ArticleProceedings of the National Academy of Sciences of the United States of America2016
Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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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.
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Who cites it
80 citing papers in PubMed, 125 citations in OpenAlex.
- Fibroblast growth factor 21 as a circulating biomarker at various stages of colorectal carcinogenesis.British journal of cancer · 2018Trial
- Steatotic Liver Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Case Series and Literature Review.Hematology reports · 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
- Exoproteome of calorie-restricted humans identifies complement deactivation as an immunometabolic checkpoint reducing inflammaging.Nature aging · 2026Article
- Article
- Immunometabolic resistors of aging in long-lived golden spiny mice.Science advances · 2026Article
- Age-related thymic involution: Mechanistic insights and rejuvenating approaches to restore immune function.Science advances · 2026Review
- Kaempferol alleviates T-cell immunosenescence and inflammaging in aged mice via the SIRT3-LKB1-AMPK-mitophagy pathway.Immunity & ageing : I & A · 2026Article
- Thymic regeneration and tumor immunotherapy.Frontiers in immunology · 2026Review
- Network-orchestrated regulation of thymic dysfunction and restoration.Frontiers in immunology · 2026Review
- Immunosenescence and organoids: pathophysiology and therapeutic opportunities.Immunity & ageing : I & A · 2025Review
- Cytoskeleton proteins, the structural basis of T-lymphocyte and TEC restructure during rapid thymus regeneration.Histology and histopathology · 2025Review
- Metabolic regulation of immunological aging.Nature aging · 2025Review
- Enhancing thymic function improves T-cell reconstitution and immune responses in aged mice.PLoS biology · 2025Article
- FGF21 promotes longevity in diet-induced obesity through metabolic benefits independent of growth suppression.Cell metabolism · 2025Article
- Burning Down the House: Thymic Repair and Regeneration After Acute Damage.Immunological reviews · 2025Review
- Endogenous thymic regeneration: restoring T cell production following injury.Nature reviews. Immunology · 2025Review
- Paracrine FGF21 dynamically modulates mTOR signaling to regulate thymus function across the lifespan.Nature aging · 2025Article
- FGF21 keeps the thymus young.Nature aging · 2025Article
- The cyclic metabolic switching theory of intermittent fasting.Nature metabolism · 2025Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Age-related thymic degeneration is associated with loss of naïve T cells, restriction of peripheral T-cell diversity, and reduced healthspan due to lower immune competence. The mechanistic basis of age-related thymic demise is unclear, but prior evidence suggests that caloric restriction (CR) can slow thymic aging by maintaining thymic epithelial cell integrity and reducing the generation of intrathymic lipid. Here we show that the prolongevity ketogenic hormone fibroblast growth factor 21 (FGF21), a member of the endocrine FGF subfamily, is expressed in thymic stromal cells along with FGF receptors and its obligate coreceptor, βKlotho. We found that FGF21 expression in thymus declines with age and is induced by CR. Genetic gain of FGF21 function in mice protects against age-related thymic involution with an increase in earliest thymocyte progenitors and cortical thymic epithelial cells. Importantly, FGF21 overexpression reduced intrathymic lipid, increased perithymic brown adipose tissue, and elevated thymic T-cell export and naïve T-cell frequencies in old mice. Conversely, loss of FGF21 function in middle-aged mice accelerated thymic aging, increased lethality, and delayed T-cell reconstitution postirradiation and hematopoietic stem cell transplantation (HSCT). Collectively, FGF21 integrates metabolic and immune systems to prevent thymic injury and may aid in the reestablishment of a diverse T-cell repertoire in cancer patients following HSCT.
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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.