t=0-120min. Results are shown as mean ± SEM. GE of glucose approximated an overalllinear pattern at 1.6 ± 0.2 kcal/min. Systolic BP was greater and HR less (P<0.01 for both)with oral when compared with ID glucose. We conclude that ID glucose has greater effectson BP and HR than oral glucose, presumably reflecting the ‘protective' effect of gastricdistension. Accordingly, the consumption of water before a meal may represent a simpleapproach to the management of postprandial hypotension. (1) Jones et al, 2001; J Am GeriatrSoc; 49:162-7. (2) O'Donovan et al, 2002; J Physiol; 540:673-9. (3) Jones et al, 2005; AmJ Physiol; 289:G240-8.

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Synbiotics Protect Against Oxidative Stress in Inflammatory Bowel Disease(IBD) By Inducing Phase 2 Response EnzymesSilvia C. Resta-Lenert, Marco Maruggi, Coleman Ho

Background: IBD is characterized by increased oxidative stress, higher risk of DNA damageand cancer, and is associated with altered bone homeostasis. All these parameters have a majorrole in aging processes. We have shown that commensals, probiotics and synbiotics(pro+pre-biotic) significantly reduce the chronic inflammation of IBD by inhibiting proinflammatorycytokines/chemokines expression, DNA damage, and by promoting calcium and vit. Dmetabolism in the gut mucosa In Vivo and In Vitro, thus ameliorating, in part, systemicdisregulated immune responses, reduced bone mass, weight loss, and survival. We hypothes-ized that synbiotics may improve gut and systemic dysfunction in IBD by modulatingantioxidant defenses, i.e., phase 2 response enzymes. Methods: IL-10 and mdr1a deficientmice (n=4/group; M=F; age-matched) were treated daily for 4 weeks with probiotics or acommensal (L.acidophilus, LA, S.thermophilus, ST, or B.tethaiotaomicron, BT) with orwithout a prebiotic (inulin, In), or with vehicle alone. Blood, gut and bone tissues werecollected at the end of treatment and assayed for TGF-beta, NAD-quinone reductase (NQO1),thioredoxin reductase (TRR), total glutathione, and lipid peroxidation by protein (reducing/non reducing conditions) and mRNA analysis, by thiobarbiturate-reactive substances(TBARS), and immunoassay. Moreover, gut and bone tissues were cocultured with Caco-2cell monolayers for up to 24 hr in the presence or absence of bacterial preparations andkinases inhibitors. Caco-2 were then tested for Nrf2 (nuclear factor erythroid-related factor2)- Keap1 (Kelch-like ECH-associated protein 1) pathway activation Results: The synbioticswere more effective than bacteria alone in significantly increasing the total antioxidant powerat blood and tissue level in treated mice vs. untreated controls, and ST/LA/In was moreeffective than BT/In (in average, by a factor of 1.3). NQO1 and TRR activity increased 3.5-and 3-fold after ST/LA/In, respectively. Total glutathione levels doubled in blood and tissuesamples. Ex vivo studies showed that synbiotics induced a small decrease of the Nrf2-Keap1cytoplasmic complexes, whereas nuclear levels of Nerf-2 were simultaneously increased.ERK1/2 and PI3K inhibitors markedly reduced this effect on Nerf-2 activation. Conclusions:Our data suggest that the intestinal microbiota plays an important role in gut and systemicredox homeostasis, and that microbiota manipulation may represent an effective complement-ary therapeutic tool in chronic inflammatory conditions such as IBD and aging. Supportedby grants NIH- DK062096 and UCSD Academic Senate.

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Aging of the Colonic Bacterial Flora in AdultsPaul Enck, Julia Frick, Kurt Zimmermann, Sibylle Klosterhalfen

The colonic mircoflora and its changes with ageing has rarely been investigated. Methods:We analysed the colonic flora by conventional microbiological testing (Kyberstatus®, Institutefor Microecology, Herborn, Germany) of stool samples from 35.292 adults (46.3 ± 15.0 (18to 96) yrs, 9.564: 24.784 male : female; remaining = missing) with different intestinal andnon-intestinal diagnoses for colony forming units (CFU) (per g stool) of predominant(clostridium diff. (CD), bifidobacteria (BB), bacteroides (B)), subdominant (E. coli (EC),enterococcus (ECC), lactobacillus (LB)) and other bacteria (pseudomonas, klebsiella, proteus,citrobacter, aerobic bacteria), as well as for total CFU count with respect to age, gender,and clinical data available (e.g. stool consistency and pH). Results: The total CFU increasedsteadily with age until age 70 (with men showing higher CFU than women). Individualbacterial species either constantly increased with age (LB,B) or were stable throughout life(ECC); EC and BB were stable until approx. age 60, and then either declined (BB) orincreased (EC) for the last 3 decades (Fig, women=solid). The ratio of explained to totalCFU (%) showed a decline from 7 to 4% to remain low for the last decades, with womenshowing higher values throughout life. Stool pH increased between 60 and 90 (from 6.6 to7.2) and was higher in women, while stool consistency tended toward more solid stools atthe same time. GI diagnoses excluded, the bacterial profile of the remaining group (n=15.619, 4197:11422) was not different. Conclusion: The colonic flora exhibits differentageing pattern, and is especially variable during the last decades. The change in bacterialcolonization may be responsible for GI symptoms at higher age, and may be a consequenceof altered nutrition. Data from entirely healthy subjects would be needed for validation.

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Aging Attenuates PI3K/AKT Activation and Proliferation of Pancreatic AcinarCellsHitoshi Takahashi, Hiroshi Saito, B. M. Evers

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is important for cell growth anddifferentiation in the GI tract and pancreas. Previously, we demonstrated that pancreaticregeneration after partial pancreatectomy was markedly decreased with aging and was associ-ated with an absence of PI3K/Akt activation in pancreatic acinar cells of the aged mice.However, the effects of aging on PI3K/Akt and mechanisms for the age-associated inhibitionof pancreatic growth are still unclear. The purpose of the present study was to define theeffect of aging on proliferation and PI3K/Akt activation in isolated pancreatic acinar cells.METHODS. Pancreatic acinar cells were isolated from young (2- to 6-mo) and aged (20-to 27-mo) male C57BL/6 mice by collagenase digestion. (i) Cells were treated with insulin-like growth factor 1 (IGF-1) (0-100 nM), an activator of PI3K, and proliferation was assessedby BrdU incorporation. (ii) Activation of PI3K/Akt was evaluated by measuring phosphoryl-ated Akt (pAkt) and total Akt (as a control) by Western blot analysis. (iii) IGF-1-mediatedactivation of PI3K/Akt downstream signaling proteins (mTOR and p70S6K) was determinedby Western blot. RESULTS. (i) BrdU incorporation in pancreatic acinar cells from youngmice was significantly increased after IGF-1 (10 and 100 nM) treatment by 70% and 74%,respectively (p < 0.005 compared with control). In marked contrast, BrdU incorporation inacinar cells from aged mice was not altered after IGF-1 treatment. (ii) Activation of PI3K,as assessed by pAkt induction, was increased at 3 min after IGF-1 treatment in acinar cellsfrom young mice; however, pAkt was not induced in acinar cells from aged mice over theentire time course. (iii) Following induction of pAkt, phosphorylation of mTOR and p70S6Kwas also increased at 5 min after treatment with IGF-1 in the acinar cells from young mice.Conversely, phosphorylation of mTOR and p70S6K in pancreatic acinar cells from aged micedid not change. CONCLUSIONS. Our results demonstrate that the functional impairment ofgrowth factor-mediated pancreatic proliferation associated with aging is due to a block inPI3K/Akt pathway activation. These findings provide novel mechanistic insights into thealtered proliferation noted in certain tissues during aging.

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Screening Colonoscopy in the Elderly Improves SurvivalEmily Singh, Catherine Frennette, Williamson Strum

Background and Aims: Colorectal cancer is the third most common cause of cancer in menand women and the mortality is related to stage of disease at diagnosis. This study wasdesigned to determine if screening colonoscopy leads to diagnosis at an earlier stage ofdisease in elderly patients and thus, improves survival. We tested the null hypothesis thatpatients equal to or greater than 75 years of age without symptoms who undergo screeningcolonoscopy do not have an earlier stage of disease at the time of diagnosis than patientswith symptoms. Methods: Patient records were obtained from the Scripps Green HospitalCancer Registry, and included all patients diagnosed with pathology-proven colorectal cancerbetween January 2000 and December 2005. Patients were divided into two groups basedon age and whether the cancer was detected by screening of asymptomatic patients or byevaluation of symptoms. The patients were further divided by stage of disease at diagnosis.The stages of disease were separated into early and late at a critical point between earlystage 0-IIA and late stage IIB-IV. In addition, we evaluated survival from the time of diagnosis.Results: 276 patients met the inclusion criteria, 83 patients were asymptomatic and 193patients were symptomatic. Of the asymptomatic patients, 65 were classified as early stageand 18 as late stage. 110 of the symptomatic patients were early stage and 83 were latestage. There was a sustained difference in stage of disease favoring patients who wereasymptomatic versus symptomatic for all ages between 50 and 84 years. This difference washighly significant (p<0.00013) and disproves the null hypothesis. In addition, the benefitcarried over to survival in asymptomatic who had significantly improved compared tosymptomatic patients (p< 0.0005). Early stage disease survival was better across all ages,and this benefit extended to age 84. Conclusions: Our study demonstrates a significantlyfavorable difference for screening colonoscopies in asymptomatic vs. symptomatic patientsin finding early stage disease from age 50 through age 84 years. The favorable differenceextended through all age groups and was associated with improved survival.

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