scholarly journals Aging is associated with a systemic length-driven transcriptome imbalance

2019 ◽  
Author(s):  
Thomas Stoeger ◽  
Rogan A. Grant ◽  
Alexandra C. McQuattie-Pimentel ◽  
Kishore Anekalla ◽  
Sophia S. Liu ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Splicing Factor ◽  
Transcriptional Elongation ◽  
Gene Length ◽  
Transcriptomic Data ◽  
Human Organs ◽  
Common Basis ◽  
Expression Of Genes ◽  
Age Dependent ◽  
Differential Expression Of Genes

AbstractAging manifests itself through a decline in organismal homeostasis and a multitude of cellular and physiological functions1. Efforts to identify a common basis for vertebrate aging face many challenges; for example, while there have been documented changes in the expression of many hundreds of mRNAs, the results across tissues and species have been inconsistent2. We therefore analyzed age-resolved transcriptomic data from 17 mouse organs and 51 human organs using unsupervised machine learning3–5 to identify the architectural and regulatory characteristics most informative on the differential expression of genes with age. We report a hitherto unknown phenomenon, a systemic age-dependent length-driven transcriptome imbalance that for older organisms disrupts the homeostatic balance between short and long transcript molecules for mice, rats, killifishes, and humans. We also demonstrate that in a mouse model of healthy aging, length-driven transcriptome imbalance correlates with changes in expression of splicing factor proline and glutamine rich (Sfpq), which regulates transcriptional elongation according to gene length6. Furthermore, we demonstrate that length-driven transcriptome imbalance can be triggered by environmental hazards and pathogens. Our findings reinforce the picture of aging as a systemic homeostasis breakdown and suggest a promising explanation for why diverse insults affect multiple age-dependent phenotypes in a similar manner.

scholarly journals MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joseph C. Reynolds ◽  
Rochelle W. Lai ◽  
Jonathan S. T. Woodhead ◽  
James H. Joly ◽  
Cameron J. Mitchell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Healthy Aging ◽  
Metabolic Stress ◽  
Muscle Metabolism ◽  
Physical Capacity ◽  
Physical Decline ◽  
Age Dependent ◽  
Exercise Induced ◽  
Muscle Homeostasis ◽  
Metabolic Fitness

AbstractHealthy aging can be promoted by enhanced metabolic fitness and physical capacity. Mitochondria are chief metabolic organelles with strong implications in aging that also coordinate broad physiological functions, in part, using peptides that are encoded within their independent genome. However, mitochondrial-encoded factors that actively regulate aging are unknown. Here, we report that mitochondrial-encoded MOTS-c can significantly enhance physical performance in young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice. MOTS-c can regulate (i) nuclear genes, including those related to metabolism and proteostasis, (ii) skeletal muscle metabolism, and (iii) myoblast adaptation to metabolic stress. We provide evidence that late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) can increase physical capacity and healthspan in mice. In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation. Our data indicate that aging is regulated by genes encoded in both of our co-evolved mitochondrial and nuclear genomes.

scholarly journals Evidence for increased thermogenesis in female C57BL/6J mice housed aboard the international space station

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Carmen P. Wong ◽  
Urszula T. Iwaniec ◽  
Russell T. Turner
Keyword(s):  
Adipose Tissue ◽  
Differential Expression ◽  
International Space Station ◽  
Space Station ◽  
Interscapular Brown Adipose Tissue ◽  
International Space ◽  
Expression Of Genes ◽  
Brown Adipose ◽  
Differential Expression Of Genes ◽  
Shivering Thermogenesis

AbstractSixteen-week-old female C57BL/6J mice were sacrificed aboard the International Space Station after 37 days of flight (RR-1 mission) and frozen carcasses returned to Earth. RNA was isolated from interscapular brown adipose tissue (BAT) and gonadal white adipose tissue (WAT). Spaceflight resulted in differential expression of genes in BAT consistent with increased non-shivering thermogenesis and differential expression of genes in WAT consistent with increased glucose uptake and metabolism, adipogenesis, and β-oxidation.

Differential expression of genes that encode glycolysis enzymes in kidney and lung cancer in humans

2013 ◽  
Vol 49 (7) ◽  
pp. 707-716 ◽  
Author(s):  
N. Yu. Oparina ◽  
A. V. Snezhkina ◽  
A. F. Sadritdinova ◽  
V. A. Veselovskii ◽  
A. A. Dmitriev ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Differential Expression ◽  
Expression Of Genes ◽  
Differential Expression Of Genes

scholarly journals Age-dependent changes in electrophysiology and calcium handling – implications for pediatric cardiac research

2019 ◽  
Author(s):  
Luther M. Swift ◽  
Morgan Burke ◽  
Devon Guerrelli ◽  
Manelle Ramadan ◽  
Marissa Reilly ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Cardiac Electrophysiology ◽  
Calcium Handling ◽  
Cell Coupling ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Age Dependent ◽  
Genes Encoding ◽  
Cardiac Maturation

ABSTRACTRationaleThe heart continues to develop and mature after birth and into adolescence. Accordingly, cardiac maturation is likely to include a progressive refinement in both organ morphology and function during the postnatal period. Yet, age-dependent changes in cardiac electrophysiology and calcium handling have not yet been fully characterized.ObjectiveThe objective of this study, was to examine the relationship between cardiac maturation, electrophysiology, and calcium handling throughout postnatal development in a rat model.MethodsPostnatal rat cardiac maturation was determined by measuring the expression of genes involved in cell-cell coupling, electrophysiology, and calcium handling. In vivo electrocardiograms were recorded from neonatal, juvenile, and adult animals. Simultaneous dual optical mapping of transmembrane voltage and calcium transients was performed on isolated, Langendorff-perfused rat hearts (postnatal day 0–3, 4-7, 8-14, adult).ResultsYounger, immature hearts displayed slowed electrical conduction, prolonged action potential duration and increased ventricular refractoriness. Slowed calcium handling in the immature heart increased the propensity for calcium transient alternans which corresponded to alterations in the expression of genes encoding calcium handling proteins. Developmental changes in cardiac electrophysiology were associated with the altered expression of genes encoding potassium channels and intercalated disc proteins.ConclusionUsing an intact whole heart model, this study highlights chronological changes in cardiac electrophysiology and calcium handling throughout postnatal development. Results of this study can serve as a comprehensive baseline for future studies focused on pediatric cardiac research, safety assessment and/or preclinical testing using rodent models.

scholarly journals Increased mTOR signaling, impaired autophagic flux and cell-to-cell viral transmission are hallmarks of SARS-CoV-2 infection.

2021 ◽  
Author(s):  
Grazielle Celeste Maktura ◽  
Thomaz Luscher Dias ◽  
Erika Pereira Zambalde ◽  
Bianca Brenha ◽  
Mariene R. Amorim ◽  
...  
Keyword(s):  
Data Mining ◽  
Viral Load ◽  
Viral Infections ◽  
Vesicle Fusion ◽  
Viral Transmission ◽  
Mtor Signaling ◽  
Autophagic Flux ◽  
Transcriptomic Data ◽  
Expression Of Genes ◽  
Virus Retention

The COVID-19 disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has two characteristics that distinguish it from other viral infections. It affects more severely people with pre-existing comorbidities and viral load peaks prior to the onset of the symptoms. Investigating factors that could contribute to these characteristics, we found increased mTOR signaling and suppressed genes related to autophagy, lysosome, and vesicle fusion in Vero E6 cells infected with SARS-CoV-2. Transcriptomic data mining of bronchoalveolar epithelial cells from severe COVID-19 patients revealed that COVID-19 severity is associated with increased expression of genes related to mTOR signaling and decreased expression of genes related to au-tophagy, lysosome function, and vesicle fusion. SARS-CoV-2 infection in Vero E6 cells also re-sulted in virus retention inside the cells and trafficking of virus-bearing vesicles between neighboring cells. Our findings support a scenario where SARS-CoV-2 benefits from compromised autophagic flux and inhibited exocytosis in individuals with chronic hyperactivation of mTOR signaling, which might relate to undetectable proliferation and evasion of the immune system.

scholarly journals Complementary Contribution of Fungi and Bacteria to Lignocellulose Digestion in the Food Stored by a Neotropical Higher Termite

2021 ◽  
Vol 9 ◽  
Author(s):  
Edimar A. Moreira ◽  
Gabriela F. Persinoti ◽  
Letícia R. Menezes ◽  
Douglas A. A. Paixão ◽  
Thabata M. Alvarez ◽  
...  
Keyword(s):  
Plant Material ◽  
Plant Biomass ◽  
Carbohydrate Active Enzymes ◽  
Expression Of Genes ◽  
Its Sequence Analysis ◽  
Gut Symbionts ◽  
Cazy Genes ◽  
Complementary Set ◽  
New Evidence ◽  
Differential Expression Of Genes

Lignocellulose digestion in termites is achieved through the functional synergy between gut symbionts and host enzymes. However, some species have evolved additional associations with nest microorganisms that collaborate in the decomposition of plant biomass. In a previous study, we determined that plant material packed with feces inside the nests of Cornitermes cumulans (Syntermitinae) harbors a distinct microbial assemblage. These food nodules also showed a high hemicellulolytic activity, possibly acting as an external place for complementary lignocellulose digestion. In this study, we used a combination of ITS sequence analysis, metagenomics, and metatranscriptomics to investigate the presence and differential expression of genes coding for carbohydrate-active enzymes (CAZy) in the food nodules and the gut of workers and soldiers. Our results confirm that food nodules express a distinct set of CAZy genes suggesting that stored plant material is initially decomposed by enzymes that target the lignin and complex polysaccharides from fungi and bacteria before the passage through the gut, where it is further targeted by a complementary set of cellulases, xylanases, and esterases produced by the gut microbiota and the termite host. We also showed that the expression of CAZy transcripts associated to endoglucanases and xylanases was higher in the gut of termites than in the food nodules. An additional finding in this study was the presence of fungi in the termite gut that expressed CAZy genes. This study highlights the importance of externalization of digestion by nest microbes and provides new evidence of complementary digestion in the context of higher termite evolution.

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