The DOI matches its Crossref record; 263 of the 264 references it cites were found in a registry or an index.
Regulation of longevity by FGF21: Interaction between energy metabolism and stress responses
Abstract
Fibroblast growth factor 21 (FGF21) is a hormone-like member of FGF family which controls metabolic multiorgan crosstalk enhancing energy expenditure through glucose and lipid metabolism. In addition, FGF21 acts as a stress hormone induced by endoplasmic reticulum stress and dysfunctions of mitochondria and autophagy in several tissues. FGF21 also controls stress responses and metabolism by modulating the functions of somatotropic axis and hypothalamic-pituitary-adrenal (HPA) pathway. FGF21 is a potent longevity factor coordinating interactions between energy metabolism and stress responses. Recent studies have revealed that FGF21 treatment can alleviate many age-related metabolic disorders, e.g. atherosclerosis, obesity, type 2 diabetes, and some cardiovascular diseases. In addition, transgenic mice overexpressing FGF21 have an extended lifespan. However, chronic metabolic and stress-related disorders involving inflammatory responses can provoke FGF21 resistance and thus disturb healthy aging process. First, we will describe the role of FGF21 in interorgan energy metabolism and explain how its functions as a stress hormone can improve healthspan. Next, we will examine both the induction of FGF21 expression via the integrated stress response and the molecular mechanism through which FGF21 enhances healthy aging. Finally, we postulate that FGF21 resistance, similarly to insulin resistance, jeopardizes human healthspan and accelerates the aging process.
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“Several findings demonstrate that the overexpression of FGF21 improves healthspan”
From Human Aging and Longevity Are Characterized by High Levels of Mitokines (2019) · cites this paper as [16]
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Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873
Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., et al. (2002) · Nature Medicine · doi:10.1038/nm788 · Cited by 4,238
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359
Obesity and insulin resistance
Kahn, B. B., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10842 · Cited by 3,345
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300
Extending Healthy Life Span—From Yeast to Humans
Fontana, L., Partridge, L., & Longo, V. D. (2010) · Science · doi:10.1126/science.1172539 · Cited by 3,023
The AMPK signalling pathway coordinates cell growth, autophagy and metabolism
Mihaylova, M. M., & Shaw, R. J. (2011) · Nature Cell Biology · doi:10.1038/ncb2329 · Cited by 2,923
The integrated stress response
Pakos‐Zebrucka, K., Koryga, I., Mnich, K., Ljujic, M., Samali, A., & Gorman, A. M. (2016) · The EMBO Reports · doi:10.15252/embr.201642195 · Cited by 2,659
Brown and beige fat: Development, function and therapeutic potential
Harms, M., & Seale, P. (2013) · Nature Medicine · doi:10.1038/nm.3361 · Cited by 2,328
Rubinsztein, D. C., Mariño, G., & Kroemer, G. (2011) · Cell · doi:10.1016/j.cell.2011.07.030 · Cited by 2,107
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Items 101–121 of 121
Gu, L., Jia, C., Sheng, Z., Jiang, W. L., Xu, Z. W., Li, W., Cui, J. Y., & Zhang, H. (2024) · Cardiology Research · doi:10.14740/cr1705 · Cited by 2
Tao, N., He, Z., Duan, H., Wang, L., Yi, J., Shao, J., Lv, L., Duan, J., Cao, H., Dong, X., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1562321 · Cited by 1
Xie, X., Wang, H., Xiao, F., Jiang, X., Chen, Y., Huang, C., Tang, D., Wang, Y., Rui, S., Cheng, X., et al. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1638343 · Cited by 1
Jiao, Y., Sun, B., Lu, M., Hao, J., Guan, X., Ma, J., Li, C., & Lin, L. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117511 · Cited by 1
Gene therapy for aging: Current evidence and future directions
Zhang, Y. C., Gan, L., Wang, S., & Zhang, J. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103144 · Cited by 1
Wali, J. A., Ramos-Nieves, J. M., Binia, A., & van der Beek, E. M. (2026) · Advances in Nutrition · doi:10.1016/j.advnut.2026.100713 · Cited by 1
Biagi, F., Carlomagno, F., Carbone, M. I., Veralli, R., Gentilucci, U. V., Riva, E., Manfrini, S., Tuccinardi, D., Santis, A. D., Gnessi, L., et al. (2023) · Metabolites · doi:10.3390/metabo13111119 · Cited by 1
Liu, S.-Y., Chen, L.-K., Li, P.-H., Wu, G.-L., Wu, T.-C., Yu, Y., Lin, H., & Juan, C. (2025) · Scientific Reports · doi:10.1038/s41598-025-96249-3 · Cited by 1
Pasiyeshvili, L. M., & Ivanova, K. (2018) · Ukraïnsʹkij žurnal medicini bìologìï ta sportu · doi:10.26693/jmbs03.04.110
Microglia-derived FGF21 as a modulator of astrocytic phenotype and cerebral ischemia injuryPreprint
Liu, F., Wang, D., Zhu, L., Du, J., Lin, P., Liang, F., Wang, X. B., Tan, X., & Lin, L. (2020) · doi:10.21203/rs.3.rs-15781/v1
Puigoriol Illamola, D., Vázquez Cruz, S., Griñán Ferré, C., & Llibería, M. P. I. (2021) · The Neuroscience Chronicles · doi:10.46439/neuroscience.2.007
FGF21 inhibited NETs formation induced by myocardial I/R injury via AMPKPreprint
Gu, L., Jia, C., Sheng, Z., Jiang, W., Xu, Z., Li, W., & Zhang, H. (2024) · Research Square · doi:10.21203/rs.3.rs-4111215/v1
Dallaire‐Théroux, C., Denis, H. L., Cottez, R. J., Tremblay, C., Provencher, A., Valentin‐Escalera, J., Leclerc, M., Loiselle, A., Tournissac, M., Potvin, O., et al. (2025) · medRxiv · doi:10.1101/2025.11.26.25340689
Wang, R., Wang, J., Zhang, Z., Ma, B., Sun, S., Gao, L., & Gao, G. (2024) · Figshare · doi:10.6084/m9.figshare.26649426
Wang, R., Wang, J., Zhang, Z., Ma, B., Sun, S., Gao, L., & Gao, G. (2024) · Figshare · doi:10.6084/m9.figshare.26649429
Wang, R., Wang, J., Zhang, Z., Ma, B., Sun, S., Gao, L., & Gao, G. (2024) · Figshare · doi:10.6084/m9.figshare.26649432
Jiang, X., Guan, Y., Chen, C., & wu, X. (2026) · Medicine · doi:10.1097/md.0000000000048141
Liu, C., Zhang, Q., & Zhang, Y. (2026) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-026-05617-8
Weyrich, M., Ware, A. P., Steixner-Kumar, A. A., Windschmitt, J., Sarakpi, T., Abplanalp, W. T., Dimmeler, S., Speer, T., & Zeiher, A. M. (2026) · medRxiv · doi:10.64898/2026.08.29.26361722
Deng, X., Shen, Y., Sun, Y. H., Lu, L., & Sun, C. (2026) · MedComm · doi:10.1002/mco2.70976
Matsui, M., Saito, C., Maeda, S., Kuro‐o, M., Yamagata, K., & Kosaki, K. (2026) · Hormone and Metabolic Research · doi:10.1055/a-2961-7220
Metadata
- Authors
- Salminen, A., Kaarniranta, K., & Kauppinen, A.
- Affiliations
- University of Eastern Finland (FI)
- Corresponding author
- Salminen, Antero
- Venue
- Ageing Research Reviews
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 37
- Pages
- 79-93
- ISSN
- 1568-1637 (ISSN-L)
- OpenAlex
- W2617193312
- Cited by
- 121
- References
- 264
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 16 · 2023: 11 · 2022: 20 · 2021: 15 · 2020: 13 · 2019: 12 · 2018: 10 · 2017: 1
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Ageing Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Academy of Finland (AK297267, AK307341, KK296840)
- Kuopio University Hospital (KK5503743)
- Emil Aaltonen Foundation
- Finnish Cultural Foundation
- Finnish Eye Foundation
- Topics
- 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
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- FGF21, longevity, healthy aging, energy metabolism, stress response, integrated stress response, endoplasmic reticulum stress, mitochondrial dysfunction, autophagy, hypothalamic-pituitary-adrenal axis, somatotropic axis, FGF21 resistance, lifespan extension, transgenic mice
- MeSH terms
- Animals, Chronic Disease, Diabetes Mellitus, Type 2, Energy Metabolism, Fibroblast Growth Factors, Glucose, Humans, Insulin Resistance, Longevity, Metabolic Diseases, Mitochondria, Obesity, Stress, Physiological, Lipid Metabolism, Endoplasmic Reticulum Stress
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