ArticleNature aging2025
Paracrine FGF21 dynamically modulates mTOR signaling to regulate thymus function across the lifespan.
Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed.
- The Thymic Microenvironment Shapes Age-Related Qualitative Changes in the TCR Repertoire.Aging cell · 2026Article
- Impaired Chaperone-Mediated Autophagy Accelerates Intervertebral Disc Degeneration by Inducing MIDN Accumulation to Target TSC2 for Proteasomal Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- [Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Article
- AAV-mediated FGF21 gene therapy promotes health span extension by whole-body tissue-specific adaptations.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- A Multimodal Morphological and Immunohistochemical Analysis of the Human Thymus-Parathyroid Relationship.International journal of molecular sciences · 2026Article
- FGF21 induced by endoplasmic reticulum stress maintains medullary thymic epithelial cell function and central immune tolerance.Science advances · 2026Article
- GW9508-Induced Activation of GPR40 in Thymic Epithelial Cells: A Therapeutic Strategy to Delay Thymic Aging.Aging cell · 2026Article
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Immunosenescence and Vaccine Efficacy in Aging: Dynamic Interplay of Gut Microbiota and mTOR Signaling Pathways.Aging cell · 2026Review
- Age-related thymic involution: Mechanistic insights and rejuvenating approaches to restore immune function.Science advances · 2026Review
- Network-orchestrated regulation of thymic dysfunction and restoration.Frontiers in immunology · 2026Review
- Thymic regeneration and tumor immunotherapy.Frontiers in immunology · 2026Review
- Metabolic regulation of immunological aging.Nature aging · 2025Review
- FGF21 keeps the thymus young.Nature aging · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
Consequences of age-associated thymic atrophy include declining T-cell responsiveness to pathogens and vaccines and diminished T-cell self-tolerance. Cortical thymic epithelial cells (cTECs) are primary targets of thymic aging, and recent studies suggested that their maintenance requires mTOR signaling downstream of medullary TEC (mTEC)-derived growth factors. Here, to test this hypothesis, we generated a knock-in mouse model in which FGF21 and mCherry are expressed by most mTECs. We find that mTEC-derived FGF21 promotes temporally distinct patterns of mTORC1 and mTORC2 signaling in cTECs, promotes thymus and individual cTEC growth and maintenance, increases T-cell responsiveness to viral infection, and diminishes indicators of peripheral autoimmunity in older mice. The effects of FGF21 overexpression on thymus size and mTOR signaling were abrogated by treatment with the mTOR inhibitor rapamycin. These results reveal a mechanism by which paracrine FGF21 signaling regulates thymus size and function throughout the lifespan, as well as potential therapeutic targets for improving T-cell function and tolerance in aging.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.