{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:09:53Z","timestamp":1792523393827,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>This study aimed to identify autophagy-related microRNAs (miRNAs) in plasma exosomes as non-invasive biomarkers for brain aging and explore their potential to improve early detection of age-associated neurodegeneration. With the increasing incidence of neurodegenerative disorders, such as Alzheimer\u2019s disease (AD), frontotemporal dementia (FTD), and Parkinson\u2019s disease (PD), non-invasive diagnostic tools are urgently needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Plasma samples were collected from 200 individuals, divided into three groups, including young (20\u201340\u202fyears), middle-aged (41\u201360\u202fyears), and elderly (&amp;gt; 60\u202fyears). Exosomes were isolated, followed by small RNA sequencing (sRNA-seq) to identify differentially expressed miRNAs, and differentially expressed miRNAs related to autophagy were validated using quantitative real-time PCR (qRT-PCR). Spearman correlation analysis was performed to assess the relationship between autophagy-related miRNAs and brain aging biomarkers. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nine autophagy-related miRNAs were identified and validated as significantly upregulated in plasma exosomal from elderly, including hsa-miR-2110, hsa-miR-18a-3p, hsa-miR-766-3p, hsa-miR-4446-3p, hsa-miR-4667-5p, hsa-miR-4433b-3p, hsa-miR-146a-5p, hsa-miR-423-5p, and novel_260. These miRNAs were validated by qRT-PCR. Correlation analysis showed that several of these miRNAs, such as hsa-miR-2110 and hsa-miR-766-3p, were strongly correlated with NfL (<jats:italic>r<\/jats:italic> =\u202f0.68, <jats:italic>p<\/jats:italic>\u202f=\u202f0.002), A\u03b242 (<jats:italic>r<\/jats:italic> =\u202f0.62, <jats:italic>p<\/jats:italic>\u202f=\u202f0.004), and p-Tau181 (<jats:italic>r<\/jats:italic>\u202f=\u202f0.55, <jats:italic>p<\/jats:italic>\u202f=\u202f0.008). ROC curve analysis showed that combining these miRNAs with NfL resulted in an area under the curve (AUC) of 0.92, outperforming NfL alone (AUC\u202f=\u202f0.85) and miRNAs alone (AUC\u202f=\u202f0.84). Further subgroup analysis revealed that multiple miRNAs, such as miR-2110, miR-4446-3p, and novel_260, achieved high AUCs (&amp;gt;0.83) in distinguishing middle-aged adults (41\u201360\u202fyears) from older adults (&amp;gt;60\u202fyears), supporting their potential utility for early detection of age-associated neurodegeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study identifies a set of autophagy-related miRNAs as promising biomarkers for brain aging. The combination of these miRNAs with traditional biomarkers offers a non-invasive and highly sensitive method for early detection of brain aging, providing significant potential to enhance diagnostic accuracy in neurodegenerative diseases.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnmol.2025.1588007","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T05:23:20Z","timestamp":1749187400000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Non-invasive biomarkers for brain aging: the role of autophagy-related microRNAs in plasma exosomes"],"prefix":"10.3389","volume":"18","author":[{"given":"Qian","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhikang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunshan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"134195","DOI":"10.1016\/j.ijbiomac.2024.134195","article-title":"Plasma-derived exosome miR-10a-5p promotes premature ovarian failure by target BDNF via the TrkB\/Akt\/mTOR signaling pathway","volume":"277","author":"Bao","year":"2024","journal-title":"Int. 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