{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T05:11:27Z","timestamp":1769577087529,"version":"3.49.0"},"reference-count":75,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Down Syndrome (DS) is a neurodevelopmental disorder that is characterized by an accelerated aging process, frequently associated with the development of Alzheimer\u2019s disease (AD). Previous studies evidenced that DS patients have various metabolic anomalies, easily measurable in their serum samples, although values that were found in DS patients were compared with those of age-matched non-DS patients, thus hampering to discriminate the physiologic age-related changes of serum metabolites from those that are truly caused by the pathologic processes associated with DS. In the present study we performed a targeted metabolomic evaluation of serum samples from DS patients without dementia of two age classes (Younger DS Patients, YDSP, aging 20\u201340 years; Aged DS Patients, ADSP, aging 41\u201360 years), comparing the results with those that were obtained in two age classes of non-DS patients (Younger non-DS Patients, YnonDSP, aging 30\u201360 years; Aged-nonDS Patients, AnonDSP, aging 75\u201390 years). Of the 36 compounds assayed, 30 had significantly different concentrations in Pooled non-DS Patients (PnonDSP), compared to Pooled DS Patients (PDSP). Age categorization revealed that 11\/30 compounds were significantly different in AnonDSP, compared to YnonDSP, indicating physiologic, age-related changes of their circulating concentrations. A comparison between YDSP and ADSP showed that 19\/30 metabolites had significantly different values from those found in the corresponding classes of non-DS patients, strongly suggesting pathologic, DS-associated alterations of their serum levels. Twelve compounds selectively and specifically discriminated PnonDSP from PDSP, whilst only three discriminated YDSP from ADSP. The results allowed to determine, for the first time and to the best of our knowledge, the true, age-independent alterations of metabolism that are measurable in serum and attributable only to DS. These findings may be of high relevance for better strategies (pharmacological, nutritional) aiming to specifically target the dysmetabolism and decreased antioxidant defenses that are associated with DS.<\/jats:p>","DOI":"10.3390\/antiox11061208","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T01:43:27Z","timestamp":1655775807000},"page":"1208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Biochemical Discrimination of the Down Syndrome-Related Metabolic and Oxidative\/Nitrosative Stress Alterations from the Physiologic Age-Related Changes through the Targeted Metabolomic Analysis of Serum"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1639-0966","authenticated-orcid":false,"given":"Giacomo","family":"Lazzarino","sequence":"first","affiliation":[{"name":"UniCamillus\u2014Saint Camillus International University of Health Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-9955","authenticated-orcid":false,"given":"Angela M.","family":"Amorini","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Division of Medical Biochemistry, University of Catania, Via S. Sofia 97, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Mangione","sequence":"additional","affiliation":[{"name":"Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of the Sacred Heart of Rome, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam Wissam","family":"Saab","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Division of Medical Biochemistry, University of Catania, Via S. Sofia 97, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Di Stasio","sequence":"additional","affiliation":[{"name":"Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of the Sacred Heart of Rome, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1837-9325","authenticated-orcid":false,"given":"Michelino","family":"Di Rosa","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Sciences, School of Medicine, University of Catania, Via S. Sofia 97, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8743-0895","authenticated-orcid":false,"given":"Barbara","family":"Tavazzi","sequence":"additional","affiliation":[{"name":"UniCamillus\u2014Saint Camillus International University of Health Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5917-7279","authenticated-orcid":false,"given":"Giuseppe","family":"Lazzarino","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Division of Medical Biochemistry, University of Catania, Via S. Sofia 97, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graziano","family":"Onder","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9837-7003","authenticated-orcid":false,"given":"Angelo","family":"Carf\u00ec","sequence":"additional","affiliation":[{"name":"Department of Geriatric and Orthopedic Sciences, Catholic University of Rome, Largo Francesco Vito, 1, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1002\/ajmg.a.61636","article-title":"The burden of chronic disease, multimorbidity, and polypharmacy in adults with Down Syndrome","volume":"182","author":"Romano","year":"2020","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/ddrr.1128","article-title":"Atypical aging in Down Syndrome","volume":"18","author":"Zigman","year":"2013","journal-title":"Dev. Disabil. Res. 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