Development Of Age-related Diseases Research Articles

Особенности предпочтений людей пожилого и старческого возраста при формировании рациона

Introduction. Currently, the food market is replenished with new types of specialized food products intended for nutrition of certain population categories. Gerodietetic products are important in forming the diet for senior citizens. Therefore, gerodietetic foods are a factor of healthy lifestyle and active longevity. Functional food products should be based on age-related issues and consumer preferences. Aging weakens assimilative processes in organs and tissues, slows down the rate of redox reactions, and restructures the system of metabolism and body functions. Thus, people of advanced and gerontic age need to consume appropriate amount of vitamins and minerals, as their deficiency plays a decisive role in the development of age-related diseases. As a result, scientific justification and development of functional food products for this category is extremely important. The research objective was to study consumer preferences in relation to gerodietetic food products by collecting, processing, and analyzing marketing data.
 Study objects and methods. The research featured statistical data, as well as information obtained from consumers aged 60–77, residents of the Kemerovo region. The study involved methods of analysis, systematization of statistical and scientific information, comparison and generalization, as well as a marketing survey method.
 Results and discussion. The research started with an analysis of the structure and dynamics of the age-sex composition of the population in 2017–2019. The number of the elderly increased by 5% compared to 2017. The analysis also showed a stable quantitative prevalence of female population, i.e. 64.9% in 2017 and 64.8% in 2019. The daily diet of most survey participants included cereals, dairy products, and vegetables. The survey helped to identify the purchase factors. Price proved to be the main factor when choosing dairy products (72%). Most respondents (47%) consume dairy products daily.
 Conclusion. The marketing research defined the purchase factors for people of advanced and gerontic age in choosing food products. The obtained data can help to improve the gerodietetic products on the consumer market of Kemerovo.

Aging Affects the Capacity of Photoperiodic Adaptation Downstream from the Central Molecular Clock.

Aging impairs circadian clock function, leading to disrupted sleep-wake patterns and a reduced capability to adapt to changes in environmental light conditions. This makes shift work or the changing of time zones challenging for the elderly and, importantly, is associated with the development of age-related diseases. However, it is unclear what levels of the clock machinery are affected by aging, which is relevant for the development of targeted interventions. We found that naturally aged mice of >24 months had a reduced rhythm amplitude in behavior compared with young controls (3-6 months). Moreover, the old animals had a strongly reduced ability to adapt to short photoperiods. Recording PER2::LUC protein expression in the suprachiasmatic nucleus revealed no impairment of the rhythms in PER2 protein under the 3 different photoperiods tested (LD: 8:16, 12:12, and 16:8). Thus, we observed a discrepancy between the behavioral phenotype and the molecular clock, and we conclude that the aging-related deficits emerge downstream of the core molecular clock. Since it is known that aging affects several intracellular and membrane components of the central clock cells, it is likely that an impairment of the interaction between the molecular clock and these components is contributing to the deficits in photoperiod adaptation.

Circular RNAs: Promising Biomarkers for Age-related Diseases.

Aging is a complex biological process closely linked with the occurrence and development of age-related diseases. Despite recent advances in lifestyle management and drug therapy, the late diagnosis of these diseases causes severe complications, usually resulting in death and consequently impacting social economies. Therefore, the identification of reliable biomarkers and the creation of effective treatment alternatives for age-related diseases are needed. Circular RNAs (circRNAs) are a novel class of RNA molecules that form covalently closed loops capable of regulating gene expression at multiple levels. Several studies have reported the emerging functional roles of circRNAs in various conditions, providing new perspectives regarding cellular physiology and disease pathology. Notably, accumulating evidence demonstrates the involvement of circRNAs in the regulation of age-related pathologies, including cardio-cerebrovascular disease, neurodegenerative disease, cancer, diabetes, rheumatoid arthritis, and osteoporosis. Therefore, the association of circRNAs with these age-related pathologies highlights their potential as diagnostic biomarkers and therapeutic targets for better disease management. Here, we review the biogenesis and function of circRNAs, with a special focus on their regulatory roles in aging-related pathologies, as well as discuss their potential as biological biomarkers and therapeutic targets for these diseases.

Adiposity and dyslipidaemia are associated with epigenetic age acceleration

AbstractAdipose tissue is an endocrine organ involved in a variety of regulatory functions beyond simple fat storage. Excessive fat accumulation in the visceral tissue has been related to obesity associated comorbidities and manifestations such as hypertension, hyperglycaemia, hypercholesterolemia, and inflammatory processes. In the later stages of life, there is a shift of fat distribution from subcutaneous to visceral depots, which is associated to the development of several age-related diseases. Epigenetics has been described as a potential contributor in aging processes, being also associated with diseases and fat deposition that progress with age. The aim of this research was to investigate the relationships between aging, epigenetic processes and visceral adipose tissue.The study population included 269 adult subjects recruited in the University of Navarra, Spain. Methylation data was assessed by Infinium MethylationEPIC beadchip from Illumina. Epigenetic age acceleration was calculated using the method GrimAge (AgeAccGrim), available in the website DNA methylation Age Calculator (https://dnamage.genetics.ucla.edu/home). Anthropometric, biochemical and blood pressure measurements were assessed following standardized methods. Body composition measurements by DXA were also carried out.Statistically significant correlations were found between age acceleration and waist circumference, some DXA-measured variables (lean mass, trunk fat mass, android fat mass, visceral adipose tissue mass), glucose, HDL-cholesterol, triglycerides levels and C-reactive protein. Linear regression models showed that visceral adipose tissue mass and HDL-cholesterol were conjointly influencing the epigenetic age acceleration. In addition, a mediation by HDL-cholesterol in the relationship between AgeAccGrim and visceral adipose tissue mass was found.Collectively, these findings demonstrated that visceral adiposity and dyslipidaemia are associated with accelerated aging effects, contributing to understand the development of age-related diseases.

Copy Number of the Mitochondrial DNA of Leucocytes as an Aging Marker and Risk Factors for the Development of Age-Related Diseases in Humans

The mitochondrial DNA (mtDNA) copy number was analyzed via quantitative real-time PCR. A random subset of 996 people was studied (437 men with an average age of 67.3 ± 7.2 years and 559 women with an average age of 67.6 ± 7.1 years). They were selected from a population cohort of 9360 people who were initially examined in the international HAPIEE project (2003–2005, initial age of 45–69 years) in Novosibirsk. The participants were reexamined after 12 years in 2015–2017. The average relative mtDNA copy number in women was significantly higher than in men, regardless of age and smoking status, p = 0.001. The relative mtDNA copy number of blood leukocytes negatively correlated with age in men (p = 0.005) and women (p < 0.001). In the age-standardized analysis, the mtDNA copy number was negatively associated with waist and hip size and heart rate in people of both genders. Associations with some other indicators depend on gender. In women, the mtDNA copy number was negatively associated with the atherogenicity level, body mass indices, and blood glucose level and positively associated with HDL cholesterol. In men, the mtDNA copy number is positively related to the level of physical activity. Regardless of age, the average relative mtDNA copy number in peripheral blood leukocytes was higher in nonsmoking men than in smokers (p = 0.003). The mtDNA copy number was lower in women with diabetes mellitus than in women without it (p = 0.005). In both genders, people with an initial history of arterial hypertension had a lower mtDNA copy number in peripheral blood leukocytes after 12 years of observation than normotonics (p = 0.05). These results broadly support the hypothesis that the mtDNA copy number may act as a biomarker of age.

Where Metabolism Meets Senescence: Focus on Endothelial Cells.

Despite the decline in their proliferative potential, senescent cells display a high metabolic activity. Senescent cells have been shown to acquire a more glycolytic state even in presence of high oxygen levels, in a way similar to cancer cells. The diversion of pyruvate, the final product of glycolysis, away from oxidative phosphorylation results in an altered bioenergetic state and may occur as a response to the enhanced oxidative stress caused by the accumulation of dysfunctional mitochondria. This metabolic shift leads to increased AMP/ATP and ADP/ATP ratios, to the subsequent AMPK activation, and ultimately to p53-mediated growth arrest. Mounting evidences suggest that metabolic reprogramming is critical to direct considerable amounts of energy toward specific activities related to the senescent state, including the senescence-associated secretory phenotype (SASP) and the modulation of immune responses within senescent cell tissue microenvironment. Interestingly, despite the relative abundance of oxygen in the vascular compartment, healthy endothelial cells (ECs) produce most of their ATP content from the anaerobic conversion of glucose to lactate. Their high glycolytic rate further increases during senescence. Alterations in EC metabolism have been identified in age-related diseases (ARDs) associated with a dysfunctional vasculature, including atherosclerosis, type 2 diabetes and cardiovascular diseases. In particular, higher production of reactive oxygen species deriving from a variety of enzymatic sources, including uncoupled endothelial nitric oxide synthase and the electron transport chain, causes DNA damage and activates the NAD+-consuming enzymes polyADP-ribose polymerase 1 (PARP1). These non-physiological mechanisms drive the impairment of the glycolytic flux and the diversion of glycolytic intermediates into many pathological pathways. Of note, accumulation of senescent ECs has been reported in the context of ARDs. Through their pro-oxidant, pro-inflammatory, vasoconstrictor, and prothrombotic activities, they negatively impact on vascular physiology, promoting both the onset and development of ARDs. Here, we review the current knowledge on the cellular senescence-related metabolic changes and their contribution to the mechanisms underlying the pathogenesis of ARDs, with a particular focus on ECs. Moreover, current and potential interventions aimed at modulating EC metabolism, in order to prevent or delay ARD onset, will be discussed.

New Insights for Cellular and Molecular Mechanisms of Aging and Aging-Related Diseases: Herbal Medicine as Potential Therapeutic Approach.

Aging is a progressive disease affecting around 900 million people worldwide, and in recent years, the mechanism of aging and aging-related diseases has been well studied. Treatments for aging-related diseases have also made progress. For the long-term treatment of aging-related diseases, herbal medicine is particularly suitable for drug discovery. In this review, we discuss cellular and molecular mechanisms of aging and aging-related diseases, including oxidative stress, inflammatory response, autophagy and exosome interactions, mitochondrial injury, and telomerase damage, and summarize commonly used herbals and compounds concerned with the development of aging-related diseases, including Ginkgo biloba, ginseng, Panax notoginseng, Radix astragali, Lycium barbarum, Rhodiola rosea, Angelica sinensis, Ligusticum chuanxiong, resveratrol, curcumin, and flavonoids. We also summarize key randomized controlled trials of herbal medicine for aging-related diseases during the past ten years. Adverse reactions of herbs were also described. It is expected to provide new insights for slowing aging and treating aging-related diseases with herbal medicine.

THE GUT MICROBIOME AND AGING

The human intestinal tract (i.e., “gut”) is inhabited by over 100 trillion microorganisms; including over 1000 species of known bacteria. These organisms have co-evolved with humans over millennia to live together for mutual benefit. Though long overlooked in considerations of human health and disease treatment, gut microorganisms are highly involved in numerous metabolic reactions which influence normal host physiology. A variety of biologic, medical, and lifestyle factors appear to contribute to gut dysbiosis in late-life, and interventions specifically designed to target these factors may be useful in restoring microbial balance. Evidence from both clinical and preclinical studies suggests that gut dysbiosis is related to age-related inflammation as well as age-related conditions including frailty, Alzheimer’s disease, and perhaps even longevity. Crosstalk between the gut and multiple organ systems (brain, heart, muscle etc.) may lead to the development of age-related diseases and loss of physiological function, although the signals are not well understood. In this symposium we address the broad topic of the Gut Microbiome and Aging by presenting evidence from multiple model systems (mice, rats and monkeys) and provide a forum to discuss critical areas of research for moving forward.

Affective Behavior Shows Sex Differences in Mid-adulthood Rats Following Postnatal Immune Stimulation

Mid-adulthood represents the critical window period usually associated with the development of age-related diseases. Despite several attempts to delineate the pathological mechanisms underlying postnatal immune challenge and altered brain functions, the role of sex-dependent changes in affective behaviors of middle-aged animals requires more attention. In this study, we sought to investigate behavioral and molecular response patterns at mid-adulthood linked to early-life immune activation. Using affective behavioral test batteries, we showed that lipopolysaccharide (LPS)-induced postnatal immune challenge caused anxiety-like behaviors in both male and female Wistar rats at mid-adulthood, whereas only female rats exhibited depression-like behaviors. Our data further demonstrated a significant increase in microglial complexity and increased levels of tumor necrosis factor (TNFα), nitric oxide (NOx), and lipid peroxidation in the prefrontal cortex of female rats compared to their male counterparts and phosphate-buffered saline (PBS) littermate controls. With these results, we established significant interaction between sex differences and LPS-induced alterations in behavior and associated oxidative and immunohistochemical changes. These findings may provide an insight to better understand the neuroimmunological mechanisms of sex-dependent brain pathological manifestations occurring at mid-adulthood. [Display omitted]

Association of Short-term Change in Leukocyte Telomere Length With Cortical Thickness and Outcomes of Mental Training Among Healthy Adults

Telomere length is associated with the development of age-related diseases and structural differences in multiple brain regions. It remains unclear, however, whether change in telomere length is linked to brain structure change, and to what extent telomere length can be influenced through mental training. To assess the dynamic associations between leukocyte telomere length (LTL) and cortical thickness (CT), and to determine whether LTL is affected by a longitudinal contemplative mental training intervention. An open-label efficacy trial of three 3-month mental training modules with healthy, meditation-naive adults was conducted. Data on LTL and CT were collected 4 times over 9 months between April 22, 2013, and March 31, 2015, as part of the ReSource Project. Data analysis was performed between September 23, 2016, and June 21, 2019. Of 1582 eligible individuals, 943 declined to participate; 362 were randomly selected for participation and assigned to training or retest control cohorts, with demographic characteristics matched. The retest control cohorts underwent all testing but no training. Intention-to-treat analysis was performed. Training cohort participants completed 3 modules cultivating interoception and attention (Presence), compassion (Affect), or perspective taking (Perspective). Change in LTL and CT. Of the 362 individuals randomized, 30 participants dropped out before study initiation (initial sample, 332). Data were available for analysis of the training intervention in 298 participants (n = 222 training; n = 76 retest control) (175 women [58.7%]; mean [SD] age, 40.5 [9.3] years). The training modules had no effect on LTL. In 699 observations from all 298 participants, mean estimated changes in the relative ratios of telomere repeat copy number to single-copy gene (T/S) were for no training, 0.004 (95% CI, -0.010 to 0.018); Presence, -0.007 (95% CI, -0.025 to 0.011); Affect, -0.005 (95% CI, -0.019 to 0.010); and Perspective, -0.001 (95% CI, -0.017 to 0.016). Cortical thickness change data were analyzed in 167 observations from 67 retest control participants (37 women [55.2%], mean [SD] age, 39.6 [9.0] years). In this retest control cohort subsample, naturally occurring LTL change was related to CT change in the left precuneus extending to the posterior cingulate cortex (mean t161 = 3.22; P < .001; r = 0.246). At the individual participant level, leukocyte telomere shortening as well as lengthening were observed. Leukocyte telomere shortening was related to cortical thinning (t77 = 2.38; P = .01; r = 0.262), and leukocyte telomere lengthening was related to cortical thickening (t77 = 2.42; P = .009; r = 0.266). All analyses controlled for age, sex, and body mass index. The findings of this trial indicate an association between short-term change in LTL and concomitant change in plasticity of the left precuneus extending to the posterior cingulate cortex. This result contributes to the evidence that LTL changes more dynamically on the individual level than previously thought. Further studies are needed to determine potential long-term implications of such change in relation to cellular aging and the development of neurodegenerative disorders. No effect of contemplative mental training was noted in what may be, to date, the longest intervention with healthy adults. ClinicalTrials.gov identifier: NCT01833104.

Exosomal long noncoding RNAs in aging and age-related diseases.

Molecules secreted by cells into the internal environment during aging, including those secreted in exosomes, have long been a matter of concern. Those cells that absorb exosomes, also known as recipient cells, exhibit certain phenotypic changes because of the regulatory role of functional molecules (including proteins and nucleic acids) released in exosomes. Involvement of noncoding RNAs (ncRNAs) in the regulation of aging has received increasing attention, and long ncRNAs (lncRNAs) have become one of the research hotspots in recent years. LncRNAs carried by exosomes play a role in intercellular communication between adjacent and distant cells. Moreover, exosomal lncRNAs promote the decline of organ functions and the development of age-related diseases, including atherosclerosis, Type 2 diabetes, osteoporosis, osteoarthritis, rheumatoid arthritis, Parkinson's disease, multiple sclerosis, and cancer. Here, we review the regulatory roles of exosomal lncRNAs in aging and age-related diseases.

The influence of the microbiota on immune development, chronic inflammation, and cancer in the context of aging.

From birth, the microbiota plays an essential role in human development by educating host immune responses. Proper maturation of the immune system perturbs chronic inflammation and the pathogenesis of disease by preventing inappropriate immune responses. While many have detailed the roles of specific microbial groups in immune development and human disease, it remains to be elucidated how the microbiota influences the immune system during aging. Furthermore, it is not yet understood how age-related changes to the microbiota and immune system influence the development of age-related diseases. In this review, we outline the role of the microbiota in immune system development as well as functional changes that occur to immune cell populations during immunosenescence. In addition, we highlight how commensal microbes influence the pathogenesis of cancer, a prominent disease of aging. The information provided herein suggests that age-related changes to the microbiota and immune system should be considered in disease treatment and prevention strategies.

Interaction Among Sex, Aging, and Epigenetic Processes Concerning Visceral Fat, Insulin Resistance, and Dyslipidaemia.

The distribution of adipose tissue is influenced by gender and by age, shifting from subcutaneous to visceral depots with longevity, increasing the development of several aging-related diseases and manifestations such as obesity, metabolic syndrome, and insulin resistance. Epigenetics might have an important role in aging processes. The aim of this research was to investigate the interactions between aging and epigenetic processes and the role of visceral adipose tissue, insulin resistance, and dyslipidaemia. Two different study samples of 366 and 269 adult participants were analyzed. Anthropometric, biochemical (including the triglycerides-glucose (TyG) index), and blood pressure measurements were assessed following standardized methods. Body composition measurements by Dual-energy X-ray absorptiometry (DXA) were also performed for the second sample. Methylation data were assessed by Infinium Human Methylation BeadChip (Illumina) in peripheral white blood cells. Epigenetic age acceleration was calculated using the methods DNAmAge (AgeAcc) and GrimAge (AgeAccGrim). Age acceleration (AgeAccGrim) showed better correlations than AgeAcc with most of the measured variables (waist circumference, glucose, HOMA-IR, HDL-cholesterol, triglycerides, and TyG index) for the first sample. In the second sample, all the previous correlations were confirmed, except for HOMA-IR. In addition, many of the anthropometrical measurements assessed by DXA and C-reactive protein (CRP) were also statistically associated with AgeAccGrim. Associations separated by sex showed statistically significant correlations between AgeAccGrim and HDL-cholesterol or CRP in women, whereas, in men, the association was with visceral adipose tissue mass DXA, triglycerides and TyG index. Linear regression models (model 1 included visceral adipose tissue mass DXA and TyG index and model 2 included HDL-cholesterol and CRP) showed a significant association for men concerning visceral adipose tissue mass DXA and TyG index, while HDL-cholesterol and CRP were associated in women. Moreover, structural equation modeling showed that the TyG index was mediating the majority of the visceral adipose tissue mass action on age acceleration. Collectively, these findings showed that there are different mechanisms affecting epigenetic age acceleration depending on sex. The identified relationships between epigenetic age acceleration and disease markers will contribute to the understanding of the development of age-related diseases.

Disadaptive Disorders of Regulation of Functions with Aging

This review examines the basic theories of aging, which show the irreversibility of this process that leads to the death of cells and the body. The hypotheses of phenoptosis and apoptosis are discussed, as well as the view that disadaptation initiates free radical oxidation reactions and violates the neurohumoral regulation of functions. The review briefly examines the mechanisms of the development of age-related diseases. The hypothesis that partial adaptation and disadaptation are transitional biological processes associated with aging is proposed. A regularity that manifests itself in a reduction of the functional activity of an organ and cell metabolism in the state of disadaptation and aging (the principle of the limitation of cellular metabolism) is described. The study shows that aging leads to the progression of homeostatic disorders and changes in DNA methylation processes. The problem of the use of antioxidants, endogenous peptides, telomerase, and ozone to prevent the negative effects of oxidative stress on biomolecules and cellular structures is considered. It was proposed that the biosynthesis of biogenic amines significantly decreases during disadaptation and aging, which entails a decrease in the regulatory control of biochemical reactions by the hypothalamic-pituitary system. It is proposed that biogenic amines and their derivatives be considered substances that minimize the dysregulatory processes that reduce disadaptive manifestations in the body, stimulate cellular metabolism, and slow the aging process.

T-cell immunity against cytomegalovirus in HIV infection and aging: relationships with inflammation, immune activation, and frailty.

Both aging and treated human immunodeficiency virus (HIV) infection are characterized by low-level chronic inflammation and immune activation which contribute to the development of age-related diseases, frailty, and early mortality. Chronic cytomegalovirus (CMV) infection is highly prevalent in older adults and HIV-infected populations. A number of studies have shown that CMV induces broad and strong T-cell responses in CMV-seropositive older adults and HIV-infected individuals. CMV infection rarely develops into clinical disease in immunocompetent individuals. However, a large body of literature has shown adverse effects of chronic CMV infection on the health and longevity of these populations. It has been hypothesized that chronic CMV infection may be a driver of chronic inflammation and immune activation, and may further contribute to the development of frailty. Thus, there is a need to better understand the extent of the impact of chronic CMV infection on T-cell immunity and health in aging and HIV infection. In this review, we will address important considerations and challenges in the assessment of chronic CMV infection and CMV-specific T-cell responses. We will then review recent data on relationships between T-cell responses to CMV and levels of inflammatory markers and immune activation, as well as the onset of frailty.

A New Efficient Method for Measuring Oxygen Consumption Rate Directly ex vivo in Human Epidermal Biopsies.

Skin cells are constantly exposed to environmental influences such as air pollution, chemicals, pathogens and UV radiation. UV radiation can damage different biological structures, but most importantly cellular DNA. Mitochondria contain their own genome and accumulate UV-induced DNA mutations to a large extent. This can result, e.g., in accelerated skin aging. Understanding the impact of harmful external influences on mitochondrial function is therefore essential for a better view on the development of age-related diseases. Previous studies have been carried out on cell cultures derived from primary cells, which does not fully represent the real situation in the skin, while the mitochondrial parameters were considered barely or not at all. Here we describe a method to measure mitochondrial respiratory parameters in epithelial tissue derived from human skin biopsies using an Agilent Seahorse XF24 Flux Analyzer. Before the assay, epidermis and dermis are separated enzymatically, we then used the XF24 Islet capture microplates to position the epidermis samples to measure oxygen consumption rates (OCR) and extracellular acidification rates (ECAR). In these plates, small nets can be fixed to the plate bottom. The epidermis was placed with the vital-basal-side on the net. Active ingredients in the three ports were injected consecutively to determine the effect of each compound. This allows determining the efficiency of the individual complexes within the respiratory chain. This protocol enables the testing of toxic substances and their influence on the mitochondrial respiration parameters in human epithelial tissue.

Protective Role of Polyphenols against Vascular Inflammation, Aging and Cardiovascular Disease.

Aging is a major risk factor in the development of chronic diseases affecting various tissues including the cardiovascular system, muscle and bones. Age-related diseases are a consequence of the accumulation of cellular damage and reduced activity of protective stress response pathways leading to low-grade systemic inflammation and oxidative stress. Both inflammation and oxidative stress are major contributors to cellular senescence, a process in which cells stop proliferating and become dysfunctional by secreting inflammatory molecules, reactive oxygen species (ROS) and extracellular matrix components that cause inflammation and senescence in the surrounding tissue. This process is known as the senescence associated secretory phenotype (SASP). Thus, accumulation of senescent cells over time promotes the development of age-related diseases, in part through the SASP. Polyphenols, rich in fruits and vegetables, possess antioxidant and anti-inflammatory activities associated with protective effects against major chronic diseases, such as cardiovascular disease (CVD). In this review, we discuss molecular mechanisms by which polyphenols improve anti-oxidant capacity, mitochondrial function and autophagy, while reducing oxidative stress, inflammation and cellular senescence in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). We also discuss the therapeutic potential of polyphenols in reducing the effects of the SASP and the incidence of CVD.

2266. Persistent Inflammation in HIV Patients With Community-Acquired Pneumonia and Its Correlation With Lung Injury

BackgroundHIV patients face higher rates of morbidity compared with the general population, largely due to the earlier development of age related diseases (cardiovascular, kidney, and liver disease). While it is likely that chronic immune activation and inflammation are the main contributors to this process, it’s relation to lung injury in HIV remains unknown. Despite restoration of systemic immune function following Antiretroviral Therapy, the risk for lower respiratory tract infection remain elevated in the HIV population. The objective of the study was to assess the relationship between pulmonary inflammation and lung injury.MethodsA prospective cohort study was performed, participants include patients hospitalized in Hospital Universitario San Vicente Fundación and Clínica SOMA, in Colombia. Patients were eligible if they were over the age of 18 and had a documented HIV infection or if they have HIV with newly diagnosed community acquired pneumonia (CAP). The main exclusion criteria were chronic lung disease and immunosuppression that is not due to HIV. Patients belonged to two groups: HIV and HIV + CAP. Plasma, sputum samples and pulmonary function test measurements (PFT) were retrieved within 48 hours of hospital admission and at one month follow-up. The concentrations of 13 biomarkers were measured and correlated with PFT values, followed by a comparison between the two groups.ResultsPrinciple Component Analysis revealed that CCL3, CCL4, BAFF, APRIL, and TIMP-1 accounts for the majority of the variation between the two groups. Furthermore, Kruskal–Wallis testing demonstrates that BAFF and CCL3 are elevated in the HIV + CAP group, compared with the HIV group (P < 0.005). Other markers of bacterial translocation and monocyte activation did not differ between these groups. FVC and FEV1 measurements are lower in the HIV + CAP group compared with the HIV group, while FEV1/FVC remain constant.ConclusionThe results of this study identify a unique constellation of biomarkers in HIV patients with CAP, this constellation of biomarkers consists of pro-inflammatory cytokines and regulators of extracellular matrix remodeling, hinting at the occurrence of an inflammatory and tissue injuring process in the lungs. This is supported by the restrictive ventilation pattern seen in this group of patients.Disclosures All authors: No reported disclosures.

Induction of a senescent like phenotype and loss of gap junctional intercellular communication by carbon nanoparticle exposure of lung epithelial cells.

Inhalation of combustion-derived particles is associated with the development of age-related diseases like chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. In both diseases senescence of lung epithelial cells has been observed. Employing an in vitro system of repetitive exposure to pure carbon nanoparticles we asked whether this kind of particles are able to induce a senescent like phenotype, which might be accompanied by a loss of functionality at the level of gap junctional intercellular communication. Non-cytotoxic doses of carbon nanoparticles but not of bigger carbon particles led to an irreversible reduction of the proliferative capacity accompanied by the accumulation of the cell cycle blocking proteins p21 and p16 as well as a loss of both redox sensitive histone deacetylase SIRT1 and connexin-43. Gap junction intercellular communication detected by microinjection of fluorescent lucifer yellow was dramatically decreased after exposure. This loss of functionality was associated with a reduction of Connexin 43 at the plasma membrane. As the experimental system was chosen to study the effects of pure carbon nanoparticles in the absence of inflammatory cells, the data indicate that cumulative long-term exposure of the lung epithelium to low doses of combustion-derived nanoparticles might contribute to epithelial senescence and age-associated diseases of the airways.

Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases.

Aging is the progressive loss of organ and tissue function over time. Growing older is positively linked to cognitive and biological degeneration such as physical frailty, psychological impairment, and cognitive decline. Oxidative stress is considered as an imbalance between pro- and antioxidant species, which results in molecular and cellular damage. Oxidative stress plays a crucial role in the development of age-related diseases. Emerging research evidence has suggested that antioxidant can control the autoxidation by interrupting the propagation of free radicals or by inhibiting the formation of free radicals and subsequently reduce oxidative stress, improve immune function, and increase healthy longevity. Indeed, oxidation damage is highly dependent on the inherited or acquired defects in enzymes involved in the redox-mediated signaling pathways. Therefore, the role of molecules with antioxidant activity that promote healthy aging and counteract oxidative stress is worth to discuss further. Of particular interest in this article, we highlighted the molecular mechanisms of antioxidants involved in the prevention of age-related diseases. Taken together, a better understanding of the role of antioxidants involved in redox modulation of inflammation would provide a useful approach for potential interventions, and subsequently promoting healthy longevity.