ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2019
Klotho Deficiency Accelerates Stem Cells Aging by Impairing Telomerase Activity.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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.
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.
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Who cites it
50 citing papers in PubMed, 77 citations in OpenAlex.
- Protective mutations associated with APOE in Alzheimer's disease.Molecular psychiatry · 2026Review
- MicroRNA-Mediated Regulation of Brain Aging Hallmarks: Implications for Neurodegeneration and Neural Recovery.Brain and behavior · 2026Review
- Antiaging Properties of the Klotho Protein.Cells · 2026Review
- The Role of Klotho in Oral and Maxillofacial Diseases: Mechanisms and Research Progress.Biomolecules · 2025Review
- 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
- Association between serum Klotho levels and thrombocytosis in aging adults based on evidence from the National Health and Nutrition Examination Survey.Scientific reports · 2025Article
- 37 kDa LRP::FLAG enhances telomerase activity and reduces ageing markers in vivo.Cellular and molecular life sciences : CMLS · 2025Article
- SenNet recommendations for detecting senescent cells in different tissues.Nature reviews. Molecular cell biology · 2024Review
- Regulatory effects of the p38 mitogen-activated protein kinase-myosin light chain kinase pathway on the intestinal epithelial mechanical barrier and the mechanism of modified Pulsatilla decoction in the treatment of ulcerative colitis.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Klotho in pregnancy and intrauterine development-potential clinical implications: a review from the European Renal Association CKD-MBD Working Group.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- Gender differences in the relationship between the triglyceride-glucose index and serum Klotho concentrations among the middle-aged and elderly: a cross-sectional analysis.BMC endocrine disorders · 2024Article
- KDM6A Demethylase Regulates Renal Sodium Excretion and Blood Pressure.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Review
- Distinct role of Klotho in long bone and craniofacial bone: skeletal development, repair and regeneration.PeerJ · 2024Review
- From hyperglycemia to intervertebral disc damage: exploring diabetic-induced disc degeneration.Frontiers in immunology · 2024Review
- Evaluation of potential aging biomarkers in healthy individuals: telomerase, AGEs, GDF11/15, sirtuin 1, NAD+, NLRP3, DNA/RNA damage, and klotho.Biogerontology · 2023Article
- Article
- Role of Klotho and N-acetylcysteine in Oxidative Stress Associated with the Vitrification of Ovarian Tissue Cytoprotective Function of Klotho in Cryopreservation.Tissue engineering and regenerative medicine · 2023Article
- Brain-aging related protein expression and imaging characteristics of mice exposed to chronic hypoxia at high altitude.Frontiers in aging neuroscience · 2023Article
- Role of CD9 Sensing, AI, and Exosomes in Cellular Communication of Cancer.International journal of stem cell research and therapy · 2023Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Understanding the effect of molecular pathways involved in the age-dependent deterioration of stem cell function is critical for developing new therapies. The overexpression of Klotho (KL), an antiaging protein, causes treated animal models to enjoy extended life spans. Now, the question stands: Does KL deficiency accelerate stem cell aging and telomere shortening? If so, what are the specific mechanisms by which it does this, and is cycloastragenol (CAG) treatment enough to restore telomerase activity in aged stem cells? We found that KL deficiency diminished telomerase activity by altering the expression of TERF1 and TERT, causing impaired differentiation potential, pluripotency, cellular senescence, and apoptosis in stem cells. Telomerase activity decreased with KL-siRNA knockdown. This suggests that both KL and telomeres regulate the stem cell aging process through telomerase subunits TERF1, POT1, and TERT using the TGFβ, Insulin, and Wnt signaling. These pathways can rejuvenate stem cell populations in a CD90-dependent mechanism. Stem cell dysfunctions were largely provoked by KL deficiency and telomere shortening, owing to altered expression of TERF1, TGFβ1, CD90, POT1, TERT, and basic fibroblast growth factor (bFGF). The CAG treatment partially rescued telomerase deterioration, suggesting that KL plays a critical role in life-extension by regulating telomere length and telomerase activity.
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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.