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2015, Vol.6  No.2
Aβ-mediated increases in extracellular glutamate and the resulting excitotoxicity. (1) Aβ increases presynaptic release of glutamate. (2) Aβ elevates astrocytic calcium via stimulation of astrocytic α7 nicotinic receptors, resulting in astrocytic glutamate release via an unknown mechanism. (3) Aβ decreases glutamate clearance from the synapse, thereby prolonging the duration of glutamate in the synapse and potentially resulting in the spread of glutamate to neighboring synapses. (4) Prolonged activation of S-NMDARs and AMPARs resulting from increased extracellular glutamate is predicted to cause desensitization and internalization of NMDA/AMPA, resulting in synaptic depression. (5) Glutamate spillover activates E-NMDARs, resulting in multiple deleterious downstream events, including an increase in tau [Detail] ...

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  • Table of Content
      25 March 2015, Volume 6 Issue 2 Previous Issue    Next Issue
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    Conference Report
    Stop Aging Disease! ICAD 2014
    Ilia Stambler
    Aging and disease. 2015, 6 (2): 76-94.   DOI: 10.14336/AD.2015.0115
    Abstract   HTML   PDF (653KB) ( 1778 )

    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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    Review Article
    Modelling the p53/p66Shc Aging Pathway in the Shortest Living Vertebrate Nothobranchius Furzeri
    Priami Chiara, De Michele Giulia, Cotelli Franco, Cellerino Alessandro, Giorgio Marco, Pelicci Pier Giuseppe, Migliaccio Enrica
    Aging and disease. 2015, 6 (2): 95-108.   DOI: 10.14336/AD.2014.0228
    Abstract   HTML   PDF (757KB) ( 1391 )

    Oxidative stress induced by reactive oxygen species (ROS) increases during lifespan and is involved in aging processes. The p66Shc adaptor protein is a master regulator of oxidative stress response in mammals. Ablation of p66Shc enhances oxidative stress resistance both in vitro and in vivo. Most importantly, it has been demonstrated that its deletion retards aging in mice. Recently, new insights in the molecular mechanisms involving p66Shc and the p53 tumor suppressor genes were given: a specific p66Shc/p53 transcriptional regulation pathway was uncovered as determinant in oxidative stress response and, likely, in aging. p53, in a p66Shc-dependent manner, negatively downregulates the expression of 200 genes which are involved in the G2/M transition of mitotic cell cycle and are downregulated during physiological aging. p66Shc modulates the response of p53 by activating a p53 isoform (p44/p53, also named Delta40p53). Based on these latest results, several developments are expected in the future, as the generation of animal models to study aging and the evaluation of the use of the p53/p66Shc target genes as biomarkers in aging related diseases. The aim of this review is to investigate the conservation of the p66Shc and p53 role in oxidative stress between fish and mammals. We propose to approach this study trough a new model organism, the annual fish Nothobranchius furzeri, that has been demonstrated to develop typical signs of aging, like in mammals, including senescence, neurodegeneration, metabolic disorders and cancer.

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    Metabolic Syndrome, Aging and Involvement of Oxidative Stress
    Bonomini Francesca, Rodella Luigi Fabrizio, Rezzani Rita
    Aging and disease. 2015, 6 (2): 109-120.   DOI: 10.14336/AD.2014.0305
    Abstract   HTML   PDF (571KB) ( 2640 )

    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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    Suicide in the Global Chinese Aging Population: A Review of Risk and Protective Factors, Consequences, and Interventions
    Dong XinQi, Chang E-Shien, Zeng Ping, Simon Melissa A.
    Aging and disease. 2015, 6 (2): 121-130.   DOI: 10.14336/AD.2014.0223
    Abstract   HTML   PDF (729KB) ( 1759 )

    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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    The Role of the Tripartite Glutamatergic Synapse in the Pathophysiology of Alzheimer’s Disease
    Rudy Carolyn C., Hunsberger Holly C., Weitzner Daniel S., Reed Miranda N.
    Aging and disease. 2015, 6 (2): 131-148.   DOI: 10.14336/AD.2014.0423
    Abstract   HTML   PDF (915KB) ( 1400 )

    Alzheimer’s disease (AD) is the most common form of dementia in individuals over 65 years of age and is characterized by accumulation of beta-amyloid (Aβ) and tau. Both Aβ and tau alter synaptic plasticity, leading to synapse loss, neural network dysfunction, and eventually neuron loss. However, the exact mechanism by which these proteins cause neurodegeneration is still not clear. A growing body of evidence suggests perturbations in the glutamatergic tripartite synapse, comprised of a presynaptic terminal, a postsynaptic spine, and an astrocytic process, may underlie the pathogenic mechanisms of AD. Glutamate is the primary excitatory neurotransmitter in the brain and plays an important role in learning and memory, but alterations in glutamatergic signaling can lead to excitotoxicity. This review discusses the ways in which both beta-amyloid (Aβ) and tau act alone and in concert to perturb synaptic functioning of the tripartite synapse, including alterations in glutamate release, astrocytic uptake, and receptor signaling. Particular emphasis is given to the role of N-methyl-D-aspartate (NMDA) as a possible convergence point for Aβ and tau toxicity.

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    Laparoscopic Surgery in the Elderly: A Review of the Literature
    Bates Andrew T., Divino Celia
    Aging and disease. 2015, 6 (2): 149-155.   DOI: 10.14336/AD.2014.0429
    Abstract   HTML   PDF (541KB) ( 1093 )

    Laparoscopic techniques are gradually replacing many common surgical procedures that are performed in an increasingly aging population. Laparoscopy places different physiologic demands on the body than in open surgery. PubMed was searched for evidence related to the use of laparoscopy in the elderly population to treat common surgical pathologies. Randomized trials, systematic reviews, and meta-analyses were preferred. Currently, over 40% of all surgeries performed in the U.S. are on patients older than 65 years. By the end of the 21st century, Americans are expected to live 20 years longer than the current average. However, elderly patients clearly show higher rates of surgical morbidity and mortality overall. Laparoscopic techniques show decreased wound complications, post-operative ileus, intraoperative blood loss, and reduced need for post-operative rehabilitation. In conclusion, laparoscopic surgery is safe in the elderly population and affords multiple advantages including decreased pain and convalescence. However, the physiology of laparoscopy places demands on elderly patients that typically present with more medical comorbidities.

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    Hypoglycemia in Older People - A Less Well Recognized Risk Factor for Frailty
    Abdelhafiz Ahmed H, Rodríguez-Mañas Leocadio, Morley John E., Sinclair Alan J
    Aging and disease. 2015, 6 (2): 156-167.   DOI: 10.14336/AD.2014.0330
    Abstract   HTML   PDF (698KB) ( 1604 )

    Recurrent hypoglycemia is common in older people with diabetes and is likely to be less recognized and under reported by patients and health care professionals. Hypoglycemia in this age group is associated with significant morbidities leading to both physical and cognitive dysfunction. Repeated hospital admissions due to frequent hypoglycemia are also associated with further deterioration in patients’ general health. This negative impact of hypoglycemia is likely to eventually lead to frailty, disability and poor outcomes. It appears that the relationship between hypoglycemia and frailty is bidirectional and mediated through a series of influences including under nutrition. Therefore, attention should be paid to the management of under nutrition in the general elderly population by improving energy intake and maintaining muscle mass. Increasing physical activity and having a more conservative approach to glycemic targets in frail older people with diabetes may be worthwhile.

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Kunlin Jin, M.D., Ph.D., Professor
Ashok K. Shetty, Ph.D., Professor
David A. Greenberg, M.D., Ph.D., Professor
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