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Alzheimer’s Disease: Fatty Acids We Eat may be Linked to a Specific Protection via Low-dose Aspirin
Massimo F. L. Pomponi,Giovanni Gambassi,Massimiliano Pomponi,Carlo Masullo
Aging and Disease    2010, 1 (1): 37-59.  
Abstract1224)   HTML12)    PDF(pc) (1008KB)(2813)       Save

It has been suggested that cognitive decline in aging is the consequence of a growing vulnerability to an asymptomatic state of neuroinflammation. Moreover, it is becoming more evident that inflammation occurs in the brain of Alzheimer’s disease (AD) patients and that the classical mediators of inflammation, eicosanoids and cytokines, may contribute to the neurodegeneration. In agreement with this observation, aspirin (ASA) - a non-steroidal anti-inflammatory drug - may protect against AD and/or vascular dementia. However, both the time of prescription and the dose of ASA may be critical. A major indication for low-dose ASA is in combination with docosahexaenoic acid (DHA). DHA plays an essential role in neural function and its anti-inflammatory properties are associated with the well-known ability of this fatty acid to inhibit the production of various pro-inflammatory mediators, including eicosanoids and cytokines. Higher DHA intake is inversely correlated with relative risk of AD and DHA+ASA supplement may further decrease cognitive decline in healthy elderly adults. Although low-dose ASA may be insufficient for any anti-inflammatory action the concomitant presence of DHA favours a neuroprotective role for ASA. This depends on the allosteric effects of ASA on cyclooxygenase-2 and following production - from DHA - of specific lipid mediators (resolvins, protectins, and electrophilic oxo-derivatives). ASA and DHA might protect against AD, although controlled trials are warranted.

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NF-κB in Aging and Disease
Jeremy S. Tilstra,Cheryl L. Clauson,Laura J. Niedernhofer,Paul D. Robbins
Aging and Disease    2011, 2 (6): 449-465.  
Abstract5238)   HTML8)    PDF(pc) (1175KB)(1866)       Save

Stochastic damage to cellular macromolecules and organelles is thought to be a driving force behind aging and associated degenerative changes. However, stress response pathways activated by this damage may also contribute to aging. The IKK/NF-κB signaling pathway has been proposed to be one of the key mediators of aging. It is activated by genotoxic, oxidative, and inflammatory stresses and regulates expression of cytokines, growth factors, and genes that regulate apoptosis, cell cycle progression, cell senescence, and inflammation. Transcriptional activity of NF-κB is increased in a variety of tissues with aging and is associated with numerous age-related degenerative diseases including Alzheimer’s, diabetes and osteoporosis. In mouse models, inhibition of NF-κB leads to delayed onset of age-related symptoms and pathologies. In addition, NF-κB activation is linked with many of the known lifespan regulators including insulin/IGF-1, FOXO, SIRT, mTOR, and DNA damage. Thus NF-κB represents a possible therapeutic target for extending mammalian healthspan.

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Aging and Cardiac Fibrosis
Anna Biernacka,Nikolaos G Frangogiannis
Aging and Disease    2011, 2 (2): 158-173.  
Abstract3378)   HTML15)    PDF(pc) (830KB)(1746)       Save

The aging heart is characterized by morphological and structural changes that lead to its functional decline and are associated with diminished ability to meet increased demand. Extensive evidence, derived from both clinical and experimental studies suggests that the aging heart undergoes fibrotic remodeling. Age-dependent accumulation of collagen in the heart leads to progressive increase in ventricular stiffness and impaired diastolic function. Increased mechanical load, due to reduced arterial compliance, and direct senescence-associated fibrogenic actions appear to be implicated in the pathogenesis of cardiac fibrosis in the elderly. Evolving evidence suggests that activation of several distinct molecular pathways may contribute to age-related fibrotic cardiac remodeling. Reactive oxygen species, chemokine-mediated recruitment of mononuclear cells and fibroblast progenitors, transforming growth factor (TGF)-β activation, endothelin-1 and angiotensin II signaling mediate interstitial and perivascular fibrosis in the senescent heart. Reduced collagen degradation may be more important than increased de novo synthesis in the pathogenesis of aging-associated fibrosis. In contrast to the baseline activation of fibrogenic pathways in the senescent heart, aging is associated with an impaired reparative response to cardiac injury and defective activation of reparative fibroblasts in response to growth factors. Because these reparative defects result in defective scar formation, senescent hearts are prone to adverse dilative remodeling following myocardial infarction. Understanding the pathogenesis of interstitial fibrosis in the aging heart and dissecting the mechanisms responsible for age-associated healing defects following cardiac injury are critical in order to design new strategies for prevention of adverse remodeling and heart failure in elderly patients.

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Metabolic Syndrome, Aging and Involvement of Oxidative Stress
Francesca Bonomini,Luigi Fabrizio Rodella,Rita Rezzani
A&D    2015, 6 (2): 109-120.   DOI: 10.14336/AD.2014.0305
Abstract2859)   HTML14)    PDF(pc) (571KB)(1723)       Save

The prevalence of the metabolic syndrome, a cluster of cardiovascular risk factors associated with obesity and insulin resistance, is dramatically increasing in Western and developing countries. This disorder consists of a cluster of metabolic conditions, such as hypertriglyceridemia, hyper-low-density lipoproteins, hypo-high-density lipoproteins, insulin resistance, abnormal glucose tolerance and hypertension, that-in combination with genetic susceptibility and abdominal obesity-are risk factors for type 2 diabetes, vascular inflammation, atherosclerosis, and renal, liver and heart diseases. One of the defects in metabolic syndrome and its associated diseases is excess of reactive oxygen species. Reactive oxygen species generated by mitochondria, or from other sites within or outside the cell, cause damage to mitochondrial components and initiate degradative processes. Such toxic reactions contribute significantly to the aging process. In this article we review current understandings of oxidative stress in metabolic syndrome related disease and its possible contribution to accelerated senescence.

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Healthcare-associated Pneumonia and Aspiration Pneumonia
Kosaku Komiya,Hiroshi Ishii,Jun-ichi Kadota
Aging and Disease    2015, 6 (1): 27-37.   DOI: 10.14336/AD.2014.0127
Abstract1309)   HTML26)    PDF(pc) (689KB)(1715)       Save

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.

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Hyperglycemic Stress and Carbon Stress in Diabetic Glucotoxicity
Xiaoting Luo,Jinzi Wu,Siqun Jing,Liang-Jun Yan
A&D    2016, 7 (1): 90-110.   DOI: 10.14336/AD.2015.0702
Abstract2450)   HTML17)    PDF(pc) (1213KB)(1630)       Save

Diabetes and its complications are caused by chronic glucotoxicity driven by persistent hyperglycemia. In this article, we review the mechanisms of diabetic glucotoxicity by focusing mainly on hyperglycemic stress and carbon stress. Mechanisms of hyperglycemic stress include reductive stress or pseudohypoxic stress caused by redox imbalance between NADH and NAD+ driven by activation of both the polyol pathway and poly ADP ribose polymerase; the hexosamine pathway; the advanced glycation end products pathway; the protein kinase C activation pathway; and the enediol formation pathway. Mechanisms of carbon stress include excess production of acetyl-CoA that can over-acetylate a proteome and excess production of fumarate that can over-succinate a proteome; both of which can increase glucotoxicity in diabetes. For hyperglycemia stress, we also discuss the possible role of mitochondrial complex I in diabetes as this complex, in charge of NAD+ regeneration, can make more reactive oxygen species (ROS) in the presence of excess NADH. For carbon stress, we also discuss the role of sirtuins in diabetes as they are deacetylases that can reverse protein acetylation thereby attenuating diabetic glucotoxicity and improving glucose metabolism. It is our belief that targeting some of the stress pathways discussed in this article may provide new therapeutic strategies for treatment of diabetes and its complications.

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The Critical Need to Promote Research of Aging and Aging-related Diseases to Improve Health and Longevity of the Elderly Population
Kunlin Jin,James W. Simpkins,Xunming Ji,Miriam Leis,Ilia Stambler
Aging and Disease    2015, 6 (1): 1-5.   DOI: 10.14336/AD.2014.1210
Abstract3238)   HTML41)    PDF(pc) (734KB)(1612)       Save

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.

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Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System
Shinichi Iwasaki,Tatsuya Yamasoba
Aging and Disease    2015, 6 (1): 38-47.   DOI: 10.14336/AD.2014.0128
Abstract2961)   HTML30)    PDF(pc) (457KB)(1582)       Save

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.

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Early-life Exposure to Endocrine Disrupting Chemicals and Later-life Health Outcomes: An Epigenetic Bridge?
Vaiserman* Alexander
Aging and Disease    2014, 5 (6): 419-429.   DOI: 10.14336/AD.2014.0500419
Abstract960)   HTML21)          Save

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.

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Exercise, Inflammation and Aging
Jeffrey A. Woods,Kenneth R. Wilund,Stephen A. Martin,Brandon M. Kistler
Aging and Disease    2012, 3 (1): 130-140.  
Abstract2033)   HTML16)    PDF(pc) (620KB)(1522)       Save

Aging results in chronic low grade inflammation that is associated with increased risk for disease, poor physical functioning and mortality. Strategies that reduce age-related inflammation may improve the quality of life in older adults. Regular exercise is recommended for older people for a variety of reasons including increasing muscle mass and reducing risk for chronic diseases of the heart and metabolic systems. Only recently has exercise been examined in the context of inflammation. This review will highlight key randomized clinical trial evidence regarding the influence of exercise training on inflammatory biomarkers in the elderly. Potential mechanisms will be presented that might explain why exercise may exert an anti-inflammatory effect.

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Insulin, IGF-1 and longevity
Diana van Heemst
Aging and Disease    2010, 1 (2): 147-157.  
Abstract3142)   HTML18)    PDF(pc) (637KB)(1471)       Save

It has been demonstrated in invertebrate species that the evolutionarily conserved insulin and insulin-like growth factor (IGF) signaling (IIS) pathway plays a major role in the control of longevity. In the roundworm Caenorhabditis elegans, single mutations that diminish insulin/IGF-1 signaling can increase lifespan more than twofold and cause the animal to remain active and youthful much longer than normal. Likewise, substantial increases in lifespan are associated with mutations that reduce insulin/IGF-1 signaling in the fruit fly Drosophila melanogaster. In invertebrates, multiple insulin-like ligands exist that bind to a common single insulin/IGF-1 like receptor. In contrast, in mammals, different receptors exist that bind insulin, IGF-1 and IGF-2 with different affinities. In several mouse models, mutations that are associated with decreased GH/IGF-1 signaling or decreased insulin signaling have been associated with enhanced lifespan. However, the increased complexity of the mammalian insulin/IGF-1 system has made it difficult to separate the roles of insulin, GH and IGF-1 in mammalian longevity. Likewise, the relevance of reduced insulin and IGF-1 signaling in human longevity remains controversial. However, studies on the genetic and metabolic characteristics that are associated with healthy longevity and old age survival suggest that the conserved ancient IIS pathway may also play a role in human longevity.

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mHealth For Aging China: Opportunities and Challenges
Jing Sun,Yutao Guo,Xiaoning Wang,Qiang Zeng
A&D    2016, 7 (1): 53-67.   DOI: 10.14336/AD.2015.1011
Abstract1021)   HTML17)    PDF(pc) (874KB)(1436)       Save

The aging population with chronic and age-related diseases has become a global issue and exerted heavy burdens on the healthcare system and society. Neurological diseases are the leading chronic diseases in the geriatric population, and stroke is the leading cause of death in China. However, the uneven distribution of caregivers and critical healthcare workforce shortages are major obstacles to improving disease outcome. With the advancement of wearable health devices, cloud computing, mobile technologies and Internet of Things, mobile health (mHealth) is rapidly developing and shows a promising future in the management of chronic diseases. Its advantages include its ability to improve the quality of care, reduce the costs of care, and improve treatment outcomes by transferring in-hospital treatment to patient-centered medical treatment at home. mHealth could also enhance the international cooperation of medical providers in different time zones and the sharing of high-quality medical service resources between developed and developing countries. In this review, we focus on trends in mHealth and its clinical applications for the prevention and treatment of diseases, especially aging-related neurological diseases, and on the opportunities and challenges of mHealth in China. Operating models of mHealth in disease management are proposed; these models may benefit those who work within the mHealth system in developing countries and developed countries.

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N-Acetylserotonin and Aging-Associated Cognitive Impairment and Depression
Gregory Oxenkrug,Rebbie Ratner
Aging and Disease    2012, 3 (4): 330-338.  
Abstract588)   HTML19)    PDF(pc) (518KB)(1417)       Save

Normal brain aging is associated with depression and cognitive decline. One of the mechanisms of aging-associated emotional and cognitive impairment might be the down-regulation of biosynthesis of N-acetylserotonin (NAS), one of the methoxyindole derivatives of tryptophan (TRP). Aging is associated with decreased NAS production, largely resulting from the down-regulation of beta 1 adrenoreceptors that activate serotonin N-acetyltransferase, the enzyme catalyzing formation of NAS from serotonin. NAS exerts antidepressant-like and cognition-enhancing effects. The NAS role in cognition supported by the discovery that scotophobin, decapeptide extracted from brain and associated with cognition improvement, inhibits NAS conversion into melatonin. Furthermore, NAS (and its derivatives) attenuated cognitive impairment induced by cholinergic neurotoxin and protected against beta-amyloid neurotoxicity. Considering that NAS (but not serotonin or melatonin) is a potent agonist to high-affinity BDNF tyrosine kinase (TrkB) receptors, antidepressant and cognition-enhancing effect of NAS might be mediated by activation of TrkB receptors. NAS and TRkB gradually decreased from 1 postnatal week becoming undetectable in the brains of old rats. Additional mechanisms might include non-receptor mediated anti-inflammatory and anti-oxidative effects of NAS. Therapeutic antidepressant and cognition-improving interventions might include administration of NAS and its analogs; inhibition of tryptophan - kynurenine metabolism to increase serotonin availability as a substrate for NAS biosynthesis; up-regulation of NAS formation from serotonin and down-regulation of NAS conversion into melatonin.

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Mitochondrial Dysfunction in Alzheimer’s Disease and the Rationale for Bioenergetics Based Therapies
Isaac G. Onyango,Jameel Dennis,Shaharyah M. Khan
A&D    2016, 7 (2): 201-214.   DOI: 10.14336/AD.2015.1007
Abstract1709)   HTML20)    PDF(pc) (901KB)(1398)       Save

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder characterized by the progressive loss of cholinergic neurons, leading to the onset of severe behavioral, motor and cognitive impairments. It is a pressing public health problem with no effective treatment. Existing therapies only provide symptomatic relief without being able to prevent, stop or reverse the pathologic process. While the molecular basis underlying this multifactorial neurodegenerative disorder remains a significant challenge, mitochondrial dysfunction appears to be a critical factor in the pathogenesis of this disease. It is therefore important to target mitochondrial dysfunction in the prodromal phase of AD to slow or prevent the neurodegenerative process and restore neuronal function. In this review, we discuss mechanisms of action and translational potential of current mitochondrial and bioenergetic therapeutics for AD including: mitochondrial enhancers to potentiate energy production; antioxidants to scavenge reactive oxygen species and reduce oxidative damage; glucose metabolism and substrate supply; and candidates that target apoptotic and mitophagy pathways to remove damaged mitochondria. While mitochondrial therapeutic strategies have shown promise at the preclinical stage, there has been little progress in clinical trials thus far.

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Strength and Endurance Training Prescription in Healthy and Frail Elderly
Eduardo Lusa Cadore,Ronei Silveira Pinto,Martim Bottaro,Mikel Izquierdo
Aging and Disease    2014, 5 (3): 183-195.   DOI: 10.14336/AD.2014.0500183
Abstract2902)   HTML17)          Save

Aging is associated with declines in the neuromuscular and cardiovascular systems, resulting in an impaired capacity to perform daily activities. Frailty is an age-associated biological syndrome characterized by decreases in the biological functional reserve and resistance to stressors due to changes in several physiological systems, which puts older individuals at special risk of disability. To counteract the neuromuscular and cardiovascular declines associated with aging, as well as to prevent and treat the frailty syndrome, the strength and endurance training seems to be an effective strategy to improve muscle hypertrophy, strength and power output, as well as endurance performance. The first purpose of this review was discuss the neuromuscular adaptations to strength training, as well as the cardiovascular adaptations to endurance training in healthy and frail elderly subjects. In addition, the second purpose of this study was investigate the concurrent training adaptations in the elderly. Based on the results found, the combination of strength and endurance training (i.e., concurrent training) performed at moderate volume and moderate to high intensity in elderly populations is the most effective way to improve both neuromuscular and cardiorespiratory functions. Moreover, exercise interventions that include muscle power training should be prescribed to frail elderly in order to improve the overall physical status of this population and prevent disability.

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The p38 MAP Kinase Family as Regulators of Proinflammatory Cytokine Production in Degenerative Diseases of the CNS
Adam D. Bachstetter,Linda J. Van Eldik
Aging and Disease    2010, 1 (3): 199-211.  
Abstract1543)   HTML18)    PDF(pc) (665KB)(1356)       Save

Inflammation in the central nervous system (CNS) is a common feature of age-related neurodegenerative diseases. Proinflammatory cytokines, such as IL-1β and TNFα, are produced primarily by cells of the innate immune system, namely microglia in the CNS, and are believed to contribute to the neuronal damage seen in the disease. The p38 mitogen-activated protein kinase (MAPK) is one of the kinase pathways that regulate the production of IL-1β and TNFα. Importantly, small molecule inhibitors of the p38 MAPK family have been developed and show efficacy in blocking the production of IL-1β and TNFα. The p38 family consists of at least four isoforms (p38α, β, γ, δ) encoded by separate genes. Recent studies have begun to demonstrate unique functions of the different isoforms, with p38α being implicated as the key isoform involved in CNS inflammation. Interestingly, there is also emerging evidence that two downstream substrates of p38 may have opposing roles, with MK2 being pro-inflammatory and MSK1/2 being antiinflammatory. This review discusses the properties, function and regulation of the p38 MAPK family as it relates to cytokine production in the CNS.

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Impact of Resistance Circuit Training on Neuromuscular, Cardiorespiratory and Body Composition Adaptations in the Elderly
Salvador Romero-Arenas,Miryam Martínez-Pascual,Pedro E. Alcaraz
Aging and Disease    2013, 4 (5): 256-263.   DOI: 10.14336/AD.2013.0400256
Abstract1216)   HTML12)    PDF(pc) (444KB)(1340)       Save

Declines in maximal aerobic power and skeletal muscle force production with advancing age are examples of functional declines with aging, which can severely limit physical performance and independence, and are negatively correlated with all cause mortality. It is well known that both endurance exercise and resistance training can substantially improve physical fitness and health-related factors in older individuals. Circuit-based resistance training, where loads are lifted with minimal rest, may be a very effective strategy for increasing oxygen consumption, pulmonary ventilation, strength, and functional capacity while improving body composition. In addition, circuit training is a time-efficient exercise modality that can elicit demonstrable improvements in health and physical fitness. Hence, it seems reasonable to identify the most effective combination of intensity, volume, work to rest ratio, weekly frequency and exercise sequence to promote neuromuscular, cardiorespiratory and body composition adaptations in the elderly. Thus, the purpose of this review was to summarize and update knowledge about the effects of circuit weight training in older adults and elderly population, as a starting point for developing future interventions that maintain a higher quality of life in people throughout their lifetime.

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Age-Related Disruption of Steady-State Thymic Medulla Provokes Autoimmune Phenotype via Perturbing Negative Selection
Jiangyan Xia,Hongjun Wang,Jianfei Guo,Zhijie Zhang,Brandon Coder,Dong-Ming Su
Aging and Disease    2012, 3 (3): 248-259.  
Abstract671)   HTML28)    PDF(pc) (1942KB)(1333)       Save

The hymic medulla plays an essential role in the generation of central tolerance by eliminating self-reactive T-cell clones through thymic negative selection and developing natural regulatory T cells. Age-related FoxN1 decline induces disruption of medullary thymic epithelial cells (mTECs). However, it is unknown whether this perturbs central tolerance to increase autoimmune predisposition in the elderly. Using a loxP-floxed-FoxN1 (FoxN1flox) mouse model, which exhibits a spontaneous ubiquitous deletion of FoxN1 with age to accelerate thymic aging, we investigated whether disruption of steady-state thymic medulla results in an increase of autoimmune-prone associated with age. We demonstrated age-associated ubiquitous loss of FoxN1flox-formed two-dimensional thymic epithelial cysts were primarily located in the medulla. This resulted in disruption of thymic medullary steady state, with evidence of perturbed negative selection, including reduced expression of the autoimmune regulator (Aire) gene and disrupted accumulation of thymic dendritic cells in the medulla, which are required for negative selection. These provoke autoimmune phenotypes, including increased inflammatory cell infiltration in multiple organs in these mice. This finding in an animal model provides a mechanistic explanation of increased susceptibility to autoimmunity in aged humans, although they may not show clinic manifestations without induction.

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Voxel-based Morphometry of Brain MRI in Normal Aging and Alzheimer’s Disease
Hiroshi Matsuda
Aging and Disease    2013, 4 (1): 29-37.  
Abstract1594)   HTML13)    PDF(pc) (884KB)(1329)       Save

Voxel-based morphometry (VBM) using structural brain MRI has been widely used for assessment of normal aging and Alzheimer’s disease (AD). VBM of MRI data comprises segmentation into gray matter, white matter, and cerebrospinal fluid partitions, anatomical standardization of all the images to the same stereotactic space using linear affine transformation and further non-linear warping, smoothing, and finally performing a statistical analysis. Two techniques for VBM are commonly used, optimized VBM using statistical parametric mapping (SPM) 2 or SPM5 with non-linear warping based on discrete cosine transforms and SPM8 plus non-linear warping based on diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL). In normal aging, most cortical regions prominently in frontal and insular areas have been reported to show age-related gray matter atrophy. In contrast, specific structures such as amygdala, hippocampus, and thalamus have been reported to be preserved in normal aging. On the other hand, VBM studies have demonstrated progression of atrophy mapping upstream to Braak’s stages of neurofibrillary tangle deposition in AD. The earliest atrophy takes place in medial temporal structures. Stand-alone VBM software using SPM8 plus DARTEL running on Windows has been newly developed as an adjunct to the clinical assessment of AD. This software provides a Z-score map as a consequence of comparison of a patient’s MRI with a normal database.

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Possible Benefit of Dietary Carnosine towards Depressive Disorders
Alan R. Hipkiss*
A&D    2015, 6 (5): 300-303.   DOI: 10.14336/AD.2014.1211
Abstract1504)   HTML19)    PDF(pc) (489KB)(1315)       Save

Many stress-related and depressive disorders have been shown to be associated with one or more of the following; shortened telomeres, raised cortisol levels and increased susceptibility to age-related dysfunction. It is suggested here that insufficient availability of the neurological peptide, carnosine, may provide a biochemical link between stress- and depression-associated phenomena: there is evidence that carnosine can enhance cortisol metabolism, suppress telomere shortening and exert anti-aging activity in model systems. Dietary supplementation with carnosine has been shown to suppress stress in animals, and improve behaviour, cognition and well-being in human subjects. It is therefore proposed that the therapeutic potential of carnosine dietary supplementation towards stress-related and depressive disorders should be examined.

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Stop Aging Disease! ICAD 2014
Stambler Ilia
A&D    2015, 6 (2): 76-94.   DOI: 10.14336/AD.2015.0115
Abstract2164)   HTML52)    PDF(pc) (653KB)(1308)       Save

On November 1–2, 2014, there took place in Beijing, China, the first International Conference on Aging and Disease (ICAD 2014) of the International Society on Aging and Disease (ISOAD). The conference participants presented a wide and exciting front of work dedicated to amelioration of aging-related conditions, ranging from regenerative medicine through developing geroprotective substances, elucidating a wide range of mechanisms of aging and aging-related diseases, from energy metabolism through genetics and immunomodulation to systems biology. The conference further emphasized the need to intensify and support research on aging and aging-related diseases to provide solutions for the urgent health challenges of the aging society.

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Neuroimaging of Cerebrovascular Disease in the Aging Brain
Ajay Gupta,Sreejit Nair,Andrew D. Schweitzer,Sirish Kishore,Carl E. Johnson,Joseph P. Comunale,Apostolos J. Tsiouris,Pina C. Sanelli
Aging and Disease    2012, 3 (5): 414-425.  
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Cerebrovascular disease remains a significant public health burden with its greatest impact on the elderly population. Advances in neuroimaging techniques allow detailed and sophisticated evaluation of many manifestations of cerebrovascular disease in the brain parenchyma as well as in the intracranial and extracranial vasculature. These tools continue to contribute to our understanding of the multifactorial processes that occur in the age-dependent development of cerebrovascular disease. Structural abnormalities related to vascular disease in the brain and vessels have been well characterized with CT and MRI based techniques. We review some of the pathophysiologic mechanisms in the aging brain and cerebral vasculature and the related structural abnormalities detectable on neuroimaging, including evaluation of age-related white matter changes, atherosclerosis of the cerebral vasculature, and cerebral infarction. In addition, newer neuroimaging techniques, such as diffusion tensor imaging, perfusion techniques, and assessment of cerebrovascular reserve, are also reviewed, as these techniques can detect physiologic alterations which complement the morphologic changes that cause cerebrovascular disease in the aging brain.Further investigation of these advanced imaging techniques has potential application to the understanding and diagnosis of cerebrovascular disease in the elderly.

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Eating Disorders in Late-life
Antonina Luca, Maria Luca, Carmela Calandra
Aging and Disease    2015, 6 (1): 48-55.   DOI: 10.14336/AD.2014.0124
Abstract2033)   HTML38)    PDF(pc) (492KB)(1230)       Save

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.

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Evaluation of Cardiac Autonomic Functions in Older Parkinson’s Disease Patients: a Cross-Sectional Study
Ahmet Yalcin,Volkan Atmis,Ozlem Karaarslan Cengiz,Esat Cinar,Sevgi Aras,Murat Varli,Teslime Atli
A&D    2016, 7 (1): 28-35.   DOI: 10.14336/AD.2015.0819
Abstract680)   HTML16)          Save

In Parkinson’s disease (PD), non-motor symptoms may occur such as autonomic dysfunction. We aimed to evaluate both parasympathetic and sympathetic cardiovascular autonomic dysfunction in older PD cases. 84 PD cases and 58 controls, for a total of 142, participated in the study. Parasympathetic tests were performed using electrocardiography. Sympathetic tests were assessed by blood pressure measurement and 24-hour ambulatory blood pressure measurement. The prevalence of orthostatic hypotension in PD patients was 40.5% in PD patients and 24.1% in the control group (p> 0.05). The prevalence of postprandial hypotension was 47.9% in the PD group and 27.5% in the controls (p <0.05). The prevalence of impairment in heart rate response to deep breathing was 26.2% in the PD group and 6.9% in the control group (p <0.05). The prevalence of postprandial hypotension in PD with orthostatic hypotension was 94% and 16% in PD patients without orthostatic hypotension (p <0.05). The prevalence of impairment in heart rate response to deep breathing was 52.9% in PD patients with orthostatic hypotension and 8% in PD cases without orthostatic hypotension (p<0.05). The prevalence of impairment in heart rate response to postural change was 41% in PD cases with orthostatic hypotension and 12% in PD cases without orthostatic hypotension (p <0.05).Although there are tests for assessing cardiovascular autonomic function that are more reliable, they are more complicated, and evaluation of orthostatic hypotension by blood pressure measurement and cardiac autonomic tests by electrocardiography are recommended since these tests are cheap and easy.

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The Role of Autophagy, Mitophagy and Lysosomal Functions in Modulating Bioenergetics and Survival in the Context of Redox and Proteotoxic Damage: Implications for Neurodegenerative Diseases
Matthew Redmann,Victor Darley-Usmar,Jianhua Zhang
A&D    2016, 7 (2): 150-162.   DOI: 10.14336/AD.2015.0820
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Redox and proteotoxic stress contributes to age-dependent accumulation of dysfunctional mitochondria and protein aggregates, and is associated with neurodegeneration. The free radical theory of aging inspired many studies using reactive species scavengers such as alpha-tocopherol, ascorbate and coenzyme Q to suppress the initiation of oxidative stress. However, clinical trials have had limited success in the treatment of neurodegenerative diseases. We ascribe this to the emerging literature which suggests that the oxidative stress hypothesis does not encompass the role of reactive species in cell signaling and therefore the interception with reactive species with antioxidant supplementation may result in disruption of redox signaling. In addition, the accumulation of redox modified proteins or organelles cannot be reversed by oxidant intercepting antioxidants and must then be removed by alternative mechanisms. We have proposed that autophagy serves this essential function in removing damaged or dysfunctional proteins and organelles thus preserving neuronal function and survival. In this review, we will highlight observations regarding the impact of autophagy regulation on cellular bioenergetics and survival in response to reactive species or reactive species generating compounds, and in response to proteotoxic stress.

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Quality of Life Impact Related to Foot Health in a Sample of Older People with Hallux Valgus
Daniel López López,Lucía Callejo González,Marta Elena Losa Iglesias,Jesús Luis Saleta Canosa,David Rodríguez Sanz,Cesar Calvo Lobo,Ricardo Becerro de Bengoa Vallejo
A&D    2016, 7 (1): 45-52.   DOI: 10.14336/AD.2015.0914
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Hallux Valgus (HV) is a highly prevalent forefoot deformity in older people associated with progressive subluxation and osteoarthritis of the first metatarsophalangeal (MTP) joint and it is believed to be associated with varying degrees of HV effect on the quality of life related to foot health.The aim of this study is to compare the impact of varying degrees of HV on foot health in a sample of older people. The sample consisted of 115 participants, mean age 76.7 ± 9.1, who attended an outpatient center where self-report data were recorded. The degree of HV deformity was determined in both feet using the Manchester Scale (MS) from stage 1 (mild) to 4 (very severe). Scores obtained on the Foot Health Status Questionnaire (FHSQ) were compared. This has 13 questions that assess 4 health domains of the feet, namely pain, function, general health and footwear. The stage 4 of HV shown lower scores for the footwear domain (11.23 ± 15.6); general foot health (27.62 ± 19.1); foot pain (44.65 ± 24.5); foot function (53.04 ± 27.2); vigour (42.19 ± 16.8); social capacity (44.46 ± 28.1); and general health (41.15 ± 25.5) compared with stage 1 of HV (P<0.05) and there were no differences of physical activity (62.81 ± 24.6). Often, quality of life decreases in the elderly population based in large part on their foot health. There is a progressive reduction in health in general and foot health with increasing severity of hallux valgus deformity which appears to be associated with the presence of greater degree of HV, regardless of gender.

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mTOR Signaling from Cellular Senescence to Organismal Aging
Shaohua Xu,Ying Cai,Yuehua Wei
Aging and Disease    2014, 5 (4): 263-273.   DOI: 10.14336/AD.2014.0500263
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The TOR (target of rapamycin) pathway has been convincingly shown to promote aging in various model organisms. In mice, inhibiting mTOR (mammalian TOR) by rapamycin treatment later in life can significantly extend lifespan and mitigate multiple age-related diseases. However, the underlying mechanisms are poorly understood. Cellular senescence is strongly correlated to organismal aging therefore providing an attractive model to examine the mechanisms by which mTOR inhibition contributes to longevity and delaying the onset of related diseases. In this review, we examine the connections between mTOR and cellular senescence and discuss how understanding cellular senescence on the aspect of mTOR signaling may help to fully appreciate its role in the organismal aging. We also highlight the opposing roles of senescence in various human diseases and discuss the caveats in interpreting the emerging experimental data.

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The Role of Nutrition in Enhancing Immunity in Aging
Munkyong Pae,Simin Nikbin Meydani,Dayong Wu
Aging and Disease    2012, 3 (1): 91-129.  
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Aging is associated with declined immune function, particularly T cell-mediated activity, which contributes to increased morbidity and mortality from infectious disease and cancer in the elderly. Studies have shown that nutritional intervention may be a promising approach to reversing impaired immune function and diminished resistance to infection with aging. However, controversy exists concerning every nutritional regimen tested to date. In this article, we will review the progress of research in this field with a focus on nutrition factor information that is relatively abundant in the literature. While vitamin E deficiency is rare, intake above recommended levels can enhance T cell function in aged animals and humans. This effect is believed to contribute toward increased resistance to influenza infection in animals and reduced incidence of upper respiratory infection in the elderly. Zinc deficiency, common in the elderly, is linked to impaired immune function and increased risk for acquiring infection, which can be rectified by zinc supplementation. However, higher than recommended upper limits of zinc may adversely affect immune function. Probiotics are increasingly being recognized as an effective, immune-modulating nutritional factor. However, to be effective, they require an adequate supplementation period; additionally, their effects are strain-specific and among certain strains, a synergistic effect is observed. Increased intake of fish or n-3 PUFA may be beneficial to inflammatory and autoimmune disorders as well as to several age-related diseases. Conversely, the immunosuppressive effect of fish oils on T cell-mediated function has raised concerns regarding their impact on resistance to infection. Caloric restriction (CR) is shown to delay immunosenescence in animals, but this effect needs to be verified in humans. Timing for CR initiation may be important to determine whether CR is effective or even beneficial at all. Recent studies have suggested that CR, which is effective at improving the immune response of unchallenged animals, might compromise the host’s defense against pathogenic infection and result in higher morbidity and mortality. The studies published thus far describe a critical role for nutrition in maintaining the immune response of the aged, but they also indicate the need for a more in-depth, wholestic approach to determining the optimal nutritional strategies that would maintain a healthy immune system in the elderly and promote their resistance to infection and other immune-related diseases

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Metabolic Alterations Associated to Brain Dysfunction in Diabetes
João M. N. Duarte
A&D    2015, 6 (5): 304-321.   DOI: 10.14336/AD.2014.1104
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From epidemiological studies it is known that diabetes patients display increased risk of developing dementia. Moreover, cognitive impairment and Alzheimer’s disease (AD) are also accompanied by impaired glucose homeostasis and insulin signalling. Although there is plenty of evidence for a connection between insulin-resistant diabetes and AD, definitive linking mechanisms remain elusive. Cerebrovascular complications of diabetes, alterations in glucose homeostasis and insulin signalling, as well as recurrent hypoglycaemia are the factors that most likely affect brain function and structure. While difficult to study in patients, the mechanisms by which diabetes leads to brain dysfunction have been investigated in experimental models that display phenotypes of the disease. The present article reviews the impact of diabetes and AD on brain structure and function, and discusses recent findings from translational studies in animal models that link insulin resistance to metabolic alterations that underlie brain dysfunction. Such modifications of brain metabolism are likely to occur at early stages of neurodegeneration and impact regional neurochemical profiles and constitute non-invasive biomarkers detectable by magnetic resonance spectroscopy (MRS).

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Hippocampal Oscillatory Activity in Alzheimer’s Disease: Toward the Identification of Early Biomarkers?
Romain Goutagny,Slavica Krantic
Aging and Disease    2013, 4 (3): 134-140.  
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Alzheimer’s disease (AD) develops for a yet unknown period of time and can progress undiagnosed for years before its first clinical manifestation consisting of characteristic cognitive impairments. Current AD treatments offer only a small symptomatic benefit, likely because AD is diagnosed when the pathology is already well advanced, whereas treatments may be most efficient in the early phases of pathology. An accurate, early marker of AD is therefore needed to help diagnose AD earlier. It is now well documented that AD patients and animal models of AD exhibit reorganization of hippocampal and cortical networks. This reorganization is initiated by an early imbalance between excitation and inhibition, leading to altered network activity. The mechanisms underlying these changes are unknown but recent evidence suggests that either soluble amyloid-beta (Aß) or fibrillar forms of Aß are central to various network alterations observed in AD. However, recent evidence also suggests that Aβ over-production in animal models is not systematically linked to network over-excitation. We hypothesize here that early changes in the excitation-inhibition balance within the hippocampus occurs much earlier than currently believed and initially produces only slight changes in overall hippocampal activity. In this review, we introduce the concept according to which the subtle changes in theta and gamma rhythms might occur during the very first stages of AD and thus could be used as a possible predictor for the disease.

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A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly
Supakanya Wongrakpanich,Amaraporn Wongrakpanich,Katie Melhado,Janani Rangaswami
A&D    2018, 9 (1): 143-150.   DOI: 10.14336/AD.2017.0306
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NSAIDs, non-steroidal anti-inflammatory drugs, are one of the most commonly prescribed pain medications. It is a highly effective drug class for pain and inflammation; however, NSAIDs are known for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID induced nephrotoxicity. As our society ages, it is crucial to have comprehensive knowledge of this class of medication in the elderly population. Therefore, we reviewed the pharmacodynamics and pharmacokinetics, current guidelines for NSAIDs use, adverse effect profile, and drug interaction of NSAIDs and commonly used medications in the elderly.

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Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity
Heng Hu,Danielle N. Doll,Jiahong Sun,Sara E. Lewis,Jeffrey H. Wimsatt,Matthew J. Kessler,James W. Simpkins,Xuefang Ren
A&D    2016, 7 (1): 14-27.   DOI: 10.14336/AD.2015.0906
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Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severity as well as reveal a possible mitochondrial mechanism in the association of body temperature and stroke severity. Lipopolysaccharide (LPS) compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells (CVECs) and worsens murine experimental stroke. In this study, we report that LPS (0.1 mg/kg) exacerbates stroke infarction and neurological deficits, in the mean time LPS causes temporary hypothermia in the hyperacute stage during 6 hours post-stroke. Lower body temperature is associated with worse infarction and higher neurological deficit score in the LPS-stroke study. However, warming of the LPS-stroke mice compromises animal survival. Furthermore, a high dose of LPS (2 mg/kg) worsens neurological deficits, but causes persistent severe hypothermia that conceals the LPS exacerbation of stroke infarction. Mitochondrial respiratory chain complex I inhibitor, rotenone, replicates the data profile of the LPS-stroke study. Moreover, we have confirmed that rotenone compromises mitochondrial oxidative phosphorylation in CVECs. Lastly, the pooled data analyses of a large sample size (n=353) demonstrate that stroke mice have lower body temperature compared to sham mice within 6 hours post-surgery; the body temperature is significantly correlated with stroke outcomes; linear regression shows that lower body temperature is significantly associated with higher neurological scores and larger infarct volume. We conclude that post-stroke body temperature predicts stroke severity and mitochondrial impairment in CVECs plays a pivotal role in this hypothermic response. These novel findings suggest that body temperature is prognostic for stroke severity in experimental stroke animal models and may have translational significance for clinical stroke patients - targeting endothelial mitochondria may be a clinically useful approach for stroke therapy.

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Reorganization of Brain Networks in Aging and Age-related Diseases
Junfeng Sun,Shanbao Tong,Guo-Yuan Yang
Aging and Disease    2012, 3 (2): 181-193.  
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Aging is associated with reorganization of brain in both structure and function. In recent years, graph theoretical analysis of brain organization has drawn increasing attention, and reorganization of brain in aging has been investigated in terms of connectivity and networks in topology such as modular organization, global and local efficiency, and small-worldness. Beyond studying on abnormity in local brain regions, connectivity quantifies alternations of correlation between two regions that may be spatially far separated, and graph theoretical analysis of brain network examines the complex interactions among multiple regions. This article reviewed complex brain networks of human in normal aging or with age-related diseases such as stroke and Alzheimer’s disease after a technical introduction of brain networks and graph theoretical analysis. We further discussed the relationship between the functional and the structural brain networks of subjects in aging or with age-related diseases. Finally, we proposed several interesting topics for future research in this field.

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Mitochondrial Dysfunction during Brain Aging: Role of Oxidative Stress and Modulation by Antioxidant Supplementation
Sasanka Chakrabarti,Soumyabrata Munshi,Kalpita Banerjee,Ishita Guha Thakurta,Maitrayee Sinha,Maria Bindu Bagh
Aging and Disease    2011, 2 (3): 242-256.  
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Mitochondrial dysfunction and oxidative stress are two interdependent and reinforcing damage mechanisms that play a central role in brain aging. Oxidative stress initiated and propagated by active oxyradicals and various other free radicals in the presence of catalytic metal ions not only can damage the phospholipid, protein and DNA molecules within the cell but can also modulate cell signalling pathways and gene expression pattern and all these processes may be of critical importance in the aging of brain. The present article describes the mechanism of formation of reactive oxyradicals within mitochondria and then explains how these can initiate mitochondrial biogenesis program and activate various transcriptional factors in the cytosol to boost up the antioxidative capacity of the mitochondria and the cell. However, a high level of oxidative stress finally inflicts critical damage to the oxidative phosphorylation machinery and mitochondrial DNA (mtDNA). The latter part of the article is a catalogue showing the accumulating evidence in favour of oxidative inactivation of mitochondrial functions in aged brain and the detailed reports of various studies with antioxidant supplementation claiming variable success in preventing the age-related brain mitochondrial decay and cognitive decline. The antioxidant supplementation approach may be of potential help in the management of neurodegenerative diseases like Alzheimer’s disease. The newly developed mitochondria-targeted antioxidants have brought a new direction to experimental studies related to oxidative damage and they may provide potential drugs in near future for a variety of diseases or degenerative conditions including brain aging and neurodegenerative disorders.

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The Role of NMDA Receptors in the Development of Brain Resistance through Pre- and Postconditioning
Celso Constantino Leandra,Inês Tasca Carla,Rodrigues Boeck Carina
Aging and Disease    2014, 5 (6): 430-441.   DOI: 10.14336/AD.2014.0500430
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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.

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Hypoxia-Inducible Histone Lysine Demethylases: Impact on the Aging Process and Age-Related Diseases
Salminen Antero,Kaarniranta Kai,Kauppinen Anu
A&D    2016, 7 (2): 180-200.   DOI: 10.14336/AD.2015.0929
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Hypoxia is an environmental stress at high altitude and underground conditions but it is also present in many chronic age-related diseases, where blood flow into tissues is impaired. The oxygen-sensing system stimulates gene expression protecting tissues against hypoxic insults. Hypoxia stabilizes the expression of hypoxia-inducible transcription factor-1α (HIF-1α), which controls the expression of hundreds of survival genes related to e.g. enhanced energy metabolism and autophagy. Moreover, many stress-related signaling mechanisms, such as oxidative stress and energy metabolic disturbances, as well as the signaling cascades via ceramide, mTOR, NF-κB, and TGF-β pathways, can also induce the expression of HIF-1α protein to facilitate cell survival in normoxia. Hypoxia is linked to prominent epigenetic changes in chromatin landscape. Screening studies have indicated that the stabilization of HIF-1α increases the expression of distinct histone lysine demethylases (KDM). HIF-1α stimulates the expression of KDM3A, KDM4B, KDM4C, and KDM6B, which enhance gene transcription by demethylating H3K9 and H3K27 sites (repressive epigenetic marks). In addition, HIF-1α induces the expression of KDM2B and KDM5B, which repress transcription by demethylating H3K4me2,3 sites (activating marks). Hypoxia-inducible KDMs support locally the gene transcription induced by HIF-1α, although they can also control genome-wide chromatin landscape, especially KDMs which demethylate H3K9 and H3K27 sites. These epigenetic marks have important role in the control of heterochromatin segments and 3D folding of chromosomes, as well as the genetic loci regulating cell type commitment, proliferation, and cellular senescence, e.g. the INK4 box. A chronic stimulation of HIF-1α can provoke tissue fibrosis and cellular senescence, which both are increasingly present with aging and age-related diseases. We will review the regulation of HIF-1α-dependent induction of KDMs and clarify their role in pathological processes emphasizing that long-term stress-related insults can impair the maintenance of chromatin landscape and provoke cellular senescence and tissue fibrosis associated with aging and age-related diseases.

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Dopamine Receptors and Neurodegeneration
Claudia Rangel-Barajas,Israel Coronel,Benjamín Florán
A&D    2015, 6 (5): 349-368.   DOI: 10.14336/AD.2015.0330
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Dopamine (DA) is one of the major neurotransmitters and participates in a number of functions such as motor coordination, emotions, memory, reward mechanism, neuroendocrine regulation etc. DA exerts its effects through five DA receptors that are subdivided in 2 families: D1-like DA receptors (D1 and D5) and the D2-like (D2, D3 and D4). All DA receptors are widely expressed in the central nervous system (CNS) and play an important role in not only in physiological conditions but also pathological scenarios. Abnormalities in the DAergic system and its receptors in the basal ganglia structures are the basis Parkinson’s disease (PD), however DA also participates in other neurodegenerative disorders such as Huntington disease (HD) and multiple sclerosis (MS). Under pathological conditions reorganization of DAergic system has been observed and most of the times, those changes occur as a mechanism of compensation, but in some cases contributes to worsening the alterations. Here we review the changes that occur on DA transmission and DA receptors (DARs) at both levels expression and signals transduction pathways as a result of neurotoxicity, inflammation and in neurodegenerative processes. The better understanding of the role of DA receptors in neuropathological conditions is crucial for development of novel therapeutic approaches to treat alterations related to neurodegenerative diseases.

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Depression in the Elderly: Clinical Features and Risk Factors
Gülfizar Sözeri-Varma
Aging and Disease    2012, 3 (6): 465-471.  
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Depression in elderlies is not known quite well and thus cannot be treated adequately. The fact that elderliness is accepted as a property of depressive symptoms both by the relatives of the patients and doctors is one of the factors which make it difficult to recognize depression. Existence of multiple physical diseases in elderlies, use of multiple medicines, occurrence of pharmacokinetic and pharmacodynamics changes depending on the age necessitate to take several factors into account while diagnosing and using medicines. In this study, clinical properties and risk factors of depression in old age period was reviewed and the properties of such depressions were summarized.

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Reactive Oxygen Species Signaling in Cancer: Comparison with Aging
Igor Afanas’ev
Aging and Disease    2011, 2 (3): 219-230.  
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This work considers reactive oxygen species (ROS) signaling in solid tumors. Most (probably all) cancer cells are characterized by ROS overproduction that is they exist under conditions of incessant oxidative stress. For example ROS overproduction has been shown in prostate, pancreatic, melanoma, and glioma cells. ROS overproduction has been also demonstrated in breast, liver, bladder, colon, and ovarian cancers. Although these examples probably do not incorporate all the described data concerning ROS overproduction in cancer cells, they clearly support a proposal about enhanced oxidative stress in these cells. Therefore the mechanisms of ROS signaling in the survival and death of cancer cells and comparison with ROS signaling in senescent cells ought to be considered. It might be suggested that ROS overproduction in cancer cells is a major origin of their survival and resistance to anticancer treatment while the enhanced oxidative stress responsible for aging development. However it is of particular interest that additional ROS production by prooxidants can induce apoptosis in cancer cells. We suggest that moderate oxidative stress can stimulate proliferation and survival of cancer sells by conditioning mechanism while the enhancement of ROS overproduction by prooxidants under severe oxidative stress results in apoptosis and cell death. Aging development is always characterized by harmful ROS overproduction although the moderate increase in ROS formation in senescent cells might be not dangerous. Similar double-edged sword effects of ROS might be observed during the development of other pathologies for example diabetes mellitus.

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Suicide in the Global Chinese Aging Population: A Review of Risk and Protective Factors, Consequences, and Interventions
XinQi Dong,E-Shien Chang,Ping Zeng,Melissa A. Simon
A&D    2015, 6 (2): 121-130.   DOI: 10.14336/AD.2014.0223
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As one of the leading causes of death around the world, suicide is a global public health threat. In the Chinese population, suicides constitute one-fifth of all recorded suicides in the world. Despite the factual data on suicide rates, the understanding of various causal factors behind suicide, including risk and protective factors and adverse health care, remained incomplete among the global Chinese aging population. To fill in the knowledge void, this paper reviews the epidemiology of suicide among Chinese older adults globally as well as explores the existing intervention strategies. Using the PRISMA statement, we performed a systematic review of exiting research on the topic, including studies describing suicide among Chinese older adults in communities outside of Asia. A literature search was conducted online by using both medical and social science data-bases. Our findings highlighted that elderly suicide in Chinese populations is significantly affected by the social, cultural, and familial contexts within which the individual lived prior to committing suicide. Reviewing such research indicated that while reducing risk factors may contribute to lowering suicides amongst Chinese older adults, measures to improve protective factors are also critical. Support through ongoing family and community care relationships is necessary to improve resilience in older adults and positive aging. Future longitudinal studies on the risk factors and protective factors, and adverse health consequences are called for to devise culturally and linguistically appropriate prevention and intervention programs in global Chinese aging populations.

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