ArticleAntioxidants (Basel, Switzerland)2023
The Anti-Aging Hormone Klotho Promotes Retinal Pigment Epithelium Cell Viability and Metabolism by Activating the AMPK/PGC-1α Pathway.
Article in Antioxidants (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Relationship of fibroblast growth factor 21, Klotho, and diabetic retinopathy: a meta-analysis.Frontiers in endocrinology · 2024Pooled it
- Serum Klotho Levels and Major Age-Related Ocular Disorders: A Cross-Sectional and Genetic Association Study.Translational vision science & technology · 2026Article
- Irisin and exercise activate renal anti-aging pathways and enhance survival in young mice: a translational insight into muscle-kidney crosstalk.European journal of translational myology · 2026Article
- Multi-omics analysis of the gut-liver axis revealed the effects of different exercise interventions in NAFLD mice.BMC microbiology · 2026Article
- Role and regulation of kinases in age-related macular degeneration.Journal of translational medicine · 2026Review
- Metformin inhibits subretinal fibrosis by activating Klotho by miR-126-5p.Cytotechnology · 2025Article
- Advances in the Study of Age-Related Macular Degeneration Based on Cell or Cell-Biomaterial Scaffolds.Bioengineering (Basel, Switzerland) · 2025Review
- Klotho attenuates epithelial‑mesenchymal transition of retinal pigment epithelial cells in subretinal fibrosis by suppressing the ERK1/2 and Wnt/β‑catenin signaling pathways.International journal of molecular medicine · 2025Article
- Klotho enhances stability of chronic kidney disease atherosclerotic plaques by inhibiting GRK2/PLC-β-mediated endoplasmic reticulum stress in macrophages via modulation of the ROS/SHP1 pathway.Scientific reports · 2024Article
- IGF-1 Signaling Modulates Oxidative Metabolism and Stress Resistance in ARPE-19 Cells Through PKM2 Function.International journal of molecular sciences · 2024Article
- AMP-dependent kinase stimulates the expression of αKlotho.FEBS open bio · 2024Article
- Telomere stabilization by metformin mitigates the progression of atherosclerosis via the AMPK-dependent p-PGC-1α pathway.Experimental & molecular medicine · 2024Article
- PGC-1α repression dysregulates lipid metabolism and induces lipid droplet accumulation in retinal pigment epithelium.Cell death & disease · 2024Article
- PGC-1α regulates the interplay between oxidative stress, senescence and autophagy in the ageing retina important in age-related macular degeneration.Journal of cellular and molecular medicine · 2024Article
- Serum α-Klotho and fibroblast growth factor 23 levels are not associated with non-proliferative diabetic retinopathy in type 1 diabetes mellitus.Scientific reports · 2024Article
- Sex-dependent regulation of retinal pigment epithelium and retinal function byFrontiers in cellular neuroscience · 2024Article
- Klotho: A new therapeutic target in diabetic retinopathy?World journal of diabetes · 2023Review
- Klotho's impact on diabetic nephropathy and its emerging connection to diabetic retinopathy.Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Initially discovered by Makuto Kuro-o in 1997, Klotho is a putative aging-suppressor gene when overexpressed and accelerates aging when deleted in mice. Previously, we showed that α-Klotho regulates retinal pigment epithelium (RPE) functions and protects against oxidative stress. However, the mechanisms by which Klotho influences RPE and retinal homeostasis remain elusive. Here, by performing a series of in vitro and in vivo experiments, we demonstrate that Klotho regulates cell viability under oxidative stress, mitochondrial gene expression and activity by inducing the phosphorylation of AMPK and p38MAPK, which in turn phosphorylate and activate CREB and ATF2, respectively, triggering PGC-1α transcription. The inhibition of Klotho in human RPE cells using CRISPR-Cas9 gene editing confirmed that a lack of Klotho negatively affects RPE functions, including mitochondrial activity and cell viability. Proteomic analyses showed that myelin sheath and mitochondrial-related proteins are downregulated in the RPE/retina of
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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.