ArticleAging2010
The ASK1-Signalosome regulates p38 MAPK activity in response to levels of endogenous oxidative stress in the Klotho mouse models of aging.
Article in Aging, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 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
78 citing papers in PubMed, 115 citations in OpenAlex.
- p16 Beyond Senescence: Cancer Biology Lessons Applied to Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- The NF-κB Signalling Pathway: Mechanisms, Consequences and Therapeutic Targets.Journal of cellular and molecular medicine · 2026Review
- Efficacy of silicon-based agent against aging-related frailty.Scientific reports · 2026Article
- Thioredoxin-Binding protein 2 and apoptosis Signal-Regulating kinase 1: redox stress sensors and therapeutic targets in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- GPCR systems coordinate cellular resilience against aging-associated stress.Frontiers in molecular biosciences · 2026Review
- The controversial role of senescence-associated secretory phenotype (SASP) in cancer therapy.Molecular cancer · 2025Review
- Klotho in age-related cardiovascular diseases: Insights into mitochondrial dysfunction and cell death.International journal of cardiology. Heart & vasculature · 2025Review
- Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases.Molecular biomedicine · 2025Review
- Association of acrylamide exposure with markers of systemic inflammation and serum alpha-klotho concentrations in middle-late adulthood.Frontiers in public health · 2025Article
- Article
- The Role and Mechanism of Vascular Aging in Geriatric Vascular Diseases.Aging and disease · 2024Review
- The Senescent Heart-"Age Doth Wither Its Infinite Variety".International journal of molecular sciences · 2024Review
- Soluble Klotho, a Potential Biomarker of Chronic Kidney Disease-Mineral Bone Disorders Involved in Healthy Ageing: Lights and Shadows.International journal of molecular sciences · 2024Review
- Early aging and premature vascular aging in chronic kidney disease.Clinical kidney journal · 2023Review
- The Importance of α-Klotho in Depression and Cognitive Impairment and Its Connection to Glutamate Neurotransmission-An Up-to-Date Review.International journal of molecular sciences · 2023Review
- Elucidating the molecular mechanisms underlying the induction of autophagy by antidepressant-like substances in C57BL/6J mouse testis model upon LPS challenge.Cell communication and signaling : CCS · 2023Article
- Klotho, Oxidative Stress, and Mitochondrial Damage in Kidney Disease.Antioxidants (Basel, Switzerland) · 2023Review
- The role of neutrophils in chorioamnionitis.Frontiers in immunology · 2023Review
- Association between perfluoroalkyl and polyfluoroalkyl internal exposure and serum α-Klotho levels in middle-old aged participants.Frontiers in public health · 2023Article
- Stress signaler p38 mitogen-activated kinase activation: a cause for concern?Clinical science (London, England : 1979) · 2022Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Reactive oxygen species (ROS) and elevated levels of p38 MAPK activity accelerate physiological aging. This emphasizes the importance of understanding the molecular mechanism(s) that link ROS production to activation of the p38 mediated promotion of aging, longevity, and resistance to oxidative stress. We examined Klotho(-/-) (elevated ROS) and Klotho overexpressing mice (low ROS and resistance to ROS) to determine whether the ROS-sensitive apoptosis signal-regulating kinase (ASK1)-signalosome -> p38 MAPK pathway plays a role in the accelerated aging of Klotho(-/-), and resistance to oxidative stress and extended lifespan in the Klotho overexpressing models. Our results suggest that increased endogenous ROS generated by Klotho(-/-) and resistance to oxidative stress in Klotho overexpression are linked to the regulation of ASK1-signalosome -> p38 activity. We propose that (a) the ASK1-signalosome -> p38 MAPK pathway is activated by oxidative stress due to ablation of the Klotho gene; (b) increased longevity by Klotho overexpression is linked to suppression of the ASK1-signalosome-p38 MAPK activity; (c) the ROS-responsive ASK1-signalosome regulates physiological aging via its regulation of p38 MAPK, through a mechanism that balances the levels of inhibitory vs. activating ASK1-signalosomes. We conclude that the Klotho suppressor-of-aging activity is linked to the ASK1-signalsome, a physiological ROS-sensitive signaling center.
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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.