ArticleeLife2021
The biphasic and age-dependent impact of klotho on hallmarks of aging and skeletal muscle function.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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
40 citing papers in PubMed, 48 citations in OpenAlex.
- A Biomimetic 3D Human Skeletal Muscle Microtissue for Modeling Biological and Functional Hallmarks of Aging.Small science · 2026Article
- Comprehensive transcriptomic profiling reveals impaired polyamine metabolism as a contributor to age-related muscle decline.iScience · 2026Article
- The Age-Dependent Resident Myonuclear Multi-Omic Response to an Acute Skeletal Muscle Hypertrophic Stimulus in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Research progress on blood therapy for anti-aging.Journal of advanced research · 2026Review
- Age-related transcriptional drift and physiological adaptation in long-living Ames dwarf skeletal muscle.NAR molecular medicine · 2026Article
- Antiaging Properties of the Klotho Protein.Cells · 2026Review
- Mechanisms of protein degradation in atrophying muscles: What have we learned during the past decade?The Journal of biological chemistry · 2026Review
- Unraveling the intersection of aging and Parkinson's disease: a collaborative roadmap for advancing research models.NPJ Parkinson's disease · 2026Review
- Astaxanthin improves myogenicity of aged skeletal muscle progenitor cells in a sexually dimorphic manner.npj aging · 2026Article
- Neg-entropy is the true drug target for chronic diseases.Acta pharmaceutica Sinica. B · 2026Review
- A novel information-theoretic approach reveals loss of effective biomolecular communication in aging muscle cells.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- The Age-Dependent Resident Myonuclear Multi-Omic Response to a Skeletal Muscle Hypertrophic Stimulus.bioRxiv : the preprint server for biology · 2025Article
- GDF11-secreting cell transplant efficiently ameliorates age-related pulmonary fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The impact of frailty syndrome on skeletal muscle histology: preventive effects of exercise.FEBS open bio · 2025Article
- Causal associations between epigenetic age and thromboembolism: a bi-directional two-sample Mendelian randomization study.Clinical epigenetics · 2025Article
- Long-term effects of s-KL treatment in wild-type mice: Enhancing longevity, physical well-being, and neurological resilience.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Oligonucleotide therapeutics in sports? An antidoping perspective.Archiv der Pharmazie · 2025Review
- Klotho Protein: A Multifaceted Guardian of Healthy Aging and Its Therapeutic Potential.International journal of nanomedicine · 2025Review
- Age-Related ECM Stiffness Mediates TRAIL Activation in Muscle Stem Cell Differentiation.Advanced biology · 2024Article
- Age-related histone H3.3 accumulation associates with a repressive chromatin in mouse tibialis anterior muscle.The journal of physiological sciences : JPS · 2024Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Aging is accompanied by disrupted information flow, resulting from accumulation of molecular mistakes. These mistakes ultimately give rise to debilitating disorders including skeletal muscle wasting, or sarcopenia. To derive a global metric of growing 'disorderliness' of aging muscle, we employed a statistical physics approach to estimate the state parameter, entropy, as a function of genes associated with hallmarks of aging. Escalating network entropy reached an inflection point at old age, while structural and functional alterations progressed into oldest-old age. To probe the potential for restoration of molecular 'order' and reversal of the sarcopenic phenotype, we systemically overexpressed the longevity protein, Klotho, via AAV. Klotho overexpression modulated genes representing all hallmarks of aging in old and oldest-old mice, but pathway enrichment revealed directions of changes were, for many genes, age-dependent. Functional improvements were also age-dependent. Klotho improved strength in old mice, but failed to induce benefits beyond the entropic tipping point.
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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.