Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome

Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer's disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades bef...

Full description

Saved in:

Bibliographic Details
Published in	Frontiers in aging neuroscience Vol. 9; p. 298
Main Authors	Hoffman, Jared D., Parikh, Ishita, Green, Stefan J., Chlipala, George, Mohney, Robert P., Keaton, Mignon, Bauer, Bjoern, Hartz, Anika M. S., Lin, Ai-Ling
Format	Journal Article
Language	English
Published	Switzerland Frontiers Research Foundation 25.09.2017 Frontiers Media S.A
Subjects	Age Aging Alzheimer's disease Animal cognition Anxiety Bioinformatics Biomarkers Blood flow Blood-brain barrier brain metabolism Cerebral blood flow cognition Cognitive ability Dementia Deoxyribonucleic acid Digestive system DNA Etiology Fatty acids Feces Gene expression gut microbiome Image processing Immune response Inflammation Intestinal microflora Memory Metabolism Metabolites Microbiomes Microbiota MRI Nervous system Neurodegenerative diseases Neuroimaging Neuroscience neurovascular function Nitric oxide Risk factors United States > US neurovascular function anxiety brain metabolism gut microbiome Alzheimer’s disease cognition MRI aging
Online Access	Get full text
ISSN	1663-4365 1663-4365
DOI	10.3389/fnagi.2017.00298

Cover

Abstract	Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer's disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5-6 months of age) and compared those to old mice (18-20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased / ratio and alpha diversity. We also found impaired blood-brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the mechanisms underlying the shift from normal aging to pathological processes in the etiology of AD.
AbstractList	Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer's disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5-6 months of age) and compared those to old mice (18-20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased / ratio and alpha diversity. We also found impaired blood-brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the mechanisms underlying the shift from normal aging to pathological processes in the etiology of AD. Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow, gut microbiome, and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5-6 months of age) and compared those to old mice (18-20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments, and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier function and reduced cerebral blood flow as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the mechanisms underlying the shift from normal aging to pathological processes in the etiology of AD. Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5–6 months of age) and compared those to old mice (18–20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes / Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the mechanisms underlying the shift from normal aging to pathological processes in the etiology of AD. Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer's disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5-6 months of age) and compared those to old mice (18-20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the mechanisms underlying the shift from normal aging to pathological processes in the etiology of AD.Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer's disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5-6 months of age) and compared those to old mice (18-20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the mechanisms underlying the shift from normal aging to pathological processes in the etiology of AD. Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5–6 months of age) and compared those to old mice (18–20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the mechanisms underlying the shift from normal aging to pathological processes in the etiology of AD.
Author	Hoffman, Jared D. Hartz, Anika M. S. Chlipala, George Bauer, Bjoern Keaton, Mignon Lin, Ai-Ling Green, Stefan J. Parikh, Ishita Mohney, Robert P.
AuthorAffiliation	4 Metabolon Inc. Durham, NC, United States 6 Department of Engineering, University of Kentucky Lexington, KY, United States 1 Sanders-Brown Center on Aging, University of Kentucky Lexington, KY, United States 3 Research Resources Center, University of Illinois at Chicago Chicago, IL, United States 5 Department of Pharmaceutical Sciences, University of Kentucky Lexington, KY, United States 2 Depatment of Pharmacology and Nutritional Science, University of Kentucky Lexington, KY, United States
AuthorAffiliation_xml	– name: 5 Department of Pharmaceutical Sciences, University of Kentucky Lexington, KY, United States – name: 1 Sanders-Brown Center on Aging, University of Kentucky Lexington, KY, United States – name: 4 Metabolon Inc. Durham, NC, United States – name: 3 Research Resources Center, University of Illinois at Chicago Chicago, IL, United States – name: 2 Depatment of Pharmacology and Nutritional Science, University of Kentucky Lexington, KY, United States – name: 6 Department of Engineering, University of Kentucky Lexington, KY, United States
Author_xml	– sequence: 1 givenname: Jared D. surname: Hoffman fullname: Hoffman, Jared D. – sequence: 2 givenname: Ishita surname: Parikh fullname: Parikh, Ishita – sequence: 3 givenname: Stefan J. surname: Green fullname: Green, Stefan J. – sequence: 4 givenname: George surname: Chlipala fullname: Chlipala, George – sequence: 5 givenname: Robert P. surname: Mohney fullname: Mohney, Robert P. – sequence: 6 givenname: Mignon surname: Keaton fullname: Keaton, Mignon – sequence: 7 givenname: Bjoern surname: Bauer fullname: Bauer, Bjoern – sequence: 8 givenname: Anika M. S. surname: Hartz fullname: Hartz, Anika M. S. – sequence: 9 givenname: Ai-Ling surname: Lin fullname: Lin, Ai-Ling
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/28993728$$D View this record in MEDLINE/PubMed
BookMark	eNp1Uk1PVDEUbQxGENm7Mk3cuGDGfr92YwLDhyQQN-q26evH0MmbFtv3SPz3dmaAAIndtOk95-See897sJdy8gB8xGhOqVRfQzLLOCcId3OEiJJvwAEWgs4YFXzv2XsfHNW6Qu1QihCX78A-kUrRjsgD0J8sPTwr8d5XeBbrmMsYc4I5wNNiYoI3fjR9HqI9hr9NtdNgCjTJwUVepjg2GryYkt1w6vG2MN56eDmN8CbakvuY1_4DeBvMUP3Rw30Ifl2c_1x8n13_uLxanFzPLOdinFHCvFPYYWu5E5Jhq5DpHJKecSlJH6xDnLEQsPDYYBMsY44Y5fvAnek4PQRXO12XzUrflbg25a_OJurtRy5LbZo7O3jd94R0SHLHuWUIhb7HXDlnkKW28yE0rW87rbupX3tnfRqLGV6IvqykeKuX-V5zQUjTagJfHgRK_jP5Oup1rNYPg0k-T1VjxZRQtPls0M-voKs8ldRGpQlFmAkpKG2oT887emrlcZUNgHaANvdaiw9PEIz0JjB6Gxi9CYzeBqZRxCuKjaPZLLN5isP_if8APRbGfA
CitedBy_id	crossref_primary_10_1016_j_phymed_2022_154365 crossref_primary_10_1016_j_ijbiomac_2024_130903 crossref_primary_10_1021_acs_jafc_9b07598 crossref_primary_10_3389_fmicb_2024_1415860 crossref_primary_10_3390_microorganisms11092306 crossref_primary_10_1039_C8FO01962B crossref_primary_10_3389_fimmu_2022_917293 crossref_primary_10_3389_fnint_2018_00033 crossref_primary_10_18632_aging_101464 crossref_primary_10_3389_fcimb_2022_1048513 crossref_primary_10_18632_aging_101583 crossref_primary_10_3390_cells12182287 crossref_primary_10_3389_fmicb_2020_557342 crossref_primary_10_1016_j_apsb_2023_08_009 crossref_primary_10_1080_10408398_2021_1895064 crossref_primary_10_3390_microorganisms11020533 crossref_primary_10_1016_j_conctc_2018_11_006 crossref_primary_10_1080_1028415X_2021_1926140 crossref_primary_10_14336_AD_2020_0205 crossref_primary_10_1007_s11357_023_00963_7 crossref_primary_10_1007_s12035_021_02669_3 crossref_primary_10_1016_j_foodchem_2024_140864 crossref_primary_10_3390_nu12020290 crossref_primary_10_3389_fnagi_2018_00225 crossref_primary_10_1038_s41598_018_25190_5 crossref_primary_10_1080_10408398_2021_1882381 crossref_primary_10_4196_kjpp_2021_25_6_575 crossref_primary_10_1016_j_neuro_2019_08_005 crossref_primary_10_3389_fvets_2018_00193 crossref_primary_10_1016_j_chemosphere_2021_130952 crossref_primary_10_1080_10408398_2022_2026871 crossref_primary_10_1097_PAF_0000000000000420 crossref_primary_10_3389_fnbeh_2023_1182661 crossref_primary_10_1016_j_nbd_2020_104834 crossref_primary_10_3389_fmicb_2023_1169811 crossref_primary_10_1038_s41598_020_77587_w crossref_primary_10_3389_fnins_2019_00308 crossref_primary_10_1016_j_ijpharm_2024_125129 crossref_primary_10_1016_j_ijbiomac_2021_11_084 crossref_primary_10_3389_fnut_2019_00090 crossref_primary_10_3389_frmbi_2022_986951 crossref_primary_10_3389_fnins_2021_688090 crossref_primary_10_18632_aging_202525 crossref_primary_10_1038_s41380_022_01511_z crossref_primary_10_1128_msystems_01248_21 crossref_primary_10_1128_spectrum_00780_23 crossref_primary_10_3390_biom10030484 crossref_primary_10_1093_gerona_glae220 crossref_primary_10_1016_j_jnutbio_2022_108999 crossref_primary_10_1016_j_phymed_2021_153772 crossref_primary_10_1038_s41598_023_42381_x crossref_primary_10_1016_j_apsb_2019_07_001 crossref_primary_10_1007_s11357_021_00363_9 crossref_primary_10_1371_journal_pone_0221828 crossref_primary_10_1039_D4FO01844C crossref_primary_10_1016_j_bbrc_2022_02_042 crossref_primary_10_1016_j_arabjc_2023_105591 crossref_primary_10_18632_aging_103940 crossref_primary_10_1016_j_crbeha_2021_100042 crossref_primary_10_3389_fgene_2024_1450064 crossref_primary_10_1007_s13167_024_00379_z crossref_primary_10_1016_j_scitotenv_2023_162358 crossref_primary_10_1016_j_bbr_2018_09_010 crossref_primary_10_1016_j_nbd_2019_104580 crossref_primary_10_1111_jnc_15031 crossref_primary_10_3390_antiox13121498 crossref_primary_10_3389_fnagi_2020_00247 crossref_primary_10_1016_j_eplepsyres_2021_106826 crossref_primary_10_1038_s41598_019_56149_9 crossref_primary_10_18632_aging_206211 crossref_primary_10_3389_fnagi_2019_00056 crossref_primary_10_1007_s11655_023_3614_3 crossref_primary_10_3390_nu13093290 crossref_primary_10_1002_jsfa_12958 crossref_primary_10_3390_ijms20071632 crossref_primary_10_1155_2019_9306834 crossref_primary_10_1016_j_biopha_2024_117207 crossref_primary_10_1024_0300_9831_a000624 crossref_primary_10_3389_fcimb_2022_877914 crossref_primary_10_1038_s41598_022_10442_2 crossref_primary_10_3389_fmicb_2022_909461 crossref_primary_10_3390_nu14030668 crossref_primary_10_1146_annurev_physiol_021119_034338 crossref_primary_10_3390_molecules25030682 crossref_primary_10_1039_D3FO03805J crossref_primary_10_3389_fnagi_2023_1227203 crossref_primary_10_1096_fj_201900071R crossref_primary_10_3390_ijms21051836 crossref_primary_10_1016_j_neures_2022_02_003 crossref_primary_10_3390_nu13072446 crossref_primary_10_3389_fnins_2020_576543 crossref_primary_10_1016_j_bbrc_2023_05_075
Cites_doi	10.1186/1757-4749-1-6 10.1037/neu0000337 10.1016/j.jns.2007.01.043 10.1101/cshperspect.a006346 10.1172/jci25247 10.1111/nmo.12198 10.1016/s0197-4580(97)80312-0 10.1177/089198870101400111 10.1080/21688370.2015.1039691 10.1073/pnas.1108561108 10.1073/pnas.2635903100 10.1016/j.bbi.2007.08.009 10.1155/2012/879151 10.1038/jcbfm.2013.116 10.1161/ATVBAHA.110.207449 10.1038/nature11087 10.1016/j.jns.2013.03.007 10.1074/jbc.c500244200 10.1161/strokeaha.111.627562 10.1038/jcbfm.2013.135 10.1124/pr.107.07109 10.1155/2016/8426874 10.1016/j.cmet.2012.12.011 10.1124/mol.109.061754 10.1021/ac901536h 10.1113/jphysiol.2004.063388 10.1182/blood-2015-04-638858 10.4161/gmic.19625 10.1038/nm0596-581 10.1016/j.physbeh.2006.06.019 10.1002/ca.980080612 10.1097/psy.0000000000000223 10.1016/s0031-9384(98)00145-0 10.1016/0304-3940(95)11881-v 10.1371/journal.pone.0010667 10.1038/nmeth.f.303 10.1053/j.arrt.2003.08.002 10.1016/j.cmet.2016.06.007 10.1016/s0006-8993(00)03186-3 10.1203/01.pdr.0000156506.03057.ad 10.1371/journal.pone.0040221 10.1016/j.stem.2015.08.001 10.1177/193229680800200619 10.1002/oby.20466 10.1073/pnas.1102999108 10.1038/jcbfm.2014.114 10.1038/nri.2016.70 10.1093/gbe/evr106 10.1038/nn.4476 10.1096/fj.09-154054 10.1074/jbc.274.31.21937 10.1016/j.bbabio.2006.01.009 10.1007/s11427-016-5083-9 10.1093/epirev/mxs012 10.1038/jcbfm.1987.40 10.4137/ijtr.s36464 10.1006/nimg.1997.0318 10.1038/jcbfm.2009.197 10.1128/mbio.00042-15 10.1016/j.cell.2016.10.027 10.1002/mrm.25197 10.1186/1758-2946-2-9 10.1016/j.neuropharm.2007.06.028 10.1002/ana.24901 10.1111/j.1538-7836.2007.02540.x 10.1038/nature10213 10.1080/10618600.1996.10474713 10.1073/pnas.1000097107 10.1016/bs.irn.2016.07.005 10.18632/aging.100961 10.1016/S0022-2275(20)32052-6 10.3389/fnagi.2015.00213 10.1186/s40168-014-0050-9 10.1046/j.1471-4159.2002.01157.x 10.1016/j.febslet.2014.09.039 10.1093/eurheartj/ehu002 10.1093/bioinformatics/btq461 10.1358/mf.1999.21.9.795632 10.1016/j.tins.2013.01.005 10.1523/jneurosci.0350-15.2016 10.1128/mSystems.00009-15 10.1371/journal.pone.0105191 10.1016/j.neurobiolaging.2015.03.012 10.3389/fnagi.2014.00127 10.1126/scitranslmed.3009759 10.1016/j.taap.2011.05.015 10.1111/j.1440-1746.2010.06592.x 10.1101/sqb.2011.76.010462 10.1371/journal.pone.0024777 10.1093/femsre/fuv036 10.1002/oby.20170 10.1111/nyas.12971 10.1186/s13073-016-0296-x 10.1177/0271678x15621575 10.18632/aging.101094 10.1161/01.str.11.1.31 10.1177/0192623309336152 10.1093/bioinformatics/btt593 10.1042/cs20170220 10.1017/s0029665114000639 10.1038/ismej.2011.139 10.1016/j.neuroscience.2016.06.013 10.1038/nature05414 10.1038/sj.bjp.0705682 10.1007/s00726-016-2302-4 10.1111/acel.12266 10.1038/nrneurol.2011.2 10.1016/j.jstrokecerebrovasdis.2013.03.013 10.1016/j.mri.2015.06.010 10.1192/bjp.170.1.77 10.1371/journal.pone.0128122 10.1038/nature09922 10.1038/nrn3114
ContentType	Journal Article
Copyright	2017. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Copyright © 2017 Hoffman, Parikh, Green, Chlipala, Mohney, Keaton, Bauer, Hartz and Lin. 2017 Hoffman, Parikh, Green, Chlipala, Mohney, Keaton, Bauer, Hartz and Lin
Copyright_xml	– notice: 2017. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: Copyright © 2017 Hoffman, Parikh, Green, Chlipala, Mohney, Keaton, Bauer, Hartz and Lin. 2017 Hoffman, Parikh, Green, Chlipala, Mohney, Keaton, Bauer, Hartz and Lin
DBID	AAYXX CITATION NPM 3V. 7X7 7XB 88I 8FE 8FH 8FI 8FJ 8FK ABUWG AFKRA AZQEC BBNVY BENPR BHPHI CCPQU DWQXO FYUFA GHDGH GNUQQ HCIFZ K9. LK8 M0S M2P M7P PHGZM PHGZT PIMPY PKEHL PQEST PQGLB PQQKQ PQUKI PRINS Q9U 7X8 5PM DOA
DOI	10.3389/fnagi.2017.00298
DatabaseName	CrossRef PubMed ProQuest Central (Corporate) Health & Medical Collection ProQuest Central (purchase pre-March 2016) Science Database (Alumni Edition) ProQuest SciTech Collection ProQuest Natural Science Collection ProQuest Hospital Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central UK/Ireland ProQuest Central Essentials Biological Science Collection ProQuest Central Natural Science Collection ProQuest One Community College ProQuest Central Korea Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) Biological Sciences ProQuest Health & Medical Collection Science Database Biological Science Database ProQuest One Academic ProQuest One Academic (New) Publicly Available Content Database ProQuest One Academic Middle East (New) ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Applied & Life Sciences ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China ProQuest Central Basic MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals
DatabaseTitle	CrossRef PubMed Publicly Available Content Database ProQuest Central Student ProQuest One Academic Middle East (New) ProQuest Central Essentials ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest Natural Science Collection ProQuest Central China ProQuest Central ProQuest One Applied & Life Sciences Health Research Premium Collection Health and Medicine Complete (Alumni Edition) Natural Science Collection ProQuest Central Korea Biological Science Collection ProQuest Central (New) ProQuest Science Journals (Alumni Edition) ProQuest Biological Science Collection ProQuest Central Basic ProQuest Science Journals ProQuest One Academic Eastern Edition ProQuest Hospital Collection Health Research Premium Collection (Alumni) Biological Science Database ProQuest SciTech Collection ProQuest Hospital Collection (Alumni) ProQuest Health & Medical Complete ProQuest One Academic UKI Edition ProQuest One Academic ProQuest One Academic (New) ProQuest Central (Alumni) MEDLINE - Academic
DatabaseTitleList	PubMed Publicly Available Content Database MEDLINE - Academic
Database_xml	– sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: BENPR name: ProQuest Central url: http://www.proquest.com/pqcentral?accountid=15518 sourceTypes: Aggregation Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Medicine
EISSN	1663-4365
ExternalDocumentID	oai_doaj_org_article_bb227085d55c400fbb159dda0c3c7eff PMC5622159 28993728 10_3389_fnagi_2017_00298
Genre	Journal Article
GeographicLocations	United States--US
GeographicLocations_xml	– name: United States--US
GrantInformation_xml	– fundername: NIA NIH HHS grantid: R01 AG054459 – fundername: NINDS NIH HHS grantid: R01 NS079507 – fundername: NCATS NIH HHS grantid: UL1 TR000117 – fundername: NIA NIH HHS grantid: R01 AG039621 – fundername: NIDDK NIH HHS grantid: T32 DK007778 – fundername: NIA NIH HHS grantid: K01 AG040164 – fundername: NCRR NIH HHS grantid: S10 RR029541 – fundername: National Institutes of Health grantid: S10RR029541, UL1TR000117 – fundername: National Institute on Aging grantid: K01AG040164, R01AG039621 – fundername: American Federation for Aging Research grantid: #A12474 – fundername: National Institute of Diabetes and Digestive and Kidney Diseases grantid: T32DK007778
GroupedDBID	--- 53G 5VS 7X7 88I 8FE 8FH 8FI 8FJ 9T4 AAFWJ AAYXX ABIVO ABUWG ACGFO ACGFS ACXDI ADBBV ADRAZ AEGXH AENEX AFKRA AFPKN AIAGR ALIPV ALMA_UNASSIGNED_HOLDINGS AOIJS AZQEC BAWUL BBNVY BCNDV BENPR BHPHI BPHCQ BVXVI CCPQU CITATION DIK DWQXO E3Z EIHBH F5P FYUFA GNUQQ GROUPED_DOAJ GX1 HCIFZ HMCUK HYE KQ8 LK8 M2P M7P M~E O5R O5S OK1 PGMZT PHGZM PHGZT PIMPY PQQKQ PROAC RNS RPM TR2 UKHRP IAO IEA IHR IHW IPNFZ IPY M48 NPM RIG 3V. 7XB 8FK K9. PKEHL PQEST PQGLB PQUKI PRINS Q9U 7X8 PUEGO 5PM
ID	FETCH-LOGICAL-c556t-324ed91d1cc5d6841c90a7d08e45882bfcd0544ff16e1a1afc44d2a9ebf5da753
IEDL.DBID	M48
ISSN	1663-4365
IngestDate	Wed Aug 27 01:21:31 EDT 2025 Thu Aug 21 18:19:52 EDT 2025 Fri Sep 05 06:09:31 EDT 2025 Fri Jul 25 12:00:17 EDT 2025 Thu Jan 02 22:53:40 EST 2025 Tue Jul 01 04:03:15 EDT 2025 Thu Apr 24 22:56:53 EDT 2025
IsDoiOpenAccess	true
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Keywords	neurovascular function anxiety brain metabolism gut microbiome Alzheimer’s disease cognition MRI aging
Language	English
License	This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c556t-324ed91d1cc5d6841c90a7d08e45882bfcd0544ff16e1a1afc44d2a9ebf5da753
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Edited by: P. Hemachandra Reddy, Texas Tech University Health Sciences Center, United States Reviewed by: Ana I. Duarte, University of Coimbra, Portugal; Fan Liao, AbbVie Foundational Neuroscience Center, United States
OpenAccessLink	https://doaj.org/article/bb227085d55c400fbb159dda0c3c7eff
PMID	28993728
PQID	2301468633
PQPubID	4424411
ParticipantIDs	doaj_primary_oai_doaj_org_article_bb227085d55c400fbb159dda0c3c7eff pubmedcentral_primary_oai_pubmedcentral_nih_gov_5622159 proquest_miscellaneous_1949693684 proquest_journals_2301468633 pubmed_primary_28993728 crossref_primary_10_3389_fnagi_2017_00298 crossref_citationtrail_10_3389_fnagi_2017_00298
ProviderPackageCode	CITATION AAYXX
PublicationCentury	2000
PublicationDate	2017-09-25
PublicationDateYYYYMMDD	2017-09-25
PublicationDate_xml	– month: 09 year: 2017 text: 2017-09-25 day: 25
PublicationDecade	2010
PublicationPlace	Switzerland
PublicationPlace_xml	– name: Switzerland – name: Lausanne
PublicationTitle	Frontiers in aging neuroscience
PublicationTitleAlternate	Front Aging Neurosci
PublicationYear	2017
Publisher	Frontiers Research Foundation Frontiers Media S.A
Publisher_xml	– name: Frontiers Research Foundation – name: Frontiers Media S.A
References	Hartz (B51) 2016; 36 Sha (B94) 2010; 24 Bybee (B18) 2011; 3 Parnetti (B84) 2007; 257 Melamed (B73) 1980; 11 Dinan (B28) 2013; 25 Hill (B52) 2014; 6 Zlokovic (B117) 2011; 12 Tremlett (B98) 2017; 81 Hadley (B46) 2016 Hartz (B50) 2010; 77 Bangen (B8) 2013; 22 Foster (B37) 2013; 36 Schweinberger (B93) 2016; 48 Dou (B29) 2007; 5 Goehler (B42) 2008; 22 Ohta (B77) 2009; 37 Al-Asmakh (B1) 2015; 3 Schnorr (B92) 2016; 89 Verbeke (B101) 2014; 73 Astarita (B6) 2011; 6 Caporaso (B20) 2010; 7 Erickson (B32) 2013; 33 Chyan (B22) 1999; 274 Lyte (B69) 2006; 89 Wyss-Coray (B112) 2012; 2 Green (B43) 2015; 10 Alzheimer (B4) 1995; 8 Parikh (B82) 2016; 8 Lin (B65) 2013; 33 Wang (B106) 2011; 472 Biagi (B11) 2010; 5 Walters (B105) 2014; 588 Bachstetter (B7) 2014; 9 Park (B83) 2017; 345 Weiner (B109) 2012; 7 Harris (B48) 2012; 2012 Kozieł (B60) 2014; 13 Braniste (B14) 2014; 6 Lütjohann (B67) 2000; 41 Claesson (B24) 2011; 108 Wissmann (B110) 2013; 329 Geddes (B41) 1997; 18 Kau (B58) 2011; 474 Evans (B33) 2009; 81 Reitz (B89) 2011; 7 Foster (B36) 2016; 131 Ron-Harel (B91) 2016; 24 Everson-Rose (B34) 2015; 77 Lynch (B68) 2010; 1 Pamplona (B81) 2006; 1757 Gallant (B39) 2006; 281 Brown-Borg (B16) 2016; 1363 Zhang (B116) 2016; 8 Hartz (B49) 2012; 43 Brunet (B17) 2003; 10 Ferretti (B35) 2001; 14 de la Monte (B26) 2008; 2 Vagelatos (B100) 2013; 35 García-Calatayud (B40) 2005; 57 Lin (B66) 2015; 36 Wong (B111) 1996; 2 Lin (B63) 2014; 34 Gur (B45) 1987; 7 Verdam (B102) 2013; 21 B78 Huuskonen (B55) 2004; 141 Alsop (B2) 2015; 73 Casey (B21) 2011; 108 O’Neill (B79) 2016; 16 Walters (B104) 2015; 1 Morrison (B76) 1995; 197 Sudo (B97) 2004; 558 Cani (B19) 2012; 3 Turnbaugh (B99) 2006; 444 Rao (B86) 2009; 1 Jaeschke (B57) 2011; 26 Hong (B53) 2015; 33 Miller (B74) 2008; 60 Petit-Taboué (B85) 1998; 7 Ihaka (B87) 1996; 5 Langille (B61) 2014; 2 Sharon (B95) 2016; 167 Bell (B9) 2012; 485 Ivanisevic (B56) 2016; 8 Zhang (B115) 2014; 30 Keegan (B59) 2016; 9 Weber (B108) 2015; 126 Boumezbeur (B13) 2010; 30 Martínez-del Campo (B71) 2015; 6 Zgoda-Pols (B114) 2011; 255 Lyte (B70) 1998; 65 Reiman (B88) 2004; 101 Montine (B75) 2002; 83 Birdsill (B12) 2013; 21 Hamilton (B47) 2015; 17 Wang (B107) 2014; 35 Fung (B38) 2017; 20 Hu (B54) 2016; 59 Palermo (B80) 2017; 31 Alvarez (B3) 1999; 21 Ebmeier (B30) 1997; 170 Arendash (B5) 2001; 891 Laukens (B62) 2016; 40 Lin (B64) 2017; 37 B302 Bravo (B15) 2011; 108 Guo (B44) 2015; 7 Sood (B96) 2007; 53 Dehaven (B27) 2010; 2 Ricciotti (B90) 2011; 31 McDonald (B72) 2012; 6 Bennett (B10) 2013; 17 Wallace (B103) 2011; 76 Curi (B25) 2017; 131 Edgar (B31) 2010; 26 Xia (B113) 2016; 2016 Cirrito (B23) 2005; 115
References_xml	– volume: 1 start-page: 6 year: 2009 ident: B86 article-title: A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome publication-title: Gut Pathog. doi: 10.1186/1757-4749-1-6 – volume: 31 start-page: 255 year: 2017 ident: B80 article-title: Cognitive outcomes in early-treated adults with phenylketonuria (PKU): a comprehensive picture across domains publication-title: Neuropsychology doi: 10.1037/neu0000337 – volume: 257 start-page: 264 year: 2007 ident: B84 article-title: Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation? publication-title: J. Neurol. Sci. doi: 10.1016/j.jns.2007.01.043 – volume: 2 start-page: a006346 year: 2012 ident: B112 article-title: Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature publication-title: Cold Spring Harb. Perspect. Med. doi: 10.1101/cshperspect.a006346 – volume: 115 start-page: 3285 year: 2005 ident: B23 article-title: P-glycoprotein deficiency at the blood-brain barrier increases amyloid-β deposition in an Alzheimer disease mouse model publication-title: J. Clin. Invest. doi: 10.1172/jci25247 – volume: 25 start-page: 713 year: 2013 ident: B28 article-title: Melancholic microbes: a link between gut microbiota and depression? publication-title: Neurogastroenterol. Motil. doi: 10.1111/nmo.12198 – volume: 18 start-page: 305 year: 1997 ident: B41 article-title: Elevated phosphocholine and phosphatidylcholine following rat entorhinal cortex lesions publication-title: Neurobiol. Aging doi: 10.1016/s0197-4580(97)80312-0 – volume: 14 start-page: 52 year: 2001 ident: B35 article-title: Anxiety and Alzheimer’s disease publication-title: J. Geriatr. Psychiatry Neurol. doi: 10.1177/089198870101400111 – volume: 3 start-page: e1039691 year: 2015 ident: B1 article-title: Microbiota and the control of blood-tissue barriers publication-title: Tissue Barriers doi: 10.1080/21688370.2015.1039691 – volume: 108 start-page: 14998 year: 2011 ident: B21 article-title: Behavioral and neural correlates of delay of gratification 40 years later publication-title: Proc. Natl. Acad. Sci. U S A doi: 10.1073/pnas.1108561108 – volume: 101 start-page: 284 year: 2004 ident: B88 article-title: Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer’s dementia publication-title: Proc. Natl. Acad. Sci. U S A doi: 10.1073/pnas.2635903100 – volume: 22 start-page: 354 year: 2008 ident: B42 article-title: Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible anatomical substrates for viscerosensory modulation of exploratory behavior publication-title: Brain Behav. Immun. doi: 10.1016/j.bbi.2007.08.009 – volume: 2012 start-page: 879151 year: 2012 ident: B48 article-title: Is the gut microbiota a new factor contributing to obesity and its metabolic disorders? publication-title: J. Obes. doi: 10.1155/2012/879151 – volume: 33 start-page: 1605 year: 2013 ident: B65 article-title: Decreased in vitro mitochondrial function is associated with enhanced brain metabolism, blood flow and memory in Surf1-deficient mice publication-title: J. Cereb. Blood Flow Metab. doi: 10.1038/jcbfm.2013.116 – volume: 31 start-page: 986 year: 2011 ident: B90 article-title: Prostaglandins and inflammation publication-title: Arterioscler. Thromb. Vasc. Biol. doi: 10.1161/ATVBAHA.110.207449 – volume: 485 start-page: 512 year: 2012 ident: B9 article-title: Apolipoprotein E controls cerebrovascular integrity via cyclophilin A publication-title: Nature doi: 10.1038/nature11087 – volume: 329 start-page: 29 year: 2013 ident: B110 article-title: Immune activation in patients with Alzheimer’s disease is associated with high serum phenylalanine concentrations publication-title: J. Neurol. Sci. doi: 10.1016/j.jns.2013.03.007 – volume: 281 start-page: 5 year: 2006 ident: B39 article-title: Focally elevated creatine detected in amyloid precursor protein (APP) transgenic mice and Alzheimer disease brain tissue publication-title: J. Biol. Chem. doi: 10.1074/jbc.c500244200 – volume: 43 start-page: 514 year: 2012 ident: B49 article-title: Amyloid-β contributes to blood-brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy publication-title: Stroke doi: 10.1161/strokeaha.111.627562 – volume: 33 start-page: 1500 year: 2013 ident: B32 article-title: Blood-brain barrier dysfunction as a cause and consequence of Alzheimer’s disease publication-title: J. Cereb. Blood Flow Metab. doi: 10.1038/jcbfm.2013.135 – volume: 60 start-page: 196 year: 2008 ident: B74 article-title: Modulation of P-glycoprotein at the blood-brain barrier: opportunities to improve central nervous system pharmacotherapy publication-title: Pharmacol. Rev. doi: 10.1124/pr.107.07109 – volume: 2016 start-page: 8426874 year: 2016 ident: B113 article-title: An update on inflamm-aging: mechanisms, prevention and treatment publication-title: J. Immunol. Res. doi: 10.1155/2016/8426874 – volume: 17 start-page: 49 year: 2013 ident: B10 article-title: Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation publication-title: Cell Metab. doi: 10.1016/j.cmet.2012.12.011 – volume: 77 start-page: 715 year: 2010 ident: B50 article-title: Restoring blood-brain barrier P-glycoprotein reduces brain amyloid-beta in a mouse model of Alzheimer’s disease publication-title: Mol. Pharmacol. doi: 10.1124/mol.109.061754 – volume: 81 start-page: 6656 year: 2009 ident: B33 article-title: Integrated, nontargeted ultrahigh performance liquid chromatography/electrospray ionization tandem mass spectrometry platform for the identification and relative quantification of the small-molecule complement of biological systems publication-title: Anal. Chem. doi: 10.1021/ac901536h – volume: 558 start-page: 263 year: 2004 ident: B97 article-title: Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice publication-title: J. Physiol. doi: 10.1113/jphysiol.2004.063388 – volume: 126 start-page: 1723 year: 2015 ident: B108 article-title: Low urinary indoxyl sulfate levels early after transplantation reflect a disrupted microbiome and are associated with poor outcome publication-title: Blood doi: 10.1182/blood-2015-04-638858 – volume: 3 start-page: 279 year: 2012 ident: B19 article-title: Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity publication-title: Gut Microbes doi: 10.4161/gmic.19625 – volume: 2 start-page: 581 year: 1996 ident: B111 article-title: Inducible nitric oxide synthase gene expression in the brain during systemic inflammation publication-title: Nat. Med. doi: 10.1038/nm0596-581 – volume: 89 start-page: 350 year: 2006 ident: B69 article-title: Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia citrobacter rodentium publication-title: Physiol. Behav. doi: 10.1016/j.physbeh.2006.06.019 – volume: 8 start-page: 429 year: 1995 ident: B4 article-title: An English translation of Alzheimer’s 1907 paper, “Uber eine eigenartige Erkankung der Hirnrinde” publication-title: Clin. Anat. doi: 10.1002/ca.980080612 – volume: 77 start-page: 612 year: 2015 ident: B34 article-title: Diabetes, obesity, and the brain: new developments in biobehavioral medicine publication-title: Psychosom. Med. doi: 10.1097/psy.0000000000000223 – volume: 65 start-page: 63 year: 1998 ident: B70 article-title: Anxiogenic effect of subclinical bacterial infection in mice in the absence of overt immune activation publication-title: Physiol. Behav. doi: 10.1016/s0031-9384(98)00145-0 – volume: 197 start-page: 5 year: 1995 ident: B76 article-title: Brain polyamine levels are altered in Alzheimer’s disease publication-title: Neurosci. Lett. doi: 10.1016/0304-3940(95)11881-v – volume: 5 start-page: e10667 year: 2010 ident: B11 article-title: Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians publication-title: PLoS One doi: 10.1371/journal.pone.0010667 – volume: 7 start-page: 335 year: 2010 ident: B20 article-title: QIIME allows analysis of high-throughput community sequencing data publication-title: Nat. Methods doi: 10.1038/nmeth.f.303 – volume: 10 start-page: 310 year: 2003 ident: B17 article-title: Protein-bound uremic retention solutes publication-title: Adv. Ren. Replace. Ther. doi: 10.1053/j.arrt.2003.08.002 – volume: 24 start-page: 104 year: 2016 ident: B91 article-title: Mitochondrial biogenesis and proteome remodeling promote one-carbon metabolism for T cell activation publication-title: Cell Metab. doi: 10.1016/j.cmet.2016.06.007 – volume: 891 start-page: 42 year: 2001 ident: B5 article-title: Progressive, age-related behavioral impairments in transgenic mice carrying both mutant amyloid precursor protein and presenilin-1 transgenes publication-title: Brain Res. doi: 10.1016/s0006-8993(00)03186-3 – volume: 57 start-page: 719 year: 2005 ident: B40 article-title: Brain docosahexaenoic acid status and learning in young rats submitted to dietary long-chain polyunsaturated fatty acid deficiency and supplementation limited to lactation publication-title: Pediatr. Res. doi: 10.1203/01.pdr.0000156506.03057.ad – volume: 7 start-page: e40221 year: 2012 ident: B109 article-title: Biomarkers of inflammation, immunosuppression and stress with active disease are revealed by metabolomic profiling of tuberculosis patients publication-title: PLoS One doi: 10.1371/journal.pone.0040221 – volume: 17 start-page: 397 year: 2015 ident: B47 article-title: Aberrant lipid metabolism in the forebrain niche suppresses adult neural stem cell proliferation in an animal model of Alzheimer’s disease publication-title: Cell Stem Cell doi: 10.1016/j.stem.2015.08.001 – volume: 2 start-page: 1101 year: 2008 ident: B26 article-title: Alzheimer’s disease is type 3 diabetes-evidence reviewed publication-title: J. Diabetes Sci. Technol. doi: 10.1177/193229680800200619 – volume: 21 start-page: E607 year: 2013 ident: B102 article-title: Human intestinal microbiota composition is associated with local and systemic inflammation in obesity publication-title: Obesity (Silver Spring) doi: 10.1002/oby.20466 – volume: 108 start-page: 16050 year: 2011 ident: B15 article-title: Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve publication-title: Proc. Natl. Acad. Sci. U S A doi: 10.1073/pnas.1102999108 – volume: 34 start-page: 1440 year: 2014 ident: B63 article-title: Caloric restriction impedes age-related decline of mitochondrial function and neuronal activity publication-title: J. Cereb. Blood Flow Metab. doi: 10.1038/jcbfm.2014.114 – volume: 16 start-page: 553 year: 2016 ident: B79 article-title: A guide to immunometabolism for immunologists publication-title: Nat. Rev. Immunol. doi: 10.1038/nri.2016.70 – volume: 3 start-page: 1312 year: 2011 ident: B18 article-title: Targeted amplicon sequencing (TAS): a scalable next-gen approach to multilocus, multitaxa phylogenetics publication-title: Genome Biol. Evol. doi: 10.1093/gbe/evr106 – volume: 20 start-page: 145 year: 2017 ident: B38 article-title: Interactions between the microbiota, immune and nervous systems in health and disease publication-title: Nat. Neurosci. doi: 10.1038/nn.4476 – volume: 24 start-page: 2962 year: 2010 ident: B94 article-title: Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline publication-title: FASEB J. doi: 10.1096/fj.09-154054 – volume: 274 start-page: 21937 year: 1999 ident: B22 article-title: Potent neuroprotective properties against the Alzheimer β-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid publication-title: J. Biol. Chem. doi: 10.1074/jbc.274.31.21937 – volume: 89 start-page: 397 year: 2016 ident: B92 article-title: Integrative therapies in anxiety treatment with special emphasis on the gut microbiome publication-title: Yale J. Biol. Med. – volume: 1757 start-page: 496 year: 2006 ident: B81 article-title: Mitochondrial oxidative stress, aging and caloric restriction: the protein and methionine connection publication-title: Biochim. Biophys. Acta doi: 10.1016/j.bbabio.2006.01.009 – volume: 59 start-page: 1006 year: 2016 ident: B54 article-title: Alzheimer’s disease and gut microbiota publication-title: Sci. China Life Sci. doi: 10.1007/s11427-016-5083-9 – volume: 35 start-page: 152 year: 2013 ident: B100 article-title: Type 2 diabetes as a risk factor for Alzheimer’s disease: the confounders, interactions and neuropathology associated with this relationship publication-title: Epidemiol. Rev. doi: 10.1093/epirev/mxs012 – volume: 7 start-page: 173 year: 1987 ident: B45 article-title: The effect of anxiety on cortical cerebral blood flow and metabolism publication-title: J. Cereb. Blood Flow Metab. doi: 10.1038/jcbfm.1987.40 – volume: 9 start-page: 79 year: 2016 ident: B59 article-title: Tryptophan metabolism and its relationship with depression and cognitive impairment among HIV-infected individuals publication-title: Int. J. Tryptophan. Res. doi: 10.4137/ijtr.s36464 – volume: 7 start-page: 176 year: 1998 ident: B85 article-title: Effects of healthy aging on the regional cerebral metabolic rate of glucose assessed with statistical parametric mapping publication-title: Neuroimage doi: 10.1006/nimg.1997.0318 – volume: 30 start-page: 211 year: 2010 ident: B13 article-title: Altered brain mitochondrial metabolism in healthy aging as assessed by in vivo magnetic resonance spectroscopy publication-title: J. Cereb. Blood Flow Metab. doi: 10.1038/jcbfm.2009.197 – volume: 6 start-page: e00042-15 year: 2015 ident: B71 article-title: Characterization and detection of a widely distributed gene cluster that predicts anaerobic choline utilization by human gut bacteria publication-title: MBio doi: 10.1128/mbio.00042-15 – volume: 167 start-page: 915 year: 2016 ident: B95 article-title: The central nervous system and the gut microbiome publication-title: Cell doi: 10.1016/j.cell.2016.10.027 – volume: 73 start-page: 102 year: 2015 ident: B2 article-title: Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: a consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia publication-title: Magn. Reson. Med. doi: 10.1002/mrm.25197 – volume: 2 start-page: 9 year: 2010 ident: B27 article-title: Organization of GC/MS and LC/MS metabolomics data into chemical libraries publication-title: J. Cheminform. doi: 10.1186/1758-2946-2-9 – ident: B302 – volume: 53 start-page: 588 year: 2007 ident: B96 article-title: The effects of JWB1–84-1 on memory-related task performance by amyloid Aβ transgenic mice and by young and aged monkeys publication-title: Neuropharmacology doi: 10.1016/j.neuropharm.2007.06.028 – volume: 81 start-page: 369 year: 2017 ident: B98 article-title: The gut microbiome in human neurological disease: a review publication-title: Ann. Neurol. doi: 10.1002/ana.24901 – volume: 5 start-page: 1302 year: 2007 ident: B29 article-title: The uremic solute indoxyl sulfate induces oxidative stress in endothelial cells publication-title: J. Thromb. Haemost. doi: 10.1111/j.1538-7836.2007.02540.x – volume: 474 start-page: 327 year: 2011 ident: B58 article-title: Human nutrition, the gut microbiome and the immune system publication-title: Nature doi: 10.1038/nature10213 – volume: 5 start-page: 299 year: 1996 ident: B87 article-title: R: a language for data analysis and graphics publication-title: J. Comput. Graph. Stat. doi: 10.1080/10618600.1996.10474713 – volume: 108 start-page: 4586 year: 2011 ident: B24 article-title: Composition, variability, and temporal stability of the intestinal microbiota of the elderly publication-title: Proc. Natl. Acad. Sci. U S A doi: 10.1073/pnas.1000097107 – volume: 131 start-page: 49 year: 2016 ident: B36 article-title: Gut microbiome and behavior: focus on neuroimmune interactions publication-title: Int. Rev. Neurobiol. doi: 10.1016/bs.irn.2016.07.005 – volume: 8 start-page: 1000 year: 2016 ident: B56 article-title: Metabolic drift in the aging brain publication-title: Aging (Albany NY) doi: 10.18632/aging.100961 – volume: 41 start-page: 195 year: 2000 ident: B67 article-title: Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients publication-title: J. Lipid Res. doi: 10.1016/S0022-2275(20)32052-6 – volume: 7 start-page: 213 year: 2015 ident: B44 article-title: Early shifts of brain metabolism by caloric restriction preserve white matter integrity and long-term memory in aging mice publication-title: Front. Aging Neurosci. doi: 10.3389/fnagi.2015.00213 – volume: 2 start-page: 50 year: 2014 ident: B61 article-title: Microbial shifts in the aging mouse gut publication-title: Microbiome doi: 10.1186/s40168-014-0050-9 – volume: 83 start-page: 463 year: 2002 ident: B75 article-title: Neuronal oxidative damage from activated innate immunity is EP2 receptor-dependent publication-title: J. Neurochem. doi: 10.1046/j.1471-4159.2002.01157.x – volume: 588 start-page: 4223 year: 2014 ident: B105 article-title: Meta-analyses of human gut microbes associated with obesity and IBD publication-title: FEBS Lett. doi: 10.1016/j.febslet.2014.09.039 – volume: 35 start-page: 904 year: 2014 ident: B107 article-title: Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide publication-title: Eur. Heart J. doi: 10.1093/eurheartj/ehu002 – volume: 26 start-page: 2460 year: 2010 ident: B31 article-title: Search and clustering orders of magnitude faster than BLAST publication-title: Bioinformatics doi: 10.1093/bioinformatics/btq461 – volume: 21 start-page: 633 year: 1999 ident: B3 article-title: Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer’s disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion publication-title: Methods Find. Exp. Clin. Pharmacol. doi: 10.1358/mf.1999.21.9.795632 – volume: 36 start-page: 305 year: 2013 ident: B37 article-title: Gut-brain axis: how the microbiome influences anxiety and depression publication-title: Trends Neurosci. doi: 10.1016/j.tins.2013.01.005 – volume: 36 start-page: 1930 year: 2016 ident: B51 article-title: Aβ40 reduces P-glycoprotein at the blood-brain barrier through the ubiquitin-proteasome pathway publication-title: J. Neurosci. doi: 10.1523/jneurosci.0350-15.2016 – volume: 1 start-page: e00009-15 year: 2015 ident: B104 article-title: Improved bacterial 16S rRNA gene (V4 and V4–5) and fungal internal transcribed spacer marker gene primers for microbial community surveys publication-title: mSystems doi: 10.1128/mSystems.00009-15 – volume: 9 start-page: e105191 year: 2014 ident: B7 article-title: Generation and behavior characterization of CaMKIIβ knockout mice publication-title: PLoS One doi: 10.1371/journal.pone.0105191 – volume: 36 start-page: 2296 year: 2015 ident: B66 article-title: Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain publication-title: Neurobiol. Aging doi: 10.1016/j.neurobiolaging.2015.03.012 – volume: 6 start-page: 127 year: 2014 ident: B52 article-title: Pathogenic microbes, the microbiome, and Alzheimer’s disease (AD) publication-title: Front. Aging Neurosci. doi: 10.3389/fnagi.2014.00127 – volume-title: ggplot2: Elegant Graphics for Data Analysis year: 2016 ident: B46 – volume: 6 start-page: 263ra158 year: 2014 ident: B14 article-title: The gut microbiota influences blood-brain barrier permeability in mice publication-title: Sci. Transl. Med. doi: 10.1126/scitranslmed.3009759 – volume: 255 start-page: 48 year: 2011 ident: B114 article-title: Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: investigation of nicotinic acid receptor agonists publication-title: Toxicol. Appl. Pharmacol. doi: 10.1016/j.taap.2011.05.015 – volume: 26 start-page: 173 year: 2011 ident: B57 article-title: Reactive oxygen and mechanisms of inflammatory liver injury: present concepts publication-title: J. Gastroenterol. Hepatol. doi: 10.1111/j.1440-1746.2010.06592.x – volume: 1 start-page: 262 year: 2010 ident: B68 article-title: The impact of glial activation in the aging brain publication-title: Aging Dis. – volume: 76 start-page: 1 year: 2011 ident: B103 article-title: Bioenergetic origins of complexity and disease publication-title: Cold Spring Harb. Symp. Quant. Biol. doi: 10.1101/sqb.2011.76.010462 – volume: 6 start-page: e24777 year: 2011 ident: B6 article-title: Elevated stearoyl-CoA desaturase in brains of patients with Alzheimer’s disease publication-title: PLoS One doi: 10.1371/journal.pone.0024777 – volume: 40 start-page: 117 year: 2016 ident: B62 article-title: Heterogeneity of the gut microbiome in mice: guidelines for optimizing experimental design publication-title: FEMS Microbiol. Rev. doi: 10.1093/femsre/fuv036 – volume: 21 start-page: 1313 year: 2013 ident: B12 article-title: Low cerebral blood flow is associated with lower memory function in metabolic syndrome publication-title: Obesity (Silver Spring) doi: 10.1002/oby.20170 – volume: 1363 start-page: 40 year: 2016 ident: B16 article-title: Reduced growth hormone signaling and methionine restriction: interventions that improve metabolic health and extend life span publication-title: Ann. N Y Acad. Sci. doi: 10.1111/nyas.12971 – volume: 8 start-page: 46 year: 2016 ident: B116 article-title: Microbial metabolism of dietary components to bioactive metabolites: opportunities for new therapeutic interventions publication-title: Genome Med. doi: 10.1186/s13073-016-0296-x – volume: 37 start-page: 217 year: 2017 ident: B64 article-title: Rapamycin rescues vascular, metabolic and learning deficits in apolipoprotein E4 transgenic mice with pre-symptomatic Alzheimer’s disease publication-title: J. Cereb. Blood Flow Metab. doi: 10.1177/0271678x15621575 – volume: 8 start-page: 2814 year: 2016 ident: B82 article-title: Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions publication-title: Aging (Albany NY) doi: 10.18632/aging.101094 – volume: 11 start-page: 31 year: 1980 ident: B73 article-title: Reduction in regional cerebral blood flow during normal aging in man publication-title: Stroke doi: 10.1161/01.str.11.1.31 – volume: 37 start-page: 521 year: 2009 ident: B77 article-title: Untargeted metabolomic profiling as an evaluative tool of fenofibrate-induced toxicology in Fischer 344 male rats publication-title: Toxicol. Pathol. doi: 10.1177/0192623309336152 – volume: 30 start-page: 614 year: 2014 ident: B115 article-title: PEAR: a fast and accurate illumina paired-end reAd mergeR publication-title: Bioinformatics doi: 10.1093/bioinformatics/btt593 – volume: 131 start-page: 1329 year: 2017 ident: B25 article-title: A past and present overview of macrophage metabolism and functional outcomes publication-title: Clin. Sci. (Lond) doi: 10.1042/cs20170220 – volume: 73 start-page: 490 year: 2014 ident: B101 article-title: Modulating the microbiota in inflammatory bowel diseases: prebiotics, probiotics or faecal transplantation? publication-title: Proc. Nutr. Soc. doi: 10.1017/s0029665114000639 – volume: 6 start-page: 610 year: 2012 ident: B72 article-title: An improved greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea publication-title: ISME J. doi: 10.1038/ismej.2011.139 – volume: 345 start-page: 193 year: 2017 ident: B83 article-title: Impact of anxiety on prefrontal cortex encoding of cognitive flexibility publication-title: Neuroscience doi: 10.1016/j.neuroscience.2016.06.013 – volume: 444 start-page: 1027 year: 2006 ident: B99 article-title: An obesity-associated gut microbiome with increased capacity for energy harvest publication-title: Nature doi: 10.1038/nature05414 – volume: 141 start-page: 874 year: 2004 ident: B55 article-title: Regulation of microglial inflammatory response by sodium butyrate and short-chain fatty acids publication-title: Br. J. Pharmacol. doi: 10.1038/sj.bjp.0705682 – volume: 48 start-page: 2479 year: 2016 ident: B93 article-title: Mechanistic basis of hypermethioninemia publication-title: Amino Acids doi: 10.1007/s00726-016-2302-4 – volume: 13 start-page: 1038 year: 2014 ident: B60 article-title: Methionine restriction slows down senescence in human diploid fibroblasts publication-title: Aging Cell doi: 10.1111/acel.12266 – volume: 7 start-page: 137 year: 2011 ident: B89 article-title: Epidemiology of Alzheimer disease publication-title: Nat. Rev. Neurol. doi: 10.1038/nrneurol.2011.2 – volume: 22 start-page: 1361 year: 2013 ident: B8 article-title: APOE genotype modifies the relationship between midlife vascular risk factors and later cognitive decline publication-title: J. Stroke Cerebrovasc. Dis. doi: 10.1016/j.jstrokecerebrovasdis.2013.03.013 – volume: 33 start-page: 1098 year: 2015 ident: B53 article-title: Evaluation of EPI distortion correction methods for quantitative MRI of the brain at high magnetic field publication-title: Magn. Reson. Imaging doi: 10.1016/j.mri.2015.06.010 – volume: 170 start-page: 77 year: 1997 ident: B30 article-title: Cerebral perfusion correlates of depressed mood publication-title: Br. J. Psychiatry doi: 10.1192/bjp.170.1.77 – volume: 10 start-page: e0128122 year: 2015 ident: B43 article-title: Deconstructing the polymerase chain reaction: understanding and correcting bias associated with primer degeneracies and primer-template mismatches publication-title: PLoS One doi: 10.1371/journal.pone.0128122 – ident: B78 – volume: 472 start-page: 57 year: 2011 ident: B106 article-title: Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease publication-title: Nature doi: 10.1038/nature09922 – volume: 12 start-page: 723 year: 2011 ident: B117 article-title: Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders publication-title: Nat. Rev. Neurosci. doi: 10.1038/nrn3114
SSID	ssj0000330058
Score	2.4533257
Snippet	Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer's disease (AD). However, the contribution of aging... Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging...
SourceID	doaj pubmedcentral proquest pubmed crossref
SourceType	Open Website Open Access Repository Aggregation Database Index Database Enrichment Source
StartPage	298
SubjectTerms	Age Aging Alzheimer's disease Animal cognition Anxiety Bioinformatics Biomarkers Blood flow Blood-brain barrier brain metabolism Cerebral blood flow cognition Cognitive ability Dementia Deoxyribonucleic acid Digestive system DNA Etiology Fatty acids Feces Gene expression gut microbiome Image processing Immune response Inflammation Intestinal microflora Memory Metabolism Metabolites Microbiomes Microbiota MRI Nervous system Neurodegenerative diseases Neuroimaging Neuroscience neurovascular function Nitric oxide Risk factors
SummonAdditionalLinks	– databaseName: DOAJ Directory of Open Access Journals dbid: DOA link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lb9QwELZQD4gLAsoj0CJX4oLUaNfPxMc-2FaVlhNFvVl-wkptFrXZ_98ZJ7vaRQguXGNHcT6PPd_I428I-SSSlD5FV2fwL7WMIdemYaZmwRgXgspG4X3n-Vd9eS2vbtTNVqkvzAkb5IEH4Cbec94AL4hKBbC37D044BjdNIjQpJxx94XPbAVTZQ8WKMPeDueSEIWZScaqP5jKhZKF3LQ7fqjI9f-JY_6eKrnle2YvyPORNNKTYbAvyZPUvSJP5-Ox-D7xJz8SPb9HBVl6XnQ_EG66zPQUK0DQeephrm8X4Zh-HzNPqesiPVvnDtEZuLdigcelAVghvVj1dL4YdJru0mtyPfvy7eyyHosn1EEp3ddAlFI0LDIAPOpWAvhT18Rpm_BuKvc5RGBrMmemE3PM5SBl5M4kn1V0EMS8IXvdskvvCAUOEIFXytQ0QurMveA5OAhFktSRxViRyRpKG0ZlcSxwcWshwkDwbQHfIvi2gF-Rz5s3fg2qGn_pe4qzs-mHetjlAViJHa3E_stKKnKwnls7LtIHyzGc1K0WoiJHm2ZYXnhm4rq0XD1YZqTRRgCAFXk7mMJmJBiriobDCJsdI9kZ6m5Lt_hZJLyBdQLXMu__x799IM8QLUxi4eqA7PX3q3QITKn3H8uieAQizxRP priority: 102 providerName: Directory of Open Access Journals – databaseName: Health & Medical Collection dbid: 7X7 link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1Lj9MwELZgkRAXxJuwCzISF6SNWsev-oT2QVkhlROLerMcP5ZKS7K06f_fGScNFKG9xo40mhl7vrHH3xDygUch6hhcmSC-lCL4VBrNTMm8Mc57mYzE986Lb-riUnxdyuVw4LYZyip3e2LeqEPr8Yx8UiH2VzPF-aeb3yV2jcLb1aGFxn3ygAFUQa_WSz2esUw5krHn13AQWEvBlexvKiEvM5OEfYCwuAtJDCsz24tMmcD_f6jz3-LJv6LR_Al5PMBIetLb_Sm5F5tn5OFiuCh_TuqTq0jP18gpS88zEwgagLaJnmJPCLqIHVj_euWP6Y-hFpW6JtCzXTURnUPAyz55nAcAJ9Iv244uVj1z06_4glzOP38_uyiHdgqll1J1JUCnGAwLDEwQ1EyAOaZOh-ks4mvVqk4-AH4TKTEVmWMueSFC5UyskwwO0pqX5KBpm_iaUEAFAZCmiFpzoVJV8yp5B8lJFCqwEAoy2anS-oFrHFteXFvIOVD5NivfovJtVn5BPo5_3PQ8G3fMPUXrjPOQITt_aNdXdlhwtq6rSgOeDFJ62KdSXQNwC8FNPfc6plSQo51t7bBsN_aPkxXk_TgMCw5vUVwT2-3GMiOMMhwUWJBXvSuMkmD2ynUFEuo9J9kTdX-kWf3MpN6AQwF9mTd3i3VIHqEesGClkkfkoFtv41tARV39Lrv-LVuZDIY priority: 102 providerName: ProQuest
Title	Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome
URI	https://www.ncbi.nlm.nih.gov/pubmed/28993728 https://www.proquest.com/docview/2301468633 https://www.proquest.com/docview/1949693684 https://pubmed.ncbi.nlm.nih.gov/PMC5622159 https://doaj.org/article/bb227085d55c400fbb159dda0c3c7eff
Volume	9
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
journalDatabaseRights	– providerCode: PRVAFT databaseName: Open Access Digital Library customDbUrl: eissn: 1663-4365 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0000330058 issn: 1663-4365 databaseCode: KQ8 dateStart: 20090101 isFulltext: true titleUrlDefault: http://grweb.coalliance.org/oadl/oadl.html providerName: Colorado Alliance of Research Libraries – providerCode: PRVAON databaseName: DOAJ Directory of Open Access Journals customDbUrl: eissn: 1663-4365 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0000330058 issn: 1663-4365 databaseCode: DOA dateStart: 20090101 isFulltext: true titleUrlDefault: https://www.doaj.org/ providerName: Directory of Open Access Journals – providerCode: PRVBFR databaseName: Free Medical Journals - Free Access to All customDbUrl: eissn: 1663-4365 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0000330058 issn: 1663-4365 databaseCode: DIK dateStart: 20090101 isFulltext: true titleUrlDefault: http://www.freemedicaljournals.com providerName: Flying Publisher – providerCode: PRVFQY databaseName: GFMER Free Medical Journals customDbUrl: eissn: 1663-4365 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0000330058 issn: 1663-4365 databaseCode: GX1 dateStart: 20090101 isFulltext: true titleUrlDefault: http://www.gfmer.ch/Medical_journals/Free_medical.php providerName: Geneva Foundation for Medical Education and Research – providerCode: PRVHPJ databaseName: ROAD: Directory of Open Access Scholarly Resources customDbUrl: eissn: 1663-4365 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0000330058 issn: 1663-4365 databaseCode: M~E dateStart: 20090101 isFulltext: true titleUrlDefault: https://road.issn.org providerName: ISSN International Centre – providerCode: PRVAQN databaseName: PubMed Central customDbUrl: eissn: 1663-4365 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0000330058 issn: 1663-4365 databaseCode: RPM dateStart: 20090101 isFulltext: true titleUrlDefault: https://www.ncbi.nlm.nih.gov/pmc/ providerName: National Library of Medicine – providerCode: PRVPQU databaseName: Health & Medical Collection customDbUrl: eissn: 1663-4365 dateEnd: 20211231 omitProxy: true ssIdentifier: ssj0000330058 issn: 1663-4365 databaseCode: 7X7 dateStart: 20090730 isFulltext: true titleUrlDefault: https://search.proquest.com/healthcomplete providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Central customDbUrl: http://www.proquest.com/pqcentral?accountid=15518 eissn: 1663-4365 dateEnd: 20211231 omitProxy: true ssIdentifier: ssj0000330058 issn: 1663-4365 databaseCode: BENPR dateStart: 20090730 isFulltext: true titleUrlDefault: https://www.proquest.com/central providerName: ProQuest – providerCode: PRVFZP databaseName: Scholars Portal: Open Access Journals [open access] customDbUrl: eissn: 1663-4365 dateEnd: 20250131 omitProxy: true ssIdentifier: ssj0000330058 issn: 1663-4365 databaseCode: M48 dateStart: 20100101 isFulltext: true titleUrlDefault: http://journals.scholarsportal.info providerName: Scholars Portal
link	http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3da9swEBf9gLGXse9664IGYzCo10iW7OhhjKZtWgYuYywjb0LWRxfInDZ1YPvvdyc7YRlh7MUPlmyLu5Pud9bpd4S8ybwQlXcmDeBfUuFsSFXBVMqsUsZaGZTE887lVX45Fp8mcrJDVqdLOgHebQ3tsJ7UeDF7__P210eY8B8w4gR_exywoA9maSEbIVeDtze3KZaVwu3XrsbGLtkHV8XR7MsO_8elOkO29nhcDjxvKrJctluZW9-74boiw_82WPp3duUf7mr0kDzocCY9aQ3jEdnx9WNyr-x20p-Q6uTa07MFks7Ss0gVghqi80CHWDSClr4B85hN7RH91iWrUlM7erpKN6Ij8IjRaI9iAwBJerFsaDltqZ1--KdkPDr_enqZdvUWUitl3qSArbxTzDHQkcsHAvTVN4XrDzweZ-VVsA4AngiB5Z4ZZoIVwnGjfBWkMxD3PCN79bz2B4QCbHAARYUvikzkgVcZD9ZA9OJF7phzCTleiVLbjowca2LMNAQlKHwdha9R-DoKPyHv1k_ctEQc_-g7RO2s-yGFdrwxX1zrbkbqquK8AMDppLSwkIWqAmTnnOnbzBY-hIQcrnSrV2apOUag-SDPsoS8XjfDjMRtFlP7-fJOMyVUrjIQYEKet6awHgmGt1nBYYTFhpFsDHWzpZ5-j6zfAFQBnqkX__Hdl-Q-CgPTWrg8JHvNYulfAXZqqh7ZLSZFj-wPz68-f-nFPxBwvZiwXpwZvwFgSh42
linkProvider	Scholars Portal
linkToHtml	http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwELaqIgEXxJuFAkaCA1Kj3dhOvD4g1HZZtrTpqUV7M44fZaWSLfsQ4k_xG5lxHrAI9dZrnEij8Ty-icffEPKaeyFK70wSIL8kwtmQKJmqJLVKGWuzoDK871yc5JMz8WmaTbfIr_YuDLZVtjExBmo3t_iPvM8Q--fDnPP3l98TnBqFp6vtCI3aLI78zx9Qsi3fHY5gf98wNv5wejBJmqkCic2yfJUAgvBOpS4FSVw-FCDVwEg3GHq8tMnKYB3AGBFCmvvUpCZYIRwzypchc0bilAgI-TcEHwjk6pdT2f3TGXAkf4-37yCRJ4LnWX0yCnWg6gecO4TNZEiayNRwIxPGgQH_Q7n_Nmv-lf3Gd8mdBrbSvdrO7pEtX90nN4vmYP4BKffOPR0tkMOWjiLzCG44nQe6jzMoaOFXYG0XM7tLPze9r9RUjh603Ut0DAk2-sBuXABcSj-uV7SY1UxR3_xDcnYtin5Etqt55Z8QCijEAbIVXkou8sBKzoI1UAx5kbvUuR7pt6rUtuE2xxEbFxpqHFS-jsrXqHwdld8jb7svLmtejyve3cfd6d5DRu74YL44142D67JkTAJ-dVlmIS6GsgSg6JwZWG6lD6FHdtq91U2YWOo_Rt0jr7plcHA8tTGVn6-XOlVC5YqDAnvkcW0KnSRYLXPJQEK5YSQbom6uVLOvkUQccC-gPfX0arFekluT0-JYHx-eHD0jt1En2CzDsh2yvVqs_XNAZKvyRXQDSr5ct9_9BoQdSqQ
linkToPdf	http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwELaqIlVcEOUZKGAkOCA12o3txOsDQm2XpaVsxYGivRnHj3alkrT7EOKv8euYcZKFRai3XuNEGo3n8U08_oaQV9wLUXpn0gD5JRXOhlTJTKWZVcpYmweV433n8UlxeCo-TvLJBvnV3YXBtsouJsZA7WqL_8h7DLF_MSg474W2LeLzcPTu8irFCVJ40tqN02hM5Nj__AHl2_zt0RD2-jVjo_dfDg7TdsJAavO8WKSAJrxTmctAKlcMBEjYN9L1Bx4vcLIyWAeQRoSQFT4zmQlWCMeM8mXInZE4MQLC_y3JBcd2MjmRq_87fY5E8PEmHiT1VPAib05JoSZUvYAziLCxDAkUmRqsZcU4POB_iPffxs2_MuHoLrnTQli619jcNtnw1T2yNW4P6e-Tcu_M0-EM-WzpMLKQ4ObTOtB9nEdBx34Blncxtbv0a9sHS03l6EHXyURHkGyjP-zGBcCo9MNyQcfThjXqu39ATm9E0Q_JZlVX_jGhgEgcoFzhJai9CKzkLFgDhZEXhcucS0ivU6W2Lc85jtu40FDvoPJ1VL5G5euo_IS8WX1x2XB8XPPuPu7O6j1k544P6tmZbp1dlyVjErCsy3MLMTKUJYBG50zfcit9CAnZ6fZWtyFjrv8YeEJerpbB2fEEx1S-Xs51poQqFAcFJuRRYworSbBy5pKBhHLNSNZEXV-ppueRUBwwMCA_9eR6sV6QLfA4_eno5PgpuY0qwb4Zlu-QzcVs6Z8BOFuUz6MXUPLtpt3uN9xlTt8
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Age+Drives+Distortion+of+Brain+Metabolic%2C+Vascular+and+Cognitive+Functions%2C+and+the+Gut+Microbiome&rft.jtitle=Frontiers+in+aging+neuroscience&rft.au=Hoffman%2C+Jared+D&rft.au=Parikh%2C+Ishita&rft.au=Green%2C+Stefan+J&rft.au=Chlipala%2C+George&rft.date=2017-09-25&rft.issn=1663-4365&rft.eissn=1663-4365&rft.volume=9&rft.spage=298&rft_id=info:doi/10.3389%2Ffnagi.2017.00298&rft.externalDBID=NO_FULL_TEXT
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1663-4365&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1663-4365&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1663-4365&client=summon