{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:42:17Z","timestamp":1784133737236,"version":"3.55.0"},"reference-count":128,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"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:p>Nutrition is increasingly recognized as a central determinant of brain health across the lifespan. Beyond their classical roles as energetic substrates, dietary components and their bioactive metabolites may act as signaling molecules capable of reshaping neuronal and glial phenotypes through integrated metabolic, epigenetic, and immunological mechanisms. Emerging evidence positions nutritional inputs as dynamic regulators of synaptic integrity, cellular bioenergetics, neurotransmission, neuroimmune interactions, and blood\u2013brain barrier function. These effects occur across multiple temporal and spatial scales, from acute modulation of neuronal excitability to long-term reprogramming of gene expression and chromatin landscapes. This mini-review integrates current molecular neuroscience perspectives to propose a systems-level framework in which nutritional signals act across interconnected regulatory layers linking peripheral metabolism with central nervous system homeostasis. We examine nutrient-sensing pathways that preserve proteostasis and synaptic resilience, as well as metabolic and membrane-associated processes that govern neuronal excitability, network stability, and mitochondrial quality control. Furthermore, we discuss how dietary modulation may influence glial activation states, neuroinflammatory cascades, and epigenetic remodeling, and how gut-derived metabolites contribute to these processes. Understanding nutrition as an active signaling network rather than a passive support system may offer novel opportunities for preventive and therapeutic intervention in neurodegenerative disorders such as Alzheimer\u2019s disease and Parkinson\u2019s disease, as well as in age-associated cognitive decline. We propose that targeted nutritional modulation represents a tractable strategy to reprogram brain aging trajectories toward enhanced resilience, functional plasticity, and long-term cognitive health.<\/jats:p>","DOI":"10.3389\/fnmol.2026.1825800","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T05:36:44Z","timestamp":1776749804000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Nutrition as a systems regulator of brain aging trajectories"],"prefix":"10.3389","volume":"19","author":[{"given":"Ludmila","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Max Planck Institute for Human Development, Center for Lifespan Psychology","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Di Benedetto","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Human Development, Center for Lifespan Psychology","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Human Development, Center for Lifespan Psychology","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3390\/medicina60010191","article-title":"Effect of calorie restriction and intermittent fasting regimens on brain-derived neurotrophic factor levels and cognitive function in humans: A systematic review.","volume":"60","author":"Alkurd","year":"2024","journal-title":"Medicina"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0165224","DOI":"10.1128\/msystems.01652-24","article-title":"Meta biome: A multiscale model integrating agent-based and metabolic networks to reveal spatial regulation in gut mucosal microbial communities.","volume":"10","author":"Aminian-Dehkordi","year":"2025","journal-title":"mSystems"},{"key":"B3","doi-asserted-by":"publisher","first-page":"102515","DOI":"10.1016\/j.arr.2024.102515","article-title":"Microglia and gut microbiota: A double-edged sword in Alzheimer\u2019s disease.","volume":"101","author":"Bano","year":"2024","journal-title":"Ageing Res. 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