ArticleAging2010
Klotho interferes with a novel FGF-signalling pathway and insulin/Igf-like signalling to improve longevity and stress resistance in Caenorhabditis elegans.
Article in Aging, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
63 citing papers in PubMed, 103 citations in OpenAlex.
- Aerobic Exercise Combined with Multisensory Stimulation Training Improves Cognitive Frailty by Modulating Circulating Klotho.International journal of molecular sciences · 2026Article
- Serum alpha klotho levels in Parkinson's Disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Anemia and Mineral Bone Disorder in Kidney Disease Patients: The Role of FGF-23 and Other Related Factors.International journal of molecular sciences · 2024Review
- KLOTHO KL-VS heterozygosity is associated with diminished age-related neuroinflammation, neurodegeneration, and synaptic dysfunction in older cognitively unimpaired adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Influence of Oleacein, an Olive Oil and Olive Mill Wastewater Phenolic Compound, onFoods (Basel, Switzerland) · 2024Article
- Non-Classical Effects of FGF23: Molecular and Clinical Features.International journal of molecular sciences · 2024Review
- A PAI-1 antagonist ameliorates hypophosphatemia in the Hyp vitamin D-resistant rickets model mouse.FEBS open bio · 2024Article
- Klotho increases antioxidant defenses in astrocytes and ubiquitin-proteasome activity in neurons.Scientific reports · 2023Article
- Cell Survival, Death, and Proliferation in Senescent and Cancer Cells: the Role of (Poly)phenols.Advances in nutrition (Bethesda, Md.) · 2023Review
- Platelet factors are induced by longevity factor klotho and enhance cognition in young and aging mice.Nature aging · 2023Article
- Article
- KL1 Domain of Longevity Factor Klotho Mimics the Metabolome of Cognitive Stimulation and Enhances Cognition in Young and Aging Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Klotho an Autophagy Stimulator as a Potential Therapeutic Target for Alzheimer's Disease: A Review.Biomedicines · 2022Review
- AD-associated CSF biomolecular changes are attenuated in KL-VS heterozygotes.Alzheimer's & dementia (Amsterdam, Netherlands) · 2022Article
- Upregulation of Klotho Aggravates Insulin Resistance in Gestational Diabetes Mellitus Trophoblast Cells.Genetics research · 2022Article
- The FGFR4 Homolog KIN-9 Regulates Lifespan and Stress Responses inFrontiers in aging · 2022Article
- Article
- Stress increases in exopher-mediated neuronal extrusion require lipid biosynthesis, FGF, and EGF RAS/MAPK signaling.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Loss of αklotho causes reduced motor ability and short lifespan in zebrafish.Scientific reports · 2021Article
- In search of alternatively spliced alpha-Klotho Kl1 protein in mouse brain.FASEB bioAdvances · 2021Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Klotho exerts anti-aging properties in mammals in two different ways. While membrane-bound Klotho, which is primarily expressed in the kidney, acts as an obligate co-receptor of FGF23 to regulate phosphate homeostasis, secreted Klotho, resulting from the shedding of the KL1-KL2 ectodomain into the bloodstream, inhibits Insulin/IGF1 signalling. However, the underlying molecular mechanisms are not fully understood. Here, we investigated the biological role of Klotho in Caenorhabditis elegans. Two redundant homologues of the klotho gene exist in C. elegans and encode predicted proteins homologous to the glucosidase-like KL1 domain of mammalian Klotho. We have used a genetic approach to investigate the functional activity of Klotho in C. elegans. Here, we report that whereas Klotho requires EGL-15 (FGFR) and EGL-17 to promote longevity and oxidative stress resistance, it is not involved in the regulation of fluid homeostasis, controlled by LET-756. Besides revealing a new post-developmental role for EGL-17, our data suggest that the KL1 form of Klotho is involved in FGF23-independent FGF signalling. We also report a genetic interaction between Klotho and the DAF-2 (Ins/IGF1R)/DAF-16 (FOXO) pathway. While the regulation of longevity requires functional DAF-2/DAF-16 signalling, the control of oxidative stress resistance involves a DAF-2- independent, DAF-16-dependent pathway, suggesting that Klotho may target either DAF-2 or DAF-16, depending of environmental conditions. Thus, the predictive KL1 form of Klotho appears to crosstalk with both FGF and Insulin/IGF1/FOXO pathways to exert anti-aging properties in C. elegans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.