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ISSN 2152-5250
Since 2010
2015 impact factor: 3.697
5 year impact factor: 3.602
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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.   DOI: null
Abstract   HTML   PDF (1008KB)

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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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
Abstract   HTML   PDF (457KB)

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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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
Aging and Disease    2016, 7 (1): 28-35.   DOI: 10.14336/AD.2015.0819
Abstract   HTML   PDF (0KB)

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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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.   DOI: null
Abstract   HTML   PDF (1175KB)

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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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
Abstract   HTML   PDF (689KB)

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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Exercise, Inflammation and Aging
Jeffrey A. Woods,Kenneth R. Wilund,Stephen A. Martin,Brandon M. Kistler
Aging and Disease    2012, 3 (1): 130-140.   DOI: null
Abstract   HTML   PDF (620KB)

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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Metabolic Syndrome, Aging and Involvement of Oxidative Stress
Francesca Bonomini,Luigi Fabrizio Rodella,Rita Rezzani
Aging and Disease    2015, 6 (2): 109-120.   DOI: 10.14336/AD.2014.0305
Abstract   HTML   PDF (571KB)

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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Aging and Cardiac Fibrosis
Anna Biernacka,Nikolaos G Frangogiannis
Aging and Disease    2011, 2 (2): 158-173.   DOI: null
Abstract   HTML   PDF (830KB)

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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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
Abstract   HTML   PDF (734KB)

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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Hyperglycemic Stress and Carbon Stress in Diabetic Glucotoxicity
Xiaoting Luo,Jinzi Wu,Siqun Jing,Liang-Jun Yan
Aging and Disease    2016, 7 (1): 90-110.   DOI: 10.14336/AD.2015.0702
Abstract   HTML   PDF (1213KB)

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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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
Abstract   HTML   PDF (0KB)

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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Insulin, IGF-1 and longevity
Diana van Heemst
Aging and Disease    2010, 1 (2): 147-157.   DOI: null
Abstract   HTML   PDF (637KB)

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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Stop Aging Disease! ICAD 2014
Stambler Ilia
Aging and Disease    2015, 6 (2): 76-94.   DOI: 10.14336/AD.2015.0115
Abstract   HTML   PDF (653KB)

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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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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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.   DOI: null
Abstract   HTML   PDF (651KB)

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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The Role of Nutrition in Enhancing Immunity in Aging
Munkyong Pae,Simin Nikbin Meydani,Dayong Wu
Aging and Disease    2012, 3 (1): 91-129.   DOI: null
Abstract   HTML   PDF (970KB)

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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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
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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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Possible Benefit of Dietary Carnosine towards Depressive Disorders
Alan R. Hipkiss*
Aging and Disease    2015, 6 (5): 300-303.   DOI: 10.14336/AD.2014.1211
Abstract   HTML   PDF (489KB)

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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Voxel-based Morphometry of Brain MRI in Normal Aging and Alzheimer’s Disease
Hiroshi Matsuda
Aging and Disease    2013, 4 (1): 29-37.   DOI: null
Abstract   HTML   PDF (884KB)

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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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.   DOI: null
Abstract   HTML   PDF (1435KB)

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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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.   DOI: null
Abstract   HTML   PDF (665KB)

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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Cytokines: Their Role in Stroke and Potential Use as Biomarkers and Therapeutic Targets
Danielle N. Doll,Taura L. Barr,James W. Simpkins
Aging and Disease    2014, 5 (5): 294-306.   DOI: 10.14336/AD.2014.0500294
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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.

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Herbal Formula Danggui-Shaoyao-San Promotes Neurogenesis and Angiogenesis in Rat Following Middle Cerebral Artery Occlusion
Changhong Ren,Brian Wang,Ning Li,Kunlin Jin,Xunming Ji
Aging and Disease    2015, 6 (4): 245-253.   DOI: 10.14336/AD.2014.1126
Abstract   HTML   PDF (1378KB)

Current studies demonstrated that traditional Chinese herbal formula Danggui-Shaoyao-San (DSS) is not only used for the treatment of menstrual disorder, but has also found its use in neurological diseases. However, the neuroprotective role of DSS on ischemia-induced brain injury is still unclear. The aim of the present study is to explore the effect of DSS in ischemic brain injury. Total 30 adult female Sprague-Dawley rats underwent 90 min transient middle cerebral artery occlusion (MCAO). DSS (600 mg/kg) was administered through the intragastric route at the time of reperfusion and then performed every day thereafter until sacrifice. Results showed that DSS treatment significantly improved neurobehavioral outcomes (N=10 per group, P<0.05). Immunohistochemical staining showed that microvessel density in the perifocal region of DSS-treated rats was significantly increased compared to the saline-treated group (N=4 per group, P<0.01). Similarly, the numbers of BrdU+/DCX+ cells in the subventricular zone were increased in DSS-treated rats compared to the saline-treated group (P<0.05). Furthermore, we demonstrated that DSS treatment activated vascular endothelial growth factor (N=4 per group,P<0.05) and promoted eNOS phosphorylation (N=4 per group,P<0.05). Thus, we concluded that DSS promoted focal angiogenesis and neurogenesis, and attenuated ischemia-induced brain injury in rats after MCAO, suggesting that DSS is a potential drug for ischemic stroke therapy.

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Thymus Size and Age-related Thymic Involution: Early Programming, Sexual Dimorphism, Progenitors and Stroma
Jingang Gui,Lisa Maria Mustachio,Dong-Ming Su,Ruth W. Craig
Aging and Disease    2012, 3 (3): 280-290.   DOI: null
Abstract   HTML   PDF (756KB)

Age-related thymic involution is characterized by a progressive regression in thymus size and a diminishment of thymic structure. A decrease in thymic compartments leads to the reduction of thymopoiesis. Thymic involution is closely associated with immunosenescence, a degeneration of the immune system primarily due to the alterations in T-cell composition. Strategies to improve the consequences of the aging thymus are currently under investigation. A wide array of knowledge has revealed a series of factors that are essential in the overall determination of thymic function and immune response. Evidence indicates that early programming of the thymus, sexual dimorphism, and the efficiency of specific T-cell progenitors and the thymic microenvironment are all crucial determinants of immune activity from early life through advanced ages. To fully understand the processes involved in age-related thymic involution, such determinants must be considered. The central purpose of this review is to emphasize previous and most recent evidence suggesting that these factors contribute to the influence of long-term immunity and ultimately shape the progression of thymic involution in advanced age.

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Successful Aging as a Continuum of Functional Independence: Lessons from Physical Disability Models of Aging
Kristin A. Lowry,Abbe N. Vallejo,Stephanie A. Studenski
Aging and Disease    2012, 3 (1): 5-15.   DOI: null
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Successful aging is a multidimensional construct that could be viewed as a continuum of achievement. Based on the disability model proposed by the WHO International Classification of Functioning, Disability and Health, successful aging includes not only the presence or absence of disease, but also aspects of mobility and social participation. Here we review definitions of successful aging and discuss relevance of the disability model in the evaluation of successful aging and frailty. In particular, we summarize evidences that highlight the importance of measures of mobility (ability to walk and perform activities of daily living), and social participation in identifying and locating older adults across the range of the successful aging continuum. Lastly, we discuss the role of inflammation in age-related decline and in frailty. Future research directions are proposed, including identifying causal pathways among inflammatory markers, disability, and frailty. A better understanding of immunological functioning in late life may help unlock novel ways to promote successful aging.

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Autonomic Cardiovascular Damage during Post-menopause: the Role of Physical Training
Hugo C. D. Souza, Geisa C. S. V. Tezini
Aging and Disease    2013, 4 (6): 320-328.   DOI: 10.14336/AD.2013.0400320
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Menopause is part of the aging process and is characterized by the natural cessation of menstruation; during this time, the production of ovarian hormones, especially estrogen, is sharply reduced. This reduction can cause symptoms and disorders that affect most women and can interfere with their quality of life. Women are also more susceptible to cardiovascular diseases during this period, considering that these ovarian hormones would be associated with a protective effect on the cardiovascular system, by acting at various levels, contributing to the body homeostasis. Among several effects on the cardiovascular system, the ovarian hormones seem to play an important role in the autonomic control of heart rate and blood pressure. A reduction in ovarian hormones causes an autonomic imbalance and increases the risk of cardiovascular diseases. In fact, this increased risk is justified by the key role the autonomic nervous system plays in all cardiac regulatory mechanisms, exerting a tonic and reflexive influence on the main variables of the cardiovascular system. The autonomic system controls various cardiovascular parameters, such as the modulation of heart rate and blood pressure, myocardial contractility and venous capacitance, directly participating in the regulation of cardiac output. Over the years, the standard treatment for menopause symptoms and disorders has been hormone replacement therapy (HRT). However, many studies have indicated the risks of HRT, which justify the need for new non-pharmacological therapies. To this end, physical training, mainly aerobic, has been applied with excellent results on the cardiovascular autonomic nervous system, as it reduces the risk of cardiac diseases and improves the survival rate with direct beneficial effects on the quality of life of these women during the aging process.

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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
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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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Mitochondrial Dysfunction in Alzheimer’s Disease and the Rationale for Bioenergetics Based Therapies
Isaac G. Onyango,Jameel Dennis,Shaharyah M. Khan
Aging and Disease    2016, 7 (2): 201-214.   DOI: 10.14336/AD.2015.1007
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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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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
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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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Aging and Neurogenesis, a Lesion from Alzheimer’s Disease
Philippe Taupin
Aging and Disease    2010, 1 (2): 158-168.   DOI: null
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The evidence that neurogenesis occurs in the adult brain and neural stem cells (NSCs) reside in the adult central nervous system (CNS) of mammals opens new avenues and opportunities for our understanding of development and for therapy. Newly generated neuronal cells of the adult brain would contribute to the physio-pathology of the nervous system and the adult brain may be amenable to repair. The contribution of adult neurogenesis to the functioning of the nervous system remains to be elucidated and adult NSCs have yet to be brought to therapy. It is generally accepted that NSCs in the adult brain have a regenerative capacity. Yet, evidences suggest that they may also contribute to pathological developments in neurological diseases. Alzheimer’s disease (AD) is a neurodegenerative disease and the hippocampus is one of the regions of the brain the most affected by the disease. AD is characterized by neurodegeneration, amyloid plaques, neurofibrillary tangles, aneuploidy and enhanced neurogenesis in the adult brain. The process of adult neurogenesis holds the potential to generate populations of cells that are aneuploid, particularly in the neurogenic regions. Aneuploid newly generated neuronal cells of the adult brain would contribute to the pathology of AD. Adult neurogenesis would not only contribute to regenerative attempts in the CNS, but also to the pathogenesis of neurological diseases and disorders.

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