Function Of Human Age Research Articles

Diversity of navel microbiome in young adults.

Introduction. Human skin microbial communities represent a tremendous source of genetic diversity that evolves as a function of human age. Microbiota differs between regions of oily and moist skin, and appears to stabilize with age.Aim. We have a minimal understanding of the time frame required for the stabilization of skin microbiota, and the role played by gender. In the current study, we examined the microbiota present in the navel region of college-attending young adults in the age group of 18-25 years and investigated if diversity is associated with gender (male and female).Method. The study involved 16 female and six male subjects. Isolated DNA samples from navel swabs were processed using the Nextera XT library preparation kit and sequenced using the MiSeq platform. Data were analysed using QIIME and statistical analysis performed in R.Results. Microbiota of navel skin is dominated by Corynebacterium and Staphylococcus and includes opportunistic pathogens like Clostridium and Pseudomonas. Also present as the major component of the flora were the organisms normally associated with the gastrointestinal tract such as Acinetobacter, Campylobacter, Klebsiella and organisms from the Enterobacteriaceae and Moraxellaceae families. Comparison of alpha and beta diversity of the microbiota in the male and female navel regions suggests that the flora is not statistically different (P>0.05). However, pairwise comparison suggests that the abundance of 12 specific genera varied with gender, including higher abundance of Klebsiella and Enterobacter in females.Conclusion. Our findings indicate that the navel skin microbiota of young adults has a core microbiota of Corynebacterium and Staphylococcus. We also noted the presence of a significant number of opportunistic pathogens. A minor gender difference in the abundance of individual organisms was also observed.

Spectroscopic determination of intracellular quercetin uptake using erythrocyte model and its implications in human aging.

The present study was carried out to detect intracellular quercetin uptake by RBCs during human aging. The study was carried out on 95 normal healthy subjects of both the sexes. Intracellular quercetin uptake was estimated by performing ethyl acetate extraction. A significant (p < 0.001) decline in intracellular quercetin uptake by human RBCs was observed in elderly as compared to young population, while plasma membrane redox system (PMRS) activity was significantly decreasing as a function of human age. To the best of our knowledge, we are the first to present quercetin uptake by erythrocytes during aging in humans with this study. It is hypothesized that intracellular uptake of quercetin may serve as an intracellular electron donor for plasma membrane redox system in red blood cells during cellular aging which plays an important role in extracellular dehydroascorbate reduction and ascorbate recycling.

Age-related epigenome-wide DNA methylation and hydroxymethylation in longitudinal mouse blood

ABSTRACTDNA methylation at cytosine-phosphate-guanine (CpG) dinucleotides changes as a function of age in humans and animal models, a process that may contribute to chronic disease development. Recent studies have investigated the role of an oxidized form of DNA methylation – 5-hydroxymethylcytosine (5hmC) – in the epigenome, but its contribution to age-related DNA methylation remains unclear. We tested the hypothesis that 5hmC changes with age, but in a direction opposite to 5-methylcytosine (5mC), potentially playing a distinct role in aging. To characterize epigenetic aging, genome-wide 5mC and 5hmC were measured in longitudinal blood samples (2, 4, and 10 months of age) from isogenic mice using two sequencing methods – enhanced reduced representation bisulfite sequencing and hydroxymethylated DNA immunoprecipitation sequencing. Examining the epigenome by age, we identified 28,196 unique differentially methylated CpGs (DMCs) and 8,613 differentially hydroxymethylated regions (DHMRs). Mouse blood showed a general pattern of epigenome-wide hypermethylation and hypo-hydroxymethylation with age. Comparing age-related DMCs and DHMRs, 1,854 annotated genes showed both differential 5mC and 5hmC, including one gene – Nfic – at five CpGs in the same 250 bp chromosomal region. At this region, 5mC and 5hmC levels both decreased with age. Reflecting these age-related epigenetic changes, Nfic RNA expression in blood decreased with age, suggesting that age-related regulation of this gene may be driven by 5hmC, not canonical DNA methylation. Combined, our genome-wide results show age-related differential 5mC and 5hmC, as well as some evidence that changes in 5hmC may drive age-related DNA methylation and gene expression.

Basal neutrophil function in human aging: Implications in endothelial cell adhesion

Much attention has been drawn to the pro-inflammatory condition that accompanies aging. This study compared parameters from non-stimulated neutrophils, obtained from young (18-30 years old [y.o.]) and elderly (65-80 y.o.) human volunteers. Measured as an inflammatory marker, plasmatic concentration of hs-CRP was found higher in elderly individuals. Non-stimulated neutrophil production of ROS and NO was, respectively, 38 and 29% higher for the aged group. From the adhesion molecules evaluated, only CD11b expression was elevated in neutrophils from the aged group, whereas no differences were found for CD11a, CD18, or CD62. A 69% higher non-stimulated in vitro neutrophil/endothelial cell adhesion was observed for neutrophils isolated from elderly donors. Our results suggest that with aging, neutrophils may be constitutively producing more reactive species in closer proximity to endothelial cells of vessel walls, which may both contribute to vascular damage and reflect a neutrophil intracellular disrupted redox balance, altering neutrophil function in aging.

Quercetin-modulated erythrocyte membrane sodium-hydrogen exchanger during human aging: correlation with ATPase’s

Content: Quercetin uptake by erythrocytes is rapid. The sodium-hydrogen exchanger (NHE) is a secondary active transporter, regulating intracellular pH, Na+ concentration and cell volume. Objective: The aim of present study was to investigate NHE as a function of human age and effect of quercetin on its activity. The NHE activity was correlated with erythrocytes ATPases. Materials and methods: We analyzed normal, healthy subjects of both sexes (20–82 years). NHE activity was estimated in terms of amiloride-sensitive H+-efflux from acid-loaded cells. Results: A significant age-dependent increase in NHE activity was observed during aging in humans. Concentration (10−3 M to 10−8 M)-dependent in vitro treatment with quercetin causes inhibition of NHE activity. The Na+/K+ -ATPase (r = 0.8882) and Ca2+-ATPase (r = 0.9540) activities positively correlated with it. Discussion and conclusion: The present data show an additional mechanism where dietary flavonoids may exerts beneficial effect during aging.

Age-dependent detection of erythrocytes glucose-6-phosphate dehydrogenase and its correlation with oxidative stress

Context: Glucose-6-phosphate dehydrogenase (G6PD) is an important enzyme of hexose monophosphate shunt, involved in the biosynthesis of reduced nicotinamide adenine dinucleotide phosphate hydrogen (NADPH). Objective: This study was designed to investigate age-dependent changes in human erythrocyte G6PD activity. The G6PD activity pattern was correlated with reduced glutathione (GSH) and total antioxidant potential in terms of FRAP (ferric reducing ability of plasma) value. Materials and methods: We analyzed normal, healthy subjects of both sexes between the ages of 20 and 80 years. G6PD activity was determined by Burties method. Results: We observe a significant age-dependent decrease in G6PD activity (p < 0.0001). It was positively correlated with GSH (r = 0.5706) and total antioxidant potential (r = 0.7723) as a function of human age. Discussion and conclusion: Our findings on erythrocyte G6PD and their correlation with GSH and FRAP provide evidence of a higher oxidative stress in old age population.

Naive T cell maintenance and function in human aging.

In studies of immune aging, naive T cells frequently take center stage. Describing the complexity of the human naive T cell repertoire remains a daunting task; however, emerging data suggest that homeostatic mechanisms are robust enough to maintain a large and diverse CD4 T cell repertoire with age. Compartment shrinkage and clonal expansions are challenges for naive CD8 T cells. In addition to population aspects, identification of potentially targetable cellular defects is receiving renewed interest. The last decade has seen remarkable progress in identifying genetic and biochemical pathways that are pertinent for aging in general and that are instructive to understand naive T cell dysfunction. One hallmark sets naive T cell aging apart from most other tissues except stem cells: they initiate but do not complete differentiation programs toward memory cells. Maintaining quiescence and avoiding differentiation may be the ultimate challenge to maintain the functions unique for naive T cells.

Age-related changes in erythrocyte membrane sulfhydryl groups and β-D-glucuronidase activity

Background: Aging is associated with oxidative stress but its underlying mechanisms remain poorly understood. The aim of this study was to investigate alterations in human erythrocyte membrane sulfhydryl groups and levels of β-D-glucuronidase during aging. Methods: The study was carried with a cohort of 52 normal, healthy subjects of both sexes. They were divided into three groups: young, middle-aged and old. Blood samples were taken, and membrane sulfhydryl groups and β-D-glucuronidase activity were measured within 24 hours. Results: Results showed significantly (p<0.001) decreased sulfhydryl group levels as a function of human age. A significant (p< 0.001) decrease in erythrocyte membrane β-D-glucuronidase activity was also observed in subjects in the ‘old’ group. Conclusions: We conclude that aging is associated with systemic oxidative stress that is able to influence the integrity of cell membranes and their antioxidant capacity. Evaluation of sulfhydryl groups and β-Dglucuronidase activity provides a useful and early indication of structural and functional alterations of the red blood cell membrane during human aging. Citation: Kumar P, Maurya PK (2015) Age-related changes

Biomarkers of oxidative stress in erythrocytes as a function of human age.

Despite more than 300 theories to explain the aging process, oxidative stress theory offers the best mechanism to explain aging and age related disorders. Several studies has shown the importance of oxidative stress during aging. PubMed, Science Direct and Springer online data bases are taken into consideration to write this mini-review. Human erythrocytes are most abundant and specialized cells in the body. Erythrocytes were extensively studied due to their metabolism and gas transport functions. Recent studies on erythrocytes have provided us detailed information of cell membrane and its structural organization that may help in studying the aging and age associated changes. The susceptibility of an organism is associated with the antioxidant potential of the body. Erythrocytes have potent antioxidant protection consisting of enzymatic and non-enzymatic pathways that counteract with reactive oxygen species, thus maintaining the redox regulation in the body. The non-enzymatic and enzymatic antioxidants and other biomarkers associated with erythrocyte membrane transport functions are the main content of this review. Biomarkers of oxidative stress in erythrocytes and its membrane were taken into the consideration during human aging that will be the main subject of this mini- review.

Epigallocatechin-3-Gallate Protects Erythrocyte Ca(2+)-ATPase and Na(+)/K(+)-ATPase Against Oxidative Induced Damage During Aging in Humans.

The main purpose of this study was to investigate the protective role of epigallocatechin-3-gallate on tertiary butyl hydroperoxide induced oxidative damage in erythrocyte during aging in humans. Human erythrocyte membrane bound Ca(2+)-ATPase and Na(+)/K(+)-ATPase activities were determined as a function of human age. Protective role of epigallocatechin-3-gallate was evaluated by in vitro experiments by adding epigallocatechin-3-gallate in concentration dependent manner (final concentration range 10(-7)M to 10(-4)M) to the enzyme assay medium. Oxidative stress was induced in vitro by incubating washed erythrocyte ghosts with tertiary butyl hydroperoxide (10(-5) M final concentration). We have reported concentration dependent effect of epigallocatechin-3-gallate on tertiary butyl hydroperoxide induced damage on activities of Ca(2+)-ATPase and Na(+)/K(+)-ATPase during aging in humans. We have detected a significant (p < 0.001) decreased activity of Ca(2+)-ATPase and Na(+)/K(+) -ATPase as a function of human age. Epigallocatechin-3-gallate protected ATPases against tertiary butyl hydroperoxide induced damage in concentration dependent manner during aging in humans. Epigallocatechin-3-gallate is a powerful antioxidant that is capable of protecting erythrocyte Ca(2+)-ATPase and Na(+)/K(+) -ATPase against oxidative stress during aging in humans. We may propose hypothesis that a high intake of catechin rich diet may provide some protection against development of aging and age related diseases.

L-Cysteine Efflux in Erythrocytes As A Function of Human Age: Correlation with Reduced Glutathione and Total Anti-Oxidant Potential

Thiol compounds such as cysteine (Cys) and reduced glutathione (GSH) play an important role in human aging and age-related diseases. In erythrocytes, GSH is synthesized by glutamic acid, cysteine, and glycine, but the rate of GSH synthesis is determined only by the availability of L-cysteine. Cysteine supplementation has been shown to ameliorate several parameters that are known to degenerate during human aging. We have studied L-cysteine efflux in vitro in human erythrocytes as a function of age by suspending cells in solution containing 10 mM L-cysteine for uptake; later cells were re-suspended in phosphate-buffered saline (PBS)-glucose to allow efflux. Change in the free sulfhydryl (-SH) concentration was then measured to calculate the rate of efflux. The GSH/oxidized glutathione (GSSG) ratio was taken as a control to study the oxidation/reduction state of the erythrocyte. The total anti-oxidant potential of plasma was measured in terms of ferric reducing ability of plasma (FRAP) values. We have shown a significant (p<0.0001) decline in the efflux of L-cysteine in erythrocytes during human aging, and the GSH/GSSG ratio decreases as a function of human age. The decline in L-cysteine efflux during aging correlates with the decrease in GSH and the FRAP value. This finding may help to explain the shift in the redox status and low GSH concentration that might determine the rate of L-cysteine efflux observed in erythrocytes and an important factor in the development of oxidative stress in erythrocytes during aging.

Plasma Protein Hydroperoxides During Aging in Humans: Correlation with Paraoxonase 1 (PON1) Arylesterase Activity and Plasma Total Thiols

Oxidative stress is thought to play a major role in the development of several age-dependent diseases. Proteins are major targets for oxidative attack. Protein hydroperoxides are formed by hydroxyl and singlet oxygen attack on protein, forming relatively stable hydroperoxides on histidine, tyrosine and tryptophan residues. This study investigated the levels of plasma protein hydroperoxides and antioxidant potential of plasma during aging in humans. We correlated the protein hydroperoxide formation with plasma antioxidant potential, paraoxonase 1 (PON1) arylesterase activity and plasma total thiols. The protein hydroperoxides and antioxidant potential were measured in plasma of human subjects aged between 20 and 81 years of both genders. Increase in plasma protein hydroperoxides and decrease in plasma antioxidant potential were observed as function of human age. This study provides strong correlation between plasma protein hydroperoxides formation and decrease in plasma antioxidant potential during aging. PON1 arylesterase activity and plasma total thiols levels were also found to show significant correlation with increasing levels of plasma protein hydroperoxides during aging. The plasma protein hydroperoxides provide a reliable marker of long-term redox balance and degree of oxidative stress during aging process.

Erythrocyte membrane transporters during human ageing: Modulatory role of tea catechins

Ageing is associated with many physiological and cellular changes, many of which are due to alterations in the plasma membrane. The functions of membrane transporter proteins are crucial for the maintenance of ionic homeostasis between the extra- and intracellular environments. The aim of the present study was to determine the status of erythrocyte membrane transporters, specifically Ca(2+) -ATPases, Na(+) /K(+) -ATPases and the Na(+) /H(+) exchanger (NHE), during ageing in humans. Furthermore, because tea catechins have been reported to possess strong anti-oxidant potential, the study was extended to evaluate the effect of (-)-epicatechin (EC), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate (EGCG) on these transporters as a function of human age. The study was performed on 97 normal healthy subjects (62 men, 35 women; 16-80 years old). To investigate the effects of tea catechins, subjects were divided into three groups: young (<40 years old; n = 34); middle-aged (40-60 years old; n = 32); and old (>60 years old; n = 31). Erythrocyte ghosts/cell suspension from each group were incubated with ECG, EGCG, EGC and EC (10 μmol/L) for 30 min at 37°C prior to assay. Ageing significantly increased NHE activity and decreased Ca(2+) -ATPase activity. There were no significant changes in Na(+) /K(+) -ATPase activity during the ageing process. (-)-Epigallocatechin-3-gallate, EGC, ECG and EC effectively mitigated the changes in membrane transporter activity in erythrocytes from all age groups; however, the effect was more pronounced in the old age group. We hypothesize that impairment in -bound transporters may be one of the possible mechanisms underlying the pathological events during ageing. A higher intake of catechin-rich food may provide some protection against age-dependent diseases.

Human Plasma Paraoxonase 1 (PON1) Arylesterase Activity During Aging: Correlation with Susceptibility of LDL Oxidation

The role of free radicals has long been proposed as a cause for the aging process. Oxidative stress is considered a major factor for altering many physiological processes and enzymatic activities during aging and is also known to play a major role in the development of several age-dependent diseases. Paraoxonase 1 (PON1) is an anti-atherosclerotic enzyme that mainly prevents accumulation of lipoperoxides and inhibits the lipid oxidation in low-density lipoproteins (LDL). This study was undertaken to investigate the antioxidant behavior of PON1 by measuring its arylesterase activity. The susceptibility of LDL for oxidation and the radical scavenging activity of plasma were also measured during aging in humans. Arylesterase activity of PON1 was measured in plasma of human subjects between 20 and 81 years of age of both genders. The susceptibility of LDL for oxidation and radical scavenging activity were measured in plasma. Decrease in plasma arylesterase activity of PON1, increase in susceptibility of LDL for oxidation and decrease in plasma radical scavenging activity were observed as a function of human age. The study provides evidence of a relationship between PON1 activity, LDL oxidation and free radical scavenging activity of plasma. The present results emphasize the dependency of PON1 activity to prevailing oxidative stress during human aging. Our findings assume significance in view of the possible categorization of PON1 as a longevity gene.

Concord Grape Juice Supplementation and Neurocognitive Function in Human Aging

Polyphenol compounds found in berry fruits, in particular flavonoids, have been associated with health benefits including improvement in cognition and neuronal function with aging. Concord grape juice contains polyphenols, including anthocyanins and flavanols, and previous research has shown improvement in a number of human health conditions with grape juice supplementation. In the current study, older adult subjects with mild cognitive impairment consumed Concord grape juice or placebo for 16 weeks and were administered assessments of memory function and brain activation pre- and postintervention. Participants who consumed grape juice showed reduced semantic interference on memory tasks. Relatively greater activation in anterior and posterior regions of the right hemisphere was also observed with functional magnetic resonance imaging in the grape juice treated subjects. These findings provide further evidence that Concord grape juice can enhance neurocognitive function in older adults with mild memory decline.

Erythrocyte sialic acid content during aging in humans: correlation with markers of oxidative stress.

Sialic acids are substituted neuraminic acid derivatives which are typically found at the outermost end of glycan chains on the membrane in all cell types. The role of erythrocyte membrane sialic acids during aging has been established however the relationship between sialic acid and oxidative stress is not fully understood. The present work was undertaken to analyze the relationship between erythrocyte membrane sialic acid with its plasma level, membrane and plasma lipid hydroperoxide levels and plasma total antioxidant capacity. Results show that sialic acid content decreases significantly (P < 0.001) in RBC membrane (r = −0.901) and increases in plasma (r = 0.860) as a function of age in humans. Lipid peroxidation measured in the form of hydroperoxides increases significantly (P < 0.001) in plasma (r = 0.830) and RBC membranes (r = 0.875) with age in humans. The Trolox Equivalent Total Antioxidant Capacity (TETAC) of plasma was found to be significantly decreased (P < 0.001, r = −0.844). We observe significant correlations between decrease of erythrocyte membrane sialic acid and plasma lipid hydroperoxide and TETAC. Based on the observed correlations, we hypothesize that increase in oxidative stress during aging may influence the sialic acid decomposition from membrane thereby altering the membrane configuration affecting many enzymatic and transporter activities. Considering the importance of plasma sialic acid as a diagnostic parameter, it is important to establish age-dependent reference.

Erythrocyte Sialic Acid Content during Aging in Humans: Correlation with Markers of Oxidative Stress

Sialic acids are substituted neuraminic acid derivatives which are typically found at the outermost end of glycan chains on the membrane in all cell types. The role of erythrocyte membrane sialic acids during aging has been established however the relationship between sialic acid and oxidative stress is not fully understood. The present work was undertaken to analyze the relationship between erythrocyte membrane sialic acid with its plasma level, membrane and plasma lipid hydroperoxide levels and plasma total antioxidant capacity. Results show that sialic acid content decreases significantly (P&lt; 0.001) in RBC membrane (r= −0.901) and increases in plasma (r= 0.860) as a function of age in humans. Lipid peroxidation measured in the form of hydroperoxides increases significantly (P&lt; 0.001) in plasma (r= 0.830) and RBC membranes (r= 0.875) with age in humans. The Trolox Equivalent Total Antioxidant Capacity (TETAC) of plasma was found to be significantly decreased (P&lt; 0.001,r= −0.844). We observe significant correlations between decrease of erythrocyte membrane sialic acid and plasma lipid hydroperoxide and TETAC. Based on the observed correlations, we hypothesize that increase in oxidative stress during aging may influence the sialic acid decomposition from membrane thereby altering the membrane configuration affecting many enzymatic and transporter activities. Considering the importance of plasma sialic acid as a diagnostic parameter, it is important to establish age-dependent reference.

Intracellular uptake of (‐)epicatechin by human erythrocytes as a function of human age

The present studies were carried out to determine the intracellular uptake of (-)epicatechin by erythrocytes during aging in humans. (-)Epicatechin uptake was estimated by performing ethyl acetate extraction while the total antioxidant potential of the (-)epicatechin was estimated in terms of FRAP (ferric reducing ability of plasma) values. A significant (p < 0.001) decrease in (-)epicatechin uptake by human erythrocytes was observed as a function of age. It is hypothesized that the uptake of (-)epicatechin in human erythrocytes has an important role in the regulation of PMRS (plasma membrane redox system) activity during normal human aging.

Age-Dependent Changes in Glutathione-S-Transferase: Correlation with Total Plasma Antioxidant Potential and Red Cell Intracellular Glutathione

The correlation between antioxidant capacity and oxidative damage during aging has been reported in several tissues in different species. Glutathione-S-transferases (GST) can metabolise endogenous and exogenous toxins and carcinogens by catalysing the conjugation of diverse electrophiles with reduced glutathione (GSH). We observe a significant (P < 0.001) increase in plasma GST activity as a function of human age (r=0.5675). A significant (P < 0.001) positive correlation (r=0.8979) is observed between GST activity and total plasma antioxidant potential measured as ferric reducing ability of the plasma (FRAP). GST activity and red cell intracellular GSH also show a significant positive correlation (r=0.7014). We hypothesize that the increased activity of plasma GST is a manifestation of increased generation of ROS and a concomitant decrease in the level of plasma antioxidant capacity during aging.

L-Cysteine Influx in Erythrocytes as a Function of Human Age

In erythrocytes, although three amino acids are required for the synthesis of reduced glutathione (GSH), the rate of GSH synthesis is determined only by the availability of L-cysteine. Cysteine supplementation has been shown to ameliorate several parameters that are known to degenerate during human aging; this has led to an interesting hypothesis that aging could be a cysteine deficiency syndrome. In the present study, we measured L-cysteine influx in human erythrocytes by suspending cells in solution containing 10 mM L-cysteine. We show a significant decline in the influx of L-cysteine in erythrocytes during aging in humans. The decrease in cysteine influx correlates with the decrease in antioxidant potential of plasma measured in terms of FRAP (ferric-reducing ability of plasma) during aging. We conclude that a decreased influx of L-cysteine may be an important factor contributing to the development of oxidative stress in human erythrocytes during aging.