Healthy ageing: 13 papers
Peer-reviewed work on the endothelial glycocalyx, microvascular health and the ingredients in our formulas, newest first. Abstracts are indexed here and every paper links to the journal.
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Published paper
Evaluation of Microvascular Rarefaction in Vascular Cognitive Impairment and Heart Failure (CRUCIAL): Study Protocol for an Observational Study
This is a study protocol (not results) for CRUCIAL, a consortium of four observational cohort studies investigating whether microvascular rarefaction \u2014 loss of perfused and structural microvessels \u2014 contributes to vascular cognitive impairment from cerebral small vessel disease and to heart failure with preserved ejection fraction. Investigators plan to compare advanced brain and cardiac MRI measures of microvascular density with easier surrogate measures, including sublingual capillary assessment, retinal optical coherence tomography angiography, and RNA from circulating extracellular vesicles. In the aortic stenosis surgical cohort, myocardial biopsies will provide histological validation of microvascular density.
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Published paper
Effect of Glycocalyx-targeted Therapy on Vascular Function in Older Adults: A Randomized Controlled Trial
In this small double-blind, placebo-controlled pilot trial, 23 older adults took a glycocalyx-targeted supplement (Endocalyx Pro, 3,712 mg/day) or placebo for 12 weeks. The supplement did not significantly change overall sublingual glycocalyx thickness (perfused boundary region), brachial artery flow-mediated dilation, blood pressure, or aortic stiffness. Two secondary/exploratory signals were seen: greater capillary glycocalyx thickness among participants not on antihypertensive medication, and improved FMD normalized to shear rate.
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Published paper
Glycocalyx-targeted therapy ameliorates age-related arterial dysfunction
In mice, researchers reduced glycocalyx thickness by knocking down hyaluronan synthase 2 (Has2) and found this reproduced hallmarks of arterial aging: impaired endothelium-dependent dilation and increased aortic stiffness. Conversely, feeding old mice for 10 weeks with a glycocalyx-component supplement (Endocalyx, containing high-molecular-weight hyaluronan, glucosamine sulfate, fucoidan and superoxide dismutase) or with high-molecular-weight hyaluronan alone restored glycocalyx thickness and barrier function and improved endothelial function, aortic stiffness and blood pressure. Aortic wall composition (collagen, elastin) in supplemented old mice also resembled that of young mice.
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Published paper
Evaluation of miCRovascular rarefaction in vascUlar Cognitive Impairment and heArt faiLure (CRUCIAL): Study protocol for an observational study
This is a published study protocol (no results yet) for CRUCIAL, a multicenter observational program investigating whether microvascular rarefaction - loss of perfused small vessels - is a shared mechanism in vascular cognitive impairment and heart failure with preserved ejection fraction. Participants across four cohorts (75 VCI, 60 HFpEF, 60 aortic stenosis, 200 aging controls) undergo advanced brain and cardiac MRI, cognitive testing, echocardiography, retinal OCT angiography, sublingual videomicroscopy with the GlycoCheck system, blood biomarkers, and (in the surgical cohort) myocardial biopsy. The aim is to validate cheaper non-invasive surrogate markers of microvascular density against imaging and histology.
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Published paper
Association of Gestational Diabetes With Subclinical Cardiovascular Disease on Echocardiogram and Endothelial Function Testing (Abstract 12986)
This conference abstract reports a cross-sectional analysis of 217 women assessed roughly nine years after pregnancy, 53 of whom had a history of gestational diabetes. Women with prior gestational diabetes showed greater left ventricular wall thickness, worse diastolic function, and worse endothelial and glycocalyx measures (EndoPAT reactive hyperemia index and GlycoCheck parameters). Some hypertrophy differences were explained by BMI, hypertension, and diabetes, but the diastolic and vascular findings persisted after adjustment.
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Published paper
Impaired Endothelial Glycocalyx Predicts Adverse Outcome in Subjects Without Overt Cardiovascular Disease: a 6-Year Follow-up Study
In 600 subjects free of overt cardiovascular disease, researchers measured the perfused boundary region (PBR) in sublingual microvessels using sidestream dark-field imaging as an index of endothelial glycocalyx integrity, then followed them for 6 years. Higher PBR (indicating a thinner glycocalyx) independently predicted major adverse cardiovascular events beyond conventional risk factors and the European Heart SCORE.
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Published paper
Effect of gestational age and postnatal age on the endothelial glycocalyx in neonates
This prospective observational study used sidestream dark-field imaging with GlycoCheck software to measure the perfused boundary region (PBR, an inverse marker of endothelial glycocalyx thickness) in the skin microcirculation of 85 term and 39 preterm newborns. Preterm infants, especially those born before 30 weeks, had lower PBR (i.e., larger glycocalyx dimensions) than term infants, and PBR rose (glycocalyx thinned) with increasing postnatal age. Extremely preterm infants reached higher PBR values by 6-7 weeks of life than moderately preterm or term babies measured at the same corrected gestational age.
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Published paper
Sublingual endothelial glycocalyx and atherosclerosis. A cross-sectional study
In the largest study of its kind, sublingual perfused boundary region (PBR, an indirect index of endothelial glycocalyx thickness) was measured once in 6,169 multi-ethnic adults and related to classical cardiovascular risk factors and self-reported cardiovascular disease. The smallest glycocalyx size (highest PBR quartile) was independently associated with female sex, older age, and diabetes, but not with prevalent cardiovascular disease, coronary heart disease/revascularization, or stroke. The authors conclude that PBR-estimated glycocalyx size does not track a high cardiovascular risk profile in a general population.
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Published paper
Induced Trf2 deletion leads to aging vascular phenotype in mice associated with arterial telomere uncapping, senescence signaling, and oxidative stress
Researchers deleted the telomere-protecting protein Trf2 in adult mice to force telomere 'uncapping' without shortening telomeres, then measured artery and microvessel function. Trf2 deletion produced senescence signaling, oxidative stress, impaired nitric-oxide-dependent vasodilation, thinner endothelial glycocalyx, reduced microvascular perfusion, and modestly higher systolic blood pressure — a pattern resembling normal vascular aging.
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Published paper
Advanced age results in a diminished endothelial glycocalyx
Researchers compared the endothelial glycocalyx in young and old mice (using intravital and electron microscopy) and in younger and older humans (using sublingual intravital microscopy with automated analysis). In both species, older subjects had a thinner, more penetrable glycocalyx along with reduced markers of microvascular perfusion. The findings suggest glycocalyx deterioration accompanies age-related microvascular dysfunction across mammalian species.
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Published paper
Characteristics and determinants of the sublingual microcirculation in populations of different ethnicity
This population-based study used sidestream/oblique epi-illumination sublingual capillaroscopy with GlycoCheck software to measure capillary density and the perfused boundary region (PBR, an inverse proxy for glycocalyx thickness) in 252 Han Chinese, 220 She Chinese and 254 Flemish adults. Higher cardiovascular risk (age, BMI, cholesterol, Framingham score) was associated with greater functional capillary recruitment, and in perfused capillaries a higher BMI and higher blood pressure were associated with lower PBR (i.e. apparently thicker glycocalyx). Associations were consistent across the three ethnic groups, although absolute PBR and capillary density differed between Chinese and Flemish participants.
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Published paper
Deeper penetration of erythrocytes into the endothelial glycocalyx is associated with impaired microvascular perfusion
In a population-based sample of 915 middle-aged Dutch adults, researchers used sidestream dark-field imaging with automated GlycoCheck software to measure the perfused boundary region (PBR, a marker of how deeply red blood cells penetrate the endothelial glycocalyx) in sublingual microvessels. Deeper red-cell penetration (higher PBR) was strongly associated with poorer microvascular perfusion, measured as the percentage of time vessel segments contained red blood cells. The authors interpret a low PBR (thicker glycocalyx) as reflecting more efficient microvascular perfusion.
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Published paper
Skeletal muscle capillary density and microvascular function are compromised with aging and type 2 diabetes
This cross-sectional comparison measured muscle capillary density (from biopsies), whole-body insulin sensitivity, and sublingual microvascular measures in 15 young men, 15 older men, and 15 older men with type 2 diabetes. Both aging and type 2 diabetes were associated with fewer capillary contacts per muscle fiber and lower insulin sensitivity. Men with type 2 diabetes also showed a thicker erythrocyte-perfused boundary region on sidestream dark-field imaging, consistent with impaired endothelial glycocalyx function.
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