ArticleNature communications2018
Age-related declines in α-Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
111 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.
- A systematic review and meta-analysis demonstrating Klotho as an emerging exerkine.Scientific reports · 2022Pooled it
- Exercise enhances aged chondrocyte health through microRNA-29-enriched extracellular vesicles.Nature aging · 2026Article
- Therapeutic Lithium Enhances Klotho Expression and Mitochondrial Size and Branching in Human Cardiac Fibroblasts Involving Nuclear Factor-kappa B Inhibition.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Article
- The Impact of Ageing on Skeletal Muscle: Roles of Mitochondrial Dysregulation, Systemic Communication, and Exercise.Journal of cellular physiology · 2026Review
- Hyperbranched poly(β-amino ester)s-mediated delivery of engineered Klotho mRNA rescues senescence and restores cellular homeostasis in aged and Klotho deficient iMSCs.Drug delivery and translational research · 2026Article
- Aerobic Exercise Combined with Multisensory Stimulation Training Improves Cognitive Frailty by Modulating Circulating Klotho.International journal of molecular sciences · 2026Article
- Research progress on blood therapy for anti-aging.Journal of advanced research · 2026Review
- Application Advances of Lentiviral Vectors: From Gene Therapy to Vaccine Development.Molecular biotechnology · 2026Review
- Aging induces sarcopenia by disrupting the crosstalk between the skeletal muscle microenvironment and myofibers.Journal of advanced research · 2026Review
- 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
- Modulation of PKCα/ETS1 by klotho restores CYB5R4-dependent mitochondrial function in proximal tubular epithelial cells to attenuate the progression of diabetic kidney disease.Cardiovascular diabetology · 2026Article
- Antiaging Properties of the Klotho Protein.Cells · 2026Review
- Efficacy of silicon-based agent against aging-related frailty.Scientific reports · 2026Article
- Astaxanthin improves myogenicity of aged skeletal muscle progenitor cells in a sexually dimorphic manner.npj aging · 2026Article
- Underexplored terrain: effects of high priority environmental toxicants on skeletal muscle.Journal of toxicology and environmental health. Part B, Critical reviews · 2026Review
- α-Klotho Supplementation Mitigates Cumulative Exercise-Induced Fatigue via Coordinated NRF2-Mediated Antioxidant Defense and AKT/GS-Driven Hepatic Glycogen Supercompensation in Mice.International journal of molecular sciences · 2025Article
- Regulation of stem cell aging and cellular proliferation by Klotho-Sirt1 pathways in heart, kidney and small intestine.npj aging · 2025Article
- Klotho Deficiency Promotes Skeletal Muscle Weakness and Is Associated with Impaired Motor Unit Connectivity.International journal of molecular sciences · 2025Article
- Transcriptomic Response to Neuromuscular Electrical Stimulation in Muscle, Brain, and Plasma EVs in WT and Klotho-Deficient Mice.International journal of molecular sciences · 2025Article
- A Reassessment of Sarcopenia from a Redox Perspective as a Basis for Preventive and Therapeutic Interventions.International journal of molecular sciences · 2025Review
51 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
While young muscle is capable of restoring the original architecture of damaged myofibers, aged muscle displays a markedly reduced regeneration. We show that expression of the "anti-aging" protein, α-Klotho, is up-regulated within young injured muscle as a result of transient Klotho promoter demethylation. However, epigenetic control of the Klotho promoter is lost with aging. Genetic inhibition of α-Klotho in vivo disrupted muscle progenitor cell (MPC) lineage progression and impaired myofiber regeneration, revealing a critical role for α-Klotho in the regenerative cascade. Genetic silencing of Klotho in young MPCs drove mitochondrial DNA (mtDNA) damage and decreased cellular bioenergetics. Conversely, supplementation with α-Klotho restored mtDNA integrity and bioenergetics of aged MPCs to youthful levels in vitro and enhanced functional regeneration of aged muscle in vivo in a temporally-dependent manner. These studies identify a role for α-Klotho in the regulation of MPC mitochondrial function and implicate α-Klotho declines as a driver of impaired muscle regeneration with age.
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What Socratic holds
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 Socratic graph.