Systemic modulation of brain aging and plasticity: from gut microbiome to circulating factors

Participate in this topic

Submit your idea

You will be redirected to our submission process.

Submit your manuscript summarySubmit your manuscript

About this Research Topic

Submission deadlines

  1. Manuscript Summary Submission Deadline 31 March 2026 | Manuscript Submission Deadline 23 October 2026

  2. This Research Topic is currently accepting articles.

    1. Check author guidelines

Background

Systemic factors, including gut-derived metabolites, immune mediators, and blood‑borne factors, play essential roles in regulating key aspects of neural plasticity by modulating synaptic remodeling, neurogenesis, vascular dynamics, and glial function. Across lifespan, these peripheral systems (and their inputs) undergo substantial shift. Age-associated changes in the gut microbiome, immune network, and circulating environment significantly alter the brain’s adaptive capacity, contributing to decline in cognitive performance and circuit flexibility.

Rodent studies provide compelling evidence that multiple strategies such as heterochronic parabiosis, young-plasma administration, exercise and caloric restriction can restore specific features of youthful plasticity, supporting the concept of systemically driven brain rejuvenation. support the concept of systemic-driven brain plasticity restoration. Recent work also shows that systemic interventions such as gut microbiome depletion or enrichment, and administration of specific circulating proteins (e.g., GDF11, Klotho, PF4), can partially reverse aging-associated deficits. These effects appear to operate through glial modulation, neurogenesis, synaptic remodeling, and improved neurovascular function.

Growing attention highlights the role of extracellular vesicles as potent carriers of systemic signals able to influence brain function, alongside exercise-induced circulating factors and immune-modulatory cytokines, able to reactivate latent regenerative programs in the aging brain.

This Research Topic aims to advance mechanistic understanding of how systemic cues shape neural circuit dynamics in aging, identifying pathways that drive vulnerability or resilience, and determine how systemic manipulation can reopen windows of plasticity or enhance cognitive function later in life.

Contributions will explore how systemic interventions affect the aging brain’s capacity for repair. Functional outputs such as hippocampal neurogenesis, synaptic plasticity, and behavioral performance in learning and memory tasks will serve as key readouts. The integration of multi-omics approaches will be critical to map the molecular pathways through which systemic states alter neural circuit function and integrity. We welcome contributions that span from molecular mechanisms to system-level interpretations.

Topics of interest:

• Gut microbiome remodeling in aging and rejuvenation: Age-related microbial shifts and interventions (e.g., depletion, enrichment, fecal transfer) that modulate cognition and neuroplasticity.

• Immune cytokines and neural plasticity in aging: Role of systemic immune signals (e.g., IL-6, TNF-α) in modulating hippocampal neurogenesis and synaptic remodeling in aged brains.

• Circulating rejuvenating factors and their impact on brain function: effects of GDF11, Klotho, PF4 and other systemic proteins on excitability, neurogenesis, myelination, and cognitive performance in aged rodents.

• Mechanisms of brain accessibility and cellular targeting: understanding how systemic factors act on the brain, whether they cross the BBB, act through endothelial or perivascular pathways, signal via receptors on specific brain cell types (e.g., astrocytes, microglia, oligodendrocytes, neurons), or exert indirect effects via vascular, immune, or metabolic interfaces.

• Neurovascular integrity and inflammation-driven circuit breakdown: interactions between systemic inflammation, endothelial aging, BBB alterations, and circuit integrity. Extracellular vesicle-mediated communication across BBB: how exosomes and microvesicles transmit peripheral molecular signals across the BBB, impacting brain structure and function.

• Exercise-induced peripheral factors and brain plasticity: Identification and impact of systemic factors (e.g., irisin, BDNF precursors) released during exercise on neurogenesis and connectivity.

• Systemic drivers of glial cell aging and reactivity: how systemic factors drive aging-related changes in astrocytes and microglia, influencing brain repair and plasticity.

• Multi-omics dissection of brain–body crosstalk in aging: integrative metabolomics, transcriptomics, proteomics and epigenomic approaches to decode systemic regulators of neural aging.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

  • Brief Research Report
  • Data Report
  • Editorial
  • FAIR² Data
  • General Commentary
  • Hypothesis and Theory
  • Methods
  • Mini Review
  • Opinion

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

  • Brief Research Report
  • Data Report
  • Editorial
  • FAIR² Data
  • General Commentary
  • Hypothesis and Theory
  • Methods
  • Mini Review
  • Opinion
  • Original Research
  • Perspective
  • Review
  • Systematic Review
  • Technology and Code

Keywords: microbiome, gut, neural circuit, plasticity, aging, neuroinflammation, modulation, peripheral systems, neurogenesis

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Topic editors

Frequently asked questions

  • Frontiers' Research Topics are collaborative hubs built around an emerging theme.Defined, managed, and led by renowned researchers, they bring communities together around a shared area of interest to stimulate collaboration and innovation.

    Unlike section journals, which serve established specialty communities, Research Topics are pioneer hubs, responding to the evolving scientific landscape and catering to new communities.

  • The goal of Frontiers' publishing program is to empower research communities to actively steer the course of scientific publishing. Our program was implemented as a three-part unit with fixed field journals, flexible specialty sections, and dynamically emerging Research Topics, connecting communities of different sizes and maturity.

    Research Topics originate from the scientific community. Many of our Research Topics are suggested by existing editorial board members who have identified critical challenges or areas of interest in their field.

  • As an editor, Research Topics will help you build your journal, as well as your community, around emerging, cutting-edge research. As research trailblazers, Research Topics attract high-quality submissions from leading experts all over the world.

    A thriving Research Topic can potentially evolve into a new specialty section if there is sustained interest and a growing community around it.

  • Each Research Topic must be approved by the specialty chief editor, and it falls under the editorial oversight of our editorial boards, supported by our in-house research integrity team. The same standards and rigorous peer review processes apply to articles published as part of a Research Topic as for any other article we publish.

    In 2023, 80% of the Research Topics we published were edited or co-edited by our editorial board members, who are already familiar with their journal's scope, ethos, and publishing model. All other topics are guest edited by leaders in their field, each vetted and formally approved by the specialty chief editor.

  • Publishing your article within a Research Topic with other related articles increases its discoverability and visibility, which can lead to more views, downloads, and citations. Research Topics grow dynamically as more published articles are added, causing frequent revisiting, and further visibility.

    As Research Topics are multidisciplinary, they are cross-listed in several fields and section journals – increasing your reach even more and giving you the chance to expand your network and collaborate with researchers in different fields, all focusing on expanding knowledge around the same important topic.

    Our larger Research Topics are also converted into ebooks and receive social media promotion from our digital marketing team.

     

  • Frontiers offers multiple article types, but it will depend on the field and section journals in which the Research Topic will be featured. The available article types for a Research Topic will appear in the drop-down menu during the submission process.

    Check available article types here 

  • Yes, we would love to hear your ideas for a topic. Most of our Research Topics are community-led and suggested by researchers in the field. Our in-house editorial team will contact you to talk about your idea and whether you’d like to edit the topic. If you’re an early-stage researcher, we will offer you the opportunity to coordinate your topic, with the support of a senior researcher as the topic editor. 

    Suggest your topic here 

  • A team of guest editors (called topic editors) lead their Research Topic. This editorial team oversees the entire process, from the initial topic proposal to calls for participation, the peer review, and final publications.

    The team may also include topic coordinators, who help the topic editors send calls for participation, liaise with topic editors on abstracts, and support contributing authors. In some cases, they can also be assigned as reviewers.

  • As a topic editor (TE), you will take the lead on all editorial decisions for the Research Topic, starting with defining its scope. This allows you to curate research around a topic that interests you, bring together different perspectives from leading researchers across different fields and shape the future of your field. 

     

    You will choose your team of co-editors, curate a list of potential authors, send calls for participation and oversee the peer review process, accepting or recommending rejection for each manuscript submitted.

  • As a topic editor, you're supported at every stage by our in-house team. You will be assigned a single point of contact to help you on both editorial and technical matters. Your topic is managed through our user-friendly online platform, and the peer review process is supported by our industry-first AI review assistant (AIRA).

  • If you’re an early-stage researcher, we will offer you the opportunity to coordinate your topic, with the support of a senior researcher as the topic editor. This provides you with valuable editorial experience, improving your ability to critically evaluate research articles and enhancing your understanding of the quality standards and requirements for scientific publishing, as well as the opportunity to discover new research in your field, and expand your professional network.

  • Yes, certificates can be issued on request. We are happy to provide a certificate for your contribution to editing a successful Research Topic.

  • Research Topics thrive on collaboration and their multi-disciplinary approach around emerging, cutting-edge themes, attract leading researchers from all over the world.

  • As a topic editor, you can set the timeline for your Research Topic, and we will work with you at your pace. Typically, Research Topics are online and open for submissions within a few weeks and remain open for participation for 6 – 12 months. Individual articles within a Research Topic are published as soon as they are ready.

    Find out more about our Research Topics

  • Our fee support program ensures that all articles that pass peer review, including those published in Research Topics, can benefit from open access – regardless of the author's field or funding situation.

    Authors and institutions with insufficient funding can apply for a discount on their publishing fees. A fee support application form is available on our website.

  • In line with our mission to promote healthy lives on a healthy planet, we do not provide printed materials. All our articles and ebooks are available under a CC-BY license, so you can share and print copies.

     

Manuscripts can be submitted to this Research Topic via the main journal or any other participating journal.

Submit your idea

You will be redirected to our submission process.

Submit your manuscript summarySubmit your manuscript

Share on WeChat

Scan with WeChat to share this article