{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:14:20Z","timestamp":1787004860343,"version":"build-2736575974"},"reference-count":122,"publisher":"Georg Thieme Verlag KG","issue":"01","funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["CA267\/13-3 and CA267\/14-1"],"award-info":[{"award-number":["CA267\/13-3 and CA267\/14-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Z Gastroenterol"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Aging is characterized by the progressive decline of biological integrity and its\n      compensatory mechanisms as well as immunological dysregulation. This goes along with an\n      increasing risk of frailty and disease. Against this background, we here specifically focus on\n      the aging of the human liver. For the first time, we shed light on the intertwining\n      evolutionary underpinnings of the liver\u2019s declining regenerative capacity, the phenomenon of\n      inflammaging, and the biotransformation capacity in the process of aging. In addition, we\n      discuss how aging influences the risk for developing nonalcoholic fatty liver disease,\n      hepatocellular carcinoma, and\/or autoimmune hepatitis, and we describe chronic diseases as\n      accelerators of biological aging.<\/jats:p>","DOI":"10.1055\/a-1955-5297","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T18:57:16Z","timestamp":1673290636000},"page":"83-94","source":"Crossref","is-referenced-by-count":10,"title":["The Aging Human Liver: The Weal and Woe of Evolutionary Legacy"],"prefix":"10.1055","volume":"61","author":[{"given":"Robert K.","family":"Gieseler","sequence":"additional","affiliation":[{"name":"Medizinische Klinik, Universit\u00e4tsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Schreiter","sequence":"additional","affiliation":[{"name":"Medizinische Klinik, Universit\u00e4tsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Canbay","sequence":"additional","affiliation":[{"name":"Medizinische Klinik, Universit\u00e4tsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"ref1","volume-title":"Developmental Biology. 6th ed. Sunderland, MA","author":"SF Gilbert","year":"2000"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1111\/apt.16016","article-title":"Patterns and predictors of mortality and disease progression among patients with\n          non-alcoholic fatty liver disease","volume":"52","author":"A Canbay","year":"2020","journal-title":"Aliment Pharmacol Ther"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"7280","DOI":"10.3390\/ijms23137280","article-title":"Mitochondrial Dysfunction Plays Central Role in Nonalcoholic Fatty Liver\n          Disease","volume":"23","author":"R Ramanathan","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1016\/S0140-6736(20)32511-3","article-title":"Non-alcoholic fatty liver disease","volume":"397","author":"EE Powell","year":"2021","journal-title":"Lancet"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21161","article-title":"Recent progress in understanding, diagnosing, and treating hepatocellular\n          carcinoma","volume":"62","author":"M Maluccio","year":"2012","journal-title":"CA Cancer J Clin"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality\n          Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e06449","DOI":"10.1016\/j.heliyon.2021.e06449","article-title":"Liver regeneration observed across the different classes of vertebrates from an\n          evolutionary perspective","volume":"7","author":"B Delgado-Coello","year":"2021","journal-title":"Heliyon"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1096\/fasebj.10.10.8751714","article-title":"Liver regeneration versus direct hyperplasia","volume":"10","author":"A Columbano","year":"1996","journal-title":"FASEB J"},{"issue":"S 01","key":"ref9","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1002\/hep.20969","article-title":"Liver regeneration","volume":"32","author":"N Fausto","year":"2000","journal-title":"J Hepatol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e00036","DOI":"10.7554\/eLife.00036","article-title":"Mammalian genes induce partially reprogrammed pluripotent stem cells in\n          nonmammalian vertebrate and invertebrate species","volume":"2","author":"RA Rossell\u00f3","year":"2013","journal-title":"eLife"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e10042","DOI":"10.1002\/ggn2.10042","article-title":"Genetic, Epigenetic, and Post-Transcriptional Basis of Divergent Tissue\n          Regenerative Capacities Among Vertebrates","volume":"2","author":"S Khyeam","year":"2021","journal-title":"Adv Genet (Hoboken)"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.gde.2015.03.002","article-title":"The lure of zebrafish in liver research: regulation of hepatic growth in\n          development and regeneration","volume":"32","author":"AG Cox","year":"2015","journal-title":"Curr Opin Genet Dev"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1097\/PAP.0000000000000312","article-title":"Regression of Hepatic Fibrosis and Evolution of Cirrhosis: A Concise\n          Review","volume":"28","author":"S Khan","year":"2021","journal-title":"Adv Anat Pathol"},{"key":"ref14","first-page":"332","article-title":"Peter Brian Medawar: father of transplantation","volume":"180","author":"TE Starzl","year":"1995","journal-title":"J Am Coll Surg"},{"key":"ref15","first-page":"44","volume-title":"Chapter 2: An Unsolved Problem of Biology","author":"PB Medawar","year":"1952"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e12965","DOI":"10.1111\/acel.12965","article-title":"Molecular footprint of Medawar's mutation accumulation process in mammalian\n          aging","volume":"18","author":"ZG Turan","year":"2019","journal-title":"Aging Cell"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"8556","DOI":"10.18632\/aging.102345","article-title":"Conserved aging-related signatures of senescence and inflammation in different\n          tissues and species","volume":"11","author":"E Barth","year":"2019","journal-title":"Aging (Albany NY)"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1111\/acel.12128","article-title":"Liver diseases and aging: friends or foes?","volume":"12","author":"F Sheedfar","year":"2013","journal-title":"Aging Cell"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41575-020-0342-4","article-title":"Liver regeneration: Biological and pathological mechanisms and implications. Nat.\n          Rev. Gastroenterol","volume":"18","author":"GK Michalopoulos","year":"2021","journal-title":"Hepatol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"8414","DOI":"10.3390\/ijms21218414","article-title":"Liver Regeneration after Hepatectomy and Partial Liver Transplantation","volume":"21","author":"S Yagi","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1038\/s41575-020-0342-4","article-title":"Liver regeneration","volume":"213","author":"GK Michalopoulos","year":"2007","journal-title":"J Cell Physiol"},{"key":"ref22","first-page":"509","article-title":"The Influence of Age upon the Incorporation of Thymidine-2-C14 into the DNA of\n          Regenerating Rat Liver","volume":"24","author":"NLR Bucher","year":"1964","journal-title":"Cancer Res"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.tem.2009.01.005","article-title":"Aging and liver regeneration","volume":"20","author":"NA Timchenko","year":"2009","journal-title":"Trends Endocrinol Metab"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1016\/j.cub.2017.11.008","article-title":"Improved Modeling of Compositional Heterogeneity Supports Sponges as Sister to All\n          Other Animals","volume":"27","author":"R Feuda","year":"2017","journal-title":"Curr Biol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/978-3-540-88552-8_3","article-title":"Paleoclimate and evolution: emergence of sponges during the\n          neoproterozoic","volume":"47","author":"WE M\u00fcller","year":"2009","journal-title":"Prog Mol Subcell Biol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s12862-018-1230-1","article-title":"Divergence times in demosponges (Porifera): first insights from new mitogenomes\n          and the inclusion of fossils in a birth-death clock model","volume":"18","author":"A Schuster","year":"2018","journal-title":"BMC Evol Biol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1111\/imr.12474","article-title":"Evolution of the complement system: from defense of the single cell to guardian of\n          the intravascular space","volume":"274","author":"M Elvington","year":"2016","journal-title":"Immunol Rev"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"747","DOI":"10.4049\/jimmunol.173.2.747","article-title":"C3a and C3b activation products of the third component of complement (C3) are\n          critical for normal liver recovery after toxic injury","volume":"173","author":"MM Markiewski","year":"2004","journal-title":"J Immunol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1016\/j.molimm.2008.03.008","article-title":"Evidence for non-traditional activation of complement factor C3 during murine\n          liver regeneration","volume":"45","author":"A Clark","year":"2008","journal-title":"Mol Immunol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"641","DOI":"10.4049\/jimmunol.1101925","article-title":"A complement\u2013IL-4 regulatory circuit controls liver regeneration","volume":"188","author":"RA DeAngelis","year":"2012","journal-title":"J Immunol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2500","DOI":"10.4049\/jimmunol.1600628","article-title":"Systems Analysis of the Complement-Induced Priming Phase of Liver\n          Regeneration","volume":"197","author":"JS Min","year":"2016","journal-title":"J Immunol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"5412","DOI":"10.4049\/jimmunol.0804179","article-title":"The regulation of liver cell survival by complement","volume":"182","author":"MM Markiewski","year":"2009","journal-title":"J Immunol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/0167-5699(94)90158-9","article-title":"Evidence for the early appearance of interleukins and tumor necrosis factor in the\n          phylogenesis of vertebrates","volume":"15","author":"W Ahne","year":"1994","journal-title":"Immunol Today"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"9567","DOI":"10.1073\/pnas.1405912111","article-title":"Evolution of TNF-induced apoptosis reveals 550 My of functional\n          conservation","volume":"111","author":"SD Quistad","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nri3843","article-title":"Fever and the thermal regulation of immunity: the immune system feels the\n          heat","volume":"15","author":"SS Evans","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1084\/jem.20030374","article-title":"The proinflammatory mediators C3a and C5a are essential for liver\n          regeneration","volume":"198","author":"CW Strey","year":"2003","journal-title":"J Exp Med"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/0-387-34134-X_2","article-title":"Liver regeneration: a link to inflammation through complement","volume":"586","author":"RA De Angelis","year":"2006","journal-title":"Adv Exp Med Biol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1002\/hep.28822","article-title":"MET and epidermal growth factor signaling: The pillars of liver\n          regeneration?","volume":"64","author":"JH Albrecht","year":"2016","journal-title":"Hepatology"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"2378","DOI":"10.1002\/pro.5560031222","article-title":"Molecular evolution and domain structure of plasminogen-related growth factors\n          (HGF\/SF and HGF1\/MSP)","volume":"3","author":"LE Donate","year":"1994","journal-title":"Protein Sci"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"28071","DOI":"10.1038\/srep28071","article-title":"Evolution of the EGFR pathway in Metazoa and its diversification in the planarian\n          Schmidtea mediterranea","volume":"6","author":"S Barber\u00e1n","year":"2016","journal-title":"Sci Rep"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/hep.1840130422","article-title":"Hepatocyte growth factor (hepatopoietin A) rapidly increases in plasma before DNA\n          synthesis and liver regeneration stimulated by partial hepatectomy and carbon\n          tetrachloride administration","volume":"13","author":"PM Lindroos","year":"1991","journal-title":"Hepatology"},{"key":"ref42","first-page":"1695","article-title":"Immediate early detection of urokinase receptor after partial hepatectomy and its\n          implications for initiation of liver regeneration","volume":"21","author":"WM Mars","year":"1995","journal-title":"Hepatology"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0167-0115(83)90108-8","article-title":"Exocrine secretion of epidermal growth factor from Brunner\u2019s glands. Stimulation\n          by VIP and acetylcholine","volume":"7","author":"P Kirkegaard","year":"1983","journal-title":"Regul Pept"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0079-6336(00)80006-6","article-title":"Brunner\u2019s glands: a structural, histochemical and pathological profile","volume":"35","author":"WJ Krause","year":"2000","journal-title":"Prog Histochem Cytochem"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1002\/hep.28721","article-title":"Combined systemic elimination of MET and epidermal growth factor receptor\n          signaling completely abolishes liver regeneration and leads to liver\n          decompensation","volume":"64","author":"S Paranjpe","year":"2016","journal-title":"Hepatology"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/1471-2148-9-28","article-title":"Emergence, development and diversification of the TGF-\u03b2 signaling pathway within\n          the animal kingdom","volume":"9","author":"L Huminiecki","year":"2009","journal-title":"BMC Evol Biol"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.3390\/ijms19041154","article-title":"Identification and evolution of TGF-\u03b2 signaling pathway members in twenty-four\n          animal species and expression in Tilapia.","volume":"19","author":"S Zheng","year":"2018","journal-title":"Int J Mol Sci"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"4256352","DOI":"10.1155\/2017\/4256352","article-title":"Liver Regeneration: Analysis of the Main Relevant Signaling Molecules","volume":"2017","author":"Y Tao","year":"2017","journal-title":"Mediators Inflamm"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1002\/j.1460-2075.1991.tb08012.x","article-title":"Genomic structure and restricted neural expression of the zebrafish wnt-1 (int-1)\n          gene","volume":"10","author":"A Molven","year":"1991","journal-title":"EMBO J"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1126\/science.1143578","article-title":"Augmented Wnt signaling in a mammalian model of accelerated aging","volume":"317","author":"H Liu","year":"2007","journal-title":"Science"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"110851","DOI":"10.1016\/j.biopha.2020.110851","article-title":"WNT\/\u03b2-catenin signaling in the development of liver cancers","volume":"132","author":"S He","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/j.arr.2010.06.004","article-title":"Impact of aging on dendritic cell functions in humans","volume":"10","author":"A Agrawal","year":"2011","journal-title":"Ageing Res Rev"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"8459","DOI":"10.3748\/wjg.v19.i46.8459","article-title":"Liver physiology and liver diseases in the elderly","volume":"19","author":"K Tajiri","year":"2013","journal-title":"World J Gastroenterol"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging. An evolutionary perspective on immunosenescence","volume":"908","author":"C Franceschi","year":"2000","journal-title":"Ann N Y Acad Sci"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1007\/s40266-018-0556-0","article-title":"Autoimmune Hepatitis in the Elderly: Diagnosis and Pharmacologic\n          Management","volume":"35","author":"S Rizvi","year":"2018","journal-title":"Drugs Aging"},{"issue":"03","key":"ref56","doi-asserted-by":"publisher","first-page":"M146","DOI":"10.1093\/gerona\/56.3.m146","article-title":"Frailty in older adults: evidence for a phenotype","volume":"56","author":"LP Fried","year":"2001","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1007\/s11357-020-00247-4","article-title":"Association of inflammatory mediators with frailty status in older adults: results\n          from a systematic review and meta-analysis","volume":"42","author":"D Marcos-P\u00e9rez","year":"2020","journal-title":"Geroscience"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0167-5699(96)80544-5","article-title":"Dendritic cells: from ontogenetic orphans to myelomonocytic descendants","volume":"17","author":"JH Peters","year":"1996","journal-title":"Immunol Today"},{"key":"ref59","first-page":"25","article-title":"In-vitro differentiation of mature dendritic cells from human blood\n          monocytes","volume":"6","author":"R Gieseler","year":"1998","journal-title":"Dev Immunol"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/nri3046","article-title":"Human dendritic cell deficiency: the missing ID?","volume":"11","author":"M Collin","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/j.arr.2010.06.004","article-title":"Impact of aging on dendritic cell functions in humans","volume":"10","author":"A Agrawal","year":"2011","journal-title":"Ageing Res Rev"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"708186","DOI":"10.3389\/fimmu.2021.708186","article-title":"Macrophages: The Good, the Bad, and the Gluttony","volume":"12","author":"EA Ross","year":"2021","journal-title":"Front Immunol"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1126\/science.356266","article-title":"Bone marrow origin of hepatic macrophages (Kupffer cells) in humans","volume":"201","author":"RP Gale","year":"1978","journal-title":"Science"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1126\/science.1219179","article-title":"A lineage of myeloid cells independent of Myb and hematopoietic stem\n          cells","volume":"336","author":"C Schulz","year":"2012","journal-title":"Science"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nature13989","article-title":"Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid\n          progenitors","volume":"518","author":"E Gomez Perdiguero","year":"2015","journal-title":"Nature"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"e12829","DOI":"10.1111\/acel.12829","article-title":"Effects of aging on liver microcirculatory function and sinusoidal\n          phenotype","volume":"17","author":"R Maeso-D\u00edaz","year":"2018","journal-title":"Aging Cell"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/s41374-019-0342-6","article-title":"STING expression in monocyte-derived macrophages is associated with the\n          progression of liver inflammation and fibrosis in patients with nonalcoholic fatty liver\n          disease","volume":"100","author":"X Wang","year":"2020","journal-title":"Lab Invest"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.canlet.2019.11.001","article-title":"Macrophages-induced long noncoding RNA H19 up-regulation triggers and activates\n          the miR-193b\/MAPK1 axis and promotes cell aggressiveness in hepatocellular\n          carcinoma","volume":"469","author":"Y Ye","year":"2020","journal-title":"Cancer Lett"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"e13512","DOI":"10.1111\/acel.13512","article-title":"Necroptosis contributes to chronic inflammation and fibrosis in aging\n          liver","volume":"20","author":"S Mohammed","year":"2021","journal-title":"Aging Cell"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"e22125","DOI":"10.1096\/fj.202101426R","article-title":"Endothelial dysfunction in pathological processes of chronic liver disease during\n          aging","volume":"36","author":"Y Wan","year":"2022","journal-title":"FASEB J"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/j.cmet.2020.10.026","article-title":"The Power of Plasticity-Metabolic Regulation of Hepatic Stellate Cells","volume":"33","author":"P Trivedi","year":"2021","journal-title":"Cell Metab"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1055\/s-2006-927395","article-title":"Inflammation, damage repair and liver fibrosis \u2013 role of cytokines and different\n          cell types","volume":"45","author":"B Saile","year":"2007","journal-title":"Z Gastroenterol"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1159\/000065506","article-title":"Aging Liver. A review","volume":"48","author":"A Anantharaju","year":"2002","journal-title":"Gerontology"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"2721","DOI":"10.3390\/nu12092721","article-title":"Sex-Dependent Wheel Running Effects on High Fat Diet Preference, Metabolic\n          Outcomes, and Performance on the Barnes Maze in Rats","volume":"12","author":"TY Yang","year":"2020","journal-title":"Nutrients"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"101259","DOI":"10.1016\/j.arr.2021.101259","article-title":"Aging adipose: Depot location dictates age-associated expansion and\n          dysfunction","volume":"67","author":"H Von Bank","year":"2021","journal-title":"Ageing Res Rev"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"111162","DOI":"10.1016\/j.exger.2020.111162","article-title":"How does adipose tissue contribute to inflammageing?","volume":"143","author":"M Zamboni","year":"2021","journal-title":"Exp Gerontol"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"e26818","DOI":"10.5812\/hepatmon.26818","article-title":"Association of Tumor Necrosis Factor-alpha Polymorphisms and Risk of Coronary\n          Artery Disease in Patients With Non-alcoholic Fatty Liver Disease","volume":"15","author":"Y Cheng","year":"2015","journal-title":"Hepat Mon"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ijcard.2018.01.046","article-title":"Circulating Interleukin-6 is a biomarker for coronary atherosclerosis in\n          nonalcoholic fatty liver disease: Results from the Multi-Ethnic Study of\n          Atherosclerosis","volume":"259","author":"TG Simon","year":"2018","journal-title":"Int J Cardiol"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.3390\/life12081189","article-title":"New Insights into Non-Alcoholic Fatty Liver Disease and Coronary Artery Disease:\n          The Liver-Heart Axis","volume":"12","author":"GD Cazac","year":"2022","journal-title":"Life (Basel)"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1080\/21623945.2021.1982164","article-title":"Association of cell death mechanisms and fibrosis in visceral white adipose tissue\n          with pathological alterations in the liver of morbidly obese patients with\n          NAFLD","volume":"10","author":"AS Leven","year":"2021","journal-title":"Adipocyte"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"155179","DOI":"10.1016\/j.metabol.2022.155179","article-title":"Towards harnessing the value of organokine crosstalk to predict the risk for\n          cardiovascular disease in non-alcoholic fatty liver disease","volume":"130","author":"T Baars","year":"2022","journal-title":"Metabolism"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1080\/08820139.2018.1537570","article-title":"The Impact of the Microbiome on Immunosenescence","volume":"47","author":"D Amsterdam","year":"2018","journal-title":"Immunol Invest"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41514-017-0020-0","article-title":"Fighting Against a Protean Enemy: Immunosenescence, Vaccines, and Healthy\n          Aging","volume":"4","author":"G Del Giudice","year":"2018","journal-title":"NPJ Aging Mech Dis"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"111372","DOI":"10.1016\/j.exger.2021.111372","article-title":"D-galactose-induced liver aging model: Its underlying mechanisms and potential\n          therapeutic interventions","volume":"150","author":"KF Azman","year":"2021","journal-title":"Exp Gerontol"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.arr.2019.02.002","article-title":"The peculiar aging of human liver: A geroscience perspective within transplant\n          context","volume":"51","author":"C Morsiani","year":"2019","journal-title":"Ageing Res Rev"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.3390\/pharmaceutics13122009","article-title":"Transcriptome-Wide Analysis of Human Liver Reveals Age-Related Differences in the\n          Expression of Select Functional Gene Clusters and Evidence for a PPP1R10-Governed \u2018Aging\n          Cascade\u2019","volume":"13","author":"T Schreiter","year":"2021","journal-title":"Pharmaceutics"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1111\/acel.12549","article-title":"Identification of miR-31\u20135p, miR-141\u20133p, miR-200c-3p, and GLT1 as human liver\n          aging markers sensitive to donor-recipient age-mismatch in transplants","volume":"16","author":"M Capri","year":"2017","journal-title":"Aging Cell"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"681449","DOI":"10.3389\/fimmu.2021.681449.","article-title":"Aging and Options to Halt Declining Immunity to Virus Infections","volume":"12","author":"M\u00c1 Palacios-Pedrero","year":"2021","journal-title":"Front Immunol"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1124\/pr.108.00001","article-title":"Molecular mechanisms and therapeutic targets in steatosis and\n          steatohepatitis","volume":"60","author":"N Anderson","year":"2008","journal-title":"Pharmacol Rev"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1097\/00042737-200107000-00004","article-title":"Cytokines in the liver","volume":"13","author":"G Ramadori","year":"2001","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1002\/hep.21752","article-title":"Palmitic acid induces production of proinflammatory cytokine interleukin-8 from\n          hepatocytes","volume":"46","author":"S Joshi-Barve","year":"2007","journal-title":"Hepatology"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.1111\/liv.14571","article-title":"Bacterial antigen translocation and age as BMI-independent contributing factors on\n          systemic inflammation in NAFLD patients","volume":"40","author":"I G\u00f3mez-Hurtado","year":"2020","journal-title":"Liver Int"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1111\/acel.12128","article-title":"Liver diseases and aging: friends or foes?","volume":"12","author":"F Sheedfar","year":"2013","journal-title":"Aging Cell"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.immuni.2021.02.003","article-title":"Cytoplasmic DNA sensing by KU complex in aged CD4+ T cell potentiates T cell\n          activation and aging-related autoimmune inflammation","volume":"54","author":"Y Wang","year":"2021","journal-title":"Immunity"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"e184","DOI":"10.1007\/978-3-642-27340-7_4","article-title":"DNA Methylation and Immune Cell Markers Demonstrate Evidence of Accelerated Aging\n          in Patients with Chronic Hepatitis B Virus or Hepatitis C Virus, with or without Human\n          Immunodeficienct Virus Co-infection","volume":"73","author":"Y Gindin","year":"2021","journal-title":"Clin Infect Dis"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"R115","DOI":"10.1186\/gb-2013-14-10-r115","article-title":"DNA methylation age of human tissues and cell types","volume":"14","author":"S Horvath","year":"2013","journal-title":"Genome Biol"},{"key":"ref97","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.18632\/aging.100861","article-title":"Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their\n          offspring","volume":"7","author":"S Horvath","year":"2015","journal-title":"Aging (Albany NY)"},{"key":"ref98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1172\/jci.insight.96685","article-title":"DNA methylation signatures reflect aging in patients with nonalcoholic\n          steatohepatitis","volume":"3","author":"R Loomba","year":"2018","journal-title":"JCI Insight"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s41232-016-0025-2","article-title":"Liver regeneration and fibrosis after inflammation","volume":"36","author":"M Tanaka","year":"2016","journal-title":"Inflamm Regen"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"B315","DOI":"10.1093\/gerona\/53a.5.b315","article-title":"Aging and the liver: an update","volume":"53","author":"DL Schmucker","year":"1998","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/S2468-1253(20)30006-6","article-title":"Drug-induced liver injury in older people","volume":"5","author":"MI Lucena","year":"2020","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"362","DOI":"10.2174\/1574888X15666200213105155","article-title":"Stem Cell Aging in Lifespan and Disease: A State-of-the-Art Review","volume":"15","author":"S Sameri","year":"2020","journal-title":"Curr Stem Cell Res Ther"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"3606","DOI":"10.3390\/ijms21103606","article-title":"The Role of Autophagy for the Regeneration of the Aging Liver","volume":"21","author":"F Xu","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"10","key":"ref104","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1089\/ars.2021.0048","article-title":"The Aging Liver: Redox Biology and Liver Regeneration","volume":"35","author":"F Bellanti","year":"2021","journal-title":"Antioxid Redox Signal"},{"key":"ref105","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3727\/105221620X15960509906371","article-title":"The Dynamic Interplay Between Mast Cells, Aging\/Cellular Senescence, and Liver\n          Disease","volume":"20","author":"D Kundu","year":"2020","journal-title":"Gene Expr"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"103575","DOI":"10.1016\/j.etap.2020.103575","article-title":"Environmental pollutants exposure: A potential contributor for aging and\n          age-related diseases","volume":"83","author":"Y Liu","year":"2021","journal-title":"Environ Toxicol Pharmacol"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"100913","DOI":"10.1016\/j.arr.2019.100913","article-title":"Effects of light on aging and longevity","volume":"53","author":"J Shen","year":"2019","journal-title":"Ageing Res Rev"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1176\/ajp.102.3.325","article-title":"Ageing and detoxication; studies in hippuric acid synthesis during psychoses of\n          the involutional and old age group","volume":"102","author":"K Stern","year":"1945","journal-title":"Am J Psychiatry"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1097\/00000658-194002000-00004","article-title":"Studies of liver function by means of Quick\u2019s hippuric acid test","volume":"111","author":"JG Probstein","year":"1940","journal-title":"Ann Surg"},{"key":"ref110","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.csbj.2019.07.021","article-title":"Hallmarks of Aging in the Liver","volume":"17","author":"NJ Hunt","year":"2019","journal-title":"Comput Struct Biotechnol J"},{"key":"ref111","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/bs.acc.2019.07.012","article-title":"Organokines in disease","volume":"94","author":"HS Chung","year":"2020","journal-title":"Adv Clin Chem"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"13670","DOI":"10.1038\/s41598-017-13722-4","article-title":"Hippurate as a metabolomic marker of gut microbiome diversity: Modulation by diet\n          and relationship to metabolic syndrome","volume":"7","author":"T Pallister","year":"2017","journal-title":"Sci Rep"},{"key":"ref113","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1038\/s41591-018-0061-3","article-title":"Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese\n          women","volume":"24","author":"L Hoyles","year":"2018","journal-title":"Nat Med"},{"key":"ref114","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1136\/gutjnl-2020-323314","article-title":"Human and preclinical studies of the host\u2013gut microbiome co-metabolite hippurate\n          as a marker and mediator of metabolic health","volume":"70","author":"F Brial","year":"2021","journal-title":"Gut"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.3390\/biomedicines10061216","article-title":"Association of Metabolomic Change and Treatment Response in Patients with\n          Non-Alcoholic Fatty Liver Disease","volume":"10","author":"KS Lee","year":"2022","journal-title":"Biomedicines"},{"key":"ref116","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3109\/03602538908994145","article-title":"Influence of aging on chemically induced hepatotoxicity: role of age-related\n          changes in metabolism","volume":"20","author":"LE Rikans","year":"1989","journal-title":"Drug Metab Rev"},{"key":"ref117","doi-asserted-by":"publisher","first-page":"e62439","DOI":"10.1371\/journal.pone.0062439","article-title":"Novel algorithm for non-invasive assessment of fibrosis in NAFLD","volume":"8","author":"JP Sowa","year":"2013","journal-title":"PLoS One"},{"key":"ref118","doi-asserted-by":"publisher","first-page":"e101444","DOI":"10.1371\/journal.pone.0101444","article-title":"Non-invasive separation of alcoholic and non-alcoholic liver disease with\n          predictive modeling","volume":"9","author":"JP Sowa","year":"2014","journal-title":"PLoS One"},{"key":"ref119","doi-asserted-by":"publisher","first-page":"e0214436","DOI":"10.1371\/journal.pone.0214436","article-title":"Non-invasive assessment of NAFLD as systemic disease \u2013 A machine learning\n          perspective","volume":"14","author":"A Canbay","year":"2019","journal-title":"PLoS One"},{"key":"ref120","doi-asserted-by":"publisher","first-page":"101706","DOI":"10.1016\/j.artmed.2019.101706","article-title":"The virtual doctor: An interactive clinical-decision-support system based on deep\n          learning for non-invasive prediction of diabetes","volume":"100","author":"S Sp\u00e4nig","year":"2019","journal-title":"Artif Intell Med"},{"key":"ref121","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/nature14541","article-title":"Probabilistic machine learning and artificial intelligence","volume":"521","author":"Z Ghahramani","year":"2015","journal-title":"Nature"},{"key":"ref122","doi-asserted-by":"crossref","first-page":"E1195","DOI":"10.1152\/ajpendo.00513.2004","article-title":"PPAR\u03b32 regulates lipogenesis and lipid accumulation in steatotic\n          hepatocytes","volume":"288","author":"SE Schadinger","year":"2005","journal-title":"Am J Physiol Endocrinol Metab"}],"container-title":["Zeitschrift f\u00fcr Gastroenterologie"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1955-5297.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T22:51:08Z","timestamp":1764111068000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1955-5297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":122,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2023,1,9]]},"published-print":{"date-parts":[[2023,1]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1955-5297","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0044-2771","1439-7803"],"issn-type":[{"value":"0044-2771","type":"print"},{"value":"1439-7803","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1]]}}}