scholarly journals Neutrophil response to cyclophosphamide predicts resilience to age-related learning impairment

2020 ◽  
Vol 2 (4) ◽  
pp. 230-231
Author(s):  
Katie Nickel ◽  
◽  
Marianne Bjorner ◽  
Warren Ladiges ◽  
Lida Zhu
Keyword(s):  
Middle Age ◽  
Punch Biopsy ◽  
Dependent Manner ◽  
Cell Counts ◽  
Age Related ◽  
Age Dependent ◽  
White Blood Cell Counts ◽  
Improved Learning ◽  
Learning Impairment ◽  
Neutrophil Response

The ability to respond to stress, defined as resilience, was measured by white blood cell counts in C57BL/6 mice of various ages receiving a nonlethal dose of cyclophosphamide (CYP). Neutrophil counts dipped and then rebounded in a consistent and age-dependent manner. Low neutrophil rebound correlated with improved learning in middle-age mice suggesting CYP-nduced neutrophil response may predict resilience to aging. Keywords: Resilience to aging, wound healing, ear punch biopsy, aging mice

scholarly journals Random errors in protein synthesis activate an age-dependent program of muscle atrophy in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
James Moore ◽  
Rashid Akbergenov ◽  
Martina Nigri ◽  
Patricia Isnard-Petit ◽  
Amandine Grimm ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Atrophy ◽  
Strength Analysis ◽  
Dependent Manner ◽  
Random Errors ◽  
Age Related ◽  
Related Phenotype ◽  
Age Dependent ◽  
Translation Accuracy ◽  
Transcriptomic Changes

AbstractRandom errors in protein synthesis are prevalent and ubiquitous, yet their effect on organismal health has remained enigmatic for over five decades. Here, we studied whether mice carrying the ribosomal ambiguity (ram) mutation Rps2-A226Y, recently shown to increase the inborn error rate of mammalian translation, if at all viable, present any specific, possibly aging-related, phenotype. We introduced Rps2-A226Y using a Cre/loxP strategy. Resulting transgenic mice were mosaic and showed a muscle-related phenotype with reduced grip strength. Analysis of gene expression in skeletal muscle using RNA-Seq revealed transcriptomic changes occurring in an age-dependent manner, involving an interplay of PGC1α, FOXO3, mTOR, and glucocorticoids as key signaling pathways, and finally resulting in activation of a muscle atrophy program. Our results highlight the relevance of translation accuracy, and show how disturbances thereof may contribute to age-related pathologies.

Transgene Dose- and Age-Dependent Development of Myeloproliferative Neoplasm Phenotypes In JAK2V617F Transgene Mice

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1980-1980
Author(s):  
Wanting Ho ◽  
Wanming Zhao ◽  
Zhizhuang Joe Zhao
Keyword(s):  
Transgenic Mice ◽  
Copy Number ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Gene Copy ◽  
Cell Transplant ◽  
Dependent Manner ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Age Dependent

Abstract Abstract 1980 Myeloproliferative neoplasms (MPNs) are heterogeneous hematologic disorders represented by three main phenotypes: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The major molecular lesion in these diseases is JAK2V617F, which occurs in over 95% patients with PV and in over 50% of patients with ET or PMF. The pathogenic effects of JAK2V617F have been demonstrated by retrovirus-mediated gene transfer, transgenic, and knock-in mouse models, but the precise mode of JAK2V617F action is not clear. Interestingly, in the knock-in model, expression of JAK2V617F causes severe PV-like disease but not ET-like phenotype as seen in patients. To verify the pathogenic role of JAK2V617F, we further characterized the phenotypes of three lines of JAK2V617F transgenic mice generated by using the vav gene promoter which drives expression of transgenes in the hematopoietic system. These mice developed MPN-like phenotypes in a transgene dose- and age-dependent manner. Line A mice have a JAK2V617F gene copy number of 13; they develop MPN phenotype with marked increases in blood counts and enlarged spleens as early as 4–6 weeks after birth. In contrast, lines B and D mice have a transgene copy number of 2 and 1, respectively, and it takes nearly 70 weeks for these mice to show MPN-like phenotypes. The phenotype of line A mice is particularly noteworthy. Essentially all the hemizygous line A mice displayed an ET-like phenotype with marked elevations in platelet counts (usually over 4000×109/L by the age of 15 weeks), but only a slight increase in red cell and white cell counts. In contrast, all the homozygous mice exhibited a clear PV-like phenotype with elevations in all three types of blood cells, although their platelets hardly ever went over 4000×109/L. The hemizygous mice developed myelofibrosis after 30 weeks while the homozygous mice showed the symptom within only 10 weeks. As expected, the increased blood cell counts and formation of myelofibrosis are associated with mobilization of hematopoietic stem/progenitor cells to peripheral hematopoietic tissues (blood, spleen, and liver). By conducting stem cell transplant experiments, we further proved that JAK2V617F-induced ET and PV-like phenotypes are transplantable. Our study demonstrates that transgenic expression of JAK2V617F is capable of producing all three phenotypes of MPNs in a transgense dose- and age-dependent manner. Our transgenic mice thus represent an excellent model system to study MPNs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Serum Copper and Haematological Values of Sheep of Different Physiological Stages in the Dry and Wet Seasons of Central Trinidad

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
A. Mohammed ◽  
M. Campbell ◽  
F. G. Youssef
Keyword(s):  
Cell Volume ◽  
Packed Cell Volume ◽  
Serum Copper ◽  
Wet Season ◽  
Cell Counts ◽  
Blood Cell Counts ◽  
Age Related ◽  
Physiological Stage ◽  
White Blood Cell Counts ◽  
Hematological Values

A study was conducted to determine serum copper (Cu) concentrations and hematological values of 174 sheep from four medium sized farms, pertaining to physiological stage, in the late dry and late wet seasons of Central Trinidad. Serum Cu was significantly lower in the dry than in the wet season (P<0.001) with a corresponding high percentage of samples with low Cu levels in the former. 31% of dry nonpregnant sheep exhibited a nonregenerative anaemia. Also, hemoglobin and packed cell volume values varied (P<0.001) including lymphocyte (P<0.01) counts, among growing animals compared with other physiological stages. Significant variations also occurred among neutrophil (P<0.05) and eosinophil (P<0.05) values in sheep. Highest haemoglobin and packed cell volume, white blood cell counts, and lymphocyte values in growing sheep compared with other stages were probably age related.

scholarly journals Age-Related Alteration in Serum Adiponectin in Rats and Its Association with Insulin Resistance Markers

2019 ◽  
Author(s):  
Marziyeh Feyzi ◽  
Mohammad Reza Tabandeh ◽  
Mehrdad Shariati ◽  
Mohammad Amin Edalatmanesh
Keyword(s):  
Insulin Resistance ◽  
Male Rats ◽  
Serum Adiponectin ◽  
Oral Glucose ◽  
Dependent Manner ◽  
Age Progression ◽  
Age Related ◽  
Glucose Ingestion ◽  
Age Dependent ◽  
Old Rats

Introduction: Adiponectin is one of the most important adipose derived hormone that conflicting data are available about serum changes of adiponectin at different ages.The present study was done to determine the age related changes in serum adiponectin and its association with insulin resistance (IR) indices in aging in male rats. Methods: In this study, serum samples were obtained from male rats at different ages, including 2, 5, 10, 18, 52 and 72 weeks age (n=10 in each age group). Oral glucose tolerance and glucose stimulated insulin secretion tests were measured using determination of glucose concentrations at 15, 30, 45 and 60 min after oral ingestion of glucose (1 mg/kg body weight) for each animal. Serum adiponectin and insulin levels were determined using species specific ELISA kits. HOMA-IR was calculated based on glucose and insulin concentrations. Data were analyzed using SPSS version 16 software (SPSS Inc., Chicago, IL) also using one way analysis of variance and LSD posthoc tests. Results: Our results showed an age dependent decrease in serum adiponectin concentration, and 72-week old rats had the lowest level of adiponectin compared with those in other ages (p<0.05). IR indices, including fasting glucose, insulin, HOMA-IR and response to oral glucose ingestion was increased in an age dependent manner and 72-week old rats showed the highest levels of the IR indices. Conclusion: Regarding the role of adiponectin in glucose homeostasis and insulin sensitization, it seems that reduction of serum adiponectin with age progression may be an important mechanism of insulin resistance in aging.

Age-related Changes in Brain Regional Activity during Chewing: A Functional Magnetic Resonance Imaging Study

2003 ◽  
Vol 82 (8) ◽  
pp. 657-660 ◽  
Author(s):  
M. Onozuka ◽  
M. Fujita ◽  
K. Watanabe ◽  
Y. Hirano ◽  
M. Niwa ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Dependent Manner ◽  
Prefrontal Area ◽  
Gum Chewing ◽  
Regional Activity ◽  
Healthy Humans ◽  
Age Related ◽  
Age Dependent ◽  
The Right ◽  
Age Related Changes

Age-related changes in mastication-induced brain neuronal activity have been suggested. However, in humans, little is known about the anatomical regions involved. Using fMRI during cycles of rhythmic gum-chewing and no chewing, we have examined the effect of aging on brain regional activity during chewing in young adult (19–26 yrs), middle-aged (42–55 yrs), and aged (65–73 yrs) healthy humans. In all subjects, chewing resulted in a bilateral increase in the BOLD signals in the sensorimotor cortex, cerebellum, thalamus, supplementary motor area, and insula, and a unilateral increase in the right prefrontal area. In the first three regions, the signal increases were attenuated in an age-dependent manner, whereas, in the right prefrontal area, the converse was seen. The remaining two regions showed no significant differences with ages. These results indicate that chewing causes regional increases in neuronal activity in the brain, some of which are age-dependent.

scholarly journals Corticosteroid modulation of interleukin-1 hematopoietic effects and toxicity in a murine system

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1457-1463
Author(s):  
J Rinehart ◽  
EW Delamater ◽  
L Keville ◽  
J Measel
Keyword(s):  
Interleukin 1 ◽  
Cell Number ◽  
Chemotherapeutic Agents ◽  
Dependent Manner ◽  
Cell Counts ◽  
Colony Forming Units ◽  
White Blood Cell Counts ◽  
Macrophage Colony ◽  
Therapeutic Doses

Interleukin-1 (IL-1) has been shown to ameliorate the hematopoietic toxicities of antitumor chemotherapeutic agents in both mice and humans. However, IL-1 toxicity in humans is considerable and is similar to the systemic inflammatory toxicities induced by IL-3, IL-6, and other cytokines with pleiotropic biologic activities, eg, fever, nausea, malaise, and hypotension. We hypothesized that corticosteroids may reduce IL-1 toxicity without reducing IL-1 hematopoietic effects in vivo. C3H/HeJ mice (female, 6 weeks) were treated for 7 days subcutaneously with cortisone acetate (CA), (0.1, 0.25, or 0.5 mg/d/mouse), intraperitoneally with IL-1 (1 or 2 micrograms/d/mouse), or both. As expected, IL-1 increased white blood cell counts, splenic granulocyte-macrophage colony-forming units, and spleen cell number, and protected mice from lethal doses of carboplatin (200 mg/kg; Paraplatin, Bristol Laboratories, Evansville, IN) administered the day after completion of the 7 days of IL-1 administration. CA did not significantly block the hematopoietic effects of IL-1 or the ability of IL-1 to protect mice from the hematopoietic toxicity of carboplatin. IL- 1 administered to mice at 8 micrograms/d/mouse for 5 days induced decreased activity, roughening of hair, diarrhea, pancytopenia, multiple metabolic abnormalities, and death in 60% of mice. IL-1 at the therapeutic doses (0.5 to 2 micrograms/d) was not toxic. CA in a dose- dependent manner blocked all of the above mentioned toxicities when administered 24 hours and 30 minutes before each IL-1 injection. CA also decreased IL-1-induced increase in plasma tumor necrosis factor levels at the time point examined.

scholarly journals 5-HT Obesity Medication Efficacy via POMC Activation is Maintained During Aging

Endocrinology ◽  
2014 ◽  
Vol 155 (10) ◽  
pp. 3732-3738 ◽  
Author(s):  
Luke K. Burke ◽  
Barbora Doslikova ◽  
Giuseppe D'Agostino ◽  
Alastair S. Garfield ◽  
Gala Farooq ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Arcuate Nucleus ◽  
Middle Age ◽  
Age Related ◽  
Obese Population ◽  
Age Dependent ◽  
Medication Efficacy ◽  
Obesity Treatments ◽  
Reduced Activity ◽  
Global Aging

Abstract The phenomenon commonly described as the middle-age spread is the result of elevated adiposity accumulation throughout adulthood until late middle-age. It is a clinical imperative to gain a greater understanding of the underpinnings of age-dependent obesity and, in turn, how these mechanisms may impact the efficacy of obesity treatments. In particular, both obesity and aging are associated with rewiring of a principal brain pathway modulating energy homeostasis, promoting reduced activity of satiety pro-opiomelanocortin (POMC) neurons within the arcuate nucleus of the hypothalamus (ARC). Using a selective ARC-deficient POMC mouse line, here we report that former obesity medications augmenting endogenous 5-hydroxytryptamine (5-HT) activity d-fenfluramine and sibutramine require ARC POMC neurons to elicit therapeutic appetite-suppressive effects. We next investigated whether age-related diminished ARC POMC activity therefore impacts the potency of 5-HT obesity pharmacotherapies, lorcaserin, d-fenfluramine, and sibutramine and report that all compounds reduced food intake to a comparable extent in both chow-fed young lean (3–5 months old) and middle-aged obese (12–14 months old) male and female mice. We provide a mechanism through which 5-HT anorectic potency is maintained with age, via preserved 5-HT–POMC appetitive anatomical machinery. Specifically, the abundance and signaling of the primary 5-HT receptor influencing appetite via POMC activation, the 5-HT2CR, is not perturbed with age. These data reveal that although 5-HT obesity medications require ARC POMC neurons to achieve appetitive effects, the anorectic efficacy is maintained with aging, findings of clinical significance to the global aging obese population.

scholarly journals Corticosteroid modulation of interleukin-1 hematopoietic effects and toxicity in a murine system

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1457-1463 ◽  
Author(s):  
J Rinehart ◽  
EW Delamater ◽  
L Keville ◽  
J Measel
Keyword(s):  
Interleukin 1 ◽  
Cell Number ◽  
Chemotherapeutic Agents ◽  
Dependent Manner ◽  
Cell Counts ◽  
Colony Forming Units ◽  
White Blood Cell Counts ◽  
Macrophage Colony ◽  
Therapeutic Doses

Abstract Interleukin-1 (IL-1) has been shown to ameliorate the hematopoietic toxicities of antitumor chemotherapeutic agents in both mice and humans. However, IL-1 toxicity in humans is considerable and is similar to the systemic inflammatory toxicities induced by IL-3, IL-6, and other cytokines with pleiotropic biologic activities, eg, fever, nausea, malaise, and hypotension. We hypothesized that corticosteroids may reduce IL-1 toxicity without reducing IL-1 hematopoietic effects in vivo. C3H/HeJ mice (female, 6 weeks) were treated for 7 days subcutaneously with cortisone acetate (CA), (0.1, 0.25, or 0.5 mg/d/mouse), intraperitoneally with IL-1 (1 or 2 micrograms/d/mouse), or both. As expected, IL-1 increased white blood cell counts, splenic granulocyte-macrophage colony-forming units, and spleen cell number, and protected mice from lethal doses of carboplatin (200 mg/kg; Paraplatin, Bristol Laboratories, Evansville, IN) administered the day after completion of the 7 days of IL-1 administration. CA did not significantly block the hematopoietic effects of IL-1 or the ability of IL-1 to protect mice from the hematopoietic toxicity of carboplatin. IL- 1 administered to mice at 8 micrograms/d/mouse for 5 days induced decreased activity, roughening of hair, diarrhea, pancytopenia, multiple metabolic abnormalities, and death in 60% of mice. IL-1 at the therapeutic doses (0.5 to 2 micrograms/d) was not toxic. CA in a dose- dependent manner blocked all of the above mentioned toxicities when administered 24 hours and 30 minutes before each IL-1 injection. CA also decreased IL-1-induced increase in plasma tumor necrosis factor levels at the time point examined.

scholarly journals Age-dependent changes of total and differential white blood cell counts in children

2020 ◽  
Vol 133 (16) ◽  
pp. 1900-1907
Author(s):  
Kun Li ◽  
Ya-Guang Peng ◽  
Ruo-Hua Yan ◽  
Wen-Qi Song ◽  
Xiao-Xia Peng ◽  
...  
Keyword(s):  
Blood Cell ◽  
White Blood Cell ◽  
Cell Counts ◽  
Blood Cell Counts ◽  
Age Dependent ◽  
White Blood Cell Counts ◽  
Differential White Blood Cell

scholarly journals Changes in Locomotor Activity and Oxidative Stress-Related Factors after the Administration of an Amino Acid Mixture by Generation and Age

2021 ◽  
Vol 22 (18) ◽  
pp. 9822
Author(s):  
Yejin Ahn ◽  
Ki-Bae Hong ◽  
Suhyeon Kim ◽  
Hyung Joo Suh ◽  
Kyungae Jo
Keyword(s):  
Oxidative Stress ◽  
Sleep Time ◽  
Behavioral Changes ◽  
Acid Mixture ◽  
Dependent Manner ◽  
Reaction Products ◽  
Related Factors ◽  
Age Related ◽  
Age Dependent ◽  
And Oxidative Stress

Amino acids, as nutrients, are expected to improve sleep disorders. This study aimed to evaluate the generation- and age-dependent sleep-improving effects of γ-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) coadministration. The differentially expressed genes and generation-related behavior after the administration of a GABA/5-HTP mixture were measured in a Drosophila model, while age-related changes in gene expression and oxidative stress-related parameters were measured in a mouse model. The GABA/5-HTP-treated group showed significant behavioral changes compared to the other groups. Sequencing revealed that the GABA/5-HTP mixture influenced changes in nervous system-related genes, including those involved in the regulation of the expression of behavioral and synaptic genes. Additionally, total sleep time increased with age, and nighttime sleep time in the first- and third-generation flies was significantly different from that of the control groups. The GABA/5-HTP mixture induced significant changes in the expression of sleep-related receptors in both models. Furthermore, the GABA/5-HTP mixture reduced levels of ROS and ROS reaction products in an age-dependent manner. Therefore, the increase in behavioral changes caused by GABA/5-HTP mixture administration was effective in eliminating ROS activity across generations and ages.

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