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Causal Inference Approaches Reveal Associations Between LDL Oxidation, NO Metabolism, Telomere Length and DNA Integrity Within the MARK-AGE Study
Genomic instability markers are important hallmarks of aging, as previously evidenced within the European study of biomarkers of human aging, MARK-AGE; however, establishing the specific metabolic determinants of vascular aging is challenging. The objective of the present study was to evaluate the impact of the susceptibility to oxidation of serum LDL particles (LDLox) and the plasma metabolisation products of nitric oxide (NOx) on relevant genomic instability markers. The analysis was performed on a MARK-AGE cohort of 1326 subjects (635 men and 691 women, 35-75 years old) randomly recruited from the general population. The Inverse Probability of Treatment Weighting causal inference algorithm was implemented in order to assess the potential causal relationship between the LDLox and NOx octile-based thresholds and three genomic instability markers measured in mononuclear leukocytes: the percentage of telomeres shorter than 3 kb, the initial DNA integrity, and the DNA damage after irradiation with 3.8 Gy. The results showed statistically significant telomere shortening for LDLox, while NOx yielded a significant impact on DNA integrity. Overall, the effect on the genomic instability markers was higher than for the confirmed vascular aging determinants, such as low HDL cholesterol levels, indicating a meaningful impact even for small changes in LDLox and NOx values.
Valeanu, A., Margina, D., Moreno-Villanueva, M., Blasco, M., Sikora, E., Mosieniak, G., Capri, M., Breusing, N., Bernhardt, J., Schön, C., Toussaint, O., Debacq-Chainiaux, F., Grubeck-Loebenstein, B., Weinberger, B., Fiegl, S., Gonos, E. S., Hervonen, A., Slagboom, E. P., de Craen, A., ... Gradinaru, D
Antioxidants, 14(8), 933
read full publicationZinc-Induced Metallothionein in Centenarian Offspring From a Large European Population: The MARK-AGE Project
Metallothionein (MT) family are cysteine-rich proteins that regulate zinc (Zn) homeostasis and protect against oxidative damage. Studies in transgenic mice have shown that MT favourably influence longevity, although their role in human aging is not completely understood. Within the European multicenter study MARK-AGE, we analysed MT induction after Zn treatment in peripheral blood mononuclear cells (PBMCs) and its relation with redox biomarkers in 2,936 age-stratified subjects (35-75 years) including the general population (RASIG), centenarian offspring (GO), and their spouses (SGO).
Giacconi R, Costarelli L, Piacenza F, Basso A, Bürkle A, Moreno-Villanueva M, Grune T, Weber D, Stuetz W, Gonos ES, Schön C, Grubeck-Loebenstein B, Sikora E, Toussaint O, Debacq-Chainiaux F, Franceschi C, Hervonen A, Slagboom E, Ciccarone F, Zampieri M, Caiafa P, Jansen E, Dollé MET, Breusing N, Mocchegiani E, Malavolta M
J Gerontol A Biol Sci Med Sci. 2018 May 9; 73(6):745-753. doi: 10.1093/gerona/glx192
read full publicationEffects of cartilage-supporting nutritional supplementation on knee osteoarthritis symptoms and quality of life in a 12-week randomized double-blind placebo-controlled pilot study
Osteoarthritis (OA) is a prevalent degenerative joint disease, often affecting the elderly, characterized by cartilage degradation and bone remodelling, leading to pain, stiffness, and impaired movement. This 12-week, randomized, double-blind, placebo-controlled pilot study investigated the efficacy of a formulation containing collagen type II, glucosamine hydrochloride and chondroitin sulfate, in alleviating knee OA symptoms in subjects with mild to moderate knee pain. Fifty-four participants were enrolled, with 52 completing the study. Participants were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS), performance-based physical function tests and global assessment tests. Results indicated significant improvements in the verum group compared to placebo. KOOS subscales showed improvements in symptoms (8.16%, p < 0.05), sport/recreation (25.25%, p < 0.01), and quality of life (27.66%, p < 0.001). Stiffness improved by 14.68% (p < 0.05) in the verum group. Both groups exhibited significant pain reduction (KOOS pain, p < 0.001 and p < 0.01 for verum and placebo, respectively). Performance-based measures, such as the Chair Stand test, improved significantly in both groups, though other metrics showed no significant differences. The verum group exhibited a linear improvement over 12 weeks, contrasting with the placebo group's initial response and subsequent plateau. SF-36 Physical Component scores improved in both groups (p < 0.05), but mental health scores remained unchanged. Global assessment favoured the verum group, with more participants reporting OA improvement and recommending the product (p < 0.01). Biomarkers hsCRP and COMP showed no significant changes, likely due to sample variability. While the study did not achieve its primary endpoint, the nutritional formulation demonstrated an excellent safety profile and encouraging improvements in patient-reported symptoms and quality of life, warranting larger confirmatory trials.
Fladerer-Grollitsch JP, Klein T, Kompek A, Steiner N, Menzel D, Schön C
Sci Rep. 2025 Jul 15;15(1):25625
read full publicationAntioxidants linked with physical, cognitive and psychological frailty: Analysis of candidate biomarkers and markers derived from the MARK-AGE study
Frailty among elderly people leads to an increased risk for negative health outcomes. To prevent frailty, we need a better understanding of the underlying mechanisms and early detection of individuals at risk. Both may be served by identifying candidate (bio)markers, i.e. biomarkers and markers, for the physical, cognitive, and psychological frailty domains. We used univariate (Rank-ANOVA) and multivariate (elastic net) approaches on the RASIG study population (age range: 35-74 years, n = 2220) of the MARK-AGE study to study up to 331 (bio)markers between individuals with and without frailty for each domain. Biomarkers and markers identified by both approaches were studied further regarding their association with frailty using logistic regression. Univariately, we found lower levels of antioxidants, including β-cryptoxanthin and zeaxanthin, in those who were physically, cognitively or psychologically frail. Additionally, self-reported health was worse in these three frail groups. Multivariately, we observed lower levels of β-cryptoxanthin and zeaxanthin in the cognitively frail. Levels of these carotenoids were inversely associated with the risk of being cognitively frail after adjusting for confounders. Antioxidants and self-reported health are potential (bio)markers to detect persons at risk of becoming frail. The biomarkers identified may indicate the involvement of inflammation in frailty, especially for physical and cognitive frailty.
Rietman ML, Spijkerman AMW, Wong A, van Steeg H, Bürkle A, Moreno-Villanueva M, Sindlinger T, Franceschi C, Grubeck-Loebenstein B, Bernhardt J, Slagboom PE, Toussaint O, Debacq-Chainiaux F, Sikora E, Gonos ES, Breusing N, Stuetz W, Weber D, Grune T, Basso A, Piacenza F, Malavolta M, Collino S, Jansen EHJM, Verschuren WMM, Dollé MET
Mech Ageing Dev. 2018 Apr 30. pii: S0047-6374(18)30025-3. doi: 10.1016/j.mad.2018.04.007
read full publicationProspective uncontrolled clinical study shows rapid and long lasting relief of heartburn and acid related gastric discomfort with Refluthin
Heartburn and acid regurgitation are main symptoms of gastro-esophageal reflux, a widespread complaint with a significant impact on quality of life (QoL). Refluthin® for Heartburn chewable tablets (Refluthin) are a symptomatic treatment option containing a combination of an antacid (CaCO3, MgCO3) and a polysaccharide-rich extract with mucoprotective substances from Opuntia ficus-indica cladodes. To investigate performance and safety of Refluthin in the rapid and long lasting relief of heartburn and acid related gastric discomfort under practical use conditions, a prospective, clinical, uncontrolled, open-label study was conducted. Adults with symptomatic heartburn, acid regurgitation, and/or recurrent acid related gastric discomfort took one tablet Refluthin up to four times/day as needed for up to 4 weeks. Endpoints were both time to onset and duration of symptom relief; reflux symptom intensity/frequency; global assessments (QoL, performance, satisfaction, usability, tolerability); and safety. 81/100 participants (81%) responded with a first symptom relief within ≤ 20 min in ≥ 50% of the individual applications. Long lasting effects of > 120 min were reported by 83/100 (83%) participants. Significant reductions in heartburn event frequency and intensity were seen within the 4 weeks of intermittent use (p < 0.0001, respectively). Global assessment results and safety-relevant findings were also favourable. Results thus demonstrated a distinct rapid and long lasting symptom relief after intake of Refluthin, with a safe and easy use. The significant reductions in frequency and intensity of heartburn events over time indicate sustained effects under treatment. These long-term effects might be explainable by soothing and protection of the irritated mucous membrane by Refluthin.
Madisch A, Pace F, Menzel D, Funk P, Stracke B, Schön C, Labenz J
Sci Rep. 2025 May 7;15(1):15896
read full publicationPlasmolysed herbal yeast (Strath®) improves micronutrient bioavailability – An in vitro study using Caco-2 intestinal epithelial cells
The use of yeasts enriched with distinct micronutrients as supplement in human nutrition increased over the last years. A special plasmolyzed herbal yeast was investigated to demonstrate its beneficial effect on the bioavailability of important micronutrients for human nutrition such as iron, zinc, magnesium and vitamin B1. The well-established Caco-2 model was applied for this investigation. The plasmolyzed herbal yeast underwent an in vitro simulation of the gastro-intestinal digest process before applied to the Caco-2 model. The results demonstrate an improved bioavailability of the micronutrients iron, zinc, magnesium and vitamin B1 in the presence of the plasmolyzed herbal yeast.
Engelhart-Jentzsch K, Schlöffel I, Winter S
Agro FOOD Ind. Hi Tech 2018, 29(2), 44-47
read full publicationGUARANTEED EFFECTIVE AND UNCONDITIONAL: THE CONTACTRECORD
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