scholarly journals Tissue-Specific Landscape of Metabolic Dysregulation during Ageing

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 235
Author(s):  
Fangrong Zhang ◽  
Jakob Kerbl-Knapp ◽  
Alena Akhmetshina ◽  
Melanie Korbelius ◽  
Katharina Barbara Kuentzel ◽  
...  
Keyword(s):  
Metabolic Changes ◽  
Specific Level ◽  
Tissue Specific ◽  
Drug Candidates ◽  
Mixed Genetic Background ◽  
Metabolic Dysregulation ◽  
Age Related ◽  
Kidney Liver ◽  
The Brain ◽  
Target Effects

The dysregulation of cellular metabolism is a hallmark of ageing. To understand the metabolic changes that occur as a consequence of the ageing process and to find biomarkers for age-related diseases, we conducted metabolomic analyses of the brain, heart, kidney, liver, lung and spleen in young (9–10 weeks) and old (96–104 weeks) wild-type mice [mixed genetic background of 129/J and C57BL/6] using NMR spectroscopy. We found differences in the metabolic fingerprints of all tissues and distinguished several metabolites to be altered in most tissues, suggesting that they may be universal biomarkers of ageing. In addition, we found distinct tissue-clustered sets of metabolites throughout the organism. The associated metabolic changes may reveal novel therapeutic targets for the treatment of ageing and age-related diseases. Moreover, the identified metabolite biomarkers could provide a sensitive molecular read-out to determine the age of biologic tissues and organs and to validate the effectiveness and potential off-target effects of senolytic drug candidates on both a systemic and tissue-specific level.

scholarly journals Tissue-Specific Landscape of Metabolic Dysregulation During Ageing

2020 ◽  
Author(s):  
Fangrong Zhang ◽  
Jakob Kerbl-Knapp ◽  
Alena Akhmetshina ◽  
Melanie Korbelius ◽  
Katharina Küntzel ◽  
...  
Keyword(s):  
Metabolic Changes ◽  
Wild Type ◽  
Specific Level ◽  
Tissue Specific ◽  
Drug Candidates ◽  
Mixed Genetic Background ◽  
Metabolic Dysregulation ◽  
Age Related ◽  
Kidney Liver ◽  
Target Effects

The dysregulation of cellular metabolism is a hallmark of ageing. To understand the metabolic changes that occur as a consequence of the ageing process and to find biomarkers for age-related diseases, we conducted a metabolomic analysis of brain, heart, kidney, liver, lung and spleen in young (9-10 weeks) and old (96-104 weeks) wild type (mixed genetic background of 129/J and C57BL/6) mice using NMR spectroscopy. We found differences in metabolic fingerprints of all tissues and identified several metabolites to be altered in most tissues, suggesting that they may be universal biomarkers of ageing. In addition, we found distinct tissue-clustered sets of metabolites throughout the organism. The associated metabolic changes may reveal novel therapeutic targets for the treatment of ageing and age-related diseases. Moreover, the identified metabolite biomarkers could provide a sensitive molecular read-out to age determine the age of biologic tissues and to validate the effectiveness and potential off-target effects of senolytic drug candidates on both a systemic and tissue-specific level.

scholarly journals Age related metabolic modifications in the migraine brain

Cephalalgia ◽  
2019 ◽  
Vol 39 (8) ◽  
pp. 978-987 ◽  
Author(s):  
Marco Lisicki ◽  
Kevin D'Ostilio ◽  
Gianluca Coppola ◽  
Vincenzo Parisi ◽  
Alain Maertens de Noordhout ◽  
...  
Keyword(s):  
Disease Duration ◽  
Cerebral Metabolism ◽  
Episodic Migraine ◽  
Cross Sectional Study ◽  
Positive Control ◽  
Metabolic Changes ◽  
Cross Sectional ◽  
Age Related ◽  
Continuous Interaction ◽  
The Brain

Purpose The aim of this study was to evaluate the possibility that migraine patients exhibit specific age-related metabolic changes in the brain, which occur regardless of disease duration or the frequency of attacks. Methods We analysed the relation between brain glucose (18F-fluorodeoxyglucose) uptake and age in healthy volunteers (n = 20) and episodic migraine patients (n = 19). In the latter, we additionally compared the correlation between 18F-fluorodeoxyglucose uptake and disease duration and monthly migraine days. Results In contrast to controls, in migraine patients advancing age was positively correlated to increased metabolism in the brainstem (especially the posterior pons), hippocampus, fusiform gyrus and parahippocampus. Conversely, no significant correlations between cerebral metabolism and disease duration or migraine days were observed. Conclusions Findings of this cross-sectional study show that episodic migraine patients exhibit specific metabolic brain modifications while ageing. As such, age is correlated with metabolic changes in key regions of the brain previously associated with migraine's pathophysiology to a better extent than disease duration or the number of monthly migraine days. More than the repeated headache attacks, the continuous interaction with the environment seemingly models the brain of migraine sufferers in an adaptive manner. A positive control (e.g. chronic pain) is missing in this study and therefore findings cannot be proven to be migraine-specific.

The Rat SA Gene Shows Genotype-Dependent Tissue-Specific Expression

1994 ◽  
Vol 87 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Michael A. Kaiser ◽  
David Lodwick ◽  
Nilesh J. Samani
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Northern Blotting ◽  
Specific Expression ◽  
Tissue Specific ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Wistar Kyoto Rat ◽  
Wistar Kyoto ◽  
Kidney Liver ◽  
The Brain

1. SA is a recently identified gene implicated in blood pressure regulation in rodent models of genetic hypertension. In this study we have examined, by Northern blotting, its expression in tissues of the spontaneously hypertensive rat, the Wistar-Kyoto rat and F2 rats, derived from a cross of the spontaneously hypertensive rat with the Wistar-Kyoto rat. 2. We demonstrate that the gene is expressed in a tissue-specific manner. Expression was detected in four sites: kidney, liver, brain and testes. 3. In the kidney and liver expression was higher in the spontaneously hypertensive rat than in the Wistar-Kyoto rat, whereas in the brain and testes the pattern was reversed. 4. In the F2 rats, the levels of SA mRNA in the liver, brain and testes were found to be primarily determined by the genotype at the SA gene locus. 5. The findings suggest the presence of strain-specific cis- and more than one tissue-specific trans-acting factors regulating the expression of the rat SA gene.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain's pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain's disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain’s pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain’s disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

scholarly journals Nociceptin Increases Antioxidant Expression in the Kidney, Liver and Brain of Diabetic Rats

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 621
Author(s):  
Ernest Adeghate ◽  
Crystal M. D’Souza ◽  
Zulqarnain Saeed ◽  
Saeeda Al Jaberi ◽  
Saeed Tariq ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Kidney Tubules ◽  
Onset Of Diabetes ◽  
Endogenous Antioxidants ◽  
Kidney Liver ◽  
Convoluted Tubules ◽  
The Brain

Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous antioxidants in kidney, liver, cerebral cortex (CC), and hippocampus after the onset of diabetes mellitus, using enzyme-linked immunosorbent assay and immunohistochemistry. Exogenous NC (aa chain 1–17; 10 µg/kg body weight) was given intraperitoneally to normal and diabetic rats for 5 days. Our results showed that catalase (CAT) is present in the proximal (PCT) and distal (DCT) convoluted tubules of kidney, hepatocytes, and neurons of CC and hippocampus. The expression of CAT was significantly (p < 0.05) reduced in the kidney of normal and diabetic rats after treatment with NC. However, NC markedly (p < 0.001) increased the expression CAT in the liver and neurons of CC of diabetic rats. Superoxide dismutase (SOD) is widely distributed in the PCT and DCT of kidney, hepatocytes, and neurons of CC and hippocampus. NC significantly (p < 0.001) increased the expression of SOD in hepatocytes and neurons of CC and the hippocampus but not in the kidney. Glutathione reductase (GRED) was observed in kidney tubules, hepatocytes and neurons of the brain. NC markedly increased (p < 0.001) the expression of GRED in PCT and DCT cells of the kidney and hepatocytes of liver and neurons of CC. In conclusion, NC is a strong inducer of CAT, SOD, and GRED expression in the kidney, liver and brain of diabetic rats.

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