{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:35:57Z","timestamp":1787646957335,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:00:00Z","timestamp":1762646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007650","name":"Fundaci\u00f3n Canaria de Investigaci\u00f3n Sanitaria","doi-asserted-by":"publisher","award":["PIFIISC22\/15"],"award-info":[{"award-number":["PIFIISC22\/15"]}],"id":[{"id":"10.13039\/100007650","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Humanin (HN) and MOTS-c are mitochondrial-derived peptides (MDPs) known for their neuroprotective and metabolic functions. Their circulating and tissue levels decline with age and in neurodegenerative diseases such as Alzheimer\u2019s disease (AD). This study aimed to evaluate whether blood and plasma gene expression and plasma protein levels of HN and MOTS-c are associated with AD markers, their role in the conversion from mild cognitive impairment (MCI) to AD, and their overall association with the disease. A case\u2013control study was conducted, including patients with AD and MCI, and individuals with subjective cognitive decline (SCD) as controls. Gene expression levels were quantified from total RNA isolated from blood and plasma, normalised to mitochondrial DNA copy number (mtDNA-CN). ELISA was used to measure plasma HN and MOTS-c protein concentrations. HN and MOTS-c transcript levels differed significantly among study groups, whereas plasma protein concentrations did not discriminate between AD and MCI. In silico and RNA decay assays revealed faster degradation of HN mRNA and delayed but stable recovery of MOTS-c mRNA. Overall, blood and plasma transcript levels\u2014but not circulating protein levels\u2014of these MDPs were significantly reduced in AD compared to SCD, suggesting their potential as early biomarkers of Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms262210866","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T08:57:55Z","timestamp":1762765075000},"page":"10866","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Insights into the Biomarker Potential of Humanin and Mots-c Expression and Telomere Length in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1663-3673","authenticated-orcid":false,"given":"Francisco","family":"Rodr\u00edguez-Esparrag\u00f3n","sequence":"first","affiliation":[{"name":"Research Unit, Hospital Universitario de Gran Canaria Dr. Negr\u00edn, 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Fundaci\u00f3n Canaria Instituto de Investigaci\u00f3n Sanitaria de Canarias (FIISC), 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, 38296 La Laguna, Tenerife, Spain"},{"name":"CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara E.","family":"Cazorla-Rivero","sequence":"additional","affiliation":[{"name":"Research Unit, Hospital Universitario de Gran Canaria Dr. Negr\u00edn, 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Fundaci\u00f3n Canaria Instituto de Investigaci\u00f3n Sanitaria de Canarias (FIISC), 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Faculty of Health Sciences, Middle Atlantic University (UNAM), 35017 Las Palmas, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Torrealba","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Canaria Instituto de Investigaci\u00f3n Sanitaria de Canarias (FIISC), 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Department of Neurology and Clinical Neurophysiology, Hospital Universitario de Gran Canaria Dr. Negr\u00edn, 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Department of Medical and Surgical Sciences, Universidad de Las Palmas de Gran Canaria, 35001 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8557-860X","authenticated-orcid":false,"given":"\u00c1ngeles","family":"C\u00e1novas-Molina","sequence":"additional","affiliation":[{"name":"Research Unit, Hospital Universitario de Gran Canaria Dr. Negr\u00edn, 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Fundaci\u00f3n Canaria Instituto de Investigaci\u00f3n Sanitaria de Canarias (FIISC), 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Chronic Pain Unit, Hospital Universitario de Gran Canaria Dr. Negr\u00edn, 35019 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayose N.","family":"Gonz\u00e1lez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Canaria Instituto de Investigaci\u00f3n Sanitaria de Canarias (FIISC), 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Department of Neurology and Clinical Neurophysiology, Hospital Universitario de Gran Canaria Dr. Negr\u00edn, 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Faculty of Health Sciences, Universidad Fernando Pessoa Canarias, 35450 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Mart\u00edn-Alfaro","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Canaria Instituto de Investigaci\u00f3n Sanitaria de Canarias (FIISC), 35019 Las 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Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6076-9610","authenticated-orcid":false,"given":"Carmen G.","family":"P\u00e9rez-Santana","sequence":"additional","affiliation":[{"name":"Research Unit, Hospital Universitario de Gran Canaria Dr. Negr\u00edn, 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Fundaci\u00f3n Canaria Instituto de Investigaci\u00f3n Sanitaria de Canarias (FIISC), 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Instituto Universitario de Sanidad Animal y Seguridad Alimentaria (IUSA), Universidad de Las Palmas de Gran Canaria (ULPGC), 35416 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Bartolom\u00e9","sequence":"additional","affiliation":[{"name":"Research Unit, Hospital Universitario de Gran Canaria Dr. Negr\u00edn, 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Fundaci\u00f3n Canaria Instituto de 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Spain"},{"name":"CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Chronic Pain Unit, Hospital Universitario de Gran Canaria Dr. Negr\u00edn, 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negr\u00edn, 35019 Las Palmas de Gran Canaria, Spain"},{"name":"Molecular and Translational Pharmacology Group, University Institute for Research in Biomedicine and Health (iUIBS), Universidad de Las Palmas de Gran Canaria, 35016 Las Palmas de Gran Canaria, Spain"},{"name":"Spanish Group of Clinical Research in Radiation Oncology (GICOR), 28290 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.5582\/irdr.2024.01026","article-title":"Guardians of Memory: The Urgency of Early Dementia Screening in an Aging 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