The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
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]
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“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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Citations
Cites
Guide for the Care and Use of Laboratory Animals: Eighth Edition
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The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance
Vandanmagsar, B., Youm, Y.-H., Ravussin, A., Galgani, J. E., Stadler, K., Mynatt, R. L., Ravussin, E., Stephens, J. M., & Dixit, V. D. (2011) · Nature Medicine · doi:10.1038/nm.2279 · Cited by 2,655
Self-citationProjection of an Immunological Self Shadow Within the Thymus by the Aire Protein
Anderson, M. S., Venanzi, E. S., Klein, L., Chen, Z.-B., Berzins, S., Turley, S., von Boehmer, H., Bronson, R., Dierich, A., Benoist, C., et al. (2002) · Science · doi:10.1126/science.1075958 · Cited by 2,582
FGF-21 as a novel metabolic regulator
Kharitonenkov, A., Shiyanova, T. L., Koester, A., Ford, A. M., Micanovic, R., Galbreath, E. J., Sandusky, G. E., Hammond, L. J., Moyers, J. S., Owens, R. A., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23606 · Cited by 2,125
Changes in thymic function with age and during the treatment of HIV infection
Douek, D. C., McFarland, R. D., Keiser, P. H., Gage, E. A., Massey, J. M., Haynes, B. F., Polis, M. A., Haase, A. T., Feinberg, M. B., Sullivan#, J. L., et al. (1998) · Nature · doi:10.1038/25374 · Cited by 1,893
Inagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.003 · Cited by 1,504
Self-citationBadman, M. K., Pissios, P., Kennedy, A. R., Koukos, G., Flier, J. S., & Maratos-Flier, E. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.002 · Cited by 1,495
FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis
Fisher, F. M., Kleiner, S., Douris, N., Fox, E. C., Mepani, R. J., Verdeguer, F., Wu, J., Kharitonenkov, A., Flier, J. S., Maratos-Flier, E., et al. (2012) · Genes & Development · doi:10.1101/gad.177857.111 · Cited by 1,478 · cited 1×
“These data agree with the prior finding that FGF21 causes browning of white adipose tissue (30).”
ResultIdentification of a novel FGF, FGF-21, preferentially expressed in the liver
Nishimura, T., Nakatake, Y., Konishi, M., & Itoh, N. (2000) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(00)00067-1 · Cited by 847
Understanding immunosenescence to improve responses to vaccines
Goronzy, J. J., & Weyand, C. M. (2013) · Nature Immunology · doi:10.1038/ni.2588 · Cited by 827 · cited 1×
“Given that decline in T-cell diversity is one of the major mechanisms that contributes to immune senescence and reduced immune surveillance in aging (33, 34), we next investigated the impact of FGF21 on peripheral T-cell diversity in middle-aged mice.”
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Cited by
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Kalinkovich, A., & Livshits, G. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.008 · Cited by 882
Mittelbrunn, M., & Kroemer, G. (2021) · Nature Immunology · doi:10.1038/s41590-021-00927-z · Cited by 702
Reversal of epigenetic aging and immunosenescent trends in humans.
Fahy, G. M., Brooke, R. T., Watson, J. P., Good, Z., Vasanawala, S. S., Maecker, H., Leipold, M. D., Lin, D. T. S., Kobor, M. S., & Horvath, S. (2019) · Aging Cell · doi:10.1111/acel.13028 · Cited by 477
Microglia Priming with Aging and Stress
Niraula, A., Sheridan, J. F., & Godbout, J. P. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.185 · Cited by 398
Thymic involution and rising disease incidence with age
Palmer, S., Albergante, L., Blackburn, C. C., & Newman, T. J. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1714478115 · Cited by 364
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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