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Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution
Open accessAbstract
Significance: Liver-derived metabolic hormone fibroblast growth factor 21 (FGF21) improves insulin sensitivity and extends lifespan in mice. Aging also compromises the adaptive immune system by reducing T-cell production from the thymus. In this paper, we describe a new immunological function of FGF21 as a regulator of T-cell production from thymus in aging. The overexpression of FGF21 prevents thymic lipoatrophy, which protects the mice from age-induced loss of naïve T cells. FGF21 expression in thymic epithelial cells and signaling in thymic stromal cells support thymic function in aging. Loss of FGF21 in mice increases lethality postirradiation and delays the reconstitution of thymus. Hence, we highlight FGF21 as an immunometabolic regulator that can be harnessed to delay immune senescence.
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“Our finding of an increase in FGF‐21 levels after 12 months of treatment suggests that thymic regeneration by the present treatment may be mediated in part by this cytokine (Youm, Horvath, Mangelsdorf, Kliewer, & Dixit, 2016), which we believe is a novel finding.”
From Reversal of epigenetic aging and immunosenescent trends in humans. (2019) · cites this paper as Youm, Horvath, Mangelsdorf, Kliewer, & Dixit, 2016
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“prolonged overexpression of FGF21 in mice increases insulin sensitivity and extends lifespan64,79.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [79]
In the citing paper
“The benefits of caloric restriction observed in humans have also been reported in other species, such as rats, mice, and monkeys (Colman et al, 2009;Richardson et al, 2015;Youm et al, 2016).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Youm et al, 2016
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Metadata
- Authors
- Youm, Y.-H., Horvath, T. L., Mangelsdorf, D. J., Kliewer, S. A., & Dixit, V. D.
- Affiliations
- Yale University (US)
- Section of Comparative Medicine and Program on Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, CT 06520;
- Howard Hughes Medical Institute (US)
- The University of Texas Southwestern Medical Center (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-01-11
- Volume
- 113
- Issue
- 4
- Pages
- 1026-1031
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4743827
- OpenAlex
- W2234368921
- Cited by
- 129
- References
- 48
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 16 · 2023: 10 · 2022: 7 · 2021: 12 · 2020: 12 · 2019: 10 · 2018: 8 · 2017: 14 · 2016: 12
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (R01AG043608, AG043608)
- National Institute of Allergy and Infectious Diseases (AI105097, R56AI105097, R01AI105097)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK067158, R01DK090556, DK090556)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- FGF21, thymic involution, immunosenescence, caloric restriction, β-Klotho, thymic epithelial cells, naive T cells, brown adipose tissue, T cell reconstitution, hematopoietic stem cell transplantation, thymus aging
- MeSH terms
- Immunosenescence, Aging, Animals, Fibroblast Growth Factors, Mice, Inbred C57BL, Receptors, Antigen, T-Cell, T-Lymphocytes, Thymus Gland, Mice
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