The DOI matches its Crossref record; 204 of the 204 references it cites were found in a registry or an index.
Molecular Basis of Klotho: From Gene to Function in Aging
Open accessAbstract
The discovery of the Klotho (KL) gene, which was originally identified as a putative aging-suppressor gene, has generated tremendous interest and has advanced understanding of the aging process. In mice, the overexpression of the KL gene extends the life span, whereas mutations to the KL gene shorten the life span. The human KL gene encodes the α-Klotho protein, which is a multifunctional protein that regulates the metabolism of phosphate, calcium, and vitamin D. α-Klotho also may function as a hormone, although the α-Klotho receptor(s) has not been found. Point mutations of the KL gene in humans are associated with hypertension and kidney disease, which suggests that α-Klotho may be essential to the maintenance of normal renal function. Three α-Klotho protein types with potentially different functions have been identified: a full-length transmembrane α-Klotho, a truncated soluble α-Klotho, and a secreted α-Klotho. Recent evidence suggests that α-Klotho suppresses the insulin and Wnt signaling pathways, inhibits oxidative stress, and regulates phosphatase and calcium absorption. In this review, we provide an update on recent advances in the understanding of the molecular, genetic, biochemical, and physiological properties of the KL gene. Specifically, this review focuses on the structure of the KL gene and the factors that regulate KL gene transcription, the key sites in the regulation of α-Klotho enzyme activity, the α-Klotho signaling pathways, and the molecular mechanisms that underlie α-Klotho function. This current understanding of the molecular biology of the α-Klotho protein may offer new insights into its function and role in aging.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Down-Regulation of Na+/K+ATPase Activity by Human Parvovirus B19 Capsid Protein VP1
Almilaji, A., Szteyn, K., Fein, E., Pakladok, T., Munoz, C., Elvira, B., Towhid, S. T., Alesutan, I., Shumilina, E., Bock, C.-T., et al. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350083 · Cited by 8,675
Regulation of the Voltage Gated K+ Channel Kv1.3 by Recombinant Human Klotho Protein
Almilaji, A., Honisch, S., Liu, G., Elvira, B., Ajay, S. S., Hosseinzadeh, Z., Ahmed, M., Munoz, C., Sopjani, M., & Lang, F. (2014) · Kidney and Blood Pressure Research · doi:10.1159/000368472 · Cited by 5,592
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Physiological Roles of Mitochondrial Reactive Oxygen Species
Sena, L. A., & Chandel, N. S. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.09.025 · Cited by 2,632
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
Suppression of Aging in Mice by the Hormone Klotho
Kurosu, H., Yamamoto, M., Clark, J. D., Pastor, J. V., Nandi, A., Gurnani, P., McGuinness, O. P., Chikuda, H., Yamaguchi, M., Kawaguchi, H., et al. (2005) · Science · doi:10.1126/science.1112766 · Cited by 1,935
Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C. L., McDonald, J. G., Luo, G., Jones, S. A., Goodwin, B., Richardson, J. A., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.09.001 · Cited by 1,865
Klotho converts canonical FGF receptor into a specific receptor for FGF23
Urakawa, I., Yamazaki, Y., Shimada, T., Iijima, K., Hasegawa, H., Okawa, K., Fujita, T., Fukumoto, S., & Yamashita, T. (2006) · Nature · doi:10.1038/nature05315 · Cited by 1,850
Shimada, T., Kakitani, M., Yamazaki, Y., Hasegawa, H., Takeuchi, Y., Fujita, T., Fukumoto, S., Tomizuka, K., & Yamashita, T. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19081 · Cited by 1,596
Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23
White, K. E., Evans, W. E., O'Riordan, J. L. H., Speer, M. C., Econs, M. J., Lorenz-Depiereux, B., Grabowski, M., Meitinger, T., & Strom, T. M. (2000) · Nature Genetics · doi:10.1038/81664 · Cited by 1,528
Cited by
Renal Aging: Causes and Consequences
O’Sullivan, E. D., Hughes, J., & Ferenbach, D. A. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015121308 · Cited by 484
Exosome Determinants of Physiological Aging and Age-Related Neurodegenerative Diseases
D’Anca, M., Fenoglio, C., Serpente, M., Arosio, B., Cesari, M., Scarpini, E. A., & Galimberti, D. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00232 · Cited by 154
Klotho controls the brain-immune system interface in the choroid plexus
Zhu, L., Stein, L. R., Kim, D., Ho, K., Yu, G.-Q., Zhan, L., Larsson, T. E., & Mucke, L. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1808609115 · Cited by 148
Antiinflammatory Actions of Klotho: Implications for Therapy of Diabetic Nephropathy
Typiak, M., & Piwkowska, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020956 · Cited by 107
Differences in the immune-inflammatory profiles of unipolar and bipolar depression
Brunoni, A. R., Supasitthumrong, T., Teixeira, A. L., Vieira, E. L., Gattaz, W. F., Benseñor, I. M., Lotufo, P. A., Lafer, B., Berk, M., Carvalho, A. F., et al. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.10.037 · Cited by 94
Metadata
- Authors
- Xu, Y., & Sun, Z.
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2015-02-19
- Volume
- 36
- Issue
- 2
- Pages
- 174-193
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W2169020430
- Cited by
- 549
- References
- 204
- FWCI
- 23.94
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Molecular Basis of Klotho: From Gene to Function in Aging. https://app.cochat.ai/papers/10.1210/er.2013-1079
- The paper
- Xu, Y., & Sun, Z. (2015). Molecular Basis of Klotho: From Gene to Function in Aging. Endocrine Reviews. https://doi.org/10.1210/er.2013-1079
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
