ArticleAging cell2018
Activation of DNA demethylases attenuates aging-associated arterial stiffening and hypertension.
Article in Aging cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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
33 citing papers in PubMed, 44 citations in OpenAlex.
- Serum Mucin-1 (CA15-3) in Relation to Pulse Pressure Amplification in Untreated Chinese Patients.Journal of clinical hypertension (Greenwich, Conn.) · 2026Article
- Fibulin 2 Deficiency Drives Epigenetic Hypertension.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Pathophysiology of vascular ageing and the effect of novel cardio-renal protective medications in preventing progression of chronic kidney disease in people living with diabetes.Diabetic medicine : a journal of the British Diabetic Association · 2025Review
- Epigenetic Regulation of Innate and Adaptive Immune Cells in Salt-Sensitive Hypertension.Circulation research · 2025Review
- TNFα Induces DNA and Histone Hypomethylation and Pulmonary Artery Smooth Muscle Cell Proliferation Partly via Excessive Superoxide Formation.Antioxidants (Basel, Switzerland) · 2024Article
- Dietary High Salt Intake Exacerbates SGK1-Mediated T Cell Pathogenicity in L-NAME/High Salt-Induced Hypertension.International journal of molecular sciences · 2024Article
- KDM6A Demethylase Regulates Renal Sodium Excretion and Blood Pressure.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Inverted U-shaped relationship between serum vitamin B12 and α-Klotho levels in US adults: a cross-sectional study.Frontiers in nutrition · 2024Article
- Multi-ancestry epigenome-wide analyses identify methylated sites associated with aortic augmentation index in TOPMed MESA.Scientific reports · 2023Article
- Initiation of 3,3-dimethyl-1-butanol at midlife prevents endothelial dysfunction and attenuates in vivo aortic stiffening with ageing in mice.The Journal of physiology · 2022Article
- Chronological attenuation of NPRA/PKG/AMPK signaling promotes vascular aging and elevates blood pressure.Aging cell · 2022Article
- Aging impairs arterial compliance via Klotho-mediated downregulation of B-cell population and IgG levels.Cellular and molecular life sciences : CMLS · 2022Article
- Progressive aortic stiffness in aging C57Bl/6 mice displays altered contractile behaviour and extracellular matrix changes.Communications biology · 2022Article
- Klotho expression in peripheral blood circulating cells is associated with vascular and systemic inflammation in atherosclerotic vascular disease.Scientific reports · 2022Article
- Long non-coding RNA MEG3 regulates the progress of osteoarthritis by regulating the miR-34a/Klotho axis.Annals of translational medicine · 2022Article
- Pathophysiology and genetics of salt-sensitive hypertension.Frontiers in physiology · 2022Review
- Human iPSC-Derived Neurons as A Platform for Deciphering the Mechanisms behind Brain Aging.Biomedicines · 2021Review
- Estrogen inhibits renal Na-Pi Co-transporters and improves klotho deficiency-induced acute heart failure.Redox biology · 2021Article
- Kidney-SpecificHypertension (Dallas, Tex. : 1979) · 2021Article
- MicroRNA 379 Regulates Klotho Deficiency-Induced Cardiomyocyte Apoptosis Via Repression of Smurf1.Hypertension (Dallas, Tex. : 1979) · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
DNA methylation increases with age. The objective of this study was to investigate whether compound H, a potential activator of DNA demethylases, attenuates aging-related arterial stiffness and hypertension. Aged mice (24-27 months) and adult mice (12 months) were used. Pulse wave velocity (PWV), a direct measure of arterial stiffness, and blood pressure (BP) were increased significantly in aged mice. Notably, daily treatments with compound H (15 mg/kg, IP) for 2 weeks significantly attenuated the aging-related increases in PWV and BP. Compound H abolished aging-associated downregulation of secreted Klotho (SKL) levels in both kidneys and serum likely by enhancing DNA demethylase activity and decreasing DNA methylation. Aging-related arterial stiffness was associated with accumulation of stiffer collagen and degradation of compliant elastin which are accompanied by increased expression of MMP2, MMP9, TGF-β1, and TGF-β3. These changes were effectively attenuated by compound H, suggesting rejuvenation of aged arteries. Compound H also rescued downregulation of Sirt1 deacetylase, AMPKα, and eNOS activities in aortas of aged mice. In cultured smooth muscle cells (SMCc) Klotho-deficient serum upregulated expression of MMPs and TGFβ which, however, was not affected by compound H. In conclusion, compound H attenuates aging-associated arterial stiffness and hypertension by activation of DNA demethylase which increases renal SKL expression and consequently circulating SKL levels leading to activation of the Sirt1-AMPK-eNOS pathway in aortas of aged mice.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.