Site density of mouse intestinal glucose transporters declines with age

1993 ◽  
Vol 264 (2) ◽  
pp. G285-G293 ◽  
Author(s):  
R. P. Ferraris ◽  
J. Hsiao ◽  
R. Hernandez ◽  
B. Hirayama
Keyword(s):  
Glucose Transporter ◽  
Glucose Transporters ◽  
Proximal Jejunum ◽  
Site Density ◽  
Phlorizin Binding ◽  
Age Related ◽  
Old Mice ◽  
Effect Of Age ◽  
Distal Jejunum ◽  
Young Mice

To evaluate the effect of age on nutrient transport, the absorption rates of D-glucose, D-fructose, L-alanine, L-aspartate, L-leucine, L-lysine, L-proline, folic acid, and nicotinamide were determined in isolated jejunal tissues of young (6.7 mo old) and aged (23.7 and 27.0 mo old) mice (COBS:SFW). D-Glucose and D-fructose uptakes per milligram tissue were approximately 20-120% higher in the proximal jejunum and 15-50% higher in the distal jejunum of young mice. Amino acid and vitamin uptakes per milligram were also higher in young mice, but differences were not statistically significant. The number of Na(+)-D-glucose transporters per milligram tissue as estimated by specific phlorizin binding decreased with age. There was no age-related change in passive L-glucose permeability, in Kd of specific phlorizin binding, in transporter turnover rate, and in the molecular weight of the Na(+)-D-glucose transporter. Thus a reduction in D-glucose transporter site density fully accounts for the age-related decline in D-glucose transport rate per milligram small intestine.

scholarly journals Effect of age on susceptibility to Salmonella Typhimurium infection in C57BL/6 mice

2009 ◽  
Vol 58 (12) ◽  
pp. 1559-1567 ◽  
Author(s):  
Zhihong Ren ◽  
Raina Gay ◽  
Adam Thomas ◽  
Munkyong Pae ◽  
Dayong Wu ◽  
...  
Keyword(s):  
Immune Response ◽  
Ex Vivo ◽  
The Elderly ◽  
Mesenteric Lymph ◽  
Age Related ◽  
Serovar Typhimurium ◽  
Lymph Node Cells ◽  
Old Mice ◽  
Effect Of Age ◽  
Young Mice

Ageing is associated with a decline in immune function, which predisposes the elderly to a higher incidence of infections. Information on the mechanism of the age-related increase in susceptibility to Salmonella enterica serovar Typhimurium (S. Typhimurium) is limited. In particular, little is known regarding the involvement of the immune response in this age-related change. We employed streptomycin (Sm)-pretreated C57BL/6 mice to develop a mouse model that would demonstrate age-related differences in susceptibility and immune response to S. Typhimurium. In this model, old mice inoculated orally with doses of 3×108 or 1×106 c.f.u. S. Typhimurium had significantly greater S. Typhimurium colonization in the ileum, colon, Peyer's patches, spleen and liver than young mice. Old mice had significantly higher weight loss than young mice on days 1 and 2 post-infection. In response to S. Typhimurium infection, old mice failed to increase ex vivo production of IFN-γ and TNF-α in the spleen and mesenteric lymph node cells to the same degree as observed in young mice; this was associated with their inability to maintain the presence of neutrophils and macrophages at a ‘youthful’ level. These results indicate that Sm-pretreated C57BL/6 old mice are more susceptible to S. Typhimurium infection than young mice, which might be due to impaired IFN-γ and TNF-α production as well as a corresponding change in the number of neutrophils and macrophages in response to S. Typhimurium infection compared to young mice.

Effect of diet on glucose transporter site density along the intestinal crypt-villus axis

1992 ◽  
Vol 262 (6) ◽  
pp. G1060-G1068 ◽  
Author(s):  
R. P. Ferraris ◽  
S. A. Villenas ◽  
B. A. Hirayama ◽  
J. Diamond
Keyword(s):  
Brush Border ◽  
Glucose Transporter ◽  
Binding Constants ◽  
High Carbohydrate Diet ◽  
Carbohydrate Diet ◽  
High Carbohydrate ◽  
Site Density ◽  
Phlorizin Binding ◽  
High Affinity Binding Site ◽  
A Site

High-carbohydrate diets stimulate intestinal brush-border glucose uptake and increase the number of glucose-protectable phlorizin binding sites, but it has been unknown where along the crypt-villus axis these effects are expressed. We attacked this problem by three methods. First, by measuring phlorizin binding to isolated mouse enterocytes fractionated along the crypt-villus axis by the Weiser method, we identified a high-affinity binding site predominating from villus tip to midvillus and a site of possibly lower affinity predominating in the crypts. A high-carbohydrate diet increased by severalfold the density of the villus sites and probably also of the crypt sites, without changing their binding constants. Second, autoradiography revealed increased glucose-protectable phlorizin binding along the whole crypt-villus axis on a high-carbohydrate diet. Finally, a polyclonal antibody against the Na(+)-glucose cotransporter recognized a protein in the brush-border membrane of villus cells. Hence, substrate-dependent upregulation of intestinal glucose transport involves increased numbers of transporters along the crypt-villus axis.

scholarly journals A238 ABSENCE OF AGE-RELATED MEMORY DECLINE IN GERM-FREE MICE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 288-289
Author(s):  
N Kraimi ◽  
G De Palma ◽  
J Lu ◽  
D Bowdish ◽  
E Verdu ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Spatial Memory ◽  
Cognitive Decline ◽  
Memory Performance ◽  
Alternation Rate ◽  
Memory Decline ◽  
Germ Free ◽  
Age Related ◽  
Old Mice ◽  
Young Mice

Abstract Background Age-associated deterioration of cognitive function and memory capacity occur in a variety of mammals, from humans to rodents. For example, significant memory deficits have been reported in conventionally raised (SPF) old mice compared to conventionally raised young mice submitted to a spatial memory task (Prevot et al., Mol Neuropsychiatry 2019). Microbiota to brain signaling is now well established in mice, but the extent to which this influences age-related memory decline is unknown. Aims Our project aims to determine whether the intestinal microbiota contributes to age-related changes in brain function. We address the hypothesis that age-related cognitive decline is attenuated in the absence of the intestinal microbiota. Methods We studied locomotor behavior and spatial memory performance in young germ-free (GF) mice (2–3 months of age, n=24) and senescent GF mice (13–27 months old, n=22) maintained in axenic conditions, and compared them to conventionally raised (SPF) mice. We used the Y-maze test based on a spontaneous alternations task to assess cognition, with alternation rate as a proxy of spatial working memory performance. The locomotor activity was measured using the open-field test. Results GF old mice traveled less distance (458.9 cm) than GF young mice (875.7 cm, p < 0.001) but these differences in locomotor activity did not influence spatial memory performance. Indeed, both GF old and GF young mice had an identical alternation rate of 73.3% (p > 0.05). This contrasted with the memory impairment found in old SPF mice that displayed lower alternation rate of 58.3%, compared to that found in young SPF mice (76.2%, p = 0.13). Conclusions We conclude that the absence of age-related memory decline in germ-free mice is consistent with a role for the microbiota in the cognitive decline associated with aging, likely through action on the immune system, well documented in SPF mice (Thevaranjan et al., Cell Host & Microbe 2017). We propose that novel microbiota-targeted therapeutic strategies may delay or prevent the cognitive decline of aging. Funding Agencies CIHRBalsam Family Foundation

scholarly journals Necroptosis contributes to chronic inflammation and fibrosis in aging liver

2021 ◽  
Author(s):  
Sabira Mohammed ◽  
Nidheesh Thadathil ◽  
Ramasamy Selvarani ◽  
Evan H Nicklas ◽  
Dawei Wang ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Proinflammatory Cytokines ◽  
Term Treatment ◽  
Low Grade ◽  
Short Term Treatment ◽  
M1 Macrophages ◽  
Cell Death Pathway ◽  
Age Related ◽  
Old Mice ◽  
Young Mice

Inflammaging, characterized by an increase in low-grade chronic inflammation with age, is a hallmark of aging and is strongly associated with various age-related diseases, including chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Because necroptosis is a cell death pathway that induces inflammation through the release of DAMPs, we tested the hypothesis that age-associated increase in necroptosis contributes to chronic inflammation in aging liver. Phosphorylation of MLKL and MLKL-oligomers, markers of necroptosis, as well as phosphorylation of RIPK3 and RIPK1 were significantly upregulated in the livers of old mice relative to young mice and this increase occurred in the later half of life (i.e., after 18 months of age). Markers of M1 macrophages, expression of proinflammatory cytokines (TNFα, IL6 and IL-1β), and markers of fibrosis were significantly upregulated in the liver with age and the change in necroptosis paralleled the changes in inflammation and fibrosis. Hepatocytes and liver macrophages isolated from old mice showed elevated levels of necroptosis markers as well as increased expression of proinflammatory cytokines relative to young mice. Short term treatment with the necroptosis inhibitor, necrostatin-1s (Nec-1s), reduced necroptosis, markers of M1 macrophages, expression of proinflammatory cytokines, and markers of fibrosis in the livers of old mice. Thus, our data show for the first time that liver aging is associated with increased necroptosis and necroptosis contributes to chronic inflammation in the liver, which in turn appears to contribute to liver fibrosis and possibly CLD.

scholarly journals Learning-Dependent Dendritic Spine Plasticity Is Reduced in the Aged Mouse Cortex

2020 ◽  
Vol 14 ◽  
Author(s):  
Lianyan Huang ◽  
Hang Zhou ◽  
Kai Chen ◽  
Xiao Chen ◽  
Guang Yang
Keyword(s):  
Motor Cortex ◽  
Motor Learning ◽  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Learning Ability ◽  
Aged Mouse ◽  
Calcium Activity ◽  
Age Related ◽  
Old Mice ◽  
Young Mice

Aging is accompanied by a progressive decrease in learning and memory function. Synaptic loss, one of the hallmarks of normal aging, likely plays an important role in age-related cognitive decline. But little is known about the impact of advanced age on synaptic plasticity and neuronal function in vivo. In this study, we examined the structural dynamics of postsynaptic dendritic spines as well as calcium activity of layer 5 pyramidal neurons in the cerebral cortex of young and old mice. Using transcranial two-photon microscopy, we found that in both sensory and motor cortices, the elimination rates of dendritic spines were comparable between young (3–5 months) and mature adults (8–10 months), but seemed higher in old mice (>20 months), contributing to a reduction of total spine number in the old brain. During the process of motor learning, old mice compared to young mice had fewer new spines formed in the primary motor cortex. Motor training-evoked somatic calcium activity in layer 5 pyramidal neurons of the motor cortex was also lower in old than young mice, which was associated with the decline of motor learning ability during aging. Together, these results demonstrate the effects of aging on learning-dependent synapse remodeling and neuronal activity in the living cortex and suggest that synaptic deficits may contribute to age-related learning impairment.

Developmental changes in glucose transport, lipid composition, and fluidity of jejunal BBM

1997 ◽  
Vol 273 (3) ◽  
pp. R1086-R1093 ◽  
Author(s):  
C. M. Vazquez ◽  
N. Rovira ◽  
V. Ruiz-Gutierrez ◽  
J. M. Planas
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Lipid Composition ◽  
Brush Border Membrane ◽  
Glucose Transporter ◽  
Specific Binding ◽  
Molar Ratio ◽  
Site Density ◽  
Age Related ◽  
Age Dependent

Na(+)-dependent D-glucose uptake was studied in jejunal brush-border membrane (BBM) vesicles of chickens at 2 days and 1, 2, 5-6, and 12-14 wk of age. Both initial rates and accumulation ratios of the Na(+)-dependent D-glucose transport were significantly higher during the 1st wk than at other ages. To explain the age-related changes observed in the transport of D-glucose, the phlorizin-specific binding, Na+ permeability, lipid composition, and fluidity were studied. Transporter site density was quantified using 50 mumol/l phlorizin and found to be higher during the 1st wk. During the 2nd wk it decreased and then remained constant. Permeability of Na+, studied using 22Na+, showed that fluxes were similar during the first 6 wk, and a significant decrease was observed in the oldest group. Furthermore, membrane fluidity results showed a significant age-dependent decrease that correlated well with both the increased molar ratio of cholesterol to phospholipid and the decreased ratio of lipid to protein found during development. In conclusion, changes in the density of Na(+)-dependent D-glucose transporter as well as in lipid content and fluidity might be involved in the changes observed in D-glucose uptake during the posthatching development.

scholarly journals Prevention of age-related T cell apoptosis defect in CD2-fas-transgenic mice.

1995 ◽  
Vol 182 (1) ◽  
pp. 129-137 ◽  
Author(s):  
T Zhou ◽  
C K Edwards ◽  
J D Mountz
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
Cell Function ◽  
Thymic Involution ◽  
Age Related ◽  
Induced Apoptosis ◽  
And Function ◽  
Old Mice ◽  
Young Mice

T cell dysfunction and thymic involution are major immunologic abnormalities associated with aging. Fas (CD95) is a bifunctional molecule that is critical for apoptosis and stimulation during T cell development, but the role of Fas during aging has not been determined. Fas expression and function on T cells from old (22-26-mo-old) mice was compared with young (2-mo-old) mice and old CD2-fas-transgenic mice. Fas expression and ligand-induced apoptosis were decreased on T cells from old mice compared with young mice. This correlated with an age-related increase in CD44+Fas- T cells. There was a marked decrease in the proliferation of T cells from old mice after anti-CD3 stimulation compared with young mice. Anti-CD3-stimulated T cells from young mice exhibited increased production of interleukin (IL)-2 and decreased production of interferon-gamma and IL-10 compared with old mice. There was an age-related decrease in the total thymocyte count from 127 +/- 10 cells in young mice compared with 26 +/- 8 x 10(6) in old mice. In 26-mo-old CD2-fas-transgenic mice, Fas and CD44 expression, Fas-induced apoptosis, T cell proliferation, and cytokine production were comparable to that of the young mice. These results suggest that T cell senescence with age is associated with defective apoptosis, and that the CD2-fas transgene allows maintenance of Fas apoptosis function and T cell function in aged mice comparable to that of young mice.

Crypt-villus site of glucose transporter induction by dietary carbohydrate in mouse intestine

1992 ◽  
Vol 262 (6) ◽  
pp. G1069-G1073 ◽  
Author(s):  
R. P. Ferraris ◽  
J. Diamond
Keyword(s):  
Cell Migration ◽  
Glucose Transporter ◽  
Time Lag ◽  
Dietary Carbohydrate ◽  
Site Density ◽  
Phlorizin Binding ◽  
Carbohydrate Level ◽  
Induction Process ◽  
Mouse Intestine ◽  
Carbohydrate Levels

Intestinal brush-border glucose uptake rate is regulated by dietary carbohydrate level. However, this uptake response takes a day or more after a change in dietary carbohydrate level. Is this dietary signal perceived in the crypts, and is the glucose transporter activity of enterocytes irreversibly programmed there? If so, this time lag could reflect cell migration times along the crypt-villus axis, since glucose transport is not fully expressed until cells reach the midvillus. Alternatively, however, the time lag could arise from the induction process itself, if glucose transporter activity in mature villus enterocytes can be reversibly reprogrammed by dietary carbohydrate levels. Hence, we measured glucose-protectable phlorizin binding (as a measure of glucose transporter site density) in mouse enterocytes fractionated along the crypt-villus axis by the Weiser method, as a function of time after an abrupt switch in dietary carbohydrate level. For an increase or decrease in dietary carbohydrate, an increase or decrease in phlorizin binding site density first appeared in the crypts and marched over the course of several days to the villus tips. Hence, the signal for glucose transporter regulation is perceived in the crypts, and the observed lag in uptake is due largely to cell migration times.

scholarly journals Age-associated perturbations in glutathione synthesis in mouse liver

2007 ◽  
Vol 405 (3) ◽  
pp. 583-589 ◽  
Author(s):  
Dikran Toroser ◽  
Rajindar S. Sohal
Keyword(s):  
Mouse Liver ◽  
De Novo ◽  
Catalytic Efficiency ◽  
Fold Increase ◽  
Age Related ◽  
Tissue Homogenates ◽  
Synthetic Capacity ◽  
Rate Limiting ◽  
Old Mice ◽  
Young Mice

The nature of the mechanisms underlying the age-related decline in glutathione (GSH) synthetic capacity is at present unclear. Steady-state kinetic parameters of mouse liver GCL (glutamate–cysteine ligase), the rate-limiting enzyme in GSH synthesis, and levels of hepatic GSH synthesis precursors from the trans-sulfuration pathway, such as homocysteine, cystathionine and cysteine, were compared between young and old C57BL/6 mice (6- and 24-month-old respectively). There were no agerelated differences in GCL Vmax, but the apparent Km for its substrates, cysteine and glutamate, was higher in the old mice compared with the young mice (∼800 compared with ∼300 μM, and ∼710 compared with 450 μM, P<0.05 for cysteine and glutamate in young and old mice respectively). Amounts of cysteine, cystathionine and Cys-Gly increased with age by 91, 24 and 28% respectively. Glutathione (GSH) levels remained unchanged with age, whereas GSSG content showed an 84% increase, suggesting a significant pro-oxidizing shift in the 2GSH/GSSG ratio. The amount of the toxic trans-sulfuration/glutathione biosynthetic pathway intermediate, homocysteine, was 154% higher (P<0.005) in the liver of old mice compared with young mice. The conversion of homocysteine into cystathionine, a rate-limiting step in trans-sulfuration catalysed by cystathionine β-synthase, was comparatively less efficient in the old mice, as indicated by cystathionine/homocysteine ratios. Incubation of tissue homogenates with physiological concentrations of homocysteine caused an up to 4.4-fold increase in the apparent Km of GCL for its glutamate substrate, but had no effect on Vmax. The results suggest that perturbation of the catalytic efficiency of GCL and accumulation of homocysteine from the trans-sulfuration pathway may adversely affect de novo GSH synthesis during aging.

scholarly journals NREM consolidation and increased spindle counts improve age-related memory impairments and hippocampal representations

2020 ◽  
Author(s):  
Robin K. Yuan ◽  
Matthew R. Lopez ◽  
Manuel-Miguel Ramos-Alavarez ◽  
Marc E. Normandin ◽  
Arthur S. Thomas ◽  
...  
Keyword(s):  
Sleep Quality ◽  
Cognitive Decline ◽  
Recognition Task ◽  
Sleep Architecture ◽  
Sleep Restriction ◽  
Poor Sleep ◽  
Age Related ◽  
Age Related Cognitive Decline ◽  
Old Mice ◽  
Young Mice

SummaryAge-related changes in sleep patterns have been linked to cognitive decline. Specifically, increasing age is associated with increasing fragmentation of sleep and wake cycles. However, it remains unknown if improvements in sleep architecture can ameliorate cellular and cognitive deficits. We evaluated how changes in sleep architecture following sleep restriction affected hippocampal representations and memory in young and old mice. After training in a hippocampus- dependent object/place recognition task, control animals were allowed to sleep ad libitum, while experimental animals underwent 5 hours of sleep restriction (SR). Interestingly, old SR mice exhibited successful object/place learning comparable to young control mice, whereas young SR and old control mice did not. Successful learning correlated with the presence of two hippocampal cell types: 1) “Context” cells, which remained stable throughout training and testing, and 2) “Object” cells, which shifted their preferred firing location when objects were introduced to the context and moved during testing. As expected, EEG analysis revealed more fragmented sleep and fewer spindles in old controls than young controls during the post-training sleep period. However, following the acute SR session, old animals exhibited increased consolidation of NREM and increased spindle count, while young mice only displayed changes in REM bout length. These results indicate that consolidation of NREM sleep and increases in spindle count serve to ameliorate age-related memory deficits and allow hippocampal representations to adapt to changing environments.eTORC BlurbAge-related cognitive decline is associated with poor sleep quality. This study shows that acute sleep restriction serves to improve memory, hippocampal representations, and sleep quality in old mice, having the opposite effect in young animals. These findings indicate that improving sleep quality may mitigate age-related cognitive decline.HighlightsAcute sleep restriction improves memory in old mice, but adversely affects young onesAcute sleep restriction makes hippocampal representations more flexible in old miceAcute sleep restriction improves sleep quality and increases spindle count in old miceAcute sleep restriction decreases hippocampal flexibility in young mice

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