alongside analogous data from rats and humans. We found that rodents recapitulate mitochondrial changes observed in human sarcopenia, while inflammatory responses are conserved at pathway but not gene level. Perturbations in the extracellular matrix are shared by rats, while mice recapitulate changes in RNA processing and autophagy. We inferred transcription regulators of early and late transcriptome changes, which could be targeted therapeutically. Our study demonstrates that phenotypic measurements, such as muscle mass, are better indicators of muscle health than chronological age and should be considered when analyzing aging-related molecular data.

scholarly journals The ATP Synthase Deficiency in Human Diseases

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 325
Author(s):  
Chiara Galber ◽  
Stefania Carissimi ◽  
Alessandra Baracca ◽  
Valentina Giorgio
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Mitochondrial Protein ◽  
High Energy ◽  
Neurocognitive Disorders ◽  
Human Diseases ◽  
Age Related ◽  
Muscle Tissues ◽  
Mitochondrial Atp Synthase ◽  
Genes Encoding

Human diseases range from gene-associated to gene-non-associated disorders, including age-related diseases, neurodegenerative, neuromuscular, cardiovascular, diabetic diseases, neurocognitive disorders and cancer. Mitochondria participate to the cascades of pathogenic events leading to the onset and progression of these diseases independently of their association to mutations of genes encoding mitochondrial protein. Under physiological conditions, the mitochondrial ATP synthase provides the most energy of the cell via the oxidative phosphorylation. Alterations of oxidative phosphorylation mainly affect the tissues characterized by a high-energy metabolism, such as nervous, cardiac and skeletal muscle tissues. In this review, we focus on human diseases caused by altered expressions of ATP synthase genes of both mitochondrial and nuclear origin. Moreover, we describe the contribution of ATP synthase to the pathophysiological mechanisms of other human diseases such as cardiovascular, neurodegenerative diseases or neurocognitive disorders.

Supplementation with Selenium Restores Age-Related Decline in Immune Cell Function

1995 ◽  
Vol 209 (4) ◽  
pp. 369-375 ◽  
Author(s):  
M. Roy ◽  
L. Kiremidjian-Schumacher ◽  
H. I. Wishe ◽  
M. W. Cohen ◽  
G. Stotzky
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Immune Cell Function ◽  
Age Related

scholarly journals Age-Related Mitochondrial DNA Depletion and the Impact on Pancreatic Beta Cell Function

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e115433 ◽  
Author(s):  
Donna L. Nile ◽  
Audrey E. Brown ◽  
Meutia A. Kumaheri ◽  
Helen R. Blair ◽  
Alison Heggie ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Age Related ◽  
Mitochondrial Dna Depletion ◽  
Pancreatic Beta Cell Function ◽  
The Impact

Congenital neutropenia

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 344-350 ◽  
Author(s):  
Christoph Klein
Keyword(s):  
Ribosomal Proteins ◽  
Mitochondrial Proteins ◽  
Phenotypic Traits ◽  
Genetic Defects ◽  
Congenital Neutropenia ◽  
Lysosomal Function ◽  
Genes Encoding ◽  
And Function ◽  
Neutrophil Differentiation ◽  
Remarkable Progress

Abstract Congenital neutropenia comprises a variety of genetically heterogeneous phenotypic traits. Molecular elucidation of the underlying genetic defects has yielded important insights into the physiology of neutrophil differentiation and function. Non-syndromic variants of congenital neutropenia are caused by mutations in ELA2, HAX1, GFI1, or WAS. Syndromic variants of congenital neutropenia may be due to mutations in genes controlling glucose metabolism (SLC37A4, G6PC3) or lysosomal function (LYST, RAB27A, ROBLD3/p14, AP3B1, VPS13B). Furthermore, defects in genes encoding ribosomal proteins (SBDS, RMRP) and mitochondrial proteins (AK2, TAZ) are associated with congenital neutropenia syndromes. Despite remarkable progress in the field, many patients with congenital neutropenia cannot yet definitively be classified by genetic terms. This review addresses diagnostic and therapeutic aspects of congenital neutropenia and covers recent molecular and pathophysiological insights of selected congenital neutropenia syndromes.

Abstract 426: Laminin Downregulation Facilitates Cardiomyocyte Coupling in situ to Increase Contractile Function

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Ayla Sessions ◽  
Gaurav Kaushik ◽  
Adam Engler
Keyword(s):  
Basement Membrane ◽  
Contractile Function ◽  
Current Model ◽  
Model Systems ◽  
Model Organisms ◽  
Muscle Physiology ◽  
Heart Tube ◽  
Age Related ◽  
New Evidence

Aging is associated with extensive remodeling of the heart, including basement membrane extracellular matrix (ECM) components that surround cardiomyocytes. Remodeling is thought to contribute to impaired cardiac mechanotransduction, but the contribution of specific basement membrane ECM components to age-related cardiac remodeling is unclear, owing to current model systems being complex and slow to age. To investigate the effect of basement membrane remodeling on mechanical function in genetically tractable, rapidly aging, and simple model organisms, we employed Drosophila melanogaster, which has a simple trilayered heart tube composed of only basement membrane ECM. We observed differential regulation of collagens between laboratory Drosophila strains , i.e. yellow-white ( yw ) and white-1118 ( w 1118 ), leading to changes in muscle physiology, which were linked to severity of dysfunction with age. Therefore, we sought to understand the extent to which basement membrane ECM modulates lateral cardiomyocyte coupling and contractile function during aging. Cardiac-restricted knockdown of ECM genes Pericardin , Laminin A , and Viking in Drosophila prevented age-associated heart tube restriction and increased contractility, even under viscous load. Most notably, reduction of Laminin A expression decreased levels of other genes that co-assemble in ECM, leading to overall preservation of contractile velocity and extension of median organismal lifespan by 3 weeks or 39%. These data provide new evidence of a direct link between basement membrane ECM homeostasis, contractility, and maintenance of lifespan.

Hairless regulates heterochromatin maintenance and muscle stem cell function as a histone demethylase antagonist

2021 ◽  
Vol 118 (37) ◽  
pp. e2025281118
Author(s):  
Ling Liu ◽  
Cristina Rodriguez-Mateo ◽  
Polly Huang ◽  
Albin Huang ◽  
Alexander Lieu ◽  
...  
Keyword(s):  
Cell Function ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genotoxic Stress ◽  
Histone Demethylases ◽  
Muscle Stem Cell ◽  
Muscle Stem Cells ◽  
Histone 3 ◽  
Age Related ◽  
Regenerative Ability

Skeletal muscle possesses remarkable regenerative ability because of the resident muscle stem cells (MuSCs). A prominent feature of quiescent MuSCs is a high content of heterochromatin. However, little is known about the mechanisms by which heterochromatin is maintained in MuSCs. By comparing gene-expression profiles from quiescent and activated MuSCs, we found that the mammalian Hairless (Hr) gene is expressed in quiescent MuSCs and rapidly down-regulated upon MuSC activation. Using a mouse model in which Hr can be specifically ablated in MuSCs, we demonstrate that Hr expression is critical for MuSC function and muscle regeneration. In MuSCs, loss of Hr results in reduced trimethylated Histone 3 Lysine 9 (H3K9me3) levels, reduced heterochromatin, increased susceptibility to genotoxic stress, and the accumulation of DNA damage. Deletion of Hr leads to an acceleration of the age-related decline in MuSC numbers. We have also demonstrated that despite the fact that Hr is homologous to a family of histone demethylases and binds to di- and trimethylated H3K9, the expression of Hr does not lead to H3K9 demethylation. In contrast, we show that the expression of Hr leads to the inhibition of the H3K9 demethylase Jmjd1a and an increase in H3K9 methylation. Taking these data together, our study has established that Hr is a H3K9 demethylase antagonist specifically expressed in quiescent MuSCs.

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