{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:35:34Z","timestamp":1790789734712,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Thome foundation","award":["na"],"award-info":[{"award-number":["na"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Blindness from age-related macular degeneration (AMD) is an escalating problem, yet AMD pathogenesis is incompletely understood and treatments are limited. The intestinal microbiota is highly influential in ocular and extraocular diseases with inflammatory components, such as AMD. This article reviews data supporting the role of the intestinal microbiota in AMD pathogenesis. Multiple groups have found an intestinal dysbiosis in advanced AMD. There is growing evidence that environmental factors associated with AMD progression potentially work through the intestinal microbiota. A high-fat diet in apo-E-\/- mice exacerbated wet and dry AMD features, presumably through changes in the intestinal microbiome, though other independent mechanisms related to lipid metabolism are also likely at play. AREDS supplementation reversed some adverse intestinal microbial changes in AMD patients. Part of the mechanism of intestinal microbial effects on retinal disease progression is via microbiota-induced microglial activation. The microbiota are at the intersection of genetics and AMD. Higher genetic risk was associated with lower intestinal bacterial diversity in AMD. Microbiota-induced metabolite production and gene expression occur in pathways important in AMD pathogenesis. These studies suggest a crucial link between the intestinal microbiota and AMD pathogenesis, thus providing a novel potential therapeutic target. Thus, the need for large longitudinal studies in patients and germ-free or gnotobiotic animal models has never been more pressing.<\/jats:p>","DOI":"10.3390\/jcm10102072","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T10:59:12Z","timestamp":1620817152000},"page":"2072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["A Review of the Role of the Intestinal Microbiota in Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"10","author":[{"given":"Phoebe","family":"Lin","sequence":"first","affiliation":[{"name":"Casey Eye Institute, Oregon Health &amp; Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"McClintic","sequence":"additional","affiliation":[{"name":"Retina Consultants, LLC, Salem, OR 97302, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urooba","family":"Nadeem","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Skondra","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40662-016-0063-5","article-title":"Epidemiology of age-related macular degeneration (AMD): Associations with cardiovascular disease phenotypes and lipid factors","volume":"3","author":"Pennington","year":"2016","journal-title":"Eye Vis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1001\/archophthalmol.2009.58","article-title":"Vision Health Cost-Effectiveness Study Group. Forecasting age-related macular degeneration through the year 2050: The potential impact of new treatments","volume":"127","author":"Rein","year":"2009","journal-title":"Arch. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2415-10-31","article-title":"Clinical risk factors for age-related macular degeneration: A systematic review and meta-analysis","volume":"10","author":"Chakravarthy","year":"2010","journal-title":"BMC Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/ceo.13343","article-title":"Role of diet and food intake in age-related macular degeneration: A systematic review","volume":"47","author":"Chapman","year":"2019","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1093\/aje\/kwr005","article-title":"Abdominal Obesity and Age-related Macular Degeneration","volume":"173","author":"Adams","year":"2011","journal-title":"Am. J. Epidemiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.15252\/emmm.201606531","article-title":"Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization","volume":"8","author":"Andriessen","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1034\/j.1600-0420.1999.770413.x","article-title":"Age related macular degeneration in monozygotic twins and their spouses in Iceland","volume":"77","author":"Gottfredsdottir","year":"1999","journal-title":"Acta Ophthalmol. Scand."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/ng.3448","article-title":"A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants","volume":"48","author":"Fritsche","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14682","DOI":"10.1073\/pnas.222551899","article-title":"Drusen proteome analysis: An approach to the etiology of age-related macular degeneration","volume":"99","author":"Crabb","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Scholl, H.P.N., Issa, P.C., Walier, M., Janzer, S., Pollok-Kopp, B., B\u00f6rncke, F., Fritsche, L.G., Chong, N.V., Fimmers, R., and Wienker, T. (2008). Systemic complement activation in age-related macular degeneration. PLoS ONE, 3.","DOI":"10.1371\/annotation\/511a1029-bc43-4510-a4ca-c1db31810acc"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/nm.2717","article-title":"NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components","volume":"18","author":"Doyle","year":"2012","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.cell.2012.03.036","article-title":"DICER1 Loss and Alu RNA Induce Age-Related Macular Degeneration via the NLRP3 Inflammasome and MyD88","volume":"149","author":"Tarallo","year":"2012","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ardeljan, D., Wang, Y., Park, S., Shen, D., Chu, X.K., Yu, C.-R., Abu-Asab, M., Tuo, J., Eberhart, C.G., and Olsen, T.W. (2014). Interleukin-17 Retinotoxicity Is Prevented by Gene Transfer of a Soluble Interleukin-17 Receptor Acting as a Cytokine Blocker: Implications for Age-Related Macular Degeneration. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095900"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"230ra44","DOI":"10.1126\/scitranslmed.3007616","article-title":"IL-18 Attenuates Experimental Choroidal Neovascularization as a Potential Therapy for Wet Age-Related Macular Degeneration","volume":"6","author":"Doyle","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1001\/archopht.123.6.774","article-title":"Progression of age-related macular degeneration: Prospective assessment of C-reactive protein, interleukin 6, and other cardiovascular biomarkers","volume":"123","author":"Seddon","year":"2005","journal-title":"Arch. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/j.1440-1827.2011.02695.x","article-title":"Macrophage polarization in the maculae of age-related macular degeneration: A pilot study","volume":"61","author":"Cao","year":"2011","journal-title":"Pathol. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1172\/JCI31692","article-title":"CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration","volume":"117","author":"Feumi","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S0014-4835(02)00332-9","article-title":"Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration","volume":"76","author":"Gupta","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/art.38967","article-title":"Brief Report: Intestinal Dysbiosis in Ankylosing Spondylitis","volume":"67","author":"Costello","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/ceo.13493","article-title":"Importance of the intestinal microbiota in ocular inflammatory diseases: A review","volume":"47","author":"Lin","year":"2019","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/art.40359","article-title":"Gut Microbiota Perturbations in Reactive Arthritis and Postinfectious Spondyloarthritis","volume":"70","author":"Manasson","year":"2018","journal-title":"Arthritis Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Miyake, S., Kim, S., Suda, W., Oshima, K., Nakamura, M., Matsuoka, T., Chihara, N., Tomita, A., Sato, W., and Kim, S.-W. (2015). Dysbiosis in the Gut Microbiota of Patients with Multiple Sclerosis, with a Striking Depletion of Species Belonging to Clostridia XIVa and IV Clusters. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137429"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e01202","DOI":"10.7554\/eLife.01202","article-title":"Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis","volume":"2","author":"Scher","year":"2013","journal-title":"eLife"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1900\/RDS.2012.9.251","article-title":"Gut Microbiota and Type 1 Diabetes","volume":"9","author":"Vaarala","year":"2012","journal-title":"Rev. Diabet. Stud."},{"key":"ref_25","first-page":"57","article-title":"Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease","volume":"472","author":"Wang","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1167\/iovs.17-22677","article-title":"Gut Microbiota Composition and Fecal Metabolic Phenotype in Patients with Acute Anterior Uveitis","volume":"59","author":"Huang","year":"2018","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1167\/iovs.18-24813","article-title":"Disruption of Intestinal Homeostasis and Intestinal Microbiota During Experimental Autoimmune Uveitis","volume":"60","author":"Janowitz","year":"2019","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-12163-3","article-title":"Short chain fatty acids ameliorate immune-mediated uveitis partially by altering migration of lymphocytes from the intestine","volume":"7","author":"Nakamura","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1167\/iovs.16-19733","article-title":"Gut Microbial Alterations Associated With Protection From Autoimmune Uveitis","volume":"57","author":"Nakamura","year":"2016","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.immuni.2015.07.014","article-title":"Microbiota-Dependent Activation of an Autoreactive T Cell Receptor Provokes Autoimmunity in an Immunologically Privileged Site","volume":"43","author":"Horai","year":"2015","journal-title":"Immunity"},{"key":"ref_31","first-page":"1","article-title":"Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma","volume":"9","author":"Chen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.2337\/db18-0158","article-title":"Restructuring of the Gut Microbiome by Intermittent Fasting Prevents Retinopathy and Prolongs Survival indb\/dbMice","volume":"67","author":"Beli","year":"2018","journal-title":"Diabetes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jaapos.2020.03.010","article-title":"The early gut microbiome could protect against severe retinopathy of prematurity","volume":"24","author":"Skondra","year":"2020","journal-title":"J. Am. Assoc. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"40826","DOI":"10.1038\/srep40826","article-title":"Association of the Intestinal Microbiome with the Development of Neovascular Age-Related Macular Degeneration","volume":"7","author":"Zinkernagel","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1097\/ICU.0000000000000465","article-title":"The role of the intestinal microbiome in ocular inflammatory disease","volume":"29","author":"Lin","year":"2018","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_36","unstructured":"Lin, P., McClintic, S.M., Saleh, M.G., Kiang, L., Karsten, L.J., Asquith, M., Martin, T.M., and Klein, M.J. AREDS supplementation and genetic risk score are crucial determinants of microbial alterations in advanced age-related macular degeneration, in preparation."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.bpg.2013.03.005","article-title":"Intestinal microbiota: A source of novel biomarkers in inflammatory bowel diseases?","volume":"27","author":"Berry","year":"2013","journal-title":"Best Pr. Res. Clin. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1001\/jama.2015.9677","article-title":"Effect of omega-3 fatty acids, lutein\/zeaxanthin, or other nutrient supplementation on cognitive function: The AREDS2 randomized clinical trial","volume":"314","author":"Chew","year":"2015","journal-title":"JAMA"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ahrazem, O., G\u00f3mez-G\u00f3mez, L., Rodrigo, M.J., Avalos, J., and Lim\u00f3n, M.C. (2016). Carotenoid Cleavage Oxygenases from Microbes and Photosynthetic Organisms: Features and Functions. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17111781"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1080\/10408398.2017.1322552","article-title":"Carotenoids biosynthesis and cleavage related genes from bacteria to plants","volume":"58","author":"Liang","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1600685","DOI":"10.1002\/mnfr.201600685","article-title":"Host-related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans","volume":"61","author":"Bohn","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_42","first-page":"5739","article-title":"The gut microbiome in advanced age-related macular degeneration","volume":"58","author":"Kiang","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_43","unstructured":"Skondra, D., Xie, B., Nadeem, U., Movahedan, A., D\u2019Souza, M., Barba, H., Deng, N., Leone, V.A., Chang, E., and Sulakhe, D. Using integrated multiomics approach to describe the role of high-fat diet induced gut-dysbiosis in age-related macular degeneration, in preparation."},{"key":"ref_44","first-page":"1","article-title":"Associations of the intestinal microbiome with the complement system in neovascular age-related macular degeneration","volume":"5","author":"Keller","year":"2020","journal-title":"NPJ Genom. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"dmm032698","DOI":"10.1242\/dmm.032698","article-title":"Pgc-1\u03b1 repression and high-fat diet induce age-related macular degeneration-like phenotypes in mice","volume":"11","author":"Zhang","year":"2018","journal-title":"Dis. Model. Mech."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"E4472","DOI":"10.1073\/pnas.1702302114","article-title":"Involvement of a gut\u2013retina axis in protection against dietary glycemia-induced age-related macular degeneration","volume":"114","author":"Rowan","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Costantini, L., Molinari, R., Farinon, B., and Merendino, N. (2017). Impact of Omega-3 Fatty Acids on the Gut Microbiota. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122645"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1126\/science.1241165","article-title":"The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic Treg Cell Homeostasis","volume":"341","author":"Smith","year":"2013","journal-title":"Science"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s00203-018-1506-2","article-title":"Smoking and the intestinal microbiome","volume":"200","author":"Savin","year":"2018","journal-title":"Arch. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-016-0776-3","article-title":"Age-related macular degeneration associated polymorphism rs10490924 in ARMS2 results in deficiency of a complement activator","volume":"14","author":"Micklisch","year":"2017","journal-title":"J. Neuroinflamma."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/hmg\/ddp472","article-title":"Genetic control of the alternative pathway of complement in humans and age-related macular degeneration","volume":"19","author":"Hecker","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","first-page":"1768","article-title":"Effects of ApoE Deficiency, Aging and High Fat Diet on Laser-Induced Choroidal Neovascularization and Bruch\u2019s Membrane-RPE Interface Morphology","volume":"48","author":"Skondra","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.trsl.2016.06.002","article-title":"The gut microbiota and inflammatory bowel diseases","volume":"179","author":"Miyoshi","year":"2017","journal-title":"Transl. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1113\/jphysiol.2004.063388","article-title":"Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice","volume":"558","author":"Sudo","year":"2004","journal-title":"J. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1093\/ilar\/ilv021","article-title":"Manipulating the Gut Microbiota: Methods and Challenges","volume":"56","author":"Ericsson","year":"2015","journal-title":"ILAR J."},{"key":"ref_56","first-page":"3273","article-title":"Gnotobiotic Animal Model of Laser-Induced Choroidal Neovascularization in Germ-Free Mice","volume":"60","author":"Movahedan","year":"2019","journal-title":"Investig. Ophthalmol Vis. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Nadeem, U., Xie, B., Movahedan, A., D\u2019Souza, M., Barba, H., Deng, N., Leone, V.A., Chang, E., Sulakhe, D., and Skondra, D. (2020). High Throughput RNA Sequencing of Mice Retina Reveals Metabolic Pathways Involved in the Gut-Retina Axis. bioRxiv.","DOI":"10.1101\/2020.10.01.318949"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1210\/er.2006-0037","article-title":"Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism","volume":"27","author":"Handschin","year":"2006","journal-title":"Endocr. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.cmet.2005.05.004","article-title":"Metabolic control through the PGC-1 family of transcription coactivators","volume":"1","author":"Lin","year":"2005","journal-title":"Cell Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"C710","DOI":"10.1152\/ajpcell.00380.2014","article-title":"Role of PGC-1\u03b1 during acute exercise-induced autophagy and mitophagy in skeletal muscle","volume":"308","author":"Vainshtein","year":"2015","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_61","first-page":"1","article-title":"Dysregulated metabolic pathways in age-related macular degeneration","volume":"10","author":"Zhang","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-11262-1","article-title":"A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration","volume":"10","author":"Handa","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/nn.4030","article-title":"Host microbiota constantly control maturation and function of microglia in the CNS","volume":"18","author":"Erny","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/nn.4051","article-title":"Go with your gut: Microbiota meet microglia","volume":"18","author":"Mosher","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1038\/nprot.2017.032","article-title":"Comprehensive analysis of mouse retinal mononuclear phagocytes","volume":"12","author":"Scholz","year":"2017","journal-title":"Nat. Protoc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.18632\/aging.101583","article-title":"Long-term intake of Lactobacillus paracasei KW3110 prevents age-related chronic inflammation and retinal cell loss in physiologically aged mice","volume":"10","author":"Morita","year":"2018","journal-title":"Aging"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/10\/2072\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:59:41Z","timestamp":1760162381000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/10\/2072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,12]]},"references-count":66,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["jcm10102072"],"URL":"https:\/\/doi.org\/10.3390\/jcm10102072","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,12]]}}}