{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:08:36Z","timestamp":1791896916539,"version":"4.3.4"},"reference-count":177,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T00:00:00Z","timestamp":1752278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Food and Drug Administration (MFDA)","award":["24192MFDS068"],"award-info":[{"award-number":["24192MFDS068"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Memory impairment, ranging from mild memory impairment to neurodegenerative diseases such as Alzheimer\u2019s disease, poses an escalating global health challenge that necessitates multi-targeted interventions to prevent progression. Health functional foods (HFFs), which include bioactive dietary compounds that not only provide basic nutrition but also function beyond that to modulate physiological pathways, offer a promising non-pharmacological strategy to preserve memory function. This review presents an integrative framework for the discovery, evaluation, and clinical translation of biomarkers responsive to HFFs in the context of preventing memory impairment. We examine both established clinical biomarkers, such as amyloid-\u03b2 and tau in the cerebrospinal fluid, neuroimaging indicators, and memory assessments, as well as emerging nutritionally sensitive markers including cytokines, microRNAs, gut microbiota signatures, epigenetic modifications, and neuroactive metabolites. By leveraging systems biology approaches, we explore how network pharmacology, gut\u2013brain axis modulation, and multi-omics integration can help to elucidate the complex interactions between HFF components and memory-related pathways such as neuroinflammation, oxidative stress, synaptic plasticity, and metabolic regulation. The review also addresses the translational pipeline for HFFs, from formulation and standardization to regulatory frameworks and clinical development, with an emphasis on precision nutrition strategies and cross-disciplinary integration. Ultimately, we propose a paradigm shift in memory health interventions, positioning HFFs as scientifically validated compounds for personalized nutrition within a preventative memory function framework.<\/jats:p>","DOI":"10.3390\/ijms26146698","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T10:55:41Z","timestamp":1752490541000},"page":"6698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A Systems Biology Approach to Memory Health: Integrating Network Pharmacology, Gut Microbiota, and Multi-Omics for Health Functional Foods"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8985-6576","authenticated-orcid":false,"given":"Heng","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5931-1477","authenticated-orcid":false,"given":"Junyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Advanced Clinical Medicine, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1600-9590","authenticated-orcid":false,"given":"Hongbao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suna","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Obesity\/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6092-8340","authenticated-orcid":false,"given":"Sunmin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Obesity\/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.5535\/arm.22027","article-title":"Dementia Epidemiology Fact Sheet 2022","volume":"46","author":"Shin","year":"2022","journal-title":"Ann. 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