Age-related influence on DNA damage, proteomic inflammatory markers and oxidative stress in hospitalized COVID-19 patients compared to healthy controls.

COVID-19 infections are accompanied by adverse changes in inflammatory pathways that are also partly influenced by increased oxidative stress and might result in elevated DNA damage. The aim of this case-control study was to examine whether COVID-19 patients show differences in oxidative stress-related markers, unconjugated bilirubin (UCB), an inflammation panel and DNA damage compared to healthy, age-and sex-matched controls. The Comet assay with and without the treatment of formamidopyrimidine DNA glycosylase (FPG) and H2O2 challenge was used to detect DNA damage in whole blood. qPCR was applied for gene expression, UCB was analyzed via HPLC, targeted proteomics were applied using Olink® inflammation panel and various oxidative stress as well as clinical biochemistry markers were analyzed in plasma. Hospitalized COVID-19 patients (n = 48) demonstrated higher serum levels of 55 inflammatory proteins (p < 0.001), including hs-C-reactive protein levels (p < 0.05), compared to healthy controls (n = 48). Interestingly, significantly increased age-related DNA damage (%-DNA in tail) after formamidopyrimidine DNA glycosylase (FPG) treatment was measured in younger (n = 24, average age 55.7 years; p < 0.05) but not in older COVID-19 patients (n = 24, average age 83.5 years; p > 0.05). Although various oxidative stress markers were not altered (e.g., FRAP, malondialdehyde, p > 0.05), a significant increased ratio of oxidized to reduced glutathione was detected in COVID-19 patients compared to healthy controls (p < 0.05). UCB levels were significantly lower in individuals with COVID-19, especially in younger COVID-19 patients (p < 0.05). These results suggest that COVID-19 infections exert effects on DNA damage related to age in hospitalized COVID-19 patients that might be driven by changes in inflammatory pathways but are not altered by oxidative stress parameters.

Effect of Repeated Bolus and Continuous Glucose Infusion on DNA Damage and Oxidative Stress Biomarkers in Healthy Male Volunteers.

Glucose variability (GV), which describes fluctuations in blood glucose levels within the day, is a phenomenon that is increasingly becoming the target of scientific attention when it comes to increased risk of coronary heart disease. Effects of GV may contribute to the development of metabolic syndrome and type 2 diabetes. Hyperglycemia can lead to oxidative stress resulting in molecular damage due to accumulation of reactive oxygen species (ROS). To discover more about the immediate effects of GV, continuous vs. bolus intravenous glucose administration was applied to 10 healthy men aged 21-30 years over a time frame of 48 h. Whole blood and plasma were analyzed for DNA damage using a comet assay with 3 different treatments (lysis buffer, H2O2, and the lesion-specific enzyme formamidopyrimidine DNA glycosylase (FPG)) as well as for the oxidative stress markers protein carbonyls (PC), unconjugated bilirubin (UCB), and ferric reducing antioxidant power (FRAP). A significant time effect was found in the three DNA damage treatments as well as in PC and UCB possibly due to circadian changes on oxidative stress, but no intervention group effect was observed for any of the markers. In conclusion, bolus vs. continuous glucose administration had no significant acute effect on DNA damage and markers of oxidative stress in healthy men.

The influence of vitamin D supplementation and strength training on health biomarkers and chromosomal damage in community-dwelling older adults.

Older adults lack of proper physical activity which is often accompanied by vitamin D deficiency. Those factors are known to contribute to health issues in the later years of life. The main goal of this intervention study was to investigate the effect of different vitamin D supplementation strategies for 4 weeks solely or combined with a 10-week strength training program on chromosomal stability in peripheral blood mononuclear cells in community-dwelling older people. One hundred women and men (65-85 years) received either vitamin D3 daily (800 IU), a monthly dose (50.000 IU) or placebo for 17 weeks. All groups received 400 mg calcium daily. The fitness status of the study participants was measured using the 30- second chair stand test, the handgrip strength test and the 6-min walk test. The cytokinesis block micronucleus cytome (CBMN) assay was applied to analyze chromosomal anomalies, including cytotoxic and genotoxic parameters. Changes in antioxidant markers were measured in plasma. Walking distance and chair stand performance improved significantly. Increased levels of the parameters of the CBMN assay were detected for all intervention groups at study end. At baseline micronuclei (MNi) frequency correlated significantly with BMI in both sexes (females: r = 0.369, p = 0.034; males: r = 0.265, p = 0.035), but not with vitamin D serum levels. In females, body fat (r = 0.372, p < 0.001) and functional parameter using the 30-s chair stand test (r = 0.311, p = 0.002) correlated significantly with MNi frequency. Interestingly, not vitamin D supplementation but 10 weeks of resistance training increased MNi frequency indicating elevated chromosomal instability and also adverse effects on antioxidant markers including glutathione and FRAP were detected in the group of community-dwelling older adults.

Association of Bioelectrical Impedance Phase Angle with Physical Performance and Nutrient Intake of Older Adults.

In recent years, the phase angle (PhA) as a raw bioelectrical impedance analysis variable has gained attention to assess cell integrity and its association to physical performance in either sports-related or clinical settings. However, data on healthy older adults are scarce. Therefore, data on body composition, physical performance and macronutrient intake from older adults (n = 326, 59.2% women, 75.2 ± 7.2 years) were retrospectively analyzed. Physical performance was evaluated by the Senior Fitness Test battery, gait speed, timed up and go and handgrip strength. Body composition was determined by the BIA and dual-energy X-ray absorptiometry (from a subgroup of n = 51). The PhA was negatively associated with the timed up and go test and age (r = -0.312 and -0.537, p < 0.001), and positively associated with the 6 min walk test, 30 s chair stand, handgrip strength, gait speed and physical performance score (r = 0.170-0.554, p < 0.05), but not protein intake (r = 0.050, p = 0.386). Hierarchical multiple regression analysis showed that especially age, sex, BMI, but also the PhA predicted the performance test outcomes. In conclusion, the PhA seems to be an interesting contributor to physical performance, but sex- and age-specific norm values still need to be determined.

The plasma proteome is favorably modified by a high protein diet but not by additional resistance training in older adults: A 17-week randomized controlled trial.

Background: The age-related loss of muscle mass significantly contributes to the development of chronic diseases, loss of mobility and dependency on others, yet could be improved by an optimized lifestyle. Objective: The goal of this randomized controlled trial was to compare the influence of a habitual diet (CON) with either a diet containing the recommended protein intake (RP) or a high protein intake (HP), both with and without strength training, on the plasma proteome in older adults. Methods: One hundred and thirty-six women and men (65-85 years) were randomly assigned to three intervention groups. CON continued their habitual diet; participants of the HP and RP group consumed either high protein or standard foods. After 6 weeks of dietary intervention, HP and RP groups additionally started a strength training intervention twice per week for 8 weeks. Twenty-four hours dietary recalls were performed every 7-10 days. Body composition was assessed and blood taken. Plasma proteomics were assessed with LC-MS. Results: Participants of the HP group doubled their baseline protein intake from 0.80 ± 0.31 to 1.63 ± 0.36 g/kg BW/d; RP increased protein intake from 0.89 ± 0.28 to 1.06 ± 0.26 g/kg BW/d. The CON group kept the protein intake stable throughout the study. Combined exercise and HP initiated notable changes, resulting in a reduction in bodyfat and increased muscle mass. Proteomics analyses revealed 14 significantly affected proteins by HP diet, regulating innate immune system, lipid transport and blood coagulation, yet the additional strength training did not elicit further changes. Conclusions: Combined HP and resistance exercise in healthy older adults seem to induce favorable changes in the body composition. Changes in the plasma proteome due to the high protein diet point to a beneficial impact for the innate immune system, lipid transport and blood coagulation system, all of which are involved in chronic disease development. Clinical trial registration: The study was registered at ClinicalTrials.gov (NCT04023513).

Effects of an increased habitual dietary protein intake followed by resistance training on fitness, muscle quality and body composition of seniors: A randomised controlled trial.

BACKGROUND & AIMS: Resistance training and a sufficient amount of dietary protein have been suggested to build up and maintain muscle mass, strength and function into old age. As there is still no consensus on the optimum amount of protein intake in older people, this study aims to evaluate first whether it is achievable to double the recommended amount, which is 1 g/kg BW/d in German speaking countries, via food administration and secondly whether this would lead to stronger improvements when subsequently combined with resistance training. METHODS: In total, 136 community-dwelling older adults (54% females, 72.9 ± 4.8 yrs) were randomly assigned to one of the three study groups: observational control (CON), recommended protein (RP + T) and high protein (HP + T) intake groups. After six weeks of observation or nutritional counselling to achieve the respective protein target levels, eight weeks of resistance training (2x/week) were applied in RP + T and HP + T groups. Parameters indicative for muscle mass, strength and function were measured at baseline (t1), before (t2) and after the training period (t3). RESULTS: Baseline protein intake for the different groups were 0.83 (CON), 0.97 (RP + T) and 0.78 (HP + T) g/kg BW/d and increased by 0.18 ± 0.31 (RP + T, p = 0.003) and 0.83 ± 0.33 (HP + T, p > 0.001) g/kg BW/d between t1 and t3 while CON remained unchanged. Most of the physical performance parameters improved over time, but no interaction effects between group and time could be observed. While body fat mass initially increased from t1 to t2 (0.8 ± 2.3 kg, p = 0.001), skeletal muscle mass decreased (-0.5 ± 1.9 kg, p = 0.025), a trend which was reversed from t2 to t3 only in HP + T group (body fat mass: -0.47 ± 2.12 kg, p = 0.041; muscle mass: 0.51 ± 1.57 kg, p = 0.021). CONCLUSION: The findings suggest that a substantial increase of habitual protein intake above the currently recommended levels is achievable within 17 weeks in community-dwelling older adults, whereby the extra amount of protein led to minor changes in body composition but not physical performance or muscle quality (NCT04023513).

The Effect of Elevated Protein Intake on DNA Damage in Older People: Comparative Secondary Analysis of Two Randomized Controlled Trials.

A high protein intake at old age is important for muscle protein synthesis, however, this could also trigger protein oxidation with the potential risk for DNA damage. The aim of this study was to investigate whether an increased protein intake at recommended level or well above would affect DNA damage or change levels of reduced (GSH) and oxidised glutathione (GSSG) in community-dwelling elderly subjects. These analyses were performed in two randomized intervention studies, in Austria and in New Zealand. In both randomized control trials, the mean protein intake was increased with whole foods, in the New Zealand study (n = 29 males, 74.2 ± 3.6 years) to 1.7 g/kg body weight/d (10 weeks intervention; p < 0.001)) in the Austrian study (n = 119 males and females, 72.9 ± 4.8 years) to 1.54 g/kg body weight/d (6 weeks intervention; p < 0.001)). In both studies, single and double strand breaks and as formamidopyrimidine-DNA glycosylase-sensitive sites were investigated in peripheral blood mononuclear cells or whole blood. Further, resistance to H2O2 induced DNA damage, GSH, GSSG and CRP were measured. Increased dietary protein intake did not impact on DNA damage markers and GSH/GSSG levels. A seasonal-based time effect (p < 0.05), which led to a decrease in DNA damage and GSH was observed in the Austrian study. Therefore, increasing the protein intake to more than 20% of the total energy intake in community-dwelling seniors in Austria and New Zealand did not increase measures of DNA damage, change glutathione status or elevate plasma CRP.

Impact of dietary and lifestyle interventions in elderly or people diagnosed with diabetes, metabolic disorders, cardiovascular disease, cancer and micronutrient deficiency on micronuclei frequency - A systematic review and meta-analysis.

Chronic diseases such as cardiovascular diseases, type 2 diabetes or cancer are the global leading cause of mortality. Lifestyle interventions are most effective in reducing metabolic risk factors, disease progression or even side effects of a disease. They are also contributing to decelerate the aging process. Genome instability is very often associated with aging or the above-mentioned diseases, and triggered by inflammation and oxidative stress. An established method to measure chromosomal damage is the cytokinesis block micronucleus (CBMN) cytome assay. The aim of this review and meta-analysis is to collect and analyse the current literature regarding the effects of a lifestyle based (dietary) intervention on changes of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in elderly subjects or people diagnosed with diabetes, metabolic disorders, cardiovascular disease, cancer or micronutrient deficiency. Although the main important diseases were considered as well as the large topic of aging, the number and methodological quality in terms of samples size, duration and rationale of the intervention or an inclusion of a control group of available intervention studies with these backgrounds was low. Most of the studies used antioxidant vitamins or folate, few investigated the whole diet. Only one study showed a physical activity intervention approach. The interventions did not lead to decreased genomic marker despite a few cancer related studies, where particularly MN frequency in mucosa lesions and leukoplakia was reduced by green tea and antioxidants. The performed meta-analysis of the available RCTs did not show a significant reduction of MNi, NBUDs or NPBs of most of the interventions performed, except for green tea. Data show in general a lack of an appropriate number of sound lifestyle based intervention studies linking cytogenetic damage and chronic diseases.

Effects of Vitamin D3 Supplementation and Resistance Training on 25-Hydroxyvitamin D Status and Functional Performance of Older Adults: A Randomized Placebo-Controlled Trial.

Vitamin D status is associated with muscle strength and performance in older adults. To examine the additive effects of vitamin D3 supplementation during resistance training, 100 seniors (65-85 years) participated in a 16-week intervention. Besides a daily dose of 400 mg of calcium, participants received either 800 IU vitamin D3 per day (VDD), 50,000 IU vitamin D3 per month (VDM) or nothing (CON). After the initial loading phase of four weeks, all groups started a 10-week resistance training program. Assessments of 25-hydroxyvitamin D (25(OH)D) status, muscle strength endurance (30-s chair stand and arm curl tests), aerobic capacity (6-min walk test) and functional mobility (gait speed and timed up and go test) were undertaken at baseline, after four weeks and at the end of the study. 25(OH)D status significantly improved in VDD and VDM, but not in CON (time x group: p = 0.021), as 15.2% of CON, 40.0% of VDD and 61.1% of VDM reached vitamin D sufficiency (>30 ng/mL; p = 0.004). Chair stand test, arm curl test, 6-min walk test, gait speed and timed up and go test improved over the whole intervention period (p < 0.05), however only chair stand and arm curl test were selectively affected by resistance training (p < 0.001). Neither muscle strength endurance, nor functional mobility or aerobic capacity were modulated by vitamin D supplementation. Therefore, the mere amelioration of 25(OH)D status of older adults does not lead to an additive effect on muscular performance during RT.