Circulating levels of fibroblast growth factor-21 increase with age independently of body composition indices among healthy individuals
Open accessAbstract
BACKGROUND: Circulating FGF21 levels are commonly elevated in disease states. There is limited information regarding concentrations of circulating FGF21 in the absence of disease, as well as age-related differences in body composition that may contribute to FGF21 regulation across groups. OBJECTIVE: The objectives of this study were to assess FGF21 levels across age groups (childhood to elder adulthood), and investigate whether body composition indices are associated with age-related differences in circulating FGF21. MATERIALS AND METHODS: We cross-sectionally analyzed serum concentrations of FGF21 in 184 healthy subjects aged 5-80y (45% male). Multiple linear regression was performed to assess the independent association of categorical age (children: 5-12y, young adults: 20-29y, adults: 30-50y, older adults: 55-64y, elder adults: 65-80y) with FGF21 concentration taking into account DXA-measured body composition indices [bone mineral density (BMD) and percent lean, trunk, and fat mass]. We also stratified analysis by tertile of FGF21. RESULTS: <0.0001, controlling for percent lean, BMD, percent fat, and percent trunk fat, respectively). By FGF21 tertile, age group was associated with FGF21 in the lowest tertile only (β=13.1, 0.19, 0.18, all P≤0.01, accounting for percent lean, fat and trunk fat, respectively), but not when accounting for BMD. CONCLUSIONS: Our findings in a healthy population display an age-related increase in serum FGF21, highlighting a potential age effect in response to metabolic demand over the lifecourse. FGF21 levels increase with age independently of body composition. At lower levels of FGF21, BMD, but not other body composition parameters, attenuates the association between FGF21 level and age, suggesting the metabolic demand of the skeleton may provide a link between FGF21 and energy metabolism.
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Circulating levels of FGF21 increase with age in humans.
“circulating levels of FGF21 have been shown to increase with age in humans (Hanks et al., 2015).”
From Age-Associated Loss of OPA1 in Muscle Impacts Muscle Mass, Metabolic Homeostasis, Systemic Inflammation, and Epithelial Senescence (2017) · cites this paper as Hanks et al., 2015
A positive correlation of serum FGF21 levels and aging-sarcopenia has been found.
“In agreement, a positive correlation of serum FGF21 levels and aging‐sarcopenia has been found.18, 21”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [21]
Serum FGF21 levels positively correlate with aging sarcopenia.
“Indeed, serum FGF21 levels positively correlated with aging sarcopenia.18, 21”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [21]
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Cites
PPAR-γ agonists inhibit production of monocyte inflammatory cytokines
Jiang, C., Ting, A. T., & Seed, B. (1998) · Nature · doi:10.1038/34184 · Cited by 2,899 · see citing works
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 · see citing works
Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb
Jiang, J., & Struhl, G. (1998) · Nature · doi:10.1038/35154 · Cited by 1,735 · see citing works
Badman, 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 · see citing works
Zhang, X., Yeung, D. C. Y., Karpisek, M., Stejskal, D., Zhou, Z.-G., Liu, F., Wong, R. L. C., Chow, W.-S., Tso, A. W. K., Lam, K. S. L., et al. (2008) · Diabetes · doi:10.2337/db07-1476 · Cited by 908 · see citing works
Gälman, C., Lundåsen, T., Kharitonenkov, A., Bina, H. A., Eriksson, M., Hafström, I., Dahlin, M., Åmark, P., Angelin, B., & Rudling, M. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.06.014 · Cited by 512 · see citing works
Byard, R. W. (2010) · doi:10.1017/cbo9780511777783.021 · Cited by 498 · see citing works
Wente, W., Efanov, A. M., Brenner, M. B., Kharitonenkov, A., Koster, A. M., Sandusky, G. E., Sewing, S., Treinies, I., Zitzer, H., & Gromada, J. (2006) · Diabetes · doi:10.2337/db05-1435 · Cited by 497 · see citing works
The starvation hormone, fibroblast growth factor-21, extends lifespan in mice
Zhang, Y., Xie, Y., Berglund, E. D., Coate, K. C., He, T. T., Katafuchi, T., Xiao, G., Potthoff, M. J., Wei, W., Wan, Y., et al. (2012) · eLife · doi:10.7554/elife.00065 · Cited by 420 · see citing works
FGF21 is an Akt‐regulated myokine
Izumiya, Y., Bina, H. A., Ouchi, N., Akasaki, Y., Kharitonenkov, A., & Walsh, K. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.10.021 · Cited by 415 · see citing works
Marrow Fat and the Bone Microenvironment: Developmental, Functional, and Pathological Implications
Rosen, C. J., Ackert‐Bicknell, C. L., Rodriguez, J. P., & Pino, A. M. (2009) · Critical Reviews in Eukaryotic Gene Expression · doi:10.1615/critreveukargeneexpr.v19.i2.20 · Cited by 353 · see citing works
Corton, J. C., Anderson, S. P., & Stauber, A. J. (2000) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.40.1.491 · Cited by 341 · see citing works
Keipert, S., Ost, M., Johann, K., Imber, F., Jastroch, M., van Schothorst, E. M., Keijer, J., & Klaus, S. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00330.2013 · Cited by 221 · cited 1× · see citing works
“More recently, skeletal muscle expression and secretion of FGF21 have been shown to lead to a fivefold increase in circulating FGF21 concentration [9].”
BackgroundExercise dosing to retain resistance training adaptations in young and older adults
BICKEL, C. S., CROSS, J. M., & BAMMAN, M. M. (2011) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e318207c15d · Cited by 203 · see citing works
Self-citationFGF21 as a Hepatokine, Adipokine, and Myokine in Metabolism and Diseases
Itoh, N. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00107 · Cited by 198 · see citing works
Fibroblast Growth Factor-21 Is Induced in Human Skeletal Muscles by Hyperinsulinemia
Hojman, P., Pedersen, M., Nielsen, A. R., Krogh-Madsen, R., Yfanti, C., Åkerstrom, T., Nielsen, S., & Pedersen, B. K. (2009) · Diabetes · doi:10.2337/db09-0713 · Cited by 198 · see citing works
Molecular determinants of FGF‐21 activity—synergy and cross‐talk with PPARγ signaling
Moyers, J. S., Shiyanova, T. L., Mehrbod, F., Dunbar, J. D., Noblitt, T. W., Otto, K. A., Reifel-Miller, A. E., & Kharitonenkov, A. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20847 · Cited by 193 · see citing works
Chen, W.-W., Li, L., Yang, G.-Y., Li, K., Qi, X.-Y., Zhu, W., Tang, Y., Liu, H., & Boden, G. (2007) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2007-985148 · Cited by 186 · see citing works
Heightened muscle inflammation susceptibility may impair regenerative capacity in aging humans
Merritt, E. K., Stec, M. J., Thalacker-Mercer, A., Windham, S. T., Cross, J. M., Shelley, D. P., Craig Tuggle, S., Kosek, D. J., Kim, J.-S., & Bamman, M. M. (2013) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00019.2013 · Cited by 127 · see citing works
Self-citationStressed Liver and Muscle Call on Adipocytes with FGF21
Luo, Y., & McKeehan, W. L. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00194 · Cited by 75 · see citing works
Semba, R. D., Sun, K., Egan, J. M., Crasto, C., Carlson, O. D., & Ferrucci, L. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2823 · Cited by 70 · see citing works
Association between serum fibroblast growth factor 21 and diabetic nephropathy
Jian, W., Peng, W., Jin, J., Chen, X., Fang, W., Wang, W., Li, Q., Dong, Y., & Su, Q. (2011) · Metabolism · doi:10.1016/j.metabol.2011.10.012 · Cited by 57 · see citing works
Gijsen, H. S., Hough, F. S., & Ferris, W. F. (2013) · Bone · doi:10.1016/j.bone.2013.06.016 · Cited by 49 · see citing works
Bone and the regulation of global energy balance
Zhang, Q., Riddle, R. C., & Clemens, T. L. (2015) · Journal of Internal Medicine · doi:10.1111/joim.12348 · Cited by 48 · see citing works
Newton, A. L., Hanks, L. J., Davis, M., & Casazza, K. (2013) · BoneKEy Reports · doi:10.1038/bonekey.2013.49 · Cited by 45 · see citing works
Self-citationCasazza, K., Hanks, L. J., Hidalgo, B., Hu, H., & Affuso, O. (2011) · Bone · doi:10.1016/j.bone.2011.08.032 · Cited by 41 · see citing works
Self-citationTaniguchi, H., Tanisawa, K., Sun, X., Cao, Z., Oshima, S., Ise, R., Sakamoto, S., & Higuchi, M. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1877 · Cited by 40 · see citing works
Guasti, L., Silvennoinen, S., Bulstrode, N., Ferretti, P., Sankilampi, U., & Dunkel, L. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1566 · Cited by 38 · see citing works
Bisgaard, A., Sørensen, K., Johannsen, T. H., Helge, J. W., Andersson, A., & Juul, A. (2014) · International Journal of Pediatric Endocrinology · doi:10.1186/1687-9856-2014-7 · Cited by 34 · see citing works
Hanks, L. J., Casazza, K., Ashraf, A. P., Wallace, S. B., & Gutiérrez, O. M. (2014) · Clinical Endocrinology · doi:10.1111/cen.12552 · Cited by 25 · see citing works
Self-citationHanks, L. J., Newton, A. L., & Casazza, K. (2013) · PubMed · Cited by 7 · see citing works
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Tezze, C., Romanello, V., Desbats, M. A., Fadini, G. P., Albiero, M., Favaro, G., Ciciliot, S., Soriano, M. E., Morbidoni, V., Cerqua, C., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.04.021 · Cited by 568 · see citing works
“, 2011), and circulating levels of FGF21 have been shown to increase with age in humans (Hanks et al., 2015).”
Fibroblast growth factor 21 controls mitophagy and muscle mass
Oost, L. J., Kustermann, M., Armani, A., Blaauw, B., & Romanello, V. (2019) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12409 · Cited by 231 · see citing works
Human Aging and Longevity Are Characterized by High Levels of Mitokines
Conte, M., Ostan, R., Fabbri, C., Santoro, A., Guidarelli, G., Vitale, G., Mari, D., Sevini, F., Capri, M., Sandri, M., et al. (2019) · The Journals of Gerontology: Series A · doi:10.1093/gerona/gly153 · Cited by 219 · see citing works
The Bone Marrow-Derived Stromal Cells: Commitment and Regulation of Adipogenesis
Tencerova, M., & Kassem, M. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00127 · Cited by 149 · see citing works
Regulation of longevity by FGF21: interaction between energy metabolism and stress responses
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.05.004 · Cited by 121 · see citing works
The Interplay between Mitochondrial Morphology and Myomitokines in Aging Sarcopenia
Romanello, V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010091 · Cited by 101 · see citing works
Effect of Various Exercise Regimens on Selected Exercise-Induced Cytokines in Healthy People
Domin, R., Dadej, D., Pytka, M., Zybek-Kocik, A., Ruchała, M., & Guzik, P. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18031261 · Cited by 79 · see citing works
Association between serum FGF21 level and sarcopenia in older adults
Jung, H.-W., Park, J. H., Kim, D. A., Jang, I.-Y., Park, S. J., Lee, J. Y., Lee, S., Kim, J. H., Yi, H.-S., Lee, E., et al. (2021) · Bone · doi:10.1016/j.bone.2021.115877 · Cited by 55 · see citing works
Age-related bone loss is associated with FGF21 but not IGFBP1 in healthy adults
Lee, S. Y., Fam, K. D., Chia, K. L., Yap, M. M. C., Goh, J., Yeo, K. P., Yap, E. P. H., Chotirmall, S. H., & Lim, C. L. (2020) · Experimental Physiology · doi:10.1113/ep088351 · Cited by 24 · see citing works
- Authors
- Hanks, L. J., Gutiérrez, O. M., Bamman, M. M., Ashraf, A., McCormick, K. L., & Casazza, K.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Hanks, Lynae J.
- Venue
- Journal of Clinical & Translational Endocrinology
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 2
- Issue
- 2
- Pages
- 77-82
- ISSN
- 2214-6237 (ISSN-L)
- PMC
- PMC4450097
- OpenAlex
- W1969937968
- Cited by
- 104
- References
- 31
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 7 · 2023: 13 · 2022: 12 · 2021: 15 · 2020: 12 · 2019: 10 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 1
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical & Translational Endocrinology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Veterans Affairs
- University of Alabama at Birmingham
- National Institutes of Health (UL1TR000165, UL1TR001417)
- Center for Exercise Medicine, University of Alabama at Birmingham
- National Institute on Aging (R01AG017896)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK079337, T32DK007545, R03DK095005, R00DK083333, P30DK079626)
- National Institute of Neurological Disorders and Stroke (R01NS080850)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Keywords
- FGF21, age-related changes, body composition, bone mineral density, lean body mass, fat mass, trunk fat, healthy adults, energy metabolism
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