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1.  Dysregulated inflammation as a risk factor for pneumonia in the elderly 
Aging and disease  2011;2(6):487-500.
Advances in modern medicine have led to an increase in the median life span and an expansion of the world’s population over the age of 65. With increasing numbers of the population surviving to the extreme of age, those at risk for the development of pneumonia will approach 2 billion by the year 2050. Numerous age-related changes in the lung likely contribute to the enhanced occurrence of pneumonia in the elderly. Inflammation in the elderly has been shown to increase risk prior to infection; age-associated inflammation enhances bacterial ligand expression in the lungs which increases the ability of bacteria to attach and invade host cells. Conversely, the elaboration of the acute inflammatory response during early infection has been found to decrease with age resulting in a delayed immune response and diminished bacterial killing. Finally, the resolution of the inflammatory response during the convalescent stage back to “baseline” is often prolonged in the elderly and associated with negative outcomes, such as adverse cardiac events. The focus of this review will be to discuss our current understanding of the potential mechanisms by which dysregulated inflammation (both prior to and following an infectious insult) enhances susceptibility to and severity of community acquired pneumonia (CAP) in the elderly with an emphasis on pneumococcal pneumonia, the leading cause of CAP.
PMCID: PMC3265328  PMID: 22288022
Aging; Pneumonia; Inflammation; Toll-like Receptors; Statins
2.  Dysregulated Inflammation as a Risk Factor for Pneumonia in the Elderly 
Aging and Disease  2011;2(6):487-500.
Advances in modern medicine have led to an increase in the median life span and an expansion of the world’s population over the age of 65. With increasing numbers of the population surviving to the extreme of age, those at risk for the development of pneumonia will approach 2 billion by the year 2050. Numerous age-related changes in the lung likely contribute to the enhanced occurrence of pneumonia in the elderly. Inflammation in the elderly has been shown to increase risk prior to infection; age-associated inflammation enhances bacterial ligand expression in the lungs which increases the ability of bacteria to attach and invade host cells. Conversely, the elaboration of the acute inflammatory response during early infection has been found to decrease with age resulting in a delayed immune response and diminished bacterial killing. Finally, the resolution of the inflammatory response during the convalescent stage back to “baseline” is often prolonged in the elderly and associated with negative outcomes, such as adverse cardiac events. The focus of this review will be to discuss our current understanding of the potential mechanisms by which dysregulated inflammation (both prior to and following an infectious insult) enhances susceptibility to and severity of community acquired pneumonia (CAP) in the elderly with an emphasis on pneumococcal pneumonia, the leading cause of CAP.
PMCID: PMC3265328  PMID: 22288022
Aging; Pneumonia; Inflammation; Toll-like Receptors; Statins
3.  The Critical Need to Promote Research of Aging and Aging-related Diseases to Improve Health and Longevity of the Elderly Population 
Aging and Disease  2014;6(1):1-5.
Due to the aging of the global population and the derivative increase in aging-related non-communicable diseases and their economic burden, there is an urgent need to promote research on aging and aging-related diseases as a way to improve healthy and productive longevity for the elderly population. To accomplish this goal, we advocate the following policies: 1) Increasing funding for research and development specifically directed to ameliorate degenerative aging processes and to extend healthy and productive lifespan for the population; 2) Providing a set of incentives for commercial, academic, public and governmental organizations to foster engagement in such research and development; and 3) Establishing and expanding coordination and consultation structures, programs and institutions involved in aging-related research, development and education in academia, industry, public policy agencies and at governmental and supra-governmental levels.
PMCID: PMC4306469  PMID: 25657847
aging; aging-related diseases; health; longevity; elderly; population
4.  Effect of Aging in the Perception of Health-Related Quality of Life in End-Stage Renal Disease Patients under Online-Hemodiafiltration 
Aging and Disease  2014;6(1):17-26.
This work aimed to evaluate how aging could influence patients’ perception of health quality of life (HRQOL), as well as, the effect of aging on dialysis adequacy and in hematological, iron status, inflammatory and nutritional markers. In this transversal study were enrolled 305 ESRD patients under online-hemodiafiltration (OL-HDF) (59.67% males; 64.9 ± 14.3 years old). Data about comorbidities, hematological data, iron status, dialysis adequacy, nutritional and inflammatory markers were collected from patient’s records. Moreover, HRQOL score, by using the Kidney Disease Quality of Life-Short Form (KDQOL-SF), was assessed. Analyzing the results according to quartiles of age, significant differences were found for some parameters evaluated by the KDQOL-SF instrument, namely for work status, physical functioning and role-physical, which decreased with increasing age. We also found a higher proportion of diabetic patients, a decrease in creatinine, iron, albumin serum levels, transferrin saturation and nPCR, with increasing age. Moreover, significant negative correlations were found between age and mean cell hemoglobin concentration, iron, transferrin saturation, albumin, nPCR, work status, physical functioning and role-physical. In conclusion, our results showed that aging is associated with a decreased work status, physical functioning and role-physical, with a decreased dialysis adequacy, iron availability and nutritional status, and with an increased proportion of diabetic patients and of patients using central venous catheter, as the vascular access. The knowledge of these changes associated with aging, which have impact in the quality of life of the patients, could be useful in their management.
PMCID: PMC4306470  PMID: 25657849
Health-related quality of life; on-line hemodiafiltration; aging; gender; dialysis adequacy; iron availability; nutritional status
5.  Healthcare-associated Pneumonia and Aspiration Pneumonia 
Aging and Disease  2014;6(1):27-37.
Healthcare-associated pneumonia (HCAP) is a new concept of pneumonia proposed by the American Thoracic Society/Infectious Diseases Society of America in 2005. This category is located between community-acquired pneumonia and hospital-acquired pneumonia with respect to the characteristics of the causative pathogens and mortality, and primarily targets elderly patients in healthcare facilities. Aspiration among such patients is recognized to be a primary mechanism for the development of pneumonia, particularly since the HCAP guidelines were published. However, it is difficult to manage patients with aspiration pneumonia because the definition of the condition is unclear, and the treatment is associated with ethical aspects. This review focused on the definition, prevalence and role of aspiration pneumonia as a prognostic factor in published studies of HCAP and attempted to identify problems associated with the concept of aspiration pneumonia.
PMCID: PMC4306471  PMID: 25657850
healthcare-associated pneumonia; aspiration pneumonia; elderly; diagnosis
6.  Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System 
Aging and Disease  2014;6(1):38-47.
Dizziness and imbalance are amongst the most common complaints in older people, and are a growing public health concern since they put older people at a significantly higher risk of falling. Although the causes of dizziness in older people are multifactorial, peripheral vestibular dysfunction is one of the most frequent causes. Benign paroxysmal positional vertigo is the most frequent form of vestibular dysfunction in the elderly, followed by Meniere’s disease. Every factor associated with the maintenance of postural stability deteriorates during aging. Age-related deterioration of peripheral vestibular function has been demonstrated through quantitative measurements of the vestibulo-ocular reflex with rotational testing and of the vestibulo-collic reflex with testing of vestibular evoked myogenic potentials. Age-related decline of vestibular function has been shown to correlate with the age-related decrease in the number of vestibular hair cells and neurons. The mechanism of age-related cellular loss in the vestibular endorgan is unclear, but it is thought that genetic predisposition and cumulative effect of oxidative stress may both play an important role. Since the causes of dizziness in older people are multi-factorial, management of this disease should be customized according to the etiologies of each individual. Vestibular rehabilitation is found to be effective in treating both unilateral and bilateral vestibular dysfunction. Various prosthetic devices have also been developed to improve postural balance in older people. Although there have been no medical treatments improving age-related vestibular dysfunction, new medical treatments such as mitochondrial antioxidants or caloric restriction, which have been effective in preventing age-related hearing loss, should be ienvestigated in the future.
PMCID: PMC4306472  PMID: 25657851
aging; vestibular; fall; rehabilitation
7.  Eating Disorders in Late-life 
Aging and Disease  2014;6(1):48-55.
Eating disorders are a heterogeneous group of complex psychiatric disorders characterized by abnormal eating behaviours that lead to a high rate of morbidity, or even death, if underestimated and untreated. The main disorders enlisted in the chapter of the Diagnostic and Statistic Manual of Mental Disorders-5 dedicated to “Feeding and Eating Disorders” are: anorexia nervosa, bulimia nervosa and binge eating disorder. Even though these abnormal behaviours are mostly diagnosed during childhood, interesting cases of late-life eating disorders have been reported in literature. In this review, these eating disorders are discussed, with particular attention to the diagnosis and management of those cases occurring in late-life.
PMCID: PMC4306473  PMID: 25657852
eating disorders; anorexia nervosa; bulimia nervosa; binge eating disorders; eating disorders in late-life
8.  The Intricate Interplay between Mechanisms Underlying Aging and Cancer 
Aging and Disease  2014;6(1):56-75.
Age is the major risk factor in the incidence of cancer, a hyperplastic disease associated with aging. Here, we discuss the complex interplay between mechanisms underlying aging and cancer as a reciprocal relationship. This relationship progresses with organismal age, follows the history of cell proliferation and senescence, is driven by common or antagonistic causes underlying aging and cancer in an age-dependent fashion, and is maintained via age-related convergent and divergent mechanisms. We summarize our knowledge of these mechanisms, outline the most important unanswered questions and suggest directions for future research.
PMCID: PMC4306474  PMID: 25657853
aging; cancer; cell cycle; cellular senescence; cell death; cellular signaling
9.  The Human Trochlear and Abducens Nerves at Different Ages - a Morphometric Study 
Aging and Disease  2014;6(1):6-16.
The trochlear and abducens nerves (TN and AN) control the movement of the superior oblique and lateral rectus muscles of the eyeball, respectively. Despite their immense clinical and radiological importance no morphometric data was available from a wide spectrum of age groups for comparison with either pathological or other conditions involving these nerves. In the present study, morphometry of the TN and AN was performed on twenty post-mortem samples ranging from 12–90 years of age. The nerve samples were processed for resin embedding and toluidine blue stained thin (1µm) sections were used for estimating the total number of myelinated axons by fractionator and the cross sectional area of the nerve and the axons by point counting methods. We observed that the TN was covered by a well-defined epineurium and had ill-defined fascicles, whereas the AN had multiple fascicles with scanty epineurium. Both nerves contained myelinated and unmyelinated fibers of various sizes intermingled with each other. Out of the four age groups (12–20y, 21–40y, 41–60y and >61y) the younger groups revealed isolated bundles of small thinly myelinated axons. The total number of myelinated fibers in the TN and AN at various ages ranged from 1100–3000 and 1600–7000, respectively. There was no significant change in the cross-sectional area of the nerves or the axonal area of the myelinated nerves across the age groups. However, myelin thickness increased significantly in the AN with aging (one way ANOVA). The present study provides baseline morphometric data on the human TN and AN at various ages.
PMCID: PMC4306475  PMID: 25657848
stereology; morphometry; ocular motor nerves; myelin thickness
10.  Aging is Associated with Impaired Renal Function, INF-gamma Induced Inflammation and with Alterations in Iron Regulatory Proteins Gene Expression 
Aging and Disease  2013;5(6):356-365.
Our aim was to contribute to a better understanding of the pathophysiology of anemia in elderly, by studying how aging affects renal function, iron metabolism, erythropoiesis and the inflammatory response, using an experimental animal model. The study was performed in male Wistar, a group of young rats with 2 months age and an old one with 18 months age. Old rats presented a significant higher urea, creatinine, interferon (INF)-gamma, ferritin and soluble transferrin receptor serum levels, as well as increased counts of reticulocytes and RDW. In addition, these rats showed significant lower erythropoietin (EPO) and iron serum levels. Concerning gene expression of iron regulatory proteins, old rats presented significantly higher mRNA levels of hepcidin (Hamp), transferrin (TF), transferrin receptor 2 (TfR2) and hemojuvelin (HJV); divalent metal transporter 1 (DMT1) mRNA levels were significantly higher in duodenal tissue; EPO gene expression was significantly higher in liver and lower in kidney, and the expression of the EPOR was significantly higher in both liver and kidney. Our results showed that aging is associated with impaired renal function, which could be in turn related with the inflammatory process and with a decline in EPO renal production. Moreover, we also propose that aging may be associated with INF-gamma-induced inflammation and with alterations upon iron regulatory proteins gene expression.
PMCID: PMC4249806  PMID: 25489488
Anemia; older population; elderly; renal failure; inflammation; erythropoietic disturbances
11.  Reduced Apoptosis by Ethanol and Its Association with PKC-δ and Akt Signaling in Ischemic Stroke 
Aging and Disease  2014;5(6):366-372.
Along with thrombolytic therapy, which has a number of limitations, stroke outcome may be improved with neuroprotective therapies that disrupt ischemic cell death. Recent research has shown a neuroprotective role of ethanol administration during ischemic stroke, such as its ability to reduce infarct volume and neurologic deficit. In order to investigate this further, we assessed the hypothesis that ethanol’s neuroprotective effect is through reduction of apoptosis and the modulation of the important apoptotic PKC-δ and Akt signaling pathway. Ethanol (1.5 g/kg) was given by intraperitoneal injections to 54 Sprague-Dawley rats after 2 hours of middle cerebral artery (MCA) occlusion, followed by 3 or 24 hours of reperfusion. We measured apoptotic cell death, PKC-δ, and Akt mRNA and protein expressions in each of ischemic groups with or without ethanol treatment using ELISA, real-time PCR and Western blot analysis. Our results showed that cell death was significantly increased in rats following 2 hour MCA occlusion and 24 hour reperfusion. Subsequently, cell death was significantly reduced by an administration of ethanol. We further found that ethanol administration, prior to either 3 or 24 hours of reperfusion, significantly decreased the expression of PKC-δ while simultaneously increasing the expression Akt at both mRNA and protein levels at the two points. In conclusion, our study suggests that ethanol administration following ischemic stroke modulates the gene and protein profile in such a way that it increased expression of anti-apoptotic Akt and decreased the pro-apoptotic PKC-δ. This ultimately results in a decrease in neuronal apoptosis, thus conferring neuroprotection.
PMCID: PMC4249807  PMID: 25489491
Ischemia/reperfusion; neuroprotection; apoptosis; ethanol; PKC-δ; Akt/PKB
12.  Use of Anthropometry for the Prediction of Regional Body Tissue Distribution in Adults: Benefits and Limitations in Clinical Practice 
Aging and Disease  2013;5(6):373-393.
Regional body composition changes with aging. Some of the changes in composition are considered major risk factors for developing obesity related chronic diseases which in turn may lead to increased mortality in adults. The role of anthropometry is well recognized in the screening, diagnosis and follow-up of adults for risk classification, regardless of age. Regional body composition is influenced by a number of intrinsic and extrinsic factors. Therapeutic measures recommended to lower cardiovascular disease risk include lifestyle changes. The aim of this review is to systematically summarize studies that assessed the relationships between anthropometry and regional body composition. The potential benefits and limitations of anthropometry for use in clinical practice are presented and suggestions for future research given.
PMCID: PMC4249808  PMID: 25489489
anthropometry; body composition; prediction formula
13.  Regulation and Role of TGFβ Signaling Pathway in Aging and Osteoarthritis Joints 
Aging and Disease  2013;5(6):394-405.
Transforming growth factor beta (TGFβ) is a major signalling pathway in joints. This superfamilly is involved in numerous cellular processes in cartilage. Usually, they are considered to favor chondrocyte differentiation and cartilage repair. However, other studies show also deleterious effects of TGFβ which may induce hypertrophy. This may be explained at least in part by alteration of TGFβ signaling pathways in aging chondrocytes. This review focuses on the functions of TGFβ in joints and the regulation of its signaling mediators (receptors, Smads) during aging and osteoarthritis.
PMCID: PMC4249809  PMID: 25489490
osteoarthritis; TGFbeta; chondrocytes; aging
14.  The Circadian Timing System: A Recent Addition in the Physiological Mechanisms Underlying Pathological and Aging Processes 
Aging and Disease  2014;5(6):406-418.
Experimental findings and clinical observations have strengthened the association between physio-pathologic aspects of several diseases, as well as aging process, with the occurrence and control of circadian rhythms. The circadian system is composed by a principal pacemaker in the suprachiasmatic nucleus (SNC) which is in coordination with a number of peripheral circadian oscillators. Many pathological entities such as metabolic syndrome, cancer and cardiovascular events are strongly connected with a disruptive condition of the circadian cycle. Inadequate circadian physiology can be elicited by genetic defects (mutations in clock genes or circadian control genes) or physiological deficiencies (desynchronization between SCN and peripheral oscillators). In this review, we focus on the most recent experimental findings regarding molecular defects in the molecular circadian clock and the altered coordination in the circadian system that are related with clinical conditions such as metabolic diseases, cancer predisposition and physiological deficiencies associated to jet-lag and shiftwork schedules. Implications in the aging process will be also reviewed.
PMCID: PMC4249810  PMID: 25489492
molecular clock; circadian physiology; peripheral oscillator; uncoupling; jet-lag; metabolic diseases
15.  Early-life Exposure to Endocrine Disrupting Chemicals and Later-life Health Outcomes: An Epigenetic Bridge? 
Aging and Disease  2014;5(6):419-429.
A growing body of evidence demonstrates that adverse events early in development, and particularly during intrauterine life, may program risks for diseases in adult life. Increasing evidence has been accumulated indicating the important role of epigenetic regulation including DNA methylation, histone modifications and miRNAs in developmental programming. Among the environmental factors which play an important role in programming of chronic pathologies, the endocrine-disrupting chemicals (EDCs) that have estrogenic, anti-estrogenic, and anti-androgenic activity are of specific concern because the developing organism is extremely sensitive to perturbation by substances with hormone-like activity. Among EDCs, there are many substances that are constantly present in the modern human environment or are in widespread use, including dioxin and dioxin-like compounds, phthalates, agricultural pesticides, polychlorinated biphenyls, industrial solvents, pharmaceuticals, and heavy metals. Apart from their common endocrine active properties, several EDCs have been shown to disrupt developmental epigenomic programming. The purpose of this review is to provide a summary of recent research findings which indicate that exposure to EDCs during in-utero and/or neonatal development can cause long-term health outcomes via mechanisms of epigenetic memory.
PMCID: PMC4249811  PMID: 25489493
endocrine-disrupting chemicals; developmental programming; epigenetics; adult-life disease
16.  The Role of NMDA Receptors in the Development of Brain Resistance through Pre- and Postconditioning 
Aging and Disease  2014;5(6):430-441.
Brain tolerance or resistance can be achieved by interventions before and after injury through potential toxic agents used in low stimulus or dose. For brain diseases, the neuroprotection paradigm desires an attenuation of the resulting motor, cognitive, emotional, or memory deficits following the insult. Preconditioning is a well-established experimental and clinical translational strategy with great beneficial effects, but limited applications. NMDA receptors have been reported as protagonists in the adjacent cellular mechanisms contributing to the development of brain tolerance. Postconditioning has recently emerged as a new neuroprotective strategy, which has shown interesting results when applied immediately, i.e. several hours to days, after a stroke event. Investigations using chemical postconditioning are still incipient, but nevertheless represent an interesting and promising clinical strategy. In the present review pre- and postconditioning are discussed as neuroprotective paradigms and the focus of our attention lies on the participation of NMDA receptors proteins in the processes related to neuroprotection.
PMCID: PMC4249812  PMID: 25489494
N-methyl-D-aspartate receptors; preconditioning; postconditioning; neuroprotection
17.  Ischemic Stroke: A Consequence of a Diseased Immune System? 
Aging and Disease  2014;5(5):292-293.
PMCID: PMC4173795  PMID: 25276488
18.  Cytokines: Their Role in Stroke and Potential Use as Biomarkers and Therapeutic Targets 
Aging and Disease  2014;5(5):294-306.
Inflammatory mechanisms both in the periphery and in the CNS are important in the pathophysiologic processes occurring after the onset of ischemic stroke (IS). Cytokines are key players in the inflammatory mechanism and contribute to the progression of ischemic damage. This literature review focuses on the effects of inflammation on ischemic stroke, and the role pro-inflammatory and anti-inflammatory cytokines play on deleterious or beneficial stroke outcome. The discovery of biomarkers and novel therapeutics for stroke has been the focus of extensive research recently; thus, understanding the roles of pro-inflammatory and anti-inflammatory cytokines that are up-regulated during stroke will help us further understand how inflammation contributes to the progression of ischemic damage and provide potential targets for novel therapeutics and biomarkers for diagnosis and prognosis of stroke.
PMCID: PMC4173796  PMID: 25276489
Stroke; Cytokines; Biomarkers
19.  The Immune Response to Acute Focal Cerebral Ischemia and Associated Post-stroke Immunodepression: A Focused Review 
Aging and Disease  2014;5(5):307-326.
It is currently well established that the immune system is activated in response to transient or focal cerebral ischemia. This acute immune activation occurs in response to damage, and injury, to components of the neurovascular unit and is mediated by the innate and adaptive arms of the immune response. The initial immune activation is rapid, occurs via the innate immune response and leads to inflammation. The inflammatory mediators produced during the innate immune response in turn lead to recruitment of inflammatory cells and the production of more inflammatory mediators that result in activation of the adaptive immune response. Under ideal conditions, this inflammation gives way to tissue repair and attempts at regeneration. However, for reasons that are just being understood, immunosuppression occurs following acute stroke leading to post-stroke immunodepression. This review focuses on the current state of knowledge regarding innate and adaptive immune activation in response to focal cerebral ischemia as well as the immunodepression that can occur following stroke. A better understanding of the intricate and complex events that take place following immune response activation, to acute cerebral ischemia, is imperative for the development of effective novel immunomodulatory therapies for the treatment of acute stroke.
PMCID: PMC4173797  PMID: 25276490
focal cerebral ischemia; cerebral ischemia; immune response; innate immunity; adaptive immunity; stroke-induced immunodepression
20.  Catecholamines, Steroids and Immune Alterations in Ischemic Stroke and Other Acute Diseases 
Aging and Disease  2014;5(5):327-339.
The outcome of stroke patients is not only determined by the extent and localization of the ischemic lesion, but also by stroke-associated infections. Stroke-induced immune alterations, which are related to stroke-associated infections, have been described over the last decade. Here we review the evidence that catecholamines and steroids induced by stroke result in stroke-induced immune alterations. In addition, we compare the immune alterations observed in other acute diseases such as myocardial infarction, brain trauma, and surgical trauma with the changes seen in stroke-induced immune alterations.
PMCID: PMC4173798  PMID: 25276491
ischemic stroke; immune; aging; catecholamines; steroids
21.  17β-Estradiol and Inflammation: Implications for Ischemic Stroke 
Aging and Disease  2014;5(5):340-345.
Although typically associated with maintenance of female reproductive function, estrogens mediate physiological processes in nearly every body tissue, including the central nervous system. Numerous pre-clinical studies have shown that estrogen, specifically 17-beta-estradiol (17β-E2), protects the brain from ischemic injury following stroke. There are multiple mechanisms of 17β-E2’s neuroprotection, including activation of several neuroprotective pathways in the brain, but 17β-E2 also mediates the local and systemic immune response to ischemic stroke. This review summarizes the immune response to stroke, sex differences in stroke pathophysiology, and the role of estrogen as an immunomodulator. This review will focus almost entirely on the role of 17β-E2; however, there will be a brief review and comparison to other forms of estrogen. Understanding the immunomodulatory action of estrogens may provide an opportunity for the use of estrogens in treatment of stroke and other inflammatory disease.
PMCID: PMC4173799  PMID: 25276492
estrogen; stroke; ischemia; inflammation; immune response; neuroprotection
22.  Epigenetics and Social Context: Implications for Disparity in Cardiovascular Disease 
Aging and Disease  2014;5(5):346-355.
Although it is well established that African Americans (AA) experience greater social stressors than non-Hispanic Whites (NHW), the extent to which early life adversity and cumulative social stressors such as perceived discrimination, neighborhood violence, subjective social status, and socioeconomic status contribute to disparity in coronary heart disease (CHD) and stroke between AA and NHW are not well understood.
The purpose of this paper is to propose a conceptual model based upon McEwen’s Allostatic Load Model suggesting how the relationships among social context, early life adversity, psychological stress, inflammation, adaptation, and epigenetic signature may contribute to the development of CHD and ischemic stroke. We hypothesize that social context and prior life adversity are associated with genome-wide as well as gene-specific epigenetic modifications that confer a proinflammatory epigenetic signature that mediates an enhanced proinflammatory state. Exposure to early life adversity, coupled with an increased allostatic load places individuals at greater risk for inflammatory based diseases, such as CHD and ischemic stroke.
Based on a review of the literature, we propose a novel model in which social context and psychological stress, particularly during early life, engenders a proinflammatory epigenetic signature, which drives a heightened inflammatory state that increases risk for CHD and stroke. In the proposed model, a proinflammatory epigenetic signature and adaptation serve as mediator variables.
Understanding the extent to which epigenetic signature bridges the psycho-social environment with inflammation and risk for CHD may yield novel biomarkers that can be used to assess risk, development, and progression of CHD/stroke. Epigenetic biomarkers may be used to inform preventive and treatment strategies that can be targeted to those most vulnerable, or to those with early signs of CHD, such as endothelial dysfunction. Furthermore, epigenetic approaches, including lifestyle modification and stress reduction programs, such as mindfulness-based stress reduction, offer promise to reduce health inequity linked to social disadvantage, as emerging evidence demonstrates that adverse epigenetic marks can be reversed.
PMCID: PMC4173800  PMID: 25276493
Stroke; Cardiovascular Disease; Epigenetics; Epigenomics; Health Status Disparities; Cytokines
23.  Accelerated Aging in Schizophrenia Patients: The Potential Role of Oxidative Stress 
Aging and Disease  2013;5(4):256-262.
Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia.
PMCID: PMC4113515  PMID: 25110609
Schizophrenia; accelerated aging; oxidative stress; free radicals; inflammation
24.  Estimation of Heterogeneity in Diagnostic Parameters of Age-related Diseases 
Aging and Disease  2014;5(4):218-225.
The heterogeneity of parameters is a ubiquitous biological phenomenon, with critical implications for biological systems functioning in normal and diseased states. We developed a method to estimate the level of objects set heterogeneity with reference to particular parameters and applied it to type II diabetes and heart disease, as examples of age-related systemic dysfunctions. The Friedman test was used to establish the existence of heterogeneity. The Newman-Keuls multiple comparison method was used to determine clusters. The normalized Shannon entropy was used to provide the quantitative evaluation of heterogeneity. There was obtained an estimate for the heterogeneity of the diagnostic parameters in healthy subjects, as well as in heart disease and type II diabetes patients, which was strongly related to their age. With aging, as with the diseases, the level of heterogeneity (entropy) was reduced, indicating a formal analogy between these phenomena. The similarity of the patterns in aging and disease suggested a kind of “early aging” of the diseased subjects, or alternatively a “disease-like” aging process, with reference to these particular parameters. The proposed method and its validation on the chronic age-related disease samples may support a way toward a formal mathematical relation between aging and chronic diseases and a formal definition of aging and disease, as determined by particular heterogeneity (entropy) changes.
PMCID: PMC4113512  PMID: 25110613
parameter heterogeneity; Friedman test; Newman-Keuls method; normalized Shannon entropy; diabetes; heart disease; age related disease; aging; system complexity
25.  Managing Sarcopenia and Its Related-Fractures to Improve Quality of Life in Geriatric Populations 
Aging and Disease  2013;5(4):226-237.
Sarcopenia, an aging-induced generalized decrease in muscle mass, strength, and function, is known to affect elderly individuals by decreasing mobile function and increasing frailty and imbalance that lead to falls and fragile fractures. Sarcopenia is a known risk factor for osteoporotic fractures, infections, and early death in some specific situations. The number of patients with sarcopenia is estimated to increase to 500 million people in the year 2050. Sarcopenia is believed to be caused by multiple factors such as disuse, malnutrition, age-related cellular changes, apoptosis, and genetic predisposition; however, this remains to be determined. Various methods have been developed, but no safe or effective treatment has been found to date. This paper is a review on the association between sarcopenia and its related-fractures and their diagnoses and management methods to prevent fractures.
PMCID: PMC4113513  PMID: 25110607
sarcopenia; sarcopenia-related fracture; osteoporosis; diagnosis; muscle mass; treatment; pathogenesis

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