{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:59:03Z","timestamp":1790402343298,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T00:00:00Z","timestamp":1590624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Iron deficiency (ID) is the most frequent nutritional deficiency in the whole population worldwide, and the second most common cause of anemia in the elderly. The prevalence of anemia is expecting to rise shortly, because of an ageing population. Even though WHO criteria define anemia as a hemoglobin serum concentration &lt;12 g\/dL in women and &lt;13 g\/dL in men, several authors propose different and specific cut-off values for the elderly. Anemia in aged subjects impacts health and quality of life, and it is associated with several negative outcomes, such as longer time of hospitalization and a higher risk of disability. Furthermore, it is an independent risk factor of increased morbidity and mortality. Even though iron deficiency anemia is a common disorder in older adults, it should be not considered as a normal ageing consequence, but a sign of underlying dysfunction. Relating to the molecular mechanism in Iron Deficiency Anemia (IDA), hepcidin has a key role in iron homeostasis. It downregulates the iron exporter ferroportin, inhibiting both iron absorption and release. IDA is frequently dependent on blood loss, especially caused by gastrointestinal lesions. Thus, a diagnostic algorithm for IDA should include invasive investigation such as endoscopic procedures. The treatment choice is influenced by the severity of anemia, underlying conditions, comorbidities, and the clinical state of the patient. Correction of anemia and iron supplementation should be associated with the treatment of the causal disease.<\/jats:p>","DOI":"10.3390\/ijms21113821","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T10:02:45Z","timestamp":1590660165000},"page":"3821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Molecular Aspects and Treatment of Iron Deficiency in the Elderly"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0559-2917","authenticated-orcid":false,"given":"Antonino Davide","family":"Romano","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Foggia, 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3657-3631","authenticated-orcid":false,"given":"Annalisa","family":"Paglia","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Foggia, 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8196-7373","authenticated-orcid":false,"given":"Francesco","family":"Bellanti","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Foggia, 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9875-019X","authenticated-orcid":false,"given":"Rosanna","family":"Villani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Foggia, 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moris","family":"Sangineto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Foggia, 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Vendemiale","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Foggia, 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Serviddio","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Foggia, 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.critrevonc.2005.09.003","article-title":"Anemia in the elderly\u2014Clinical findings and impact on health","volume":"58","author":"Balducci","year":"2006","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Busti, F., Campostrini, N., Martinelli, N., and Girelli, D. (2014). Iron deficiency in the elderly population, revisited in the hepcidin era. Front. Pharmacol., 5.","DOI":"10.3389\/fphar.2014.00083"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/ajh.20249","article-title":"Iron deficiency: A concise review","volume":"78","author":"Umbreit","year":"2005","journal-title":"Am. J. Hematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"958","DOI":"10.4065\/82.8.958","article-title":"Anemia in the Elderly: How Should We Define It, When Does It Matter, and What Can Be Done?","volume":"82","author":"Steensma","year":"2007","journal-title":"Mayo Clin. Proc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/ajh.23598","article-title":"Evaluation and management of anemia in the elderly","volume":"89","author":"Goodnough","year":"2014","journal-title":"Am. J. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1080\/17474086.2017.1285695","article-title":"Anemia in the elderly: A consequence of aging?","volume":"10","author":"Halawi","year":"2017","journal-title":"Expert Rev. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1182\/blood-2017-07-746446","article-title":"Anemia at older age: Etiologies, clinical implications, and management","volume":"131","author":"Stauder","year":"2018","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s41999-018-0048-0","article-title":"Anemia in the aged is not ageing related: Position paper on anemia in the aged by the \u201cworking group anemia\u201d of the German Geriatric Society (DGG)","volume":"9","author":"Kolb","year":"2018","journal-title":"Eur. Geriatr. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1179\/acb.2009.047","article-title":"Anaemia in the elderly","volume":"64","author":"Cytryn","year":"2009","journal-title":"Acta Clin. Belg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1017\/S1368980008002401","article-title":"Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993\u20132005","volume":"12","author":"McLean","year":"2008","journal-title":"Public Health Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/ggi.13194","article-title":"Iron deficiency anemia in older adults: A review","volume":"18","author":"Joosten","year":"2017","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8416","DOI":"10.3748\/wjg.v20.i26.8416","article-title":"Role of small bowel capsule endoscopy in the diagnosis and management of iron deficiency anemia in elderly: A comprehensive review of the current literature","volume":"20","author":"Muhammad","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_13","first-page":"46","article-title":"Efficacy and safety of direct-acting antivirals in elderly with chronic hepatitis C: Results from a retrospective cohort study","volume":"66","author":"Villani","year":"2018","journal-title":"J. Gerontol. Geriatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1182\/blood.V84.4.1056.1056","article-title":"Prediction of response to erythropoietin treatment in chronic anemia of cancer","volume":"84","author":"Ludwig","year":"1994","journal-title":"Blood"},{"key":"ref_15","first-page":"22","article-title":"Iron status in the elderly","volume":"136\u2013137","author":"Wawer","year":"2014","journal-title":"Mech. Ageing Dev."},{"key":"ref_16","first-page":"921","article-title":"Anemia in the aged\u2014A geriatric syndrome?: Second position paper on anemia in the aged by the working group anemia of the German Geriatric Society","volume":"51","author":"Rohrig","year":"2018","journal-title":"Z. Gerontol. Geriatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: A new immune-metabolic viewpoint for age-related diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"615","DOI":"10.3233\/JAD-160942","article-title":"Alterations of Clock Gene RNA Expression in Brain Regions of a Triple Transgenic Model of Alzheimer\u2019s Disease","volume":"59","author":"Bellanti","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gowanlock, Z., Sriram, S., Martin, A., Xenocostas, A., and Lazo-Langner, A. (2016). Erythropoietin Levels in Elderly Patients with Anemia of Unknown Etiology. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157279"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.maturitas.2017.12.002","article-title":"Oxidative stress is increased in sarcopenia and associated with cardiovascular disease risk in sarcopenic obesity","volume":"109","author":"Bellanti","year":"2018","journal-title":"Maturitas"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.18632\/aging.100966","article-title":"Bonnie and Clyde: Vitamin C and iron are partners in crime in iron deficiency anaemia and its potential role in the elderly","volume":"8","author":"Lane","year":"2016","journal-title":"Aging"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1038\/ki.2009.357","article-title":"Iron-refractory iron deficiency anemia: New molecular mechanisms","volume":"76","author":"Cui","year":"2009","journal-title":"Kidney Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev.physiol.69.031905.164337","article-title":"Iron homeostasis","volume":"69","author":"Andrews","year":"2007","journal-title":"Annu. Rev. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ganz, T. (2006). Hepcidin and its role in regulating systemic iron metabolism. ASH Educ. Program Book.","DOI":"10.1182\/asheducation-2006.1.29"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8780","DOI":"10.1073\/pnas.151179498","article-title":"Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice","volume":"98","author":"Nicolas","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4596","DOI":"10.1073\/pnas.072632499","article-title":"Severe iron deficiency anemia in transgenic mice expressing liver hepcidin","volume":"99","author":"Nicolas","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3776","DOI":"10.1182\/blood-2002-04-1260","article-title":"Inappropriate expression of hepcidin is associated with iron refractory anemia: Implications for the anemia of chronic disease","volume":"100","author":"Weinstein","year":"2002","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1128\/IAI.00983-13","article-title":"Hepcidin induction by pathogens and pathogen-derived molecules is strongly dependent on interleukin-6","volume":"82","author":"Rodriguez","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.2174\/13816128113196660700","article-title":"Bioenergetics and mitochondrial dysfunction in aging: Recent insights for a therapeutical approach","volume":"20","author":"Romano","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/ki.2008.245","article-title":"Association of anemia and erythropoiesis stimulating agents with inflammatory biomarkers in chronic kidney disease","volume":"74","author":"Addabbo","year":"2008","journal-title":"Kidney Int."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Besarab, A., and Hemmerich, S. (2017). Iron-Deficiency Anemia. Management of Anemia, Springer.","DOI":"10.1007\/978-1-4939-7360-6_2"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1159\/000358377","article-title":"Iron Deficiency Status Irrespective of Anemia: A Predictor of Unfavorable Outcome in Chronic Heart Failure Patients","volume":"128","author":"Rangel","year":"2014","journal-title":"Cardiology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1011","DOI":"10.1097\/MD.0000000000001011","article-title":"Diagnosis of Iron Deficiency in Inflammatory Bowel Disease by Transferrin Receptor-Ferritin Index","volume":"94","author":"Abitbol","year":"2015","journal-title":"Medicine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.gtc.2009.06.005","article-title":"Celiac Disease in the Elderly","volume":"38","author":"Rashtak","year":"2009","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mart\u00edn-Masot, R., Nestares, M.T., Diaz-Castro, J., L\u00f3pez-Aliaga, I., Mu\u00f1oz Alf\u00e9rez, M.J., Moreno-Fernandez, J., and Maldonado, J. (2019). Multifactorial etiology of anemia in celiac disease and effect of gluten-free diet: A comprehensive review. Nutrients, 11.","DOI":"10.3390\/nu11112557"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"McNamee, T., Hyland, T., Harrington, J., Cadogan, S., Honari, B., Perera, K., Fitzgerald, A.P., Perry, I.J., and Cahill, M.R. (2013). Haematinic deficiency and macrocytosis in middle-aged and older adults. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077743"},{"key":"ref_37","first-page":"278","article-title":"Iron status of the Taiwanese elderly: The prevalence of iron deficiency and elevated iron stores","volume":"14","author":"Wang","year":"2005","journal-title":"Asia Pac. J. Clin. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/ggi.12017","article-title":"Anemia in elderly patients: New insight into an old disorder","volume":"13","author":"Andres","year":"2013","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1179\/102453310X12583347010052","article-title":"Anemia and transfusions in geriatric patients: A time for evaluation","volume":"15","author":"Beyer","year":"2010","journal-title":"Hematology"},{"key":"ref_40","first-page":"S29","article-title":"Oxidative stress and aging","volume":"23","author":"Romano","year":"2010","journal-title":"J. Nephrol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1159\/000484654","article-title":"Evaluation of Parenteral Iron Therapy in Ambulatory Older Adults with Iron Deficiency Anaemia","volume":"138","author":"Casteleyn","year":"2017","journal-title":"Acta Haematol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Silverberg, D.S., Mor, R., Weu, M.T., Schwartz, D., Schwartz, I.F., and Chernin, G. (2014). Anemia and iron deficiency in COPD patients: Prevalence and the effects of correction of the anemia with erythropoiesis stimulating agents and intravenous iron. BMC Pulm. Med., 14.","DOI":"10.1186\/1471-2466-14-24"},{"key":"ref_43","first-page":"CD002042","article-title":"Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion","volume":"10","author":"Carson","year":"2016","journal-title":"Cochrane Database Syst. Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/11\/3821\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:33:17Z","timestamp":1760175197000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/11\/3821"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,28]]},"references-count":43,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["ijms21113821"],"URL":"https:\/\/doi.org\/10.3390\/ijms21113821","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,28]]}}}