{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T13:09:23Z","timestamp":1775308163449,"version":"3.50.1"},"reference-count":92,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T00:00:00Z","timestamp":1674777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000199","name":"United States Department of Agriculture","doi-asserted-by":"publisher","award":["8050-51000-107-000D"],"award-info":[{"award-number":["8050-51000-107-000D"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The age-related loss of the cognitive function is a growing concern for global populations. Many factors that determine cognitive resilience or dementia also have metabolic functions. However, this duality is not universally appreciated when the action of that factor occurs in tissues external to the brain. Thus, we examined a set of genes involved in dementia, i.e., those related to vascular dementia, Alzheimer\u2019s disease, Parkinson\u2019s disease, and the human metabolism for activity in 12 metabolically active tissues. Mining the Genotype-Tissue Expression (GTEx) data showed that most of these metabolism\u2013dementia (MD) genes (62 of 93, 67%) exhibit a higher median expression in any of the metabolically active tissues than in the brain. After identifying that several MD genes served as blood-based biomarkers of longevity in other studies, we examined the impact of the intake of food, nutrients, and other dietary factors on the expression of MD genes in whole blood in the Framingham Offspring Study (n = 2134). We observed positive correlations between flavonoids and HMOX1, taurine and UQCRC1, broccoli and SLC10A2, and myricetin and SLC9A8 (p &lt; 2.09 \u00d7 10\u22124). In contrast, dairy protein, palmitic acid, and pie were negatively correlated, respectively, with the expression of IGF1R, CSF1R, and SLC9A8, among others (p &lt; 2.92 \u00d7 10\u22124). The results of this investigation underscore the potential contributions of metabolic enzyme activity in non-brain tissues to the risk of dementia. Specific epidemiological or intervention studies could be designed using specific foods and nutrients or even dietary patterns focused on these foods and nutrients that influence the expression of some MD genes to verify the findings presented here.<\/jats:p>","DOI":"10.3390\/nu15030644","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T09:18:21Z","timestamp":1675070301000},"page":"644","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dietary Responses of Dementia-Related Genes Encoding Metabolic Enzymes"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9718-1335","authenticated-orcid":false,"given":"Laurence D","family":"Parnell","sequence":"first","affiliation":[{"name":"Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Agricultural Research Service, US Department of Agriculture, Boston, MA 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rozana","family":"Magadmi","sequence":"additional","affiliation":[{"name":"Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sloane","family":"Zwanger","sequence":"additional","affiliation":[{"name":"Skidmore College, Saratoga Springs, NY 12866, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3810-1910","authenticated-orcid":false,"given":"Barbara","family":"Shukitt-Hale","sequence":"additional","affiliation":[{"name":"Neuroscience and Aging Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Agricultural Research Service, US Department of Agriculture, Boston, MA 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao-Qiang","family":"Lai","sequence":"additional","affiliation":[{"name":"Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Agricultural Research Service, US Department of Agriculture, Boston, MA 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 M","family":"Ordov\u00e1s","sequence":"additional","affiliation":[{"name":"Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,27]]},"reference":[{"key":"ref_1","first-page":"125","article-title":"Clinical features and multidisciplinary approaches to dementia care","volume":"4","author":"Grand","year":"2011","journal-title":"J. Multidiscip. Healthc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.jalz.2009.09.004","article-title":"Dependence as a unifying construct in defining Alzheimer\u2019s disease severity","volume":"6","author":"McLaughlin","year":"2010","journal-title":"Alzheimers Dement."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2022). Alzheimer\u2019s disease facts and figures. Alzheimers Dement., 18, 700\u2013789.","DOI":"10.1002\/alz.12638"},{"key":"ref_4","first-page":"573","article-title":"Enfermedades neurodegenerativas que cursan con demencia","volume":"136","author":"Navarrete","year":"2000","journal-title":"Gac. Med. Mex."},{"key":"ref_5","unstructured":"Kryger, M.H., Roth, T., and Dement, W.C. (2011). Principles and Practice of Sleep Medicine, W.B. Saunders. [5th ed.]."},{"key":"ref_6","first-page":"1","article-title":"Dementia Mortality in the United States, 2000\u20132017","volume":"68","author":"Kramarow","year":"2019","journal-title":"Natl. Vital Stat. Rep."},{"key":"ref_7","unstructured":"GBD 2019 Collaborators (2021). Global mortality from dementia: Application of a new method and results from the Global Burden of Disease Study. Alzheimers Dement., 7, e12200."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1001\/jamaneurol.2020.2831","article-title":"Estimates of the association of dementia with US mortality levels using linked survey and mortality records","volume":"77","author":"Stokes","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1136\/jnnp-2018-318212","article-title":"Models for predicting risk of dementia: A systematic review","volume":"90","author":"Hou","year":"2019","journal-title":"J. Neurol Neurosurg. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1192\/apt.7.1.24","article-title":"Risk factors for dementia","volume":"7","author":"McCullagh","year":"2018","journal-title":"Adv. Psychiatr. Treat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"v2","DOI":"10.1136\/jnnp.2005.082867","article-title":"Epidemiology and risk factors of dementia","volume":"76","author":"Scheltens","year":"2005","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.3233\/JAD-200040","article-title":"Circulating plasma metabolites and cognitive function in a Puerto Rican cohort","volume":"76","author":"Palacios","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"841070","DOI":"10.3389\/fnut.2022.841070","article-title":"Effects of lifestyle factors on cognition in minority population of older adults: A review","volume":"9","author":"Eubank","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1001\/jama.2022.3550","article-title":"Association of race and ethnicity with incidence of dementia among older adults","volume":"327","author":"Kornblith","year":"2022","journal-title":"JAMA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s11886-021-01615-y","article-title":"Metabolic syndrome and cognitive function","volume":"23","author":"Tahmi","year":"2021","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neuron.2017.02.004","article-title":"Sleep and human aging","volume":"94","author":"Mander","year":"2017","journal-title":"Neuron"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yu, W.W., Randhawa, A.K., Blair, S.N., Sui, X., and Kuk, J.L. (2019). Age- and sex-specific all-cause mortality risk greatest in metabolic syndrome combinations with elevated blood pressure from 7 U.S. cohorts. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0218307"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s40520-019-01190-x","article-title":"Measuring physical performance in highly active older adults: Associations with age and gender?","volume":"32","author":"Tangen","year":"2020","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Smiley, A., King, D., and Bidulescu, A. (2019). The association between sleep duration and metabolic syndrome: The NHANES 2013\/2014. Nutrients, 11.","DOI":"10.3390\/nu11112582"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"D835","DOI":"10.1093\/nar\/gkz972","article-title":"ClinVar: Improvements to accessing data","volume":"48","author":"Landrum","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"D1005","DOI":"10.1093\/nar\/gky1120","article-title":"The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics","volume":"47","author":"Buniello","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bse0590001","article-title":"Enzymes: Principles and biotechnological applications","volume":"59","author":"Robinson","year":"2015","journal-title":"Essays Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s13668-018-0227-0","article-title":"Protective effects of foods containing flavonoids on age-related cognitive decline","volume":"7","author":"Gildawie","year":"2018","journal-title":"Curr. Nutr. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"765217","DOI":"10.3389\/fncel.2021.765217","article-title":"Infection and immunometabolism in the central nervous system: A possible mechanistic link between metabolic imbalance and dementia","volume":"15","author":"Shinjyo","year":"2021","journal-title":"Front. Cell Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Mietelska-Porowska, A., Doma\u0144ska, J., Want, A., Wi\u0119ckowska-Gacek, A., Chutora\u0144ski, D., Koperski, M., and Wojda, U. (2022). Induction of brain insulin resistance and Alzheimer\u2019s molecular changes by Western diet. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094744"},{"key":"ref_26","first-page":"12685","article-title":"Higher Dietary Inflammatory Index scores are associated with brain MRI markers of brain aging: Results from the Framingham Heart Study Offspring cohort","volume":"6","author":"Gokingco","year":"2022","journal-title":"Alzheimers Dement."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Vu, T.H.T., Beck, T., Bennett, D.A., Schneider, J.A., Hayden, K.M., Shadyab, A.H., Rajan, K.B., Morris, M.C., and Cornelis, M.C. (2022). Adherence to MIND diet, genetic susceptibility, and incident dementia in three US cohorts. Nutrients, 14.","DOI":"10.3390\/nu14132759"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"827","DOI":"10.3233\/JAD-201238","article-title":"Mind diet adherence and cognitive performance in the Framingham Heart Study","volume":"82","author":"Beiser","year":"2021","journal-title":"J. Alzheimers Dis."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Moat, S.J., George, R.S., and Carling, R.S. (2020). Use of dried blood spot specimens to monitor patients with inherited metabolic disorders. Int. J. Neonatal. Screen., 6.","DOI":"10.3390\/ijns6020026"},{"key":"ref_30","first-page":"238","article-title":"Metabolic disturbances in diseases with neurological involvement","volume":"5","author":"Duarte","year":"2013","journal-title":"Aging Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1203\/01.PDR.0000055867.83310.9E","article-title":"Cerebral energy metabolism in phenylketonuria: Findings by quantitative in vivo 31P MR spectroscopy","volume":"53","author":"Pietz","year":"2003","journal-title":"Pediatr. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.ijdevneu.2005.08.003","article-title":"Glutaric acid moderately compromises energy metabolism in rat brain","volume":"23","author":"Ferreira","year":"2005","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13023-017-0685-2","article-title":"The complete European guidelines on phenylketonuria: Diagnosis and treatment","volume":"12","author":"MacDonald","year":"2017","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.ymgme.2020.09.007","article-title":"Glutaric acidemia type 1: Treatment and outcome of 168 patients over three decades","volume":"131","author":"Strauss","year":"2020","journal-title":"Mol. Genet. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/humu.20043","article-title":"Functional analysis of 13 GBA mutant alleles identified in Gaucher disease patients: Pathogenic changes and \u201cmodifier\u201d polymorphisms","volume":"23","author":"Montfort","year":"2004","journal-title":"Hum. Mutat."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Van Kampen, J.M., Baranowski, D.C., Robertson, H.A., Shaw, C.A., and Kay, D.G. (2015). The progressive BSSG rat model of Parkinson\u2019s: Recapitulating multiple key features of the human disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0139694"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s12974-022-02466-2","article-title":"High-fat diet exacerbates cognitive decline in mouse models of Alzheimer\u2019s disease and mixed dementia in a sex-dependent manner","volume":"19","author":"Gannon","year":"2022","journal-title":"J. Neuroinflammation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"806006","DOI":"10.3389\/fnut.2022.806006","article-title":"Associations between dietary patterns and neuroimaging markers: A systematic review","volume":"9","author":"Townsend","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_39","unstructured":"Train the Brain Consortium (2017). Randomized trial on the effects of a combined physical\/cognitive training in aged MCI subjects: The Train the Brain study. Sci. Rep., 7, 39471."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1136\/bjsports-2021-104955","article-title":"Effects of exercise training on the cognitive function of older adults with different types of dementia: A systematic review and meta-analysis","volume":"56","author":"Balbim","year":"2022","journal-title":"Br. J. Sports Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.3233\/JAD-180439","article-title":"The association between social engagement, loneliness, and risk of dementia: A systematic review and meta-analysis","volume":"66","author":"Penninkilampi","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1212\/WNL.0000000000200583","article-title":"Associations of social isolation and loneliness with later dementia","volume":"99","author":"Shen","year":"2022","journal-title":"Neurology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"F533","DOI":"10.1152\/ajprenal.00601.2016","article-title":"From 20th century metabolic wall charts to 21st century systems biology: Database of mammalian metabolic enzymes","volume":"312","author":"Corcoran","year":"2017","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1093\/nar\/28.1.304","article-title":"The ENZYME database in 2000","volume":"28","author":"Bairoch","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_45","unstructured":"Online Mendelian Inheritance in Man, OMIM\u00ae (2021, April 09). McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD). Available online: https:\/\/omim.org\/."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/cr.2009.61","article-title":"RLEdb: A database of rate-limiting enzymes and their regulation in human, rat, mouse, yeast and E. coli","volume":"19","author":"Zhao","year":"2009","journal-title":"Cell Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lai, C.Q., Parnell, L.D., Lee, Y.C., Zeng, H., Smith, C.E., McKeown, N.M., and Ordov\u00e1s, J.M. (2022). The impact of alcoholic drinks and dietary factors on epigenetic markers associated with triglyceride levels. Clin. Epigenetics, submitted.","DOI":"10.21203\/rs.3.rs-1700692\/v1"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1093\/ajcn\/nqaa233","article-title":"Carbohydrate and fat intake associated with risk of metabolic diseases through epigenetics of CPT1A","volume":"112","author":"Lai","year":"2020","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"D1083","DOI":"10.1093\/nar\/gkx1042","article-title":"Human Ageing Genomic Resources: New and updated databases","volume":"46","author":"Tacutu","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e61073","DOI":"10.7554\/eLife.61073","article-title":"Plasma proteomic biomarker signature of age predicts health and life span","volume":"9","author":"Tanaka","year":"2020","journal-title":"Elife"},{"key":"ref_51","unstructured":"Parnell, L.D., McCaffrey, K.S., Brooks, A.W., Smith, C.E., Lai, C.Q., Christensen, J.J., Wiley, C.D., and Ordov\u00e1s, J.M. (2022). Rate-limiting enzymes in cardiometabolic health and aging in humans. Lifestyle Genom., submitted."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1756-0381-7-21","article-title":"CardioGxE, a catalog of gene-environment interactions for cardiometabolic traits","volume":"7","author":"Parnell","year":"2014","journal-title":"BioData Min."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1016\/S0022-2275(20)33406-4","article-title":"Substrate specificity of the ileal and the hepatic Na(+)\/bile acid cotransporters of the rabbit. I. Transport studies with membrane vesicles and cell lines expressing the cloned transporters","volume":"40","author":"Kramer","year":"1999","journal-title":"J. Lipid Res."},{"key":"ref_54","first-page":"361","article-title":"Personalised nutrition and health","volume":"2018","author":"Ferguson","year":"2018","journal-title":"BMJ"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1002\/1873-3468.14299","article-title":"Decline of ergothioneine in frailty and cognition impairment","volume":"596","author":"Kondoh","year":"2022","journal-title":"FEBS Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6038996","DOI":"10.1155\/2022\/6038996","article-title":"Flavonoids as promising neuroprotectants and their therapeutic potential against Alzheimer\u2019s disease","volume":"2022","author":"Minocha","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s13148-020-00984-5","article-title":"Longitudinal data in peripheral blood confirm that PM20D1 is a quantitative trait locus (QTL) for Alzheimer\u2019s disease and implicate its dynamic role in disease progression","volume":"12","author":"Wang","year":"2020","journal-title":"Clin. Epigenetics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1111\/ene.14470","article-title":"Cerebrospinal and blood levels of amino acids as potential biomarkers for Parkinson\u2019s disease: Review and meta-analysis","volume":"27","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1111\/ene.15437","article-title":"Association between liver fibrosis and incident dementia in the UK Biobank study","volume":"29","author":"Parikh","year":"2022","journal-title":"Eur. J. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10671","DOI":"10.1073\/pnas.162362299","article-title":"Tauroursodeoxycholic acid, a bile acid, is neuroprotective in a transgenic animal model of Huntington\u2019s disease","volume":"99","author":"Keene","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1080\/1028415X.2020.1859729","article-title":"Tauroursodeoxycholic acid (TUDCA) is neuroprotective in a chronic mouse model of Parkinson\u2019s disease","volume":"25","author":"Cuevas","year":"2022","journal-title":"Nutr. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.neurobiolaging.2014.08.034","article-title":"Amyloid-\u03b2 pathology is attenuated by tauroursodeoxycholic acid treatment in APP\/PS1 mice after disease onset","volume":"36","author":"Amaral","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.molimm.2021.10.014","article-title":"Inhibitory effects of sulforaphane on NLRP3 inflammasome activation","volume":"140","author":"Kiser","year":"2021","journal-title":"Mol. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/j.ygeno.2019.07.018","article-title":"Identification of molecular signatures and pathways to identify novel therapeutic targets in Alzheimer\u2019s disease: Insights from a systems biomedicine perspective","volume":"112","author":"Rahman","year":"2020","journal-title":"Genomics"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"11290","DOI":"10.1038\/s41598-022-15578-9","article-title":"Altered mitochondrial microenvironment at the spotlight of musculoskeletal aging and Alzheimer\u2019s disease","volume":"12","author":"Giannos","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.neuro.2021.01.002","article-title":"Taurine improves neuron injuries and cognitive impairment in a mouse Parkinson\u2019s disease model through inhibition of microglial activation","volume":"83","author":"Wang","year":"2021","journal-title":"Neurotoxicology"},{"key":"ref_67","first-page":"149","article-title":"Protective effect of caffeine and\/or taurine on the 6-hydroxydopamine-induced rat model of Parkinson\u2019s disease: Behavioral and neurochemical evidence","volume":"39","author":"Abuirmeileh","year":"2021","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"109356","DOI":"10.1016\/j.mehy.2019.109356","article-title":"A diet rich in taurine, cysteine, folate, B12 and betaine may lessen risk for Alzheimer\u2019s disease by boosting brain synthesis of hydrogen sulfide","volume":"132","author":"McCarty","year":"2019","journal-title":"Med. Hypotheses"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s00109-011-0771-1","article-title":"Nrf2-dependent gene expression is affected by the proatherogenic apoE4 genotype-studies in targeted gene replacement mice","volume":"89","author":"Graeser","year":"2011","journal-title":"J. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1161\/ATVBAHA.109.199687","article-title":"Specific dietary polyphenols attenuate atherosclerosis in apolipoprotein E-knockout mice by alleviating inflammation and endothelial dysfunction","volume":"30","author":"Loke","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.freeradbiomed.2015.12.027","article-title":"Cerebroprotection of flavanol (-)-epicatechin after traumatic brain injury via Nrf2-dependent and -independent pathways","volume":"92","author":"Cheng","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4397340","DOI":"10.1155\/2017\/4397340","article-title":"Flavonoids as putative inducers of the transcription factors Nrf2, FoxO, and PPAR\u03b3","volume":"2017","author":"Pallauf","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.pneurobio.2018.06.008","article-title":"The sinister face of heme oxygenase-1 in brain aging and disease","volume":"172","author":"Schipper","year":"2019","journal-title":"Prog. Neurobiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1021\/bi101082e","article-title":"Organellar Na+\/H+ exchangers: Novel players in organelle pH regulation and their emerging functions","volume":"50","author":"Ohgaki","year":"2011","journal-title":"Biochemistry"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"109641","DOI":"10.1016\/j.celrep.2021.109641","article-title":"Myricetin supplementation decreases hepatic lipid synthesis and inflammation by modulating gut microbiota","volume":"36","author":"Sun","year":"2021","journal-title":"Cell Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1080\/19490976.2017.1356979","article-title":"Application of the distance-based F test in an mGWAS investigating \u03b2 diversity of intestinal microbiota identifies variants in SLC9A8 (NHE8) and 3 other loci","volume":"9","author":"Degenhardt","year":"2018","journal-title":"Gut Microbes"},{"key":"ref_77","first-page":"192","article-title":"Myricetin protects against high glucose-induced \u03b2-cell apoptosis by attenuating endoplasmic reticulum stress via inactivation of cyclin-dependent kinase Diabetes Metab","volume":"43","author":"Karunakaran","year":"2019","journal-title":"J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1124\/jpet.120.000162","article-title":"Apigenin ameliorates insulin resistance and lipid accumulation by endoplasmic reticulum stress and SREBP-1c\/SREBP-2 pathway in palmitate-induced HepG2 cells and high-fat diet-fed mice","volume":"377","author":"Wu","year":"2021","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00018-022-04225-1","article-title":"Inhibition of colony stimulating factor-1 receptor (CSF-1R) as a potential therapeutic strategy for neurodegenerative diseases: Opportunities and challenges","volume":"79","author":"Han","year":"2022","journal-title":"Cell Mol. Life Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e12832","DOI":"10.1111\/acel.12832","article-title":"Replacement of microglia in the aged brain reverses cognitive, synaptic, and neuronal deficits in mice","volume":"17","author":"Elmore","year":"2018","journal-title":"Aging Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.neulet.2012.01.077","article-title":"Down-regulation of IGF-1\/IGF-1R in hippocampus of rats with vascular dementia","volume":"513","author":"Gong","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"104749","DOI":"10.1016\/j.neuint.2020.104749","article-title":"Tetradecyl 2,3-dihydroxybenzoate alleviates oligodendrocyte damage following chronic cerebral hypoperfusion through IGF-1 receptor","volume":"138","author":"Youssef","year":"2020","journal-title":"Neurochem. Int."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"11500","DOI":"10.1523\/JNEUROSCI.0343-15.2015","article-title":"Blocking IGF signaling in adult neurons alleviates Alzheimer\u2019s disease pathology through amyloid-\u03b2 clearance","volume":"35","author":"Gontier","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1046\/j.1532-5415.2003.51117.x","article-title":"Association between dementia and midlife risk factors: The Radiation Effects Research Foundation Adult Health Study","volume":"51","author":"Yamada","year":"2003","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1111\/jgs.12887","article-title":"Milk and dairy consumption and risk of dementia in an elderly Japanese population: The Hisayama Study","volume":"62","author":"Ozawa","year":"2014","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Huang, Q., Jia, X., Zhang, J., Huang, F., Wang, H., Zhang, B., Wang, L., Jiang, H., and Wang, Z. (2021). Diet-cognition associations differ in mild cognitive impairment subtypes. Nutrients, 13.","DOI":"10.3390\/nu13041341"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3233\/JAD-140186","article-title":"Insulin-like growth factor-I receptor stimulating activity is associated with dementia","volume":"42","author":"Janssen","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"118247","DOI":"10.1016\/j.lfs.2020.118247","article-title":"PINK1: The guard of mitochondria","volume":"259","author":"Wang","year":"2020","journal-title":"Life Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"118390","DOI":"10.1016\/j.envpol.2021.118390","article-title":"Lycopene mitigates DEHP-induced hepatic mitochondrial quality control disorder via regulating SIRT1\/PINK1\/mitophagy axis and mitochondrial unfolded protein response","volume":"292 Pt. B","author":"Zhao","year":"2022","journal-title":"Environ. Pollut."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e20","DOI":"10.1017\/jns.2019.16","article-title":"Lycopene and cognitive function","volume":"8","author":"Phillips","year":"2019","journal-title":"J. Nutr. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3158","DOI":"10.1074\/jbc.M807731200","article-title":"Aberrant expression of myeloperoxidase in astrocytes promotes phospholipid oxidation and memory deficits in a mouse model of Alzheimer disease","volume":"284","author":"Maki","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e2100606","DOI":"10.1002\/mnfr.202100606","article-title":"Food and microbiota metabolites associate with cognitive decline in older subjects: A 12-year prospective study","volume":"65","author":"Carmona","year":"2021","journal-title":"Mol. Nutr. Food Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/3\/644\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:16:46Z","timestamp":1760120206000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/3\/644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,27]]},"references-count":92,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["nu15030644"],"URL":"https:\/\/doi.org\/10.3390\/nu15030644","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,27]]}}}