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Sample records for age-related degenerative disorders

  1. GENETICS OF HUMAN AGE RELATED DISORDERS.

    PubMed

    Srivastava, I; Thukral, N; Hasija, Y

    2015-01-01

    Aging is an inevitable biological phenomenon. The incidence of age related disorders (ARDs) such as cardiovascular diseases, cancer, arthritis, dementia, osteoporosis, diabetes, neurodegenerative diseases increase rapidly with aging. ARDs are becoming a key social and economic trouble for the world's elderly population (above 60 years), which is expected to reach 2 billion by 2050. Advancement in understanding of genetic associations, particularly through genome wide association studies (GWAS), has revealed a substantial contribution of genes to human aging and ARDs. In this review, we have focused on the recent understanding of the extent to which genetic predisposition may influence the aging process. Further analysis of the genetic association studies through pathway analysis several genes associated with multiple ARDs have been highlighted such as apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), cadherin 13 (CDH13), CDK5 regulatory subunit associated protein 1 (CDKAL-1), methylenetetrahydrofolate reductase (MTHFR), disrupted in schizophrenia 1 (DISC1), nitric oxide synthase 3 (NOS3), paraoxonase 1 (PON1), indicating that these genes could play a pivotal role in ARD causation. These genes were found to be significantly enriched in Jak-STAT signalling pathway, asthma and allograft rejection. Further, interleukin-6 (IL-6), insulin (INS), vascular endothelial growth factor A (VEGFA), estrogen receptor1 (ESR1), transforming growth factor, beta 1(TGFB1) and calmodulin 1 (CALM1) were found to be highly interconnected in network analysis. We believe that extensive research on the presence of common genetic variants among various ARDs may facilitate scientists to understand the biology behind ARDs causation. PMID:26856084

  2. Biomechanics of Degenerative Spinal Disorders

    PubMed Central

    Iorio, Justin A.; Jakoi, Andre M.

    2016-01-01

    The spine has several important functions including load transmission, permission of limited motion, and protection of the spinal cord. The vertebrae form functional spinal units, which represent the smallest segment that has characteristics of the entire spinal column. Discs and paired facet joints within each functional unit form a three-joint complex between which loads are transmitted. Surrounding the spinal motion segment are ligaments, composed of elastin and collagen, and joint capsules which restrict motion to within normal limits. Ligaments have variable strengths and act via different lever arm lengths to contribute to spinal stability. As a consequence of the longer moment arm from the spinous process to the instantaneous axis of rotation, inherently weaker ligaments (interspinous and supraspinous) are able to provide resistance to excessive flexion. Degenerative processes of the spine are a normal result of aging and occur on a spectrum. During the second decade of life, the intervertebral disc demonstrates histologic evidence of nucleus pulposus degradation caused by reduced end plate blood supply. As disc height decreases, the functional unit is capable of an increased range of axial rotation which subjects the posterior facet capsules to greater mechanical loads. A concurrent change in load transmission across the end plates and translation of the instantaneous axis of rotation further increase the degenerative processes at adjacent structures. The behavior of the functional unit is impacted by these processes and is reflected by changes in the stress-strain relationship. Back pain and other clinical symptoms may occur as a result of the biomechanical alterations of degeneration. PMID:27114783

  3. Age-Related Degenerative Functional, Radiographic, and Histological Changes of the Shoulder in Non-Human Primates

    PubMed Central

    Plate, Johannes F.; Bates, Christopher M.; Mannava, Sandeep; Smith, Thomas L.; Jorgensen, Matthew J.; Register, Thomas C.; Stehle, John R.; High, Kevin P.; Shively, Carol A.; Kaplan, Jay R.; Saul, Katherine R.; Tuohy, Christopher J.

    2013-01-01

    Background Non-human primates have similar shoulder anatomy and physiology compared to humans and may represent a previously underutilized model for shoulder research. This study sought to identify naturally occurring bony and muscular degeneration in the shoulder of non-human primates and to assess relationships between structural and functional aspects of the shoulder and measures of physical function of the animals. We hypothesized that age-related degenerative changes in the shoulders of non-human primates would resemble those observed in aging humans. Methods Middle-aged (n=5, ages 9.4 to 11.8 years) and elderly (n=6, ages 19.8 to 26.4 years) female vervet monkeys were studied for changes in mobility and shoulder function, and radiographic and histologic signs of age-related degeneration. Results Four out of six (4/6) elderly animals had degenerative changes of the glenoid compared to 0/5 of the middle-aged animals (p=0.005). Elderly animals had glenoid retroversion, decreased joint space, walked slower and spent less time climbing and hanging than middle-aged vervets (p<0.05). Physical mobility and shoulder function correlated with glenoid version angle (p<0.05). Supraspinatus muscles of elderly animals were less dense (p=0.001), had decreased fiber cross-sectional area (p<0.001), but similar amounts of nuclear material (p=0.085). Degenerative rotator cuff tears were not observed in any of the eleven animals. Discussion and Conclusion The vervet monkey naturally undergoes age-related functional, radiographic and histological changes of the shoulder and may qualify as an animal model for selected translational research of shoulder osteoarthritis. Level of evidence Basic Science Study, in-vivo Animal Model PMID:23352182

  4. Loss of UCHL1 promotes age-related degenerative changes in the enteric nervous system

    PubMed Central

    Coulombe, Josée; Gamage, Prasanna; Gray, Madison T.; Zhang, Mei; Tang, Matthew Y.; Woulfe, John; Saffrey, M. Jill; Gray, Douglas A.

    2014-01-01

    UCHL1 (ubiquitin carboxyterminal hydrolase 1) is a deubiquitinating enzyme that is particularly abundant in neurons. From studies of a spontaneous mutation arising in a mouse line it is clear that loss of function of UCHL1 generates profound degenerative changes in the central nervous system, and it is likely that a proteolytic deficit contributes to the pathology. Here these effects were found to be recapitulated in mice in which the Uchl1 gene had been inactivated by homologous recombination. In addition to the previously documented neuropathology associated with loss of UCHL1 function, axonal swellings were detected in the striatum. In agreement with previously reported findings the loss of UCHL1 function was accompanied by perturbations in ubiquitin pools, but glutathione levels were also significantly depleted in the brains of the knockout mice, suggesting that oxidative defense mechanisms may be doubly compromised. To determine if, in addition to its role in the central nervous system, UCHL1 function is also required for homeostasis of the enteric nervous system the gastrointestinal tract was analyzed in UCHL1 knockout mice. The mice displayed functional changes and morphological changes in gut neurons that preceded degenerative changes in the brain. The changes were qualitatively and quantitatively similar to those observed in wild type mice of much greater age, and strongly resemble changes reported for elderly humans. UCHL1 knockout mice should therefore serve as a useful model of gut aging. PMID:24994982

  5. Genetic and degenerative disorders primarily causing other movement disorders.

    PubMed

    Pavese, Nicola; Tai, Yen F

    2016-01-01

    In this chapter, we will discuss the contributions of structural and functional imaging to the diagnosis and management of genetic and degenerative diseases that lead to the occurrence of movement disorders. We will mainly focus on Huntington's disease, Wilson's disease, dystonia, and neurodegeneration with brain iron accumulation, as they are the more commonly encountered clinical conditions within this group. PMID:27432681

  6. Glutamatergic treatment strategies for age-related memory disorders.

    PubMed

    Müller, W E; Scheuer, K; Stoll, S

    1994-01-01

    Age-related changes of N-methyl-D-aspartate (NMDA) receptors have been found in cortical areas and in the hippocampus of many species. On the basis of a variety of experimental observations it has been suggested that the decrease of NMDA receptor density might be one of the causative factors of the cognitive decline with aging. Based on these findings several strategies have been developed to improve cognition by compensating the NMDA receptor deficits in aging. The most promising approaches are the indirect activation of glutamatergic neurotransmission by agonists of the glycine site or the restoration of the age-related deficit of receptor density by several nootropics. PMID:7997073

  7. Genetic Markers in Biological Fluids for Aging-Related Major Neurocognitive Disorder

    PubMed Central

    Castro-Chavira, S.A.; Fernández, T.; Nicolini, H.; Diaz-Cintra, S.; Prado-Alcalá, R.A.

    2015-01-01

    Aging-related major neurocognitive disorder (NCD), formerly named dementia, comprises of the different acquired diseases whose primary deficit is impairment in cognitive functions such as complex attention, executive function, learning and memory, language, perceptual/motor skills, and social cognition, and that are related to specific brain regions and/or networks. According to its etiology, the most common subtypes of major NCDs are due to Alzheimer’s disease (AD), vascular disease (VaD), Lewy body disease (LBD), and frontotemporal lobar degeneration (FTLD). These pathologies are frequently present in mixed forms, i.e., AD plus VaD or AD plus LBD, thus diagnosed as due to multiple etiologies. In this paper, the definitions, criteria, pathologies, subtypes and genetic markers for the most common age-related major NCD subtypes are summarized. The current diagnostic criteria consider cognitive decline leading to major NCD or dementia as a progressive degenerative process with an underlying neuropathology that begins before the manifestation of symptoms. Biomarkers associated with this asymptomatic phase are being developed as accurate risk factor and biomarker assessments are fundamental to provide timely treatment since no treatments to prevent or cure NCD yet exist. Biological fluid assessment represents a safer, cheaper and less invasive method compared to contrast imaging studies to predict NCD appearance. Genetic factors particularly have a key role not only in predicting development of the disease but also the age of onset as well as the presentation of comorbidities that may contribute to the disease pathology and trigger synergistic mechanisms which may, in turn, accelerate the neurodegenerative process and its resultant behavioral and functional disorders. PMID:25731625

  8. Genetic markers in biological fluids for aging-related major neurocognitive disorder.

    PubMed

    Castro-Chavira, S A; Fernandez, T; Nicolini, H; Diaz-Cintra, S; Prado-Alcala, R A

    2015-01-01

    Aging-related major neurocognitive disorder (NCD), formerly named dementia, comprises of the different acquired diseases whose primary deficit is impairment in cognitive functions such as complex attention, executive function, learning and memory, language, perceptual/motor skills, and social cognition, and that are related to specific brain regions and/or networks. According to its etiology, the most common subtypes of major NCDs are due to Alzheimer' s disease (AD), vascular disease (VaD), Lewy body disease (LBD), and frontotemporal lobar degeneration (FTLD). These pathologies are frequently present in mixed forms, i.e., AD plus VaD or AD plus LBD, thus diagnosed as due to multiple etiologies. In this paper, the definitions, criteria, pathologies, subtypes and genetic markers for the most common age-related major NCD subtypes are summarized. The current diagnostic criteria consider cognitive decline leading to major NCD or dementia as a progressive degenerative process with an underlying neuropathology that begins before the manifestation of symptoms. Biomarkers associated with this asymptomatic phase are being developed as accurate risk factor and biomarker assessments are fundamental to provide timely treatment since no treatments to prevent or cure NCD yet exist. Biological fluid assessment represents a safer, cheaper and less invasive method compared to contrast imaging studies to predict NCD appearance. Genetic factors particularly have a key role not only in predicting development of the disease but also the age of onset as well as the presentation of comorbidities that may contribute to the disease pathology and trigger synergistic mechanisms which may, in turn, accelerate the neurodegenerative process and its resultant behavioral and functional disorders. PMID:25731625

  9. Consensus Paper: Management of Degenerative Cerebellar Disorders

    PubMed Central

    Ilg, W.; Bastian, A. J.; Boesch, S.; Burciu, R. G.; Celnik, P.; Claaßen, J.; Feil, K.; Kalla, R.; Miyai, I.; Nachbauer, W.; Schöls, L.; Strupp, M.; Synofzik, M.; Teufel, J.

    2015-01-01

    Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation. PMID:24222635

  10. Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders.

    PubMed

    Kaminsky, Natalie; Bihari, Ofer; Kanner, Sivan; Barzilai, Ari

    2016-06-01

    The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a "hostile" environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit. PMID:27245308

  11. Diagnosis of Age-Related Cardiovascular Disorders | NCI Technology Transfer Center | TTC

    Cancer.gov

    Researchers at the NIH, National Institute on Aging, Cardiovascular Biology Unit-Vascular Group have discovered a method for the diagnosis and prognosis of cardiovascular aging, and is seeking parties interested in in-licensing or collaborative research to co-develop, evaluate, or commercialize novel methods for diagnosing age-related cardiovascular disorders.

  12. Carnosine and Related Peptides: Therapeutic Potential in Age-Related Disorders

    PubMed Central

    Cararo, José H; Streck, Emilio L; Schuck, Patricia F; Ferreira, Gustavo da C

    2015-01-01

    Imidazole dipeptides (ID), such as carnosine (β-alanyl-L-histidine), are compounds widely distributed in excitable tissues of vertebrates. ID are also endowed of several biochemical properties in biological tissues, including antioxidant, bivalent metal ion chelating, proton buffering, and carbonyl scavenger activities. Furthermore, remarkable biological effects have been assigned to such compounds in age-related human disorders and in patients whose activity of serum carnosinase is deficient or undetectable. Nevertheless, the precise biological role of ID is still to be unraveled. In the present review we shall discuss some evidences from clinical and basic studies for the utilization of ID as a drug therapy for age-related human disorders. PMID:26425391

  13. Carnosine and Related Peptides: Therapeutic Potential in Age-Related Disorders.

    PubMed

    Cararo, José H; Streck, Emilio L; Schuck, Patricia F; Ferreira, Gustavo da C

    2015-09-01

    Imidazole dipeptides (ID), such as carnosine (β-alanyl-L-histidine), are compounds widely distributed in excitable tissues of vertebrates. ID are also endowed of several biochemical properties in biological tissues, including antioxidant, bivalent metal ion chelating, proton buffering, and carbonyl scavenger activities. Furthermore, remarkable biological effects have been assigned to such compounds in age-related human disorders and in patients whose activity of serum carnosinase is deficient or undetectable. Nevertheless, the precise biological role of ID is still to be unraveled. In the present review we shall discuss some evidences from clinical and basic studies for the utilization of ID as a drug therapy for age-related human disorders. PMID:26425391

  14. Age-related differences in cognition across the adult lifespan in autism spectrum disorder.

    PubMed

    Lever, Anne G; Geurts, Hilde M

    2016-06-01

    It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age-related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is related to subjective cognitive challenges. Neuropsychological tests assessing visual and verbal memory, generativity, and theory of mind (ToM), and a self-report measure assessing cognitive failures were administered to 236 matched participants with and without ASD, aged 20-79 years (IQ > 80). Group comparisons revealed that individuals with ASD had higher scores on visual memory, lower scores on generativity and ToM, and similar performance on verbal memory. However, ToM impairments were no longer present in older (50+ years) adults with ASD. Across adulthood, individuals with ASD demonstrated similar age-related effects on verbal memory, generativity, and ToM, while age-related differences were reduced on visual memory. Although adults with ASD reported many cognitive failures, those were not associated with neuropsychological test performance. Hence, while some cognitive abilities (visual and verbal memory) and difficulties (generativity and semantic memory) persist across adulthood in ASD, others become less apparent in old age (ToM). Age-related differences characteristic of typical aging are reduced or parallel, but not increased in individuals with ASD, suggesting that ASD may partially protect against an age-related decrease in cognitive functioning. Despite these findings, adults with ASD experience many cognitive daily challenges, which highlights the need for adequate social support and the importance of further research into this topic, including longitudinal studies. Autism Res 2016, 9: 666-676. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  15. Exercise training as a preventive tool for age-related disorders: a brief review

    PubMed Central

    Ciolac, Emmanuel Gomes

    2013-01-01

    Aging populations are a worldwide phenomenon affecting both developed and developing countries. This issue raises serious concerns for both governments and the general population. Regular participation in physical activity and/or exercise training programs can minimize the physiological alterations that occur during aging and may contribute to improvements in health and well-being. The present review will discuss the role of regular exercise training in preventing age-related physiological decline and, consequently, associated chronic diseases. Compelling evidence that regular exercise and/or physical activity can improve quality of life, prevent or control the development of chronic disease and increase life expectancy is shown. In summary, regular exercise training and/or physical activity has an important influence on aging and may help to prevent age-related disorders. PMID:23778419

  16. Glycation: the angiogenic paradox in aging and age-related disorders and diseases.

    PubMed

    Roca, F; Grossin, N; Chassagne, P; Puisieux, F; Boulanger, E

    2014-05-01

    Angiogenesis is generally a quiescent process which, however, may be modified by different physiological and pathological conditions. The "angiogenic paradox" has been described in diabetes because this disease impairs the angiogenic response in a manner that differs depending on the organs involved and disease evolution. Aging is also associated with pro- and antiangiogenic processes. Glycation, the post-translational modification of proteins, increases with aging and the progression of diabetes. The effect of glycation on angiogenesis depends on the type of glycated proteins and cells involved. This complex link could be responsible for the "angiogenic paradox" in aging and age-related disorders and diseases. Using diabetes as a model, the present work has attempted to review the age-related angiogenic paradox, in particular the effects of glycation on angiogenesis during aging.

  17. Contesting the dogma of an age-related heat shock response impairment: implications for cardiac-specific age-related disorders.

    PubMed

    Carnemolla, Alisia; Labbadia, John P; Lazell, Hayley; Neueder, Andreas; Moussaoui, Saliha; Bates, Gillian P

    2014-07-15

    Ageing is associated with the reduced performance of physiological processes and has been proposed as a major risk factor for disease. An age-related decline in stress response pathways has been widely documented in lower organisms. In particular, the heat shock response (HSR) becomes severely compromised with age in Caenorhabditis elegans. However, a comprehensive analysis of the consequences of ageing on the HSR in higher organisms has not been documented. We used both HS and inhibition of HSP90 to induce the HSR in wild-type mice at 3 and 22 months of age to investigate the extent to which different brain regions, and peripheral tissues can sustain HSF1 activity and HS protein (HSP) expression with age. Using chromatin immunoprecipitation, quantitative reverse transcription polymerase chain reaction, western blotting and enzyme linked immunosorbent assay (ELISA), we were unable to detect a difference in the level or kinetics of HSP expression between young and old mice in all brain regions. In contrast, we did observe an age-related reduction in chaperone levels and HSR-related proteins in the heart. This could result in a decrease in the protein folding capacity of old hearts with implications for age-related cardiac disorders.

  18. Delayed Umbilical Cord Blood Clamping: First Line of Defense Against Neonatal and Age-Related Disorders.

    PubMed

    Sanberg, Paul R; Divers, Ryan; Mehindru, Anuj; Mehindru, Ankur; Borlongan, Cesar V

    2014-06-01

    The aging body is unable to maintain homeostasis in cell genesis and function. Stem cell-based regenerative medicine may reverse aging and treat age-related disorders. This perspective article discusses the therapeutic effects of stem cell transplantation on neonatal diseases, which may have long-lasting benefits affecting even the aging process. In particular, the article highlights the potential of the earliest transfer of stem cells between a mother and fetus via the umbilical cord during child birth and how this process may modify the clinical practice of umbilical cord clamping. While such umbilical cord clamping is routinely performed in an expeditious manner after birth for stem cell banking, the present article advances the concept that a delay in clamping the umbilical cord may actually allow more stem cells to be delivered from the mother to the fetus. The authors' overarching hypothesis is that early umbilical cord clamping results in an artificial loss of stem cells at birth and increases the infant's susceptibility to both neonatal and age-related diseases, while delaying umbilical cord clamping is perhaps the most effective and non-invasive way to transplant stem cells in order to treat these diseases.

  19. Neuronal histaminergic system in aging and age-related neurodegenerative disorders.

    PubMed

    Shan, Ling; Swaab, Dick F; Bao, Ai-Min

    2013-07-01

    The neuronal histaminergic system is involved in many physiological functions and is severely affected in age-related neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). The properties of the neuronal histaminergic system in experimental animals and the alterations observed in postmortem brain material of PD or AD patients are reviewed. The production of neuronal histamine shows diurnal fluctuations in control subjects who had no neuropsychiatric disorders, while this fluctuation was strongly altered in patients with neurodegenerative diseases, including PD and AD. In addition, different alterations shown as expression levels of histidine decarboxylase (the key enzyme for histamine production), histamine-methyltransferase (the histamine deactivating enzyme), and histamine receptors (H(1-4)R) were found in various neurodegenerative disorders. Discrepancies between results from animal models and postmortem human brain material studies have made clear that the validation of animal models is absolutely necessary and that studies on patients and human postmortem material are essential to understand the changes of neuronal histaminergic system occurring in neuropsychiatric disorders.

  20. Emerging therapeutic roles for NAD(+) metabolism in mitochondrial and age-related disorders.

    PubMed

    Srivastava, Sarika

    2016-12-01

    Nicotinamide adenine dinucleotide (NAD(+)) is a central metabolic cofactor in eukaryotic cells that plays a critical role in regulating cellular metabolism and energy homeostasis. NAD(+) in its reduced form (i.e. NADH) serves as the primary electron donor in mitochondrial respiratory chain, which involves adenosine triphosphate production by oxidative phosphorylation. The NAD(+)/NADH ratio also regulates the activity of various metabolic pathway enzymes such as those involved in glycolysis, Kreb's cycle, and fatty acid oxidation. Intracellular NAD(+) is synthesized de novo from L-tryptophan, although its main source of synthesis is through salvage pathways from dietary niacin as precursors. NAD(+) is utilized by various proteins including sirtuins, poly ADP-ribose polymerases (PARPs) and cyclic ADP-ribose synthases. The NAD(+) pool is thus set by a critical balance between NAD(+) biosynthetic and NAD(+) consuming pathways. Raising cellular NAD(+) content by inducing its biosynthesis or inhibiting the activity of PARP and cADP-ribose synthases via genetic or pharmacological means lead to sirtuins activation. Sirtuins modulate distinct metabolic, energetic and stress response pathways, and through their activation, NAD(+) directly links the cellular redox state with signaling and transcriptional events. NAD(+) levels decline with mitochondrial dysfunction and reduced NAD(+)/NADH ratio is implicated in mitochondrial disorders, various age-related pathologies as well as during aging. Here, I will provide an overview of the current knowledge on NAD(+) metabolism including its biosynthesis, utilization, compartmentalization and role in the regulation of metabolic homoeostasis. I will further discuss how augmenting intracellular NAD(+) content increases oxidative metabolism to prevent bioenergetic and functional decline in multiple models of mitochondrial diseases and age-related disorders, and how this knowledge could be translated to the clinic for human relevance. PMID

  1. Niemann-Pick C disease gene mutations and age-related neurodegenerative disorders.

    PubMed

    Zech, Michael; Nübling, Georg; Castrop, Florian; Jochim, Angela; Schulte, Eva C; Mollenhauer, Brit; Lichtner, Peter; Peters, Annette; Gieger, Christian; Marquardt, Thorsten; Vanier, Marie T; Latour, Philippe; Klünemann, Hans; Trenkwalder, Claudia; Diehl-Schmid, Janine; Perneczky, Robert; Meitinger, Thomas; Oexle, Konrad; Haslinger, Bernhard; Lorenzl, Stefan; Winkelmann, Juliane

    2013-01-01

    Niemann-Pick type C (NPC) disease is a rare autosomal-recessively inherited lysosomal storage disorder caused by mutations in NPC1 (95%) or NPC2. Given the highly variable phenotype, diagnosis is challenging and particularly late-onset forms with predominantly neuropsychiatric presentations are likely underdiagnosed. Pathophysiologically, genetic alterations compromising the endosomal/lysosomal system are linked with age-related neurodegenerative disorders. We sought to examine a possible association of rare sequence variants in NPC1 and NPC2 with Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD) and progressive supranuclear palsy (PSP), and to genetically determine the proportion of potentially misdiagnosed NPC patients in these neurodegenerative conditions. By means of high-resolution melting, we screened the coding regions of NPC1 and NPC2 for rare genetic variation in a homogenous German sample of patients clinically diagnosed with PD (n = 563), FTLD (n = 133) and PSP (n = 94), and 846 population-based controls. The frequencies of rare sequence variants in NPC1/2 did not differ significantly between patients and controls. Disease-associated NPC1/2 mutations were found in six PD patients (1.1%) and seven control subjects (0.8%), but not in FTLD or PSP. All rare variation was detected in the heterozygous state and no compound heterozygotes were observed. Our data do not support the hypothesis that rare NPC1/2 variants confer susceptibility for PD, FTLD, or PSP in the German population. Misdiagnosed NPC patients were not present in our samples. However, further assessment of NPC disease genes in age-related neurodegeneration is warranted. PMID:24386122

  2. DNA-aptamers raised against AGEs as a blocker of various aging-related disorders.

    PubMed

    Yamagishi, Sho-Ichi; Taguchi, Kensei; Fukami, Kei

    2016-08-01

    A non-enzymatic reaction between sugars or aldehydes and the amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules, which could impair their structural integrity and function. This process begins with the conversion of reversible Schiff base adducts, and then to more stable, covalently-bound Amadori rearrangement products. Over a course of days to weeks, these early glycation products undergo further reactions, such as rearrangements and dehydration to become irreversibly crossed-linked, fluorescent protein derivatives termed advanced glycation end products (AGEs). The formation and accumulation of AGEs have been known to progress in a physiological aging process and at an accelerated rate under hyperglycemic, inflammatory and oxidative stress conditions. There is a growing body of evidence that AGEs and their receptor RAGE interaction play a role in the pathogenesis of various devastating disorders, including cardiovascular disease, Alzheimer's disease, insulin resistance, osteoporosis and cancer growth and metastasis. Furthermore, diet has been recently recognized as a major environmental source of AGEs that could also elicit pro-inflammatory reactions, thereby being involved in organ damage in vivo. Therefore, inhibition of AGE formation and/or blockade of the interaction of AGEs with RAGE may be a novel therapeutic target for aging-related disorders. This article discusses a potential utility of DNA-aptamers raised against AGEs for preventing aging and/or diabetes-associated organ damage, especially focusing on diabetic microvascular complications, vascular remodeling, metabolic derangements, and melanoma growth and expansion in animal models. PMID:27338620

  3. Improvement of neuronal bioenergetics by neurosteroids: implications for age-related neurodegenerative disorders.

    PubMed

    Grimm, Amandine; Schmitt, Karen; Lang, Undine E; Mensah-Nyagan, Ayikoe Guy; Eckert, Anne

    2014-12-01

    The brain has high energy requirements to maintain neuronal activity. Consequently impaired mitochondrial function will lead to disease. Normal aging is associated with several alterations in neurosteroid production and secretion. Decreases in neurosteroid levels might contribute to brain aging and loss of important nervous functions, such as memory. Up to now, extensive studies only focused on estradiol as a promising neurosteroid compound that is able to ameliorate cellular bioenergetics, while the effects of other steroids on brain mitochondria are poorly understood or not investigated at all. Thus, we aimed to characterize the bioenergetic modulating profile of a panel of seven structurally diverse neurosteroids (progesterone, estradiol, estrone, testosterone, 3α-androstanediol, DHEA and allopregnanolone), known to be involved in brain function regulation. Of note, most of the steroids tested were able to improve bioenergetic activity in neuronal cells by increasing ATP levels, mitochondrial membrane potential and basal mitochondrial respiration. In parallel, they modulated redox homeostasis by increasing antioxidant activity, probably as a compensatory mechanism to a slight enhancement of ROS which might result from the rise in oxygen consumption. Thereby, neurosteroids appeared to act via their corresponding receptors and exhibited specific bioenergetic profiles. Taken together, our results indicate that the ability to boost mitochondria is not unique to estradiol, but seems to be a rather common mechanism of different steroids in the brain. Thus, neurosteroids may act upon neuronal bioenergetics in a delicate balance and an age-related steroid disturbance might be involved in mitochondrial dysfunction underlying neurodegenerative disorders. PMID:25281013

  4. Sacroiliac joint motion in patients with degenerative lumbar spine disorders.

    PubMed

    Nagamoto, Yukitaka; Iwasaki, Motoki; Sakaura, Hironobu; Sugiura, Tsuyoshi; Fujimori, Takahito; Matsuo, Yohei; Kashii, Masafumi; Murase, Tsuyoshi; Yoshikawa, Hideki; Sugamoto, Kazuomi

    2015-08-01

    OBJECT Usually additional anchors into the ilium are necessary in long fusion to the sacrum for degenerative lumbar spine disorders (DLSDs), especially for adult spine deformity. Although the use of anchors is becoming quite common, surgeons must always keep in mind that the sacroiliac (SI) joint is mobile and they should be aware of the kinematic properties of the SI joint in patients with DLSDs, including adult spinal deformity. No previous study has clarified in vivo kinematic changes in the SI joint with respect to patient age, sex, or parturition status or the presence of DLSDs. The authors conducted a study to clarify the mobility and kinematic characteristics of the SI joint in patients with DLSDs in comparison with healthy volunteers by using in vivo 3D motion analysis with voxel-based registration, a highly accurate, noninvasive method. METHODS Thirteen healthy volunteers (the control group) and 20 patients with DLSDs (the DLSD group) underwent low-dose 3D CT of the lumbar spine and pelvis in 3 positions (neutral, maximal trunk flexion, and maximal trunk extension). SI joint motion was calculated by computer processing of the CT images (voxel-based registration). 3D motion of the SI joint was expressed as both 6 df by Euler angles and translations on the coordinate system and a helical axis of rotation. The correlation between joint motion and the cross-sectional area of the trunk muscles was also investigated. RESULTS SI joint motion during trunk flexion-extension was minute in healthy volunteers. The mean rotation angles during trunk flexion were 0.07° around the x axis, -0.02° around the y axis, and 0.16° around the z axis. The mean rotation angles during trunk extension were 0.38° around the x axis, -0.08° around the y axis, and 0.08° around the z axis. During trunk flexion-extension, the largest amount of motion occurred around the x axis. In patients with DLSDs, the mean rotation angles during trunk flexion were 0.57° around the x axis, 0.01

  5. Systems Pharmacology Links GPCRs with Retinal Degenerative Disorders

    PubMed Central

    Chen, Yu; Palczewski, Krzysztof

    2015-01-01

    In most biological systems, second messengers and their key regulatory and effector proteins form links between multiple cellular signaling pathways. Such signaling nodes can integrate the deleterious effects of genetic aberrations, environmental stressors, or both in complex diseases, leading to cell death by various mechanisms. Here we present a systems (network) pharmacology approach that, together with transcriptomics analyses, was used to identify different G protein–coupled receptors that experimentally protected against cellular stress and death caused by linked signaling mechanisms. We describe the application of this concept to degenerative and diabetic retinopathies in appropriate mouse models as an example. Systems pharmacology also provides an attractive framework for devising strategies to combat complex diseases by using (repurposing) US Food and Drug Administration–approved pharmacological agents. PMID:25839098

  6. dbAARD & AGP: A computational pipeline for the prediction of genes associated with age related disorders.

    PubMed

    Srivastava, Isha; Gahlot, Lokesh Kumar; Khurana, Pooja; Hasija, Yasha

    2016-04-01

    The atrocious behavioral and physiological shift with aging accelerate occurrence of deleterious disorders. Contemporary research is focused at uncovering the role of genetic associations in age-related disorders (ARDs). While the completion of the Human Genome Project and the HapMap project has generated huge amount of data on genetic variations; Genome-Wide Association Studies (GWAS) have identified genetic variations, essentially SNPs associated with several disorders including ARDs. However, a repository that houses all such ARD associations is lacking. The present work is aimed at filling this void. A database, dbAARD (database of Aging and Age Related Disorders) has been developed which hosts information on more than 3000 genetic variations significantly (p-value <0.05) associated with 51 ARDs. Furthermore, a machine learning based gene prediction tool AGP (Age Related Disorders Gene Prediction) has been constructed by employing rotation forest algorithm, to prioritize genes associated with ARDs. The tool achieved an overall accuracy in terms of precision 75%, recall 76%, F-measure 76% and AUC 0.85. Both the web resources have been made available online at http://genomeinformatics.dce.edu/dbAARD/ and http://genomeinformatics.dce.edu/AGP/ respectively for easy retrieval and usage by the scientific community. We believe that this work may facilitate the analysis of plethora of variants associated with ARDs and provide cues for deciphering the biology of aging. PMID:26836976

  7. Lutein and Age-Related Ocular Disorders in the Older Adult: A Review

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lutein, a carotenoid found in dark green, leafy vegetables, has been implicated as being protective against the acquired ocular diseases, such as cataracts and age-related macular degeneration. In the eye, lutein may act as an antioxidant and as a blue light filter to protect the underlying tissues ...

  8. Light treatment for sleep disorders: consensus report. V. Age-related disturbances.

    PubMed

    Campbell, S S; Terman, M; Lewy, A J; Dijk, D J; Eastman, C I; Boulos, Z

    1995-06-01

    Sleep maintenance insomnia is a major complaint among the elderly. As a result, an inordinate proportion of sleeping pill prescriptions go to individuals over 65 y of age. Because of the substantial problems associated with use of hypnotics in older populations, efforts have been made to develop nondrug treatments for age-related sleep disturbance, including timed exposure to bright light. Such bright light treatments are based on the assumption that age-related sleep disturbance is the consequence of alterations in the usual temporal relationship between body temperature and sleep. Although studies are limited, results strongly suggest that evening bright light exposure is beneficial in alleviating sleep maintenance insomnia in healthy elderly subjects. Less consistent, but generally positive, findings have been reported with regard to bright light treatment of sleep and behavioral disturbance in demented patients. For both groups, it is likely that homeostatic factors also contribute to sleep disturbance, and these may be less influenced by bright light interventions. PMID:7632988

  9. Light treatment for sleep disorders: consensus report. V. Age-related disturbances.

    PubMed

    Campbell, S S; Terman, M; Lewy, A J; Dijk, D J; Eastman, C I; Boulos, Z

    1995-06-01

    Sleep maintenance insomnia is a major complaint among the elderly. As a result, an inordinate proportion of sleeping pill prescriptions go to individuals over 65 y of age. Because of the substantial problems associated with use of hypnotics in older populations, efforts have been made to develop nondrug treatments for age-related sleep disturbance, including timed exposure to bright light. Such bright light treatments are based on the assumption that age-related sleep disturbance is the consequence of alterations in the usual temporal relationship between body temperature and sleep. Although studies are limited, results strongly suggest that evening bright light exposure is beneficial in alleviating sleep maintenance insomnia in healthy elderly subjects. Less consistent, but generally positive, findings have been reported with regard to bright light treatment of sleep and behavioral disturbance in demented patients. For both groups, it is likely that homeostatic factors also contribute to sleep disturbance, and these may be less influenced by bright light interventions.

  10. Neuroimaging and Genetic Risk for Alzheimer’s Disease and Addiction-Related Degenerative Brain Disorders

    PubMed Central

    Jahanshad, Neda; Leonardo, Cassandra D.; Thompson, Paul M.

    2014-01-01

    Neuroimaging offers a powerful means to assess the trajectory of brain degeneration in a variety of disorders, including Alzheimer’s disease (AD). Here we describe how multimodal imaging can be used to study the changing brain during the different stages of AD. We integrate findings from a range of studies using magnetic resonance imaging (MRI), positron emission tomography (PET), functional MRI (fMRI) and diffusion weighted imaging (DWI). Neuroimaging reveals how risk genes for degenerative disorders affect the brain, including several recently discovered genetic variants that may disrupt brain connectivity. We review some recent neuroimaging studies of genetic polymorphisms associated with increased risk for late-onset Alzheimer’s disease (LOAD). Some genetic variants that increase risk for drug addiction may overlap with those associated with degenerative brain disorders. These common associations offer new insight into mechanisms underlying neurodegeneration and addictive behaviors, and may offer new leads for treating them before severe and irreversible neurological symptoms appear. PMID:24142306

  11. Neuroimaging and genetic risk for Alzheimer's disease and addiction-related degenerative brain disorders.

    PubMed

    Roussotte, Florence F; Daianu, Madelaine; Jahanshad, Neda; Leonardo, Cassandra D; Thompson, Paul M

    2014-06-01

    Neuroimaging offers a powerful means to assess the trajectory of brain degeneration in a variety of disorders, including Alzheimer's disease (AD). Here we describe how multi-modal imaging can be used to study the changing brain during the different stages of AD. We integrate findings from a range of studies using magnetic resonance imaging (MRI), positron emission tomography (PET), functional MRI (fMRI) and diffusion weighted imaging (DWI). Neuroimaging reveals how risk genes for degenerative disorders affect the brain, including several recently discovered genetic variants that may disrupt brain connectivity. We review some recent neuroimaging studies of genetic polymorphisms associated with increased risk for late-onset Alzheimer's disease (LOAD). Some genetic variants that increase risk for drug addiction may overlap with those associated with degenerative brain disorders. These common associations offer new insight into mechanisms underlying neurodegeneration and addictive behaviors, and may offer new leads for treating them before severe and irreversible neurological symptoms appear.

  12. Degenerative Cervical Myelopathy: A Spectrum of Related Disorders Affecting the Aging Spine.

    PubMed

    Tetreault, Lindsay; Goldstein, Christina L; Arnold, Paul; Harrop, James; Hilibrand, Alan; Nouri, Aria; Fehlings, Michael G

    2015-10-01

    Cervical spinal cord dysfunction can result from either traumatic or nontraumatic causes, including tumors, infections, and degenerative changes. In this article, we review the range of degenerative spinal disorders resulting in progressive cervical spinal cord compression and propose the adoption of a new term, degenerative cervical myelopathy (DCM). DCM comprises both osteoarthritic changes to the spine, including spondylosis, disk herniation, and facet arthropathy (collectively referred to as cervical spondylotic myelopathy), and ligamentous aberrations such as ossification of the posterior longitudinal ligament and hypertrophy of the ligamentum flavum. This review summarizes current knowledge of the pathophysiology of DCM and describes the cascade of events that occur after compression of the spinal cord, including ischemia, destruction of the blood-spinal cord barrier, demyelination, and neuronal apoptosis. Important features of the diagnosis of DCM are discussed in detail, and relevant clinical and imaging findings are highlighted. Furthermore, this review outlines valuable assessment tools for evaluating functional status and quality of life in these patients and summarizes the advantages and disadvantages of each. Other topics of this review include epidemiology, the prevalence of degenerative changes in the asymptomatic population, the natural history and rates of progression, risk factors of diagnosis (clinical, imaging and genetic), and management strategies. PMID:26378358

  13. Degenerative Cervical Myelopathy: A Spectrum of Related Disorders Affecting the Aging Spine.

    PubMed

    Tetreault, Lindsay; Goldstein, Christina L; Arnold, Paul; Harrop, James; Hilibrand, Alan; Nouri, Aria; Fehlings, Michael G

    2015-10-01

    Cervical spinal cord dysfunction can result from either traumatic or nontraumatic causes, including tumors, infections, and degenerative changes. In this article, we review the range of degenerative spinal disorders resulting in progressive cervical spinal cord compression and propose the adoption of a new term, degenerative cervical myelopathy (DCM). DCM comprises both osteoarthritic changes to the spine, including spondylosis, disk herniation, and facet arthropathy (collectively referred to as cervical spondylotic myelopathy), and ligamentous aberrations such as ossification of the posterior longitudinal ligament and hypertrophy of the ligamentum flavum. This review summarizes current knowledge of the pathophysiology of DCM and describes the cascade of events that occur after compression of the spinal cord, including ischemia, destruction of the blood-spinal cord barrier, demyelination, and neuronal apoptosis. Important features of the diagnosis of DCM are discussed in detail, and relevant clinical and imaging findings are highlighted. Furthermore, this review outlines valuable assessment tools for evaluating functional status and quality of life in these patients and summarizes the advantages and disadvantages of each. Other topics of this review include epidemiology, the prevalence of degenerative changes in the asymptomatic population, the natural history and rates of progression, risk factors of diagnosis (clinical, imaging and genetic), and management strategies.

  14. Inherited catalase deficiency: is it benign or a factor in various age related disorders?

    PubMed

    Góth, László; Nagy, Teréz

    2013-01-01

    Hydrogen peroxide was - and is still - considered toxic for a wide range of living organisms. Oxidative stress occurs when there is an excess of pro-oxidants over antioxidants and it has been implicated in several diseases. Catalase is involved in hydrogen peroxide catabolism and is important in defense against oxidative stress. Acatalasemia means the inherited near-total deficiency of catalase activity, usually in reference to red cell catalase. Acatalasemia was thought at first to be an asymptotic disorder. In the absence of catalase, neither the Japanese, or Hungarian acatalasemics nor acatalasemic mice had significantly increased blood glutathione peroxidase activity. In animal models, catalase deficient tissues show much slower rates of removal of extracellular hydrogen peroxide. In catalase knock-out mice, a decreased hydrogen peroxide removing capacity and increased reactive oxygen species formation were reported. Hydrogen peroxide may cause methemoglobinemia in patients with catalase deficiency. During anesthesia for a Japanese acatalasemic patient the disinfection with hydrogen peroxide solution caused severe methemoglobinemia. Patients with inherited catalase deficiency, who are treated with uric acid oxidase (rasburicase) may experience very high concentrations of hydrogen peroxide and may suffer from methemoglobinemia and hemolysis. The high (18.5%) prevalence of diabetes mellitus in inherited catalase deficient individuals and the earlier (10 years) manifestation of the disease may be attributed to the oxidative damage of oxidant sensitive, insulin producing pancreatic beta-cells. Ninety-seven of 114 acatalasemics had diseases related to oxidative stress and aging. The oxidative stress due to catalase deficiency could contribute to the manifestation of diabetes while for the other diseases it may be one of the factors in their causations. In summary, inherited catalase deficiency is associated with clinical features, pathologic laboratory test results

  15. Bipolar and Major Depressive Disorder: Neuroimaging the Developmental-Degenerative Divide

    PubMed Central

    Savitz, Jonathan; Drevets, Wayne C

    2010-01-01

    Both major depressive disorder and bipolar disorder are the subject of a voluminous imaging and genetics literature. Here, we attempt a comprehensive review of MRI and metabolic PET studies conducted to date on these two disorders, and interpret our findings from the perspective of developmental and degenerative models of illness. Elevated activity and volume loss of the hippocampus, orbital and ventral prefrontal cortex are recurrent themes in the literature. In contrast, dorsal aspects of the PFC tend to display hypometabolism. Ventriculomegaly and white matter hyperintensities are intimately associated with depression in elderly populations and likely have a vascular origin. Important confounding influences are medication, phenotypic and genetic heterogeneity, and technological limitations. We suggest that environmental stress and genetic risk variants interact with each other in a complex manner to alter neural circuitry and precipitate illness. Imaging genetic approaches hold out promise for advancing our understanding of affective illness. PMID:19428491

  16. ERBB4 Polymorphism and Family History of Psychiatric Disorders on Age-Related Cortical Changes in Healthy Children

    PubMed Central

    Douet, Vanessa; Chang, Linda; Lee, Kristin; Ernst, Thomas

    2015-01-01

    Background Genetic variations in ERBB4 were associated with increased susceptibility for schizophrenia (SCZ) and bipolar disorders (BPD). Structural imaging studies showed cortical abnormalities in adolescents and adults with SCZ or BPD. However, less is known about subclinical cortical changes or the influence of ERBB4 on cortical development. Methods 971 healthy children (ages 3–20 years old; 462 girls and 509 boys) were genotyped for the ERBB4-rs7598440 variants, had structural MRI, and cognitive evaluation (NIH Toolbox ®). We investigated the effects of ERBB4 variants and family history of SCZ and/or BPD (FH) on cortical measures and cognitive performances across ages 3–20 years using a general additive model. Results Variations in ERBB4 and FH impact differentially the age-related cortical changes in regions often affected by SCZ and BPD. The ERBB4-TT-risk genotype children with no FH had subtle cortical changes across the age span, primarily located in the left temporal lobe and superior parietal cortex. In contrast, the TT-risk genotype children with FH had more pronounced age-related changes, mainly in the frontal lobes compared to the non-risk genotype children. Interactive effects of age, FH and ERBB4 variations were also found on episodic memory and working memory, which are often impaired in SCZ and BPD. Conclusions Healthy children carrying the risk-genotype in ERBB4 and/or with FH had cortical measures resembling those reported in SCZ or BPD. These subclinical cortical variations may provide early indicators for increased risk of psychiatric disorders and improve our understanding of the effect of the NRG1–ERBB4 pathway on brain development. PMID:25744101

  17. Age-related disorders of sleep and motor control in the rat models of functionally distinct cholinergic neuropathology.

    PubMed

    Ciric, Jelena; Lazic, Katarina; Petrovic, Jelena; Kalauzi, Aleksandar; Saponjic, Jasna

    2016-03-15

    We studied the impact of aging during sleep in the rat models of Alzheimer's (AD) and Parkinson's (PD) disease cholinergic neuropathology to determine the possible different and earlier onset of age-related sleep disorder during the neurodegenerative diseases vs. healthy aging. We used the bilateral nucleus basalis (NB) and pedunculopontine tegmental nucleus (PPT) lesioned rats as the in vivo models of functionally distinct cholinergic neuropathology, and we followed the impact of aging on sleep architecture, the electroencephalographic (EEG) microstructure and motor control across sleep/wake states. Our results have shown for the first time that the earliest signs of aging during distinct cholinergic neuropathology were expressed through a different and topographically specific EEG microstructure during rapid eye movement sleep (REM). EEG delta amplitude attenuation within the sensorimotor cortex (SMCx) during REM was the earliest sign of aging in the NB lesion. EEG sigma amplitude augmentation within the motor cortex (MCx) during REM was the earliest sign of aging in the PPT lesion. In addition, aging was differently expressed through the SMCx drive alterations, but it was commonly expressed through the MCx drive alterations during all sleep/wake states. Our study provided evidence of distinct REM sleep disorders and sleep state related cortical drives as the signs of aging onset during functionally distinct cholinergic neuropathologies (NB lesion vs. PPT lesion).

  18. Towards finding the linkage between metabolic and age-related disorders using semantic gene data network analysis.

    PubMed

    Uzzal Hossain, Mohammad; Zaffar Shibly, Abu; Md Omar, Taimur; Tous Zohora, Fatama; Sara Santona, Umme; Hossain, Md Jakir; Hosen Khoka, Md Sadek; Ara Keya, Chaman; Salimullah, Md

    2016-01-01

    A metabolic disorder (MD) occurs when the metabolic process is disturbed. This process is carried out by thousands of enzymes participating in numerous inter-dependent metabolic pathways. Critical biochemical reactions that involve the processing and transportation of carbohydrates, proteins and lipids are affected in metabolic diseases. Therefore, it is of interest to identify the common pathways of metabolic disorders by building protein-protein interactions (PPI) for network analysis. The molecular network linkages between MD and age related diseases (ARD) are intriguing. Hence, we created networks of protein-protein interactions that are related with MD and ARD using relevant known data in the public domain. The network analysis identified known MD associated proteins and predicted genes and or its products of ARD in common pathways. The genes in the common pathways were isolated from the network and further analyzed for their co-localization and shared domains. Thus, a model hypothesis is proposed using interaction networks that are linked between MD and ARD. This data even if less conclusive finds application in understanding the molecular mechanism of known diseases in relation to observed molecular events.

  19. Age-related Epstein-Barr Virus-positive lymphoproliferative disorders of the orbit and maxillary sinus : a case report.

    PubMed

    Mitsui, Takeki; Mawatari, Momoko; Koiso, Hiromi; Yokohama, Akihiko; Uchiumi, Hideki; Saitoh, Takayuki; Handa, Hiroshi; Hirato, Junko; Karasawa, Masamitsu; Murakami, Hirokazu; Kojima, Masaru; Nakamura, Shigeo; Nojima, Yoshihisa; Tsukamoto, Norifumi

    2012-01-01

    We report a rare case of age-related Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disorder (aEBVBLPD) primarily involving the orbit and maxillary sinus. Lesions in the left orbit and maxillary sinus were observed in a 59-year-old man presenting with pain in the left orbit and maxilla. Owing to the presence of Reed-Sternberg-like cells, the initial diagnosis was nodular sclerosis-type Hodgkin's lymphoma. Clinical stage was IIAE, and response to chemotherapy and radiotherapy was favorable. Further immunohistochemical and in situ hybridization analyses of the Reed-Sternberg-like giant cells revealed CD30, CD15, CD20, Bob-1, Oct-2, EBV-encoded RNAs (EBERs) and latent membrane protein-1 (LMP-1) expression. The characteristics of the present case, which included immunohistochemical findings, sites of primary lesions, absence of other lymph node lesions and relatively old age, suggested aEBVBLPD. Owing to the similarity in morphology, higher frequency at extranodal sites and poor prognosis, aEBVBLPD represents a differential diagnostic issue from classical Hodgkin's lymphoma when Reed-Sternberg cells are positive for EBV.

  20. A heme oxygenase-1 transducer model of degenerative and developmental brain disorders.

    PubMed

    Schipper, Hyman M; Song, Wei

    2015-03-09

    Heme oxygenase-1 (HO-1) is a 32 kDa protein which catalyzes the breakdown of heme to free iron, carbon monoxide and biliverdin. The Hmox1 promoter contains numerous consensus sequences that render the gene exquisitely sensitive to induction by diverse pro-oxidant and inflammatory stimuli. In "stressed" astroglia, HO-1 hyperactivity promotes mitochondrial iron sequestration and macroautophagy and may thereby contribute to the pathological iron deposition and bioenergetic failure documented in Alzheimer disease, Parkinson disease and certain neurodevelopmental conditions. Glial HO-1 expression may also impact neuroplasticity and cell survival by modulating brain sterol metabolism and the proteasomal degradation of neurotoxic proteins. The glial HO-1 response may represent a pivotal transducer of noxious environmental and endogenous stressors into patterns of neural damage and repair characteristic of many human degenerative and developmental CNS disorders.

  1. Astrocytes As the Main Players in Primary Degenerative Disorders of the Human Central Nervous System.

    PubMed

    Capani, Francisco; Quarracino, Cecilia; Caccuri, Roberto; Sica, Roberto E P

    2016-01-01

    Along the last years it has been demonstrated that non-neural cells play a major role in the pathogenesis of the primary degenerative disorders (PDDs) of the human central nervous system. Among them, astrocytes coordinate and participate in many different and complex metabolic processes, in close interaction with neurons. Moreover, increasing experimental evidence hints an early astrocytic dysfunction in these diseases. In this mini review we summarize the astrocytic behavior in PDDs, with special consideration to the experimental observations where astrocytic pathology precedes the development of neuronal dysfunction. We also suggest a different approach that could be consider in human investigations in Alzheimer's and Parkinson's disease. We believe that the study of PDDs with human brain samples may hold the key of a paradigmatic physiopathological process in which astrocytes might be the main players. PMID:26973519

  2. Cost-Effectiveness Analysis of a Reduction in Diagnostic Imaging in Degenerative Spinal Disorders

    PubMed Central

    Kim, Joanne S.M.; Dong, Joyce Z.; Brener, Stacey; Coyte, Peter C.; Rampersaud, Y. Raja

    2011-01-01

    Background: Advanced imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) are highly sensitive, but often non-specific, diagnostic tools. Despite this, CT and MRI are overutilized in degenerative spinal disorder diagnosis. From the perspective of the Ministry of Health, we evaluated against usual care the cost-effectiveness of a hypothetical triage program for non-emergent spinal disorders that reduces unnecessary imaging uses. Methods: Diagnostic and surgical data were prospectively collected on 2,046 outpatients who received consultation with the senior surgical author at Toronto Western Hospital, University Health Network, between September 2005 and April 2008. Using these data, we modelled an evidence-based diagnostic triage program wherein spine-focused clinical assessments and plain X-ray imaging would be applied prior to CT and MRI. Incremental costs were the incurred expenses from additional consultations and plain X-rays less the cost savings from the eliminated CT and MRI scans, expressed in 2009 Canadian dollars. Outcomes were expressed as the number of surgical candidates identified per MRI used in diagnosis, reflecting the efficiency of diagnostic imaging. Results: The triage program incurred $109,720 from additional consultations and plain X-rays and saved $2,117,697 from eliminated CT and MRI scans, resulting in net cost savings of $2,007,977 for the 31 months of the study period, or $777,282 per year. In usual care, 0.328~0.418 surgical candidates were identified per MRI whereas in the triage program, 0.736~0.885 surgical candidates were identified per MRI, resulting in over a twofold improvement in MRI efficiency. The triage program was therefore dominating. Applying to high-volume spine surgeons in Ontario, we estimated that the implementation of the triage program would save the province $24,234,929 per year. Interpretation: Based on the assumptions made in our modelling, eliminating unnecessary imaging in

  3. Phonological buffer and selective deficits of grammar, with distinct time onsets, in a patient with a focal degenerative disorder.

    PubMed

    Kartsounis, Luke D; Crewes, Hilary

    2007-04-01

    We report a patient with a focal degenerative disorder and very circumscribed neuropsychological deficits, the evolution of which we were able to study over a lengthy period. For years, he presented with only a speech production impediment that clinical observations and experimental studies enabled us to identify as a phonological buffer disorder. Subsequently, he developed agrammatism that appeared to be largely due to his inability to produce pronouns and auxiliary verbs. Remarkably, throughout our studies, even when he was virtually rendered mute, his ability to name objects on demand in writing remained intact. We discuss his case from clinical and theoretical perspectives.

  4. The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders

    PubMed Central

    Gao, Bifeng; Doan, An; Hybertson, Brooks M

    2014-01-01

    Nuclear factor (erythroid-derived 2)-like 2 (Nrf2; encoded in humans by the NFE2L2 gene) is a transcription factor that regulates the gene expression of a wide variety of cytoprotective phase II detoxification and antioxidant enzymes through a promoter sequence known as the antioxidant-responsive element (ARE). The ARE is a promoter element found in many cytoprotective genes; therefore, Nrf2 plays a pivotal role in the ARE-driven cellular defense system against environmental stresses. Agents that target the ARE/Nrf2 pathway have been tested in a wide variety of disorders, with at least one new Nrf2-activating drug now approved by the US Food and Drug Administration. Examination of in vitro and in vivo experimental results, and taking into account recent human clinical trial results, has led to an opinion that Nrf2-activating strategies – which can include drugs, foods, dietary supplements, and exercise – are likely best targeted at disease prevention, disease recurrence prevention, or slowing of disease progression in early stage illnesses; they may also be useful as an interventional strategy. However, this rubric may be viewed even more conservatively in the pathophysiology of cancer. The activation of the Nrf2 pathway has been widely accepted as offering chemoprevention benefit, but it may be unhelpful or even harmful in the setting of established cancers. For example, Nrf2 activation might interfere with chemotherapies or radiotherapies or otherwise give tumor cells additional growth and survival advantages, unless they already possess mutations that fully activate their Nrf2 pathway constitutively. With all this in mind, the ARE/Nrf2 pathway remains of great interest as a possible target for the pharmacological control of degenerative and immunological diseases, both by activation and by inhibition, and its regulation remains a promising biological target for the development of new therapies. PMID:24520207

  5. Single- or multiple-session viscosupplementation protocols for temporomandibular joint degenerative disorders: a randomized clinical trial.

    PubMed

    Guarda-Nardini, L; Rossi, A; Arboretti, R; Bonnini, S; Stellini, E; Manfredini, D

    2015-07-01

    The aim of the study was to compare the effectiveness of two single-session protocols, either adopting high- (protocol A) or medium-molecular weight hyaluronic acid (protocol B), with the reference five-session protocol of temporomandibular joint (TMJ) lavage plus viscosupplementation (protocol C) in the management of chronic TMJ degenerative disorders. A randomized clinical trial (RCT) with ten participants per treatment group was designed, with multiple observation points, ending at 6 months after treatment. Pain levels on a 10-point VAS scale were selected as the primary outcome variable to rate treatment effectiveness, along with a number of secondary outcome parameters. Findings showed that Group C patients had the highest decrease in pain levels. Nonparametric permutation analyses revealed that the global effect of treatment was significantly different between the three protocols (P = 0·024). Pairwise comparisons showed that the differences of treatment effect between the two single-session interventions were negligible (global P-value = 0·93). On the contrary, the five-session protocol was significantly superior to both single-session protocols (global P-values ranging from 0·003 to 0·012). In conclusion, in a population of age-, sex-, and psychosocial aspects-matched study groups, the standard of reference five-session protocol proved to be superior at 6 months as far as the decrease in pain levels was concerned, whilst there were no differences between the two single-session interventions. The absence of differences in treatment effect as for some other secondary clinical outcome variables may suggest that there is further space for future investigations attempting to reduce the number of multiple interventions for TMJ viscosupplementation.

  6. Intravitreal Autologous Bone Marrow CD34+ Cell Therapy for Ischemic and Degenerative Retinal Disorders: Preliminary Phase 1 Clinical Trial Findings

    PubMed Central

    Park, Susanna S.; Bauer, Gerhard; Abedi, Mehrdad; Pontow, Suzanne; Panorgias, Athanasios; Jonnal, Ravi; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan

    2015-01-01

    Purpose. Because human bone marrow (BM) CD34+ stem cells home into damaged tissue and may play an important role in tissue repair, this pilot clinical trial explored the safety and feasibility of intravitreal autologous CD34+ BM cells as potential therapy for ischemic or degenerative retinal conditions. Methods. This prospective study enrolled six subjects (six eyes) with irreversible vision loss from retinal vascular occlusion, hereditary or nonexudative age-related macular degeneration, or retinitis pigmentosa. CD34+ cells were isolated under Good Manufacturing Practice conditions from the mononuclear cellular fraction of the BM aspirate using a CliniMACs magnetic cell sorter. After intravitreal CD34+ cell injection, serial ophthalmic examinations, microperimetry/perimetry, fluorescein angiography, electroretinography (ERG), optical coherence tomography (OCT), and adaptive optics OCT were performed during the 6-month follow-up. Results. A mean of 3.4 million (range, 1–7 million) CD34+ cells were isolated and injected per eye. The therapy was well tolerated with no intraocular inflammation or hyperproliferation. Best-corrected visual acuity and full-field ERG showed no worsening after 6 months. Clinical examination also showed no worsening during follow-up except among age-related macular degeneration subjects in whom mild progression of geographic atrophy was noted in both the study eye and contralateral eye at 6-month follow-up, concurrent with some possible decline on multifocal ERG and microperimetry. Cellular in vivo imaging using adaptive optics OCT showed changes suggestive of new cellular incorporation into the macula of the hereditary macular degeneration study eye. Conclusions. Intravitreal autologous BM CD34+ cell therapy appears feasible and well tolerated in eyes with ischemic or degenerative retinal conditions and merits further exploration. (ClinicalTrials.gov number, NCT01736059.) PMID:25491299

  7. Autism Spectrum Disorder in Children and Adolescents with Fragile X Syndrome: Within-Syndrome Differences and Age-Related Changes

    PubMed Central

    McDuffie, Andrea; Abbeduto, Leonard; Lewis, Pamela; Kim, Jee-Seon; Kover, Sara T.; Weber, Ann; Brown, W. Ted

    2010-01-01

    The Autism Diagnostic Interview-Revised was used to examine diagnostic profiles and age-related changes in autism symptoms for a group of verbal children and adolescents with FXS, with and without autism. After controlling for nonverbal IQ, statistically significant between-group differences for lifetime and current autism symptoms were found for the Communication and Restricted Interests/Repetitive Behaviors domains, but not the Reciprocal Social Interaction domain. Effect sizes for differences in Reciprocal Social Interaction also were smaller than effect sizes for the other domains with one exception. Overall, severity of autism symptoms improved with age for all participants, with the least improvement noted for Restricted Interests and Repetitive Behaviors. FMRP did not account for unique variance in autism symptoms over and above nonverbal IQ. PMID:20567604

  8. [Age-related aspects of the extent of lipid metabolism and post-traumatic stress disorders among veterans of modern warfare].

    PubMed

    Torgashov, M N; Miakotnykh, V S; Pal'tsev, A I

    2013-01-01

    The peculiarities of violations of lipid metabolism and symptoms of post-traumatic stress disorder (PTSD) in 161 patients of 25-69 years, veterans of the military actions on the territory of Afghanistan and the Northern Caucasus were investigated. The dependence of the formation of dyslipidemia and related changes of atherosclerosis in the young age on neuroendocrine effects, accompanying the effects of combat stress and promoting accelerated aging was determined. On the other hand, with the time, after 15-25 years after participating in hostilities, the intensity of PTSD and its influence on the development of violations of lipid spectrum may decline. The leading role in the pathogenesis of dyslipidemia goes to age-related changes, accompanying a process of accelerated aging of veterans of combat operations, and to pathological disorders of metabolism in liver associated with alcohol abuse and the consequences of infectious diseases.

  9. What's on Your Mind? Conversation Topics Chosen by People With Degenerative Cognitive-Linguistic Disorders for Communication Boards

    PubMed Central

    Daniels, Darlene; Ettinger, Olivia; Mooney, Aimee; Noethe, Glory; Rowland, Charity

    2015-01-01

    Purpose Conversational topics chosen by a group of adults with degenerative cognitive-linguistic disorders for personalized communication board development were examined. The patient-generated themes commonly selected are presented to guide treatment planning and communication board development. Method Communication boards were created for 109 adults as part of a larger research project. One autobiographical topic that each participant would enjoy discussing multiple times was represented on each communication board with 16 pictures and word labels. For this review, topics were collapsed into general themes through a consensus process and examined by gender and age. Results Sixty unique conversational topics were identified from 109 participants and collapsed into 9 general themes: Hobbies, Family, Travel, Work, Home/Places I've Lived, Sports/Fitness, Religion, Animals, and World War II. Age and gender produced variations in themes chosen, though no significance in rank orders was found across groups. Conclusions Topics selected by adults with degenerative cognitive-linguistic disorders for communication boards resemble common conversational adult themes and do not center around basic needs or medical issues. Differences in gender and age for topic selection tend to be based on traditional roles. These general themes should be used when creating personalized communication boards for those who benefit from conversational aids. PMID:25835511

  10. Clinical characteristics of inflammation-associated depression: Monocyte gene expression is age-related in major depressive disorder.

    PubMed

    Grosse, Laura; Carvalho, Livia A; Wijkhuijs, Annemarie J M; Bellingrath, Silja; Ruland, Tillmann; Ambrée, Oliver; Alferink, Judith; Ehring, Thomas; Drexhage, Hemmo A; Arolt, Volker

    2015-02-01

    Increased inflammatory activation might only be present in a subgroup of depressed individuals in which immune processes are especially relevant to disease development. We aimed to analyze demographic, depression, and trauma characteristics of major depressive disorder (MDD) patients with regard to inflammatory monocyte gene expression. Fifty-six naturalistically treated MDD patients (32 ± 12 years) and 57 healthy controls (HC; 31 ± 11 years) were analyzed by the Inventory of Depressive Symptomatology (IDS) and by the Childhood Trauma Questionnaire (CTQ). We determined the expression of 38 inflammatory and immune activation genes including the glucocorticoid receptor (GR)α and GRβ genes in purified CD14(+) monocytes using quantitative-polymerase chain reaction (RT-qPCR). Monocyte gene expression was age-dependent, particularly in MDD patients. Increased monocyte gene expression and decreased GRα/β ratio were only present in MDD patients aged ⩾ 28 years. Post hoc analyses of monocyte immune activation in patients <28 years showed two subgroups: a subgroup with a severe course of depression (recurrent type, onset <15 years) - additionally characterized by panic/arousal symptoms and childhood trauma - that had a monocyte gene expression similar to HC, and a second subgroup with a milder course of the disorder (73% first episode depression, onset ⩾15 years) - additionally characterized by the absence of panic symptoms - that exhibited a strongly reduced inflammatory monocyte activation compared to HC. In conclusion, monocyte immune activation was not uniformly raised in MDD patients but was increased only in patients of 28 years and older.

  11. Erythropoietin and mTOR: A “One-Two Punch” for Aging-Related Disorders Accompanied by Enhanced Life Expectancy

    PubMed Central

    Maiese, Kenneth

    2016-01-01

    Life expectancy continues to increase throughout the world, but is accompanied by a rise in the incidence of non-communicable diseases. As a result, the benefits of an increased lifespan can be limited by aging-related disorders that necessitate new directives for the development of effective and safe treatment modalities. With this objective, the mechanistic target of rapamycin (mTOR), a 289-kDa serine/threonine protein, and its related pathways of mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), proline rich Akt substrate 40 kDa (PRAS40), AMP activated protein kinase (AMPK), Wnt signaling, and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), have generated significant excitement for furthering novel therapies applicable to multiple systems of the body. Yet, the biological and clinical outcome of these pathways can be complex especially with oversight of cell death mechanisms that involve apoptosis and autophagy. Growth factors, and in particular erythropoietin (EPO), are one avenue under consideration to implement control over cell death pathways since EPO can offer potential treatment for multiple disease entities and is intimately dependent upon mTOR signaling. In experimental and clinical studies, EPO appears to have significant efficacy in treating several disorders including those involving the developing brain. However, in mature populations that are affected by aging-related disorders, the direction for the use of EPO to treat clinical disease is less clear that may be dependent upon a number of factors including the understanding of mTOR signaling. Continued focus upon the regulatory elements that control EPO and mTOR signaling could generate critical insights for targeting a broad range of clinical maladies. PMID:27488211

  12. Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder.

    PubMed

    Boks, Marco P; van Mierlo, Hans C; Rutten, Bart P F; Radstake, Timothy R D J; De Witte, Lot; Geuze, Elbert; Horvath, Steve; Schalkwyk, Leonard C; Vinkers, Christiaan H; Broen, Jasper C A; Vermetten, Eric

    2015-01-01

    Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on ageing at the cellular level. A newly derived tool provides an additional means to investigate cellular ageing by estimating epigenetic age based on DNA methylation profiles. We therefore hypothesise that in a longitudinal study of traumatic stress both indicators of cellular ageing will show increased ageing. We expect that particularly in individuals that developed symptoms of post-traumatic stress disorder (PTSD) increases in these ageing parameters would stand out. From an existing longitudinal cohort study, ninety-six male soldiers were selected based on trauma exposure and the presence of symptoms of PTSD. All military personnel were deployed in a combat zone in Afghanistan and assessed before and 6 months after deployment. The Self-Rating Inventory for PTSD was used to measure the presence of PTSD symptoms, while exposure to combat trauma during deployment was measured with a 19-item deployment experiences checklist. These groups did not differ for age, gender, alcohol consumption, cigarette smoking, military rank, length, weight, or medication use. In DNA from whole blood telomere length was measured and DNA methylation levels were assessed using the Illumina 450K DNA methylation arrays. Epigenetic ageing was estimated using the DNAm age estimator procedure. The association of trauma with telomere length was in the expected direction but not significant (B=-10.2, p=0.52). However, contrary to our expectations, development of PTSD symptoms was associated with the reverse process, telomere lengthening (B=1.91, p=0.018). In concordance, trauma significantly accelerated epigenetic ageing (B=1.97, p=0.032) and similar to the findings in telomeres, development of PTSD symptoms was inversely associated with epigenetic ageing (B=-0.10, p=0.044). Blood cell count, medication and premorbid early life trauma exposure did not

  13. The genetics of age-related macular degeneration.

    PubMed

    Gorin, M B; Breitner, J C; De Jong, P T; Hageman, G S; Klaver, C C; Kuehn, M H; Seddon, J M

    1999-11-01

    Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics.

  14. Degenerative disease of the spine.

    PubMed

    Gallucci, Massimo; Limbucci, Nicola; Paonessa, Amalia; Splendiani, Alessandra

    2007-02-01

    Degenerative disease of the spine is a definition that includes a wide spectrum of degenerative abnormalities. Degeneration involves bony structures and the intervertebral disk, although many aspects of spine degeneration are strictly linked because the main common pathogenic factor is identified in chronic overload. During life the spine undergoes continuous changes as a response to physiologic axial load. These age-related changes are similar to pathologic degenerative changes and are a common asymptomatic finding in adults and elderly persons. A mild degree of degenerative changes is paraphysiologic and should be considered pathologic only if abnormalities determine symptoms. Imaging allows complete evaluation of static and dynamic factors related to degenerative disease of the spine and is useful in diagnosing the different aspects of spine degeneration.

  15. Autologous transplantation of genetically modified iris pigment epithelial cells: A promising concept for the treatment of age-related macular degeneration and other disorders of the eye

    NASA Astrophysics Data System (ADS)

    Semkova, Irina; Kreppel, Florian; Welsandt, Gerhard; Luther, Thomas; Kozlowski, Jolanta; Janicki, Hanna; Kochanek, Stefan; Schraermeyer, Ulrich

    2002-10-01

    Age-related macular degeneration (ARMD) is the leading cause for visual impairment and blindness in the elder population. Laser photocoagulation, photodynamic therapy and excision of neovascular membranes have met with limited success. Submacular transplantation of autologous iris pigment epithelial (IPE) cells has been proposed to replace the damaged retinal pigment epithelium following surgical removal of the membranes. We tested our hypothesis that the subretinal transplantation of genetically modified autologous IPE cells expressing biological therapeutics might be a promising strategy for the treatment of ARMD and other retinal disorders. Pigment epithelium-derived factor (PEDF) has strong antiangiogenic and neuroprotective activities in the eye. Subretinal transplantation of PEDF expressing IPE cells inhibited pathological choroidal neovascularization in rat models of laser-induced rupture of Bruch's membrane and of oxygen induced ischemic retinopathy. PEDF expressing IPE transplants also increased the survival and preserved rhodopsin expression of photoreceptor cells in the RCS rat, a model of retinal degeneration. These findings suggest a promising concept for the treatment of ARMD and other retinal disorders.

  16. Autologous platelet gel for tissue regeneration in degenerative disorders of the knee

    PubMed Central

    Napolitano, Marcello; Matera, Saverio; Bossio, Marcello; Crescibene, Antonio; Costabile, Enrico; Almolla, Joan; Almolla, Hesham; Togo, Francesco; Giannuzzi, Casimiro; Guido, Giampiero

    2012-01-01

    Background The refinement of the use of platelet-derived growth factors that has occurred over the last decade has led to a broadening of the fields of use, in particular for new treatments in orthopaedics aimed at improving tissue regeneration. Materials and methods Twenty-seven patients, aged between 18 and 81 years, with a diagnosis of degenerative joint disease lasting for more than 1 year were treated. The patients were divided into two groups, one with arthritis of the knee, the other with degenerative cartilage disease of the knee. Both groups were treated with a therapeutic protocol consisting of a cycle of three infiltrations of platelet-rich plasma at weekly intervals. The extemporaneous preparation was made from a sample of about 8 mL of venous whole blood collected into a specific Fibrin Polymer 2 test-tube from RegenLab® and centrifuged before addition of calcium gluconate. During the initial pre-treatment evaluation, specific questionnaires were administered, the Numerical Rating Scale (NRS) for subjective measurement of pain and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); these assessments were repeated 7 days after the end of the treatment and at 6 months during the follow-up. Results The parameters evaluated improved in both groups after treatment and there was a further improvement after 6 months of follow-up; furthermore, there was a substantial decrease in pain right after the first infiltration. Discussion The patients were treated on an out-patient basis by a specifically created multidisciplinary team comprising a transfusion specialist, an orthopaedist and a radiologist, who collaborate in a symbiotic manner. The out-patient protocol exploits the regenerative properties of platelet-rich plasma, which is a low cost treatment; in practice, a diagnostic-therapeutic programme of lower intensity, but of high technical and professional quality is created. The strategy also reduces both the number of hospital

  17. Associations of Mortality With Ocular Disorders and an Intervention of High-Dose Antioxidants and Zinc in the Age-Related Eye Disease Study

    PubMed Central

    2006-01-01

    Objective To assess the association of ocular disorders and high doses of antioxidants or zinc with mortality in the Age-Related Eye Disease Study (AREDS). Methods Baseline fundus and lens photographs were used to grade the macular and lens status of AREDS participants. Participants were randomly assigned to receive oral supplements of high-dose antioxidants, zinc, antioxidants plus zinc, or placebo. Risk of all-cause and cause-specific mortality was assessed using adjusted Cox proportional hazards models. Results During median follow-up of 6.5 years, 534 (11%) of 4753 AREDS participants died. In fully adjusted models, participants with advanced age-related macular degeneration (AMD) compared with participants with few, if any, drusen had increased mortality (relative risk [RR], 1.41; 95% confidence interval [CI], 1.08–1.86). Advanced AMD was associated with cardiovascular deaths. Compared with participants having good acuity in both eyes, those with visual acuity worse than 20/40 in 1 eye had increased mortality (RR, 1.36; 95% CI, 1.12–1.65). Nuclear opacity (RR, 1.40; 95% CI, 1.12–1.75) and cataract surgery (RR, 1.55; 95% CI, 1.18–2.05) were associated with increased all-cause mortality and with cancer deaths. Participants randomly assigned to receive zinc had lower mortality than those not taking zinc (RR, 0.73; 95% CI, 0.61–0.89). Conclusions The decreased survival of AREDS participants with AMD and cataract suggests that these conditions may reflect systemic rather than only local processes. The improved survival in individuals randomly assigned to receive zinc requires further study. PMID:15136320

  18. [Ibuprofen in rheumatic, degenerative and traumatic disorders of the locomotor system. Local effects and tolerance].

    PubMed

    Pollter, J

    1983-10-27

    The clinical trials carried out on Dolgit Creme containing 5% of the nonsteroidal antirheumatic active principle ibuprofen were carried out by 12 clinical examiners. The experimental and clinical tests were carried out on a total of 464 patients and/or volunteers. It has been proved that the active principle ibuprofen of the tested creme penetrates throughout the skin without causing serum concentrations which could lead to the appearance of undesirable side effects. The metabolization of ibuprofen after topical administration coincides with that following oral administration. In comparative studies with nonsteroidal antirheumatic gel it has been possible to prove the efficacy of Dolgit Creme in the treatment of the different forms of rheumatic diseases and degenerative articular changes as well as in cases of accident and sports injuries. The efficacy of Dolgit Creme compared to Placebo in a double blind trial for the assessment of the onset of action, pain alleviation, decrease of swelling, improvement of motility was at the 1%-level significantly superior. The effective dosage assessed was three or more times daily to apply a 4-10 cm strip of the creme on the affected part of the tissue and massage. Undesirable side effects appeared in less than 4% of the cases in the form of allergic skin reactions.

  19. [Presbycusis - Age Related Hearing Loss].

    PubMed

    Fischer, N; Weber, B; Riechelmann, H

    2016-07-01

    Presbycusis or age related hearing loss can be defined as a progressive, bilateral and symmetrical sensorineural hearing loss due to age related degeneration of inner ear structures. It can be considered a multifactorial complex disorder with environmental and genetic factors. The molecular, electrophysiological and histological damage at different levels of the inner ear cause a progressive hearing loss, which usually affects the high frequencies of hearing. The resulting poor speech recognition has a negative impact on cognitive, emotional and social function in older adults. Recent investigations revealed an association between hearing impairment and social isolation, anxiety, depression and cognitive decline in elderly. These findings emphasize the importance of diagnosis and treating hearing loss in the elderly population. Hearing aids are the most commonly used devices for treating presbycusis. The technical progress of implantable hearing devices allows an effective hearing rehabilitation even in elderly with severe hearing loss. However, most people with hearing impairments are not treated adequately. PMID:27392191

  20. Huntington disease: a single-gene degenerative disorder of the striatum.

    PubMed

    Nopoulos, Peggy C

    2016-03-01

    Huntington disease (HD) is an autosomal dominant, neurodegenerative disorder with a primary etiology of striatal pathology. The Huntingtin gene (HTT) has a unique feature of a DNA trinucleotide (triplet) repeat, with repeat length ranging from 10 to 35 in the normal population. Repeat lengths between 36 and 39 cause HD at reduced penetrance (some will get the disease, others won't) and when expanded to 40 or more repeats (mHTT), causes HD at full penetrance (every person with this length or beyond will definitely develop the disease). The symptoms of HD may be motor, cognitive, and psychiatric, and are consistent with the pathophysiology of frontostriatal circuitry malfunction. Expressed ubiquitously and throughout the entire life cycle (development through adulthood), mHTT causes initial dysfunction and eventual death of a specific cell population within the striatum. Although all areas of the brain are eventually affected, the primary pathology of the disease is regionally specific. As a single-gene disorder, HD has the distinction of having the potential of treatment that is aimed directly at the known pathogenic mechanism by gene silencing, providing hope for neuroprotection and ultimately, prevention.

  1. MicroRNA in central nervous system trauma and degenerative disorders.

    PubMed

    Liu, Nai-Kui; Xu, Xiao-Ming

    2011-05-01

    MicroRNAs (miRNAs) are a novel class of small noncoding RNAs that negatively regulate gene expression at the posttranscriptional level by binding to the 3'-untranslated region of target mRNAs leading to their translational inhibition or sometimes degradation. MiRNAs are predicted to control the activity of at least 20-30% of human protein-coding genes. Recent studies have demonstrated that miRNAs are highly expressed in the central nervous system (CNS) including the brain and spinal cord. Although we are currently in the initial stages of understanding how this novel class of gene regulators is involved in neurological biological functions, a growing body of exciting evidence suggests that miRNAs are important regulators of diverse biological processes such as cell differentiation, growth, proliferation, and apoptosis. Moreover, miRNAs are key modulators of both CNS development and plasticity. Some miRNAs have been implicated in several neurological disorders such as traumatic CNS injuries and neurodegenerative diseases. Recently, several studies suggested the possibility of miRNA involvement in neurodegeneration. Identifying the roles of miRNAs and their target genes and signaling pathways in neurological disorders will be critical for future research. miRNAs may represent a new layer of regulators for neurobiology and a novel class of therapeutic targets for neurological diseases.

  2. Current therapeutic developments in atrophic age-related macular degeneration.

    PubMed

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

    Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age-Related Eye Disease Study (AREDS) formulation, which has been demonstrated to slow down the progression of dry AMD. This review summarises recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem cell-based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID:26553922

  3. Current Therapeutic Development for Atrophic Age-related Macular Degeneration

    PubMed Central

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

    Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age Related Eye Disease Study (AREDS) formulation which has been demonstrated to slow down the progression of dry AMD. This review summarizes recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem-cell based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID:26553922

  4. Cognitive Impairment and Age-Related Vision Disorders: Their Possible Relationship and the Evaluation of the Use of Aspirin and Statins in a 65 Years-and-Over Sardinian Population

    PubMed Central

    Mandas, Antonella; Mereu, Rosa Maria; Catte, Olga; Saba, Antonio; Serchisu, Luca; Costaggiu, Diego; Peiretti, Enrico; Caminiti, Giulia; Vinci, Michela; Casu, Maura; Piludu, Stefania; Fossarello, Maurizio; Manconi, Paolo Emilio; Dessí, Sandra

    2014-01-01

    Neurological disorders (Alzheimer’s disease, vascular and mixed dementia) and visual loss (cataract, age-related macular degeneration, glaucoma, and diabetic retinopathy) are among the most common conditions that afflict people of at least 65 years of age. An increasing body of evidence is emerging, which demonstrates that memory and vision impairment are closely, significantly, and positively linked and that statins and aspirin may lessen the risk of developing age-related visual and neurological problems. However, clinical studies have produced contradictory results. Thus, the intent of the present study was to reliably establish whether a relationship exist between various types of dementia and age-related vision disorders, and to establish whether statins and aspirin may or may not have beneficial effects on these two types of disorders. We found that participants with dementia and/or vision problems were more likely to be depressed and displayed worse functional ability in basic and instrumental activities of daily living than controls. Mini mental state examination scores were significantly lower in patients with vision disorders compared to subjects without vision disorders. A closer association with macular degeneration was found in subjects with Alzheimer’s disease than in subjects without dementia or with vascular dementia, mixed dementia, or other types of age-related vision disorders. When we considered the associations between different types of dementia and vision disorders and the use of statins and aspirin, we found a significant positive association between Alzheimer’s disease and statins on their own or in combination with aspirin, indicating that these two drugs do not appear to reduce the risk of Alzheimer’s disease or improve its clinical evolution and may, on the contrary, favor its development. No significant association in statin use alone, aspirin use alone, or the combination of these was found in subjects without vision

  5. Cognitive Impairment and Age-Related Vision Disorders: Their Possible Relationship and the Evaluation of the Use of Aspirin and Statins in a 65 Years-and-Over Sardinian Population.

    PubMed

    Mandas, Antonella; Mereu, Rosa Maria; Catte, Olga; Saba, Antonio; Serchisu, Luca; Costaggiu, Diego; Peiretti, Enrico; Caminiti, Giulia; Vinci, Michela; Casu, Maura; Piludu, Stefania; Fossarello, Maurizio; Manconi, Paolo Emilio; Dessí, Sandra

    2014-01-01

    Neurological disorders (Alzheimer's disease, vascular and mixed dementia) and visual loss (cataract, age-related macular degeneration, glaucoma, and diabetic retinopathy) are among the most common conditions that afflict people of at least 65 years of age. An increasing body of evidence is emerging, which demonstrates that memory and vision impairment are closely, significantly, and positively linked and that statins and aspirin may lessen the risk of developing age-related visual and neurological problems. However, clinical studies have produced contradictory results. Thus, the intent of the present study was to reliably establish whether a relationship exist between various types of dementia and age-related vision disorders, and to establish whether statins and aspirin may or may not have beneficial effects on these two types of disorders. We found that participants with dementia and/or vision problems were more likely to be depressed and displayed worse functional ability in basic and instrumental activities of daily living than controls. Mini mental state examination scores were significantly lower in patients with vision disorders compared to subjects without vision disorders. A closer association with macular degeneration was found in subjects with Alzheimer's disease than in subjects without dementia or with vascular dementia, mixed dementia, or other types of age-related vision disorders. When we considered the associations between different types of dementia and vision disorders and the use of statins and aspirin, we found a significant positive association between Alzheimer's disease and statins on their own or in combination with aspirin, indicating that these two drugs do not appear to reduce the risk of Alzheimer's disease or improve its clinical evolution and may, on the contrary, favor its development. No significant association in statin use alone, aspirin use alone, or the combination of these was found in subjects without vision disorders but

  6. Degenerative retinal disorders

    SciTech Connect

    Hollyfield, J.G. Anderson, R.E. LaVail, M.M. . Dept. of Anatomy)

    1987-01-01

    This book contains papers divided among three sections. Some of the paper titles are: Molecular Genetics of Gyrate Atrophy; Molecular Site of Expression and Genetic Interaction of the rd and the rds Loci in the Retina of the Mouse; and Studies on Abnormal Cyclic GMP Metabolism in Animal Models of Retinal Degeneration: Genetic Relationships and Cellular Compartmentalization.

  7. What can we learn about age-related macular degeneration from other retinal diseases?

    PubMed

    Zack, D J; Dean, M; Molday, R S; Nathans, J; Redmond, T M; Stone, E M; Swaroop, A; Valle, D; Weber, B H

    1999-11-01

    Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics.

  8. An unusual degenerative disorder of neurons associated with a novel intranuclear hyaline inclusion (neuronal intranuclear hyaline inclusion disease). A clinicopathological study of a case.

    PubMed

    Sung, J H; Ramirez-Lassepas, M; Mastri, A R; Larkin, S M

    1980-03-01

    A 21-year-old woman with an unusual, progressive, degenerative neurological disorder is described. The disorder is characterized clinically by behavioral abnormality, peculiar involuntary movements, and ataxia starting in early childhood and subsequent development of dementia, choreoathetosis, rectal and bladder incontinence, bulbar and spinal muscular weakness, pes cavus, kyphoscoliosis, and generalized seizures. The clinical manifestations are correlated, with widespread pathological changes affecting almost all neuronal systems. The pathological changes are discussed in relation to the wide spectrum of "multisystem atrophies." Particular attention is directed to the ubiquitous occurrence of a novel intranuclear, eosinophilic, hyaline inclusion in almost all types of central, peripheral, and autonomic neurons. The ubiquitous neuronal involvement seems to explain the diffuse multiple system degeneration. The pathogenesis of the neuronal inclusions is unknown, but it is speculated that the disorder may represent a metabolic abnormality affecting the nuclear protein of neurons, rather than a viral infection. The pathological features, consisting of the neuronal intranuclear hyaline inclusions associated with multiple system atrophy, have not hitherto been described, and "neuronal intranuclear hyaline inclusion disease" is proposed as a name for the disorder. Rectal biopsy demonstrating the intranuclear hyaline inclusions in ganglion cells of the hyenteric plexuses may serve as a diagnostic procedure for the disorder. PMID:6154779

  9. Automatic age-related macular degeneration detection and staging

    NASA Astrophysics Data System (ADS)

    van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

    2013-03-01

    Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

  10. Proteomic analysis of specific brain proteins in aged SAMP8 mice treated with alpha-lipoic acid: implications for aging and age-related neurodegenerative disorders.

    PubMed

    Poon, H Fai; Farr, Susan A; Thongboonkerd, Visith; Lynn, Bert C; Banks, William A; Morley, John E; Klein, Jon B; Butterfield, D Allan

    2005-01-01

    Free radical-mediated damage to neuronal membrane components has been implicated in the etiology of Alzheimer's disease (AD) and aging. The senescence accelerated prone mouse strain 8 (SAMP8) exhibits age-related deterioration in memory and learning along with increased oxidative markers. Therefore, SAMP8 is a suitable model to study brain aging and, since aging is the major risk factor for AD and SAMP8 exhibits many of the biochemical findings of AD, perhaps as a model for and the early phase of AD. Our previous studies reported higher oxidative stress markers in brains of 12-month-old SAMP8 mice when compared to that of 4-month-old SAMP8 mice. Further, we have previously shown that injecting the mice with alpha-lipoic acid (LA) reversed brain lipid peroxidation, protein oxidation, as well as the learning and memory impairments in SAMP8 mice. Recently, we reported the use of proteomics to identify proteins that are expressed differently and/or modified oxidatively in aged SAMP8 brains. In order to understand how LA reverses the learning and memory deficits of aged SAMP8 mice, in the current study, we used proteomics to compare the expression levels and specific carbonyl levels of proteins in brains from 12-month-old SAMP8 mice treated or not treated with LA. We found that the expressions of the three brain proteins (neurofilament triplet L protein, alpha-enolase, and ubiquitous mitochondrial creatine kinase) were increased significantly and that the specific carbonyl levels of the three brain proteins (lactate dehydrogenase B, dihydropyrimidinase-like protein 2, and alpha-enolase) were significantly decreased in the aged SAMP8 mice treated with LA. These findings suggest that the improved learning and memory observed in LA-injected SAMP8 mice may be related to the restoration of the normal condition of specific proteins in aged SAMP8 mouse brain. Moreover, our current study implicates neurofilament triplet L protein, alpha-enolase, ubiquitous mitochondrial

  11. Age-Related Hyperkyphosis: Its Causes, Consequences, and Management

    PubMed Central

    Katzman, Wendy B.; Wanek, Linda; Shepherd, John A.; Sellmeyer, Deborah E.

    2010-01-01

    Age-related postural hyperkyphosis is an exaggerated anterior curvature of the thoracic spine, sometimes referred to as Dowager’s hump or gibbous deformity. This condition impairs mobility,2,31 and increases the risk of falls33 and fractures.26 The natural history of hyperkyphosis is not firmly established. Hyperkyphosis may develop from either muscle weakness and degenerative disc disease, leading to vertebral fractures and worsening hyperkyphosis, or from initial vertebral fractures that precipitate its development. PMID:20511692

  12. Stress, the immune system and vulnerability to degenerative disorders of the central nervous system in transgenic mice expressing glucocorticoid receptor antisense RNA.

    PubMed

    Marchetti, B; Morale, M C; Testa, N; Tirolo, C; Caniglia, S; Amor, S; Dijkstra, C D; Barden, N

    2001-11-01

    Current research evidence suggests that interactions between genetic and environmental factors contribute to modulate the susceptibility to degenerative disorders, including inflammatory and autoimmune diseases of the central nervous system (CNS). In this context, bidirectional communication between the neuroendocrine and immune systems during ontogeny plays a pivotal role in programming the development of neuroendocrine and immune responses in adult life, thereby influencing the predisposition to several disease entities. Glucocorticoids (GCs), the end products of the hypothalamic-pituitary-adrenocortical (HPA) axis, gender and signals generated by hypothalamic-pituitary-gonadal (HPG) axis are major players coordinating the development of immune system function and exerting powerful effects in the susceptibility to autoimmune disorders, including experimental autoimmune encephalomyelitis (EAE), the experimental model for multiple sclerosis (MS). In particular, GCs exert their beneficial immunosuppressive and anti-inflammatory effects in inflammatory disorders of the CNS, after binding to their cytoplasmic receptors (GRs). Here we review our work using transgenic (Tg) mice with a dysfunctional GR from early embryonic life on programming vulnerability to EAE. The GR-deficiency of these Tg mice confers resistance to active EAE induction. The interplay between GCs, proinflammatory mediators, gender and EAE is summarized. On the basis of our data, it does appear that exposure to a defective GR through development programs major changes in endogenous neuroendocrine and immune mechanisms controlling the vulnerability to EAE. These studies highlight the plasticity of the HPA-immune axis and its pharmacological manipulation in autoimmune diseases of the CNS.

  13. [Nineteen cases of school-aged children with degenerative or metabolic neurological disorders initially presenting with learning difficulty and/or behavior disturbance].

    PubMed

    Honzawa, Shiho; Sugai, Kenji; Akaike, Hiroto; Nakayama, Tojo; Fujikawa, Yoshinao; Komaki, Hirofumi; Nakagawa, Eiji; Sasaki, Masayuki

    2012-07-01

    We reported 19 cases of school-aged children. They were initially judged to have learning difficulty or school maladaptation because of attention deficits, hyperactive behaviors or poor school performance, followed by the diagnosis such as degenerative or metabolic neurological diseases. The patients consisted of 4 cases of adrenoleukodystrophy, 5 cases of dentatorubral-pallidoluysian atrophy, 3 cases of Sanfilippo syndrome, 3 cases of subacute sclerosing panencephalitis, and each one case of juvenile Gaucher disease, juvenile Huntington disease, juvenile metachromatic leukodystrophy and Leigh disease. They had markedly poor school performance, and/or abnormal behaviors, followed by seizures, character disorders or psychomotor regression. The diagnostic clues included brain CT scan and/or MRI, peculiar facial appearance and notable family histories. When the children were indicated to have learning difficulty or maladjustment to school life, we should make deliberate differential diagnoses before concluding that they have a learning disorder and/or attention-deficit/hyperactivity disorder. Instead they should be recommended to visit child neurologists, when they present with any problems as aforesaid.

  14. The value of adding posterior interbody fusion in the surgical treatment of degenerative lumbar spine disorders: A systematic review

    PubMed Central

    Fallatah, Salah; Wai, Eugene; Baily, Christopher S.

    2013-01-01

    Background Posterolateral fusion (PF) is a common method by which to achieve fusion in lumbar spine surgery. It has been reported that posterior interbody fusion (PIF) yields a higher fusion rate and a better functional and clinical outcome. Our objective was to determine whether PIF improves the clinical and radiologic outcomes in adults surgically treated for degenerative lumbar spine conditions compared with PF. Methods We performed a systematic search of electronic databases, bibliographies, and relevant journals and meta-analyses. Results Of 2798 citations identified, 5 studies met our inclusion criteria (none of which was a randomized controlled trial), with a total of 148 patients in the PIF group (intervention) and 159 in the PF group (control). Pooled meta-analyses showed that nonunion rates were lower in the intervention group (relative risk, 0.22; 95% confidence interval [CI], 0.08–0.62). The intervention group had a significantly higher disc height (weighted mean difference, 3.2 mm; 95% CI, 1.9–4.4 mm) and lower residual percent slippage (weighted mean difference, 6.3%; 95% CI, 3.9%–8.7%) at final follow-up. There were no significant differences in segmental or total lumbar lordosis. Because of heterogeneity of results, no conclusions could be made with regard to functional benefits. Conclusions This review suggests that PIF achieves a higher fusion rate and better correction of certain radiographic aspects of deformity over PF. It also showed a slight but not significant trend toward a better functional outcome in the PIF group. The lack of randomized controlled trials and the methodologic limitations of the available studies call for the planning and conduct of a sufficiently sized, methodologically sound study with clinically relevant outcome measures. Until this has been done, the current evidence regarding the beneficial effects of PIF should be interpreted with caution. PMID:25694900

  15. Age-Related Macular Degeneration.

    PubMed

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision.

  16. REM Sleep Behavior Disorder and REM Sleep Without Atonia as an Early Manifestation of Degenerative Neurological Disease

    PubMed Central

    McCarter, Stuart J.; St Louis, Erik K.

    2013-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by repeated episodes of dream enactment behavior and REM sleep without atonia (RSWA) during polysomnography recording. RSWA is characterized by increased phasic or tonic muscle activity seen on polysomnographic electromyogram channels. RSWA is a requisite diagnostic feature of RBD, but may also be seen in patients without clinical symptoms or signs of dream enactment as an incidental finding in neurologically normal individuals, especially in patients receiving antidepressant therapy. RBD may be idiopathic or symptomatic. Patients with idiopathic RBD often later develop other neurological features including parkinsonism, orthostatic hypotension, anosmia, or cognitive impairment. RSWA without clinical symptoms as well as clinically overt RBD also often occurs concomitantly with the α-synucleinopathy family of neurodegenerative disorders, which includes idiopathic Parkinson disease, Lewy body dementia, and multiple system atrophy. This review article considers the epidemiology of RBD, clinical and polysomnographic diagnostic standards for both RBD and RSWA, previously reported associations of RSWA and RBD with neurodegenerative disorders and other potential causes, the pathophysiology of which brain structures and networks mediate dysregulation of REM sleep muscle atonia, and considerations for the effective and safe management of RBD. PMID:22328094

  17. Minimally Invasive Unilateral vs. Bilateral Pedicle Screw Fixation and Lumbar Interbody Fusion in Treatment of Multi-Segment Lumbar Degenerative Disorders

    PubMed Central

    Liu, Xiaoyang; Li, Guangrun; Wang, Jiefeng; Zhang, Heqing

    2015-01-01

    Background The choice for instrumentation with minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in treatment of degenerative lumbar disorders (DLD) remains controversial. The goal of this study was to investigate clinical outcomes in consecutive patients with multi-segment DLD treated with unilateral pedicle screw (UPS) vs. bilateral pedicle screw (BPS) instrumented TLIF. Material/Methods Eighty-four consecutive patients who had multi-level MIS-TLIF were retrospectively reviewed. All data were collected to compare the clinical outcomes between the 2 groups. Results Both groups showed similar clinical function scores in VAS and ODI. The two groups differed significantly in operative time (P<0.001), blood loss (P<0.001), and fusion rate (P=0.043), respectively. Conclusions This study demonstrated similar clinical outcomes between UPS fixation and BPS procedure after MIS-TLIF for multi-level DLD. Moreover, UPS technique was superior in operative time and blood loss, but represented lower fusion rate than the BPS construct did. PMID:26603050

  18. [Neuropathologic markers in degenerative dementias].

    PubMed

    Hauw, J J; Seilhean, D; Colle, M A; Hogenhuys, J; Duyckaerts, C

    1998-01-01

    The number of neuropathological markers used for the diagnosis of degenerative dementias is rapidly increasing, and this is somewhat confusing: some lesions described a long time ago, such as ballooned cells, proved to be less specific than they were supposed to be; this is also the case for Lewy bodies, that have been recognised in a larger spectrum of disorders than thought a few years ago. On the contrary, for an increasing number of neuropathologists, Pick bodies are now mandatory for the diagnosis of Pick disease, and this contrasts with the prevalent opinions of the late sixties or seventies. There are a number of reasons for the changing significance of neuropathological markers. Three of them can be easily identified: 1) the burst of immunohistochemistry into neuropathology allowed an easier recognition, a better delineation and new pathophysiological approaches to old lesions, and a dramatic increase in the description of new markers, especially in glial cells; 2) in some conditions characterized by the number and distribution of some lesions rather than by their mere presence, such as aging and Alzheimer disease, a better neuroanatomical point of view permitted new insights into the concept of disease versus age-related changes; 3) more accurate clinicopathologic correlations showed clearly the need of grouping or lumping together some entities: for example, obvious relationship aroused between progressive supranuclear palsy and corticobasal degeneration; in contrast, distinguishing different disorders in the frontal lobe dementias grouped together into "Pick disease" was felt necessary. This review summarizes the main criteria for identification, and the presumed meaning of the chief markers indicating the presence of abnormally phosphorylated tau proteins, A beta peptides, and PrP proteins. Abnormally phosphorylated tau proteins can be stored in the neurons, and participate in the constitution of many lesions (neurofibrillary tangles, neuropil threads

  19. [Age-related macular degeneration].

    PubMed

    Garcia Layana, A

    1998-01-01

    Age-related macular degeneration (ARMD) is the leading cause of blindness in the occidental world. Patients suffering this process have an important reduction on their quality of life being handicapped to read, to write, to recognise faces of their friends, or even to watch the television. One of the main problems of that disease is the absence of an effective treatment able to revert the process. Laser treatment is only useful in a limited number of patients, and even in these cases recurrent lesions are frequent. These facts and the progressive ageing of our society establish the ARMD as one of the biggest aim of medical investigations for the next century, and currently is focus of attention in the most industrialised countries. One of the most promising pieces of research is focused in the investigation of the risk factors associated with the age-related macular degeneration, in order to achieve a prophylactic treatment avoiding its appearance. Diet elements such as fat ingestion or reduced antioxidant intakes are being investigated as some of these factors, what open a new possibility for a prophylactic treatment. Finally, research is looking for new therapeutic modalities such as selective radiotherapy in order to improve or maintain the vision of these patients.

  20. Age-Related Degeneration of the Egg-Laying System Promotes Matricidal Hatching in Caenorhabditis elegans

    PubMed Central

    Pickett, Christopher L.; Kornfeld, Kerry

    2014-01-01

    Summary The identification and characterization of age-related degenerative changes is a critical goal because it can elucidate mechanisms of aging biology and contribute to understanding interventions that promote longevity. Here we document a novel, age-related degenerative change in C. elegans hermaphrodites, an important model system for the genetic analysis of longevity. Matricidal hatching—intra-uterine hatching of progeny that causes maternal death—displayed an age-related increase in frequency and affected ∼70% of mated, wild-type hermaphrodites. The timing and incidence of matricidal hatching were largely independent of the levels of early and total progeny production and the duration of male exposure. Thus, matricidal hatching appears to reflect intrinsic age-related degeneration of the egg-laying system rather than use-dependent damage accumulation. Consistent with this model, mutations that extend longevity by causing dietary restriction significantly delayed matricidal hatching, indicating age-related degeneration of the egg-laying system is controlled by nutrient availability. To identify the underlying tissue defect, we analyzed serotonin signaling that triggers vulval muscle contractions. Mated hermaphrodites displayed an age-related decline in the ability to lay eggs in response to exogenous serotonin, indicating that vulval muscles and/or a further downstream function that is necessary for egg-laying degenerate in an age-related manner. By characterizing a new, age-related degenerative event displayed by C. elegans hermaphrodites, these studies contribute to understanding a frequent cause of death in mated hermaphrodites and establish a model of age-related reproductive complications that may be relevant to the birthing process in other animals such as humans. PMID:23551912

  1. Degenerative Nerve Diseases

    MedlinePlus

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many of these diseases are genetic. Sometimes the cause is a medical ...

  2. Age-related atrial fibrosis.

    PubMed

    Gramley, Felix; Lorenzen, Johann; Knackstedt, Christian; Rana, Obaida R; Saygili, Erol; Frechen, Dirk; Stanzel, Sven; Pezzella, Francesco; Koellensperger, Eva; Weiss, Christian; Münzel, Thomas; Schauerte, Patrick

    2009-03-01

    Many age-related diseases are associated with, and may be promoted by, cardiac fibrosis. Transforming growth factor (TGF)-beta, hypoxia-induced factor (HIF), and the matrix metalloproteinase (MMP) system have been implicated in fibrogenesis. Thus, we investigated whether age is related to these systems and to atrial fibrosis. Right atrial appendages (RAA) obtained during heart surgery (n = 115) were grouped according to patients' age (<50 years, 51-60 years, 61-70 years, or >70 years). Echocardiographic ejection fractions (EF) and fibrosis using Sirius-red-stained histological sections were determined. TGF-beta was determined by quantitative RT-PCR and hypoxia-related factors [HIF1 alpha, the vascular endothelial growth factor (VEGF)-receptor, CD34 (a surrogate marker for microvessel density), the factor inhibiting HIF (FIH), and prolyl hydroxylase 3 (PHD 3)] were detected by immunostaining. MMP-2 and -9 activity were determined zymographically, and mRNA levels of their common tissue inhibitor TIMP-1 were determined by RT-PCR. Younger patients (<50 years) had significantly less fibrosis (10.1% +/- 4.4% vs 16.6% +/- 8.3%) than older individuals (>70 years). While HIF1 alpha, FIH, the VEGF-receptor, and CD34 were significantly elevated in the young, TGF-beta and PHD3 were suppressed in these patients. MMP-2 and -9 activity was found to be higher while TIMP-1 levels were lower in older patients. Statistical analysis proved age to be the only factor influencing fibrogenesis. With increasing age, RAAs develop significantly more fibrosis. An increase of fibrotic and decrease of hypoxic signalling and microvessel density, coupled with differential expression of MMPs and TIMP-1 favouring fibrosis may have helped promote atrial fibrogenesis. PMID:19234766

  3. The SNAP trial: a double blind multi-center randomized controlled trial of a silicon nitride versus a PEEK cage in transforaminal lumbar interbody fusion in patients with symptomatic degenerative lumbar disc disorders: study protocol

    PubMed Central

    2014-01-01

    Background Polyetheretherketone (PEEK) cages have been widely used in the treatment of lumbar degenerative disc disorders, and show good clinical results. Still, complications such as subsidence and migration of the cage are frequently seen. A lack of osteointegration and fibrous tissues surrounding PEEK cages are held responsible. Ceramic implants made of silicon nitride show better biocompatible and osteoconductive qualities, and therefore are expected to lower complication rates and allow for better fusion. Purpose of this study is to show that fusion with the silicon nitride cage produces non-inferior results in outcome of the Roland Morris Disability Questionnaire at all follow-up time points as compared to the same procedure with PEEK cages. Methods/Design This study is designed as a double blind multi-center randomized controlled trial with repeated measures analysis. 100 patients (18–75 years) presenting with symptomatic lumbar degenerative disorders unresponsive to at least 6 months of conservative treatment are included. Patients will be randomly assigned to a PEEK cage or a silicon nitride cage, and will undergo a transforaminal lumbar interbody fusion with pedicle screw fixation. Primary outcome measure is the functional improvement measured by the Roland Morris Disability Questionnaire. Secondary outcome parameters are the VAS leg, VAS back, SF-36, Likert scale, neurological outcome and radiographic assessment of fusion. After 1 year the fusion rate will be measured by radiograms and CT. Follow-up will be continued for 2 years. Patients and clinical observers who will perform the follow-up visits will be blinded for type of cage used during follow-up. Analyses of radiograms and CT will be performed independently by two experienced radiologists. Discussion In this study a PEEK cage will be compared with a silicon nitride cage in the treatment of symptomatic degenerative lumbar disc disorders. To our knowledge, this is the first randomized controlled

  4. Mouse models of age-related mitochondrial neurosensory hearing loss.

    PubMed

    Han, Chul; Someya, Shinichi

    2013-07-01

    Hearing loss is the most common sensory disorder in the elderly population. Overall, 10% of the population has a hearing loss in the US, and this age-related hearing disorder is projected to afflict more than 28 million Americans by 2030. Age-related hearing loss is associated with loss of sensory hair cells (sensory hearing loss) and/or spiral ganglion neurons (neuronal hearing loss) in the cochlea of the inner ear. Many lines of evidence indicate that oxidative stress and associated mitochondrial dysfunction play a central role in age-related neurodegenerative diseases and are a cause of age-related neurosensory hearing loss. Yet, the molecular mechanisms of how oxidative stress and/or mitochondrial dysfunction lead to hearing loss during aging remain unclear, and currently there is no treatment for this age-dependent disorder. Several mouse models of aging and age-related diseases have been linked to age-related mitochondrial neurosensory hearing loss. Evaluation of these animal models has offered basic knowledge of the mechanism underlying hearing loss associated with oxidative stress, mitochondrial dysfunction, and aging. Here we review the evidence that specific mutations in the mitochondrial DNA or nuclear DNA that affect mitochondrial function result in increased oxidative damage and associated loss of sensory hair cells and/or spiral ganglion neurons in the cochlea during aging, thereby causing hearing loss in these mouse models. Future studies comparing these models will provide further insight into fundamental knowledge about the disordered process of hearing and treatments to improve the lives of individuals with communication disorders. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'.

  5. Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

    PubMed Central

    Madeira, Maria H.; Boia, Raquel; Santos, Paulo F.; Ambrósio, António F.; Santiago, Ana R.

    2015-01-01

    Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy. PMID:25873768

  6. MASTERS-D Study: A Prospective, Multicenter, Pragmatic, Observational, Data-Monitored Trial of Minimally Invasive Fusion to Treat Degenerative Lumbar Disorders, One-Year Follow-Up

    PubMed Central

    Manson, Neil; Buzek, David; Kosmala, Arkadiusz; Hubbe, Ulrich; Rosenberg, Wout; Pereira, Paulo; Assietti, Roberto; Martens, Frederic; Lam, Khai; Barbanti Brodano, Giovanni; Durny, Peter; Lidar, Zvi; Scheufler, Kai; Senker, Wolfgang

    2016-01-01

    The objective of the study is to assess effectiveness and safety of minimally invasive lumbar interbody fusion (MILIF) for degenerative lumbar disorders (DLD) in daily surgical practice and follow up with patients for one year after surgery. A prospective, multicenter, pragmatic, monitored, international outcome study in patients with DLD causing back/leg pain was conducted (19 centers). Two hundred fifty-two patients received standard of care available in the centers. Patients were included if they were aged >18 years, required one- or two-level lumbar fusion for DLD, and met the criteria for approved device indications. Primary endpoints: time to first ambulation (TFA) and time to surgery recovery (TSR). Secondary endpoints: patient-reported outcomes (PROs)--back and leg pain (visual analog scale), disability (Oswestry Disability Index (ODI)), health status (EQ-5D), fusion rates, reoperation rates, change in pain medication, rehabilitation, return to work, patient satisfaction, and adverse events (AEs). Experienced surgeons (≥30 surgeries pre-study) treated patients with DLD by one- or two-level MILIF and patients were evaluated for one year (NCT01143324). At one year, 92% (233/252) of patients remained in the study. Primary outcomes: TFA, 1.3 ±0.5 days and TSR, 3.2 ±2.0 days. Secondary outcomes: Most patients (83.3%) received one level MILIF; one (two-level) MILIF mean surgery duration, 128 (182) min; fluoroscopy time, 115 (154) sec; blood loss, 164 (233) mL; at one year statistically significant (P<.0001) and clinically meaningful changes from baseline were reported in all PROs--reduced back pain (2.9 ±2.5 vs. 6.2 ±2.3 at intake), reduced leg pain (2.2 ±2.6 vs. 5.9 ±2.8), and ODI (22.4% ± 18.6 vs. 45.3% ± 15.3), as well as health-related quality of life (EQ-5D index: 0.71 ±0.28 vs. 0.34 ±0.32). More of the professional workers were working at one year than those prior to surgery (70.3% vs. 55.2%). Three AEs and one serious AE were considered

  7. Nut consumption and age-related disease.

    PubMed

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments

  8. Nut consumption and age-related disease.

    PubMed

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments.

  9. Nutrition and age-related eye diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vision loss among the elderly is an important health problem. Approximately one person in three has some form of vision-reducing eye disease by the age of 65 [1]. Age-related cataract, age-related macular degeneration (AMD), diabetic retinopathy and glaucoma are the major diseases resulting in visu...

  10. Degenerative disease affecting the nervous system.

    PubMed

    Eadie, M J

    1974-03-01

    The term "degenerative disease" is one which is rather widely used in relation to the nervous system and yet one which is rarely formally and carefully defined. The term appears to be applied to disorders of the nervous system which often occur in later life and which are of uncertain cause. In the Shorter Oxford Dictionary the word degeneration is defined as "a change of structure by which an organism, or an organ, assumes the form of a lower type". However this is not quite the sense in which the word is applied in human neuropathology, where it is conventional to restrict the use of the word to those organic disorders which are of uncertain or poorly understood cause and in which there is a deterioration or regression in the level of functioning of the nervous system. The concept of degenerative disorder is applied to other organs as well as to the brain, and as disease elsewhere in the body may affect the nervous system, it seems reasonable to include within the topic of degenerative disorder affecting the nervous system those conditions in which the nervous system is involved as a result of primary degenerations in other parts of the body. PMID:25026144

  11. Degenerative disease affecting the nervous system.

    PubMed

    Eadie, M J

    1974-03-01

    The term "degenerative disease" is one which is rather widely used in relation to the nervous system and yet one which is rarely formally and carefully defined. The term appears to be applied to disorders of the nervous system which often occur in later life and which are of uncertain cause. In the Shorter Oxford Dictionary the word degeneration is defined as "a change of structure by which an organism, or an organ, assumes the form of a lower type". However this is not quite the sense in which the word is applied in human neuropathology, where it is conventional to restrict the use of the word to those organic disorders which are of uncertain or poorly understood cause and in which there is a deterioration or regression in the level of functioning of the nervous system. The concept of degenerative disorder is applied to other organs as well as to the brain, and as disease elsewhere in the body may affect the nervous system, it seems reasonable to include within the topic of degenerative disorder affecting the nervous system those conditions in which the nervous system is involved as a result of primary degenerations in other parts of the body.

  12. Degenerative cervical myelopathy.

    PubMed

    Kato, So; Fehlings, Michael

    2016-09-01

    Cervical myelopathy is the most common cause of acquired spinal cord compromise. The concept of degenerative cervical myelopathy (DCM), defined as symptomatic myelopathy associated with degenerative arthropathic changes in the spine axis, is being introduced. Given its progressive nature, treatment options have to be chosen in a timely manner. Surgical options include anterior discectomy and fusion (ACDF), anterior corpectomy and fusion (ACCF), arthroplasty (in highly select cases), posterior laminectomy with/without fusion, and laminoplasty. Indications for each should be carefully considered in individual patients. Riluzole, a sodium-glutamate antagonist, is a promising option to optimize neurologic outcomes post-surgery and is being examined in the CSM-Protect Randomized Controlled Trial. Preoperative risk assessment is mandatory for prognostication. Sagittal alignment is known to play an important role to optimize surgical outcome. Guidelines for optimal management of DCM are in process. In principle, all but the mildest cases of DCM should be offered surgery for optimal outcome. PMID:27250040

  13. The degenerative cervical spine.

    PubMed

    Llopis, E; Belloch, E; León, J P; Higueras, V; Piquer, J

    2016-04-01

    Imaging techniques provide excellent anatomical images of the cervical spine. The choice to use one technique or another will depend on the clinical scenario and on the treatment options. Plain-film X-rays continue to be fundamental, because they make it possible to evaluate the alignment and bone changes; they are also useful for follow-up after treatment. The better contrast resolution provided by magnetic resonance imaging makes it possible to evaluate the soft tissues, including the intervertebral discs, ligaments, bone marrow, and spinal cord. The role of computed tomography in the study of degenerative disease has changed in recent years owing to its great spatial resolution and its capacity to depict osseous components. In this article, we will review the anatomy and biomechanical characteristics of the cervical spine, and then we provide a more detailed discussion of the degenerative diseases that can affect the cervical spine and their clinical management. PMID:26878769

  14. The degenerative cervical spine.

    PubMed

    Llopis, E; Belloch, E; León, J P; Higueras, V; Piquer, J

    2016-04-01

    Imaging techniques provide excellent anatomical images of the cervical spine. The choice to use one technique or another will depend on the clinical scenario and on the treatment options. Plain-film X-rays continue to be fundamental, because they make it possible to evaluate the alignment and bone changes; they are also useful for follow-up after treatment. The better contrast resolution provided by magnetic resonance imaging makes it possible to evaluate the soft tissues, including the intervertebral discs, ligaments, bone marrow, and spinal cord. The role of computed tomography in the study of degenerative disease has changed in recent years owing to its great spatial resolution and its capacity to depict osseous components. In this article, we will review the anatomy and biomechanical characteristics of the cervical spine, and then we provide a more detailed discussion of the degenerative diseases that can affect the cervical spine and their clinical management.

  15. Alzheimer’s disease as homeostatic responses to age-related myelin breakdown

    PubMed Central

    Bartzokis, George

    2011-01-01

    The amyloid hypothesis (AH) of Alzheimer’s disease (AD) posits that the fundamental cause of AD is the accumulation of the peptide amyloid beta (Aβ) in the brain. This hypothesis has been supported by observations that genetic defects in amyloid precursor protein (APP) and presenilin increase Aβ production and cause familial AD (FAD). The AH is widely accepted but does not account for important phenomena including recent failures of clinical trials to impact dementia in humans even after successfully reducing Aβ deposits. Herein, the AH is viewed from the broader overarching perspective of the myelin model of the human brain that focuses on functioning brain circuits and encompasses white matter and myelin in addition to neurons and synapses. The model proposes that the recently evolved and extensive myelination of the human brain underlies both our unique abilities and susceptibility to highly prevalent age-related neuropsychiatric disorders such as late onset AD (LOAD). It regards oligodendrocytes and the myelin they produce as being both critical for circuit function and uniquely vulnerable to damage. This perspective reframes key observations such as axonal transport disruptions, formation of axonal swellings/sphenoids and neuritic plaques, and proteinaceous deposits such as Aβ and tau as by-products of homeostatic myelin repair processes. It delineates empirically testable mechanisms of action for genes underlying FAD and LOAD and provides “upstream” treatment targets. Such interventions could potentially treat multiple degenerative brain disorders by mitigating the effects of aging and associated changes in iron, cholesterol, and free radicals on oligodendrocytes and their myelin. PMID:19775776

  16. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2016-08-16

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  17. The Degenerative Spine.

    PubMed

    Clarençon, Frédéric; Law-Ye, Bruno; Bienvenot, Peggy; Cormier, Évelyne; Chiras, Jacques

    2016-08-01

    Degenerative disease of the spine is a leading cause of back pain and radiculopathy, and is a frequent indication for spine MR imaging. Disc degeneration, disc protrusion/herniation, discarhtrosis, spinal canal stenosis, and facet joint arthrosis, as well as interspinous processes arthrosis, may require an MR imaging workup. This review presents the MR imaging patterns of these diseases and describes the benefit of the MR imaging in these indications compared with the other imaging modalities like plain radiographs or computed tomography scan. PMID:27417397

  18. Physiochemical basis of human degenerative disease

    PubMed Central

    Lipinski, Boguslaw

    2015-01-01

    The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers. PMID:27486355

  19. The suprachiasmatic nucleus: age-related decline in biological rhythms.

    PubMed

    Nakamura, Takahiro J; Takasu, Nana N; Nakamura, Wataru

    2016-09-01

    Aging is associated with changes in sleep duration and quality, as well as increased rates of pathologic/disordered sleep. While several factors contribute to these changes, emerging research suggests that age-related changes in the mammalian central circadian clock within the suprachiasmatic nucleus (SCN) may be a key factor. Prior work from our group suggests that circadian output from the SCN declines because of aging. Furthermore, we have previously observed age-related infertility in female mice, caused by a mismatch between environmental light-dark cycles and the intrinsic, internal biological clocks. In this review, we address regulatory mechanisms underlying circadian rhythms in mammals and summarize recent literature describing the effects of aging on the circadian system.

  20. Depression in Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  1. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  2. Age Related Changes in Preventive Health Behavior.

    ERIC Educational Resources Information Center

    Leventhal, Elaine A.; And Others

    Health behavior may be influenced by age, beliefs, and symptomatology. To examine age-related health beliefs and behaviors with respect to six diseases (the common cold, colon-rectal cancer, lung cancer, heart attack, high blood pressure, and senility), 396 adults (196 males, 200 females) divided into three age groups completed a questionnaire…

  3. [Degenerative adult scoliosis].

    PubMed

    García-Ramos, C L; Obil-Chavarría, C A; Zárate-Kalfópulos, B; Rosales-Olivares, L M; Alpizar-Aguirre, A; Reyes-Sánchez, A A

    2015-01-01

    Adult scoliosis is a complex three-dimensional rotational deformity of the spine, resulting from the progressive degeneration of the vertebral elements in middle age, in a previously straight spine; a Cobb angle greater than 10° in the coronal plane, which also alters the sagittal and axial planes. It originates an asymmetrical degenerative disc and facet joint, creating asymmetrical loads and subsequently deformity. The main symptom is axial, radicular pain and neurological deficit. Conservative treatment includes drugs and physical therapy. The epidural injections and facet for selectively blocking nerve roots improves short-term pain. Surgical treatment is reserved for patients with intractable pain, radiculopathy and/ or neurological deficits. There is no consensus for surgical indications, however, it must have a clear understanding of the symptoms and clinical signs. The goal of surgery is to decompress neural elements with restoration, modification of the three-dimensional shape deformity and stabilize the coronal and sagittal balance. PMID:27012088

  4. [Degenerative adult scoliosis].

    PubMed

    García-Ramos, C L; Obil-Chavarría, C A; Zárate-Kalfópulos, B; Rosales-Olivares, L M; Alpizar-Aguirre, A; Reyes-Sánchez, A A

    2015-01-01

    Adult scoliosis is a complex three-dimensional rotational deformity of the spine, resulting from the progressive degeneration of the vertebral elements in middle age, in a previously straight spine; a Cobb angle greater than 10° in the coronal plane, which also alters the sagittal and axial planes. It originates an asymmetrical degenerative disc and facet joint, creating asymmetrical loads and subsequently deformity. The main symptom is axial, radicular pain and neurological deficit. Conservative treatment includes drugs and physical therapy. The epidural injections and facet for selectively blocking nerve roots improves short-term pain. Surgical treatment is reserved for patients with intractable pain, radiculopathy and/ or neurological deficits. There is no consensus for surgical indications, however, it must have a clear understanding of the symptoms and clinical signs. The goal of surgery is to decompress neural elements with restoration, modification of the three-dimensional shape deformity and stabilize the coronal and sagittal balance.

  5. Age-related changes in the rat hippocampus.

    PubMed

    Is, Merih; Comunoglu, Nil Ustundag; Comunoglu, Cem; Eren, Bulent; Ekici, Isin Dogan; Ozkan, Ferda

    2008-05-01

    The human brain is uniquely powerful in its cognitive abilities, yet the hippocampal and neocortical circuits that mediate these complex functions are highly vulnerable during aging. In this study, we analyzed age-related changes in the rat hippocampus by studying newborn (1 month), middle-aged (12 months), and older (24 months) male and female Sprague-Dawley rats. We evaluated neuronal dystrophy, neuron scattering, and granulovacuolar degeneration in the hippocampal area using light microscopy, according to age and gender. We detected significant neuronal dystrophy in the CA1, CA2, and CA3 areas in male rats, and in the CA1, CA3, and CA4 areas in female rats. Degenerative changes, indicated by neuron scattering, were observed in the CA1, CA2, and CA3 areas of male and the CA2 and CA4 areas of female rats. Changes in all areas of the hippocampus were observed with increasing age; these changes included neuronal dystrophy and neuron scattering and did not differ significantly between male and female rats.

  6. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the

  7. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the

  8. Olfactory dysfunction in degenerative ataxias.

    PubMed

    Connelly, T; Farmer, J M; Lynch, D R; Doty, R L

    2003-10-01

    Several lines of evidence suggest that the cerebellum may play a role in higher-order olfactory processing. In this study, we administered the University of Pennsylvania Smell Identification Test (UPSIT), a standardised test of olfactory function, to patients with ataxias primarily due to cerebellar pathology (spinocerebellar ataxias and related disorders) and to patients with Friedreich ataxia, an ataxia associated mainly with loss of afferent cerebellar pathways. UPSIT scores were slightly lower in both patient groups than in the control subjects, but no differences were noted between the scores of the Friedreich and the other ataxia patients. Within the Friedreich ataxia group, the smell test scores did not correlate with the number of pathologic GAA repeats (a marker of genetic severity), disease duration, or categorical ambulatory ability. UPSIT scores did not correlate with disease duration, although they correlated marginally with ambulatory status in the patients with cerebellar pathology. This study suggests that olfactory dysfunction may be a subtle clinical component of degenerative ataxias, in concordance with the hypothesis that the cerebellum or its afferents plays some role in central olfactory processing.

  9. Immunology of age-related macular degeneration

    PubMed Central

    Ambati, Jayakrishna; Atkinson, John P.; Gelfand, Bradley D.

    2014-01-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population. PMID:23702979

  10. [Epidemiology of age related macular degeneration].

    PubMed

    Leveziel, N; Delcourt, C; Zerbib, J; Dollfus, H; Kaplan, J; Benlian, P; Coscas, G; Souied, E H; Soubrane, G

    2009-06-01

    Age-related macular degeneration (ARMD) is a multifactorial and polygenic disease and is the main cause of vision loss in developed countries. The environmental factors of ARMD can modify prevalence and incidence of this disease. This article is a review of the main environmental factors currently recognized as at risk or protective factor for ARMD. Modification of these factors is of crucial importance because it could delay the onset of exudative or atrophic forms of the disease. PMID:19515460

  11. Age-Related Factors That Influence Fertility

    MedlinePlus

    ... pressure Diabetes Thyroid disease Infection in the uterus PCOS Antiphospholipid syndrome, an autoimmune disorder caused when immune ... male fertility, NIH study suggests Some women with PCOS may have adrenal disorder, NIH researchers suggest Weight ...

  12. Contrasting age related changes in autism spectrum disorder phenomenology in Cornelia de Lange, Fragile X, and Cri du Chat syndromes: Results from a 2.5 year follow-up.

    PubMed

    Cochran, Lisa; Moss, Joanna; Nelson, Lisa; Oliver, Chris

    2015-06-01

    Little is known about the way in which the characteristics of autism spectrum disorder (ASD) develop and manifest across the age span in individuals with genetic syndromes. In this study we present findings from a two and a half year follow-up of the characteristics associated with ASD in three syndromes: Cornelia de Lange (CdLS), Fragile X (FXS), and Cri du Chat (CdCS). Parents and carers of 251 individuals (CdLS=67, CdCS=42, and FXS=142) completed the Social Communication Questionnaire (SCQ) at Time 1 (T1) and again two and a half years later (T2). The FXS and CdLS groups were more likely to meet the cut-offs for both autism and ASD and show greater severity of ASD related behaviors, at both T1 and T2, compared to the CdCS group. Older individuals (>15yrs) with CdLS were more likely to meet the cut off for ASD than younger individuals (≤15 yrs) with the syndrome and more likely to show greater severity of social impairments. In FXS repetitive behaviors were found to become less prominent with age and in CdCS social impairments were reported to be more severe with age. There were no significant changes between T1 and T2 in the severity of ASD characteristics in the CdCS and CdLS groups. The FXS group showed significantly fewer repetitive behaviors and less severe impairments in social interaction over this time frame. The findings suggest that while there may be similarities in overall severity and presentation of ASD characteristics in CdLS and FXS, these characteristics have divergent patterns of development within these groups. PMID:25989416

  13. Age-related hair pigment loss.

    PubMed

    Tobin, Desmond J

    2015-01-01

    Humans are social animals that communicate disproportionately via potent genetic signals imbued in the skin and hair, including racial, ethnic, health, gender, and age status. For the vast majority of us, age-related hair pigment loss becomes the inescapable signal of our disappearing youth. The hair follicle (HF) pigmentary unit is a wonderful tissue for studying mechanisms generally regulating aging, often before this becomes evident elsewhere in the body. Given that follicular melanocytes (unlike those in the epidermis) are regulated by the hair growth cycle, this cycle is likely to impact the process of aging in the HF pigmentary unit. The formal identification of melanocyte stem cells in the mouse skin has spurred a flurry of reports on the potential involvement of melanocyte stem cell depletion in hair graying (i.e., canities). Caution is recommended, however, against simple extrapolation of murine data to humans. Regardless, hair graying in both species is likely to involve an age-related imbalance in the tissue's oxidative stress handling that will impact not only melanogenesis but also melanocyte stem cell and melanocyte homeostasis and survival. There is some emerging evidence that the HF pigmentary unit may have regenerative potential, even after it has begun to produce white hair fibers. It may therefore be feasible to develop strategies to modulate some aging-associated changes to maintain melanin production for longer. PMID:26370651

  14. [Age-related changes of the brain].

    PubMed

    Paltsyn, A A; Komissarova, S V

    2015-01-01

    The first morphological signs of aging of the brain are found in the white matter already at a young age (20-40 years), and later (40-50 years) in a gray matter. After the 40-50 years appear and in subsequently are becoming more pronounced functional manifestations of morphological changes: the weakening of sensory-motor and cognitive abilities. While in principle this dynamic of age-related changes is inevitable, the rate of their development to a large extent determined by the genetic characteristics and lifestyle of the individual. According to modem concepts age-related changes in the number of nerve cells are different in different parts of the brain. However, these changes are not large and are not the main cause of senile decline brain. The main processes that contribute to the degradation of the brain develop as in the bodies of neurons and in neuropil. In the bodies of neurons--it is a damage (usually decrease) of the level of expression of many genes, and especially of the genes determining cell communication. In neuropil: reduction in the number of synapses and the strength of synaptic connections, reduction in the number of dendritic spines and axonal buttons, reduction in the number and thickness of the dendritic branches, demyelination of axons. As the result of these events, it becomes a violation of the rate of formation and rebuilding neuronal circuits. It is deplete associative ability, brain plasticity, and memory. PMID:27116888

  15. Factors Associated With Age-related Hearing Impairment

    PubMed Central

    Moon, Il Joon; Byun, Hayoung; Woo, Sook-young; Gwak, Geum-Youn; Hong, Sung Hwa; Chung, Won-Ho; Cho, Yang-Sun

    2015-01-01

    Abstract Age-related hearing impairment (ARHI) is a complex degenerative disease in the elderly. As multiple factors interact during the development of ARHI, it is important to elucidate the major influencing factors to understand and prevent ARHI. We aimed to identify risk factors associated with the development of ARHI with a retrospective cohort from 2001 to 2010. The records of the adult subjects over 40 years of age who consecutively underwent a comprehensive health checkup including pure-tone audiometry at the Health Promotion Center were reviewed. During this period, 1560 subjects who underwent pure-tone audiometry more than twice, had no other otologic diseases, and were followed-up more than 2 years were included. A pure-tone average (PTA: 0.5, 1, 2, 4 kHz) was calculated. Development of ARHI was defined as a PTA at follow-up more than 10 dB greater than the baseline PTA. Times to the first development of ARHI were investigated. Overall, 12.7% of subjects developed ARHI within the first 4 years. High blood ionized calcium (hazard ratio [HR] 0.084), albumin (HR 0.239), systolic blood pressure (HR 0.577), thyroid hormone (T3) (HR 0.593), and alpha fetoprotein levels (HR 0.883) were associated with decreased hazard for the development of ARHI. In contrast, high blood high-density lipoprotein (HR 2.105), uric acid (HR 1.684), total protein (HR 1.423), and total bilirubin levels (HR 1.220) were potential risk factors for the development of ARHI. Development of ARHI is common among the aged population, and a variety of factors may interact during this process. The results of this study can be used for counseling of adults at high-risk of developing ARHI with regard to regular audiological check-up. PMID:26512592

  16. [Age-related changes in swallowing. Physiology and pathophysiology].

    PubMed

    Muhle, P; Wirth, R; Glahn, J; Dziewas, R

    2015-04-01

    The term presbyphagia refers to all changes of swallowing physiology that are manifested with increasing age. Alterations in the pattern of deglutition that are part of healthy aging are called primary presbyphagia. Primary presbyphagia is not an illness in itself but contributes to a more pervasive naturally diminished functional reserve, making older adults more susceptible to dysphagia. If disorders in swallowing occur in the elderly as a comorbidity of a specific disease, for example stroke or neurodegenerative disorders, this is called secondary presbyphagia. Increasing age has an impact on each stage of deglutition. In the oral preparatory phase a diminished input for smell and taste as well as a usually multifactorial cause of dry mouth are the most important influencing factors. Sarcopenia, the degenerative loss of skeletal muscle mass, strength and quality associated with aging, interferes in particular with the oropharyngeal phase. A decreased sensory feedback from the oropharyngeal mucosa leads to a delayed triggering of the swallowing reflex. Finally, a reduction in connective tissue elasticity and changes of the axial skeleton lead to various modifications of the swallowing pattern with advanced age.

  17. Closed-loop rehabilitation of age-related cognitive disorders.

    PubMed

    Mishra, Jyoti; Gazzaley, Adam

    2014-11-01

    Cognitive deficits are common in older adults, as a result of both the natural aging process and neurodegenerative disease. Although medical advancements have successfully prolonged the human lifespan, the challenge of remediating cognitive aging remains. The authors discuss the current state of cognitive therapeutic interventions and then present the need for development and validation of more powerful neurocognitive therapeutics. They propose that the next generation of interventions be implemented as closed-loop systems that target specific neural processing deficits, incorporate quantitative feedback to the individual and clinician, and are personalized to the individual's neurocognitive capacities using real-time performance-adaptive algorithms. This approach should be multimodal and seamlessly integrate other treatment approaches, including neurofeedback and transcranial electrical stimulation. This novel approach will involve the generation of software that engages the individual in an immersive and enjoyable game-based interface, integrated with advanced biosensing hardware, to maximally harness plasticity and assure adherence. Introducing such next-generation closed-loop neurocognitive therapeutics into the mainstream of our mental health care system will require the combined efforts of clinicians, neuroscientists, bioengineers, software game developers, and industry and policy makers working together to meet the challenges and opportunities of translational neuroscience in the 21st century. PMID:25520029

  18. [Treatment options for age-related infertility].

    PubMed

    Belaisch-Allart, Joëlle

    2010-06-20

    There has been a consistent trend towards delayed childbearing in most Western countries. Treatment options for age-related infertility includes controlled ovarian hyperstimulation with intrauterine insemination and in vitro fertilization (IVF). A sharp decline in pregnancy rate with advancing female age is noted with assisted reproductive technologies (ART) including IVF. Evaluation and treatment of infertility should not be delayed in women 35 years and older. No treatment other than oocyte donation has been shown to be effective for women over 40 and for those with compromised ovarian reserve, but its pratice is not easy in France hence the procreative tourism. As an increasing number of couples choose to postpone childbearing, they should be informed that maternal age is an important risk factor for failure to conceive. PMID:20623902

  19. [Epidemiology of age-related macular degeneration].

    PubMed

    Brandl, C; Stark, K J; Wintergerst, M; Heinemann, M; Heid, I M; Finger, R P

    2016-09-01

    Age-related macular degeneration (AMD) is the main cause of blindness in industrialized societies. Population-based epidemiological investigations generate important data on prevalence, incidence, risk factors, and future trends. This review summarizes the most important epidemiological studies on AMD with a focus on their transferability to Germany including existing evidence for the main risk factors for AMD development and progression. Future tasks, such as the standardization of grading systems and the use of recent retinal imaging technology in epidemiological studies are discussed. In Germany, epidemiological data on AMD are scarce. However, the need for epidemiological research in ophthalmology is currently being addressed by several recently started population-based studies. PMID:27541733

  20. Inflammation in age-related macular degeneration.

    PubMed

    Ozaki, Ema; Campbell, Matthew; Kiang, Anna-Sophia; Humphries, Marian; Doyle, Sarah L; Humphries, Peter

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly individuals in the developed world, affecting 30-50 million people worldwide. AMD primarily affects the macular region of the retina that is responsible for the majority of central, color and daytime vision. The presence of drusen, extracellular protein aggregates that accumulate under the retinal pigment epithelium (RPE), is a major pathological hallmark in the early stages of the disease. The end stage 'dry' and 'wet' forms of the disease culminate in vision loss and are characterized by focal degeneration of the RPE and cone photoreceptors, and choroidal neovascularization (CNV), respectively. Being a multifactorial and genetically heterogeneous disease, the pathophysiology of AMD remains unclear, yet, there is ample evidence supporting immunological and inflammatory processes. Here, we review the recent literature implicating some of these immune processes in human AMD and in animal models. PMID:24664703

  1. Consequences of Age-Related Cognitive Declines

    PubMed Central

    Salthouse, Timothy

    2013-01-01

    Adult age differences in a variety of cognitive abilities are well documented, and many of those abilities have been found to be related to success in the workplace and in everyday life. However, increased age is seldom associated with lower levels of real-world functioning, and the reasons for this lab-life discrepancy are not well understood. This article briefly reviews research concerned with relations of age to cognition, relations of cognition to successful functioning outside the laboratory, and relations of age to measures of work performance and achievement. The final section discusses several possible explanations for why there are often little or no consequences of age-related cognitive declines in everyday functioning. PMID:21740223

  2. Medical bioremediation of age-related diseases

    PubMed Central

    Mathieu, Jacques M; Schloendorn, John; Rittmann, Bruce E; Alvarez, Pedro JJ

    2009-01-01

    Catabolic insufficiency in humans leads to the gradual accumulation of a number of pathogenic compounds associated with age-related diseases, including atherosclerosis, Alzheimer's disease, and macular degeneration. Removal of these compounds is a widely researched therapeutic option, but the use of antibodies and endogenous human enzymes has failed to produce effective treatments, and may pose risks to cellular homeostasis. Another alternative is "medical bioremediation," the use of microbial enzymes to augment missing catabolic functions. The microbial genetic diversity in most natural environments provides a resource that can be mined for enzymes capable of degrading just about any energy-rich organic compound. This review discusses targets for biodegradation, the identification of candidate microbial enzymes, and enzyme-delivery methods. PMID:19358742

  3. Age-related macular degeneration: current treatments

    PubMed Central

    Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D

    2009-01-01

    Purpose: Although important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options. Design: Interpretative essay. Methods: Literature review and interpretation. Results: Current treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intravitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system. Conclusion: By better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity. PMID:19668560

  4. The degenerative spine: pattern recognition and guidelines to image interpretation.

    PubMed

    Parizel, P M; Van Hoyweghen, A J L; Bali, A; Van Goethem, J; Van Den Hauwe, L

    2016-01-01

    Degenerative disease of the spine, in the form of intervertebral disc degeneration and bony growth, causing osteophytes and impinging upon the spinal canal and neural foramina, is the most frequent disorder affecting the spine. In this chapter we first discuss briefly the indications for computed tomography or magnetic resonance imaging in suspected degenerative spine disease. We then describe changes of disc height, signal intensity, and disc contour with aging and repeated microtrauma, as well as the imaging techniques most appropriate to image them. A grading system for lumbar disc changes is provided. Stenosis of the canal and neural foramina is reviewed next, concluding with a description of degenerative changes affecting the vertebral endplates and bone marrow.

  5. The degenerative spine: pattern recognition and guidelines to image interpretation.

    PubMed

    Parizel, P M; Van Hoyweghen, A J L; Bali, A; Van Goethem, J; Van Den Hauwe, L

    2016-01-01

    Degenerative disease of the spine, in the form of intervertebral disc degeneration and bony growth, causing osteophytes and impinging upon the spinal canal and neural foramina, is the most frequent disorder affecting the spine. In this chapter we first discuss briefly the indications for computed tomography or magnetic resonance imaging in suspected degenerative spine disease. We then describe changes of disc height, signal intensity, and disc contour with aging and repeated microtrauma, as well as the imaging techniques most appropriate to image them. A grading system for lumbar disc changes is provided. Stenosis of the canal and neural foramina is reviewed next, concluding with a description of degenerative changes affecting the vertebral endplates and bone marrow. PMID:27430442

  6. Long noncoding RNAs in aging and age-related diseases.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-03-01

    Aging is the universal, intrinsic, genetically-controlled, evolutionarily-conserved and time-dependent intricate biological process characterised by the cumulative decline in the physiological functions and their coordination in an organism after the attainment of adulthood resulting in the imbalance of neurological, immunological and metabolic functions of the body. Various biological processes and mechanisms along with altered levels of mRNAs and proteins have been reported to be involved in the progression of aging. It is one of the major risk factors in the patho-physiology of various diseases and disorders. Recently, the discovery of pervasive transcription of a vast pool of heterogeneous regulatory noncoding RNAs (ncRNAs), including small ncRNAs (sncRNAs) and long ncRNAs (lncRNAs), in the mammalian genome have provided an alternative way to study and explore the missing links in the aging process, its mechanism(s) and related diseases in a whole new dimension. The involvement of small noncoding RNAs in aging and age-related diseases have been extensively studied and recently reviewed. However, lncRNAs, whose function is far less explored in relation to aging, have emerged as a class of major regulators of genomic functions. Here, we have described some examples of known as well as novel lncRNAs that have been implicated in the progression of the aging process and age-related diseases. This may further stimulate research on noncoding RNAs and the aging process.

  7. Long noncoding RNAs in aging and age-related diseases.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-03-01

    Aging is the universal, intrinsic, genetically-controlled, evolutionarily-conserved and time-dependent intricate biological process characterised by the cumulative decline in the physiological functions and their coordination in an organism after the attainment of adulthood resulting in the imbalance of neurological, immunological and metabolic functions of the body. Various biological processes and mechanisms along with altered levels of mRNAs and proteins have been reported to be involved in the progression of aging. It is one of the major risk factors in the patho-physiology of various diseases and disorders. Recently, the discovery of pervasive transcription of a vast pool of heterogeneous regulatory noncoding RNAs (ncRNAs), including small ncRNAs (sncRNAs) and long ncRNAs (lncRNAs), in the mammalian genome have provided an alternative way to study and explore the missing links in the aging process, its mechanism(s) and related diseases in a whole new dimension. The involvement of small noncoding RNAs in aging and age-related diseases have been extensively studied and recently reviewed. However, lncRNAs, whose function is far less explored in relation to aging, have emerged as a class of major regulators of genomic functions. Here, we have described some examples of known as well as novel lncRNAs that have been implicated in the progression of the aging process and age-related diseases. This may further stimulate research on noncoding RNAs and the aging process. PMID:26655093

  8. Curcumin, inflammation, ageing and age-related diseases.

    PubMed

    Sikora, E; Scapagnini, Giovanni; Barbagallo, Mario

    2010-01-17

    A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy between April 7 and 8th 2009. Here the lecture by Sikora with some input from the chairpersons Scapagnini and Barbagallo is summarized. Ageing is manifested by the decreasing health status and increasing probability to acquire age-related disease such as cancer, Alzheimer's disease, atherosclerosis, metabolic disorders and others. They are likely caused by low grade inflammation driven by oxygen stress and manifested by the increased level of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha, encoded by genes activated by the transcription factor NF-kappaB. It is believed that ageing is plastic and can be slowed down by caloric restriction as well as by some nutraceuticals. Accordingly, slowing down ageing and postponing the onset of age-related diseases might be achieved by blocking the NF-kappaB-dependent inflammation. In this review we consider the possibility of the spice curcumin, a powerful antioxidant and anti-inflammatory agent possibly capable of improving the health status of the elderly.

  9. Degenerative spinal disease in large felids.

    PubMed

    Kolmstetter, C; Munson, L; Ramsay, E C

    2000-03-01

    Degenerative spinal disorders, including intervertebral disc disease and spondylosis, seldom occur in domestic cats. In contrast, a retrospective study of 13 lions (Panthera leo), 16 tigers (Panthera tigris), 4 leopards (Panthera pardis), 1 snow leopard (Panthera uncia), and 3 jaguars (Panthera onca) from the Knoxville Zoo that died or were euthanatized from 1976 to 1996 indicated that degenerative spinal disease is an important problem in large nondomestic felids. The medical record, radiographic data, and the necropsy report of each animal were examined for evidence of intervertebral disc disease or spondylosis. Eight (three lions, four tigers, and one leopard) animals were diagnosed with degenerative spinal disease. Clinical signs included progressively decreased activity, moderate to severe rear limb muscle atrophy, chronic intermittent rear limb paresis, and ataxia. The age at onset of clinical signs was 10-19 yr (median = 18 yr). Radiographic evaluation of the spinal column was useful in assessing the severity of spinal lesions, and results were correlated with necropsy findings. Lesions were frequently multifocal, included intervertebral disc mineralization or herniation with collapsed intervertebral disc spaces, and were most common in the lumbar area but also involved cervical and thoracic vertebrae. Marked spondylosis was present in the cats with intervertebral disc disease, presumably subsequent to vertebral instability. Six of the animals' spinal cords were examined histologically, and five had acute or chronic damage to the spinal cord secondary to disc protrusion. Spinal disease should be suspected in geriatric large felids with decreased appetite or activity. Radiographic evaluation of the spinal column is the most useful method to assess the type and severity of spinal lesions.

  10. Degenerative spinal disease in large felids.

    PubMed

    Kolmstetter, C; Munson, L; Ramsay, E C

    2000-03-01

    Degenerative spinal disorders, including intervertebral disc disease and spondylosis, seldom occur in domestic cats. In contrast, a retrospective study of 13 lions (Panthera leo), 16 tigers (Panthera tigris), 4 leopards (Panthera pardis), 1 snow leopard (Panthera uncia), and 3 jaguars (Panthera onca) from the Knoxville Zoo that died or were euthanatized from 1976 to 1996 indicated that degenerative spinal disease is an important problem in large nondomestic felids. The medical record, radiographic data, and the necropsy report of each animal were examined for evidence of intervertebral disc disease or spondylosis. Eight (three lions, four tigers, and one leopard) animals were diagnosed with degenerative spinal disease. Clinical signs included progressively decreased activity, moderate to severe rear limb muscle atrophy, chronic intermittent rear limb paresis, and ataxia. The age at onset of clinical signs was 10-19 yr (median = 18 yr). Radiographic evaluation of the spinal column was useful in assessing the severity of spinal lesions, and results were correlated with necropsy findings. Lesions were frequently multifocal, included intervertebral disc mineralization or herniation with collapsed intervertebral disc spaces, and were most common in the lumbar area but also involved cervical and thoracic vertebrae. Marked spondylosis was present in the cats with intervertebral disc disease, presumably subsequent to vertebral instability. Six of the animals' spinal cords were examined histologically, and five had acute or chronic damage to the spinal cord secondary to disc protrusion. Spinal disease should be suspected in geriatric large felids with decreased appetite or activity. Radiographic evaluation of the spinal column is the most useful method to assess the type and severity of spinal lesions. PMID:10884118

  11. MicroRNAs in age-related diseases.

    PubMed

    Dimmeler, Stefanie; Nicotera, Pierluigi

    2013-02-01

    Aging is a complex process that is linked to an increased incidence of major diseases such as cardiovascular and neurodegenerative disease, but also cancer and immune disorders. MicroRNAs (miRNAs) are small non-coding RNAs, which post-transcriptionally control gene expression by inhibiting translation or inducing degradation of targeted mRNAs. MiRNAs target up to hundreds of mRNAs, thereby modulating gene expression patterns. Many miRNAs appear to be dysregulated during cellular senescence, aging and disease. However, only few miRNAs have been so far linked to age-related changes in cellular and organ functions. The present article will discuss these findings, specifically focusing on the cardiovascular and neurological systems.

  12. Translational strategies in aging and age-related disease.

    PubMed

    Armanios, Mary; de Cabo, Rafael; Mannick, Joan; Partridge, Linda; van Deursen, Jan; Villeda, Saul

    2015-12-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing through the use of model organisms, how to apply this knowledge in the clinic is less clear. In September, Nature Medicine, in collaboration with the Volkswagen Foundation, hosted a conference at the beautiful Herrenhausen Palace in Hannover, Germany with the goal of broadening our understanding of the aging process and its meaning as a 'risk factor' in disease. Here, several of the speakers at that conference answer questions posed by Nature Medicine.

  13. Translational strategies in aging and age-related disease.

    PubMed

    Armanios, Mary; de Cabo, Rafael; Mannick, Joan; Partridge, Linda; van Deursen, Jan; Villeda, Saul

    2015-12-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing through the use of model organisms, how to apply this knowledge in the clinic is less clear. In September, Nature Medicine, in collaboration with the Volkswagen Foundation, hosted a conference at the beautiful Herrenhausen Palace in Hannover, Germany with the goal of broadening our understanding of the aging process and its meaning as a 'risk factor' in disease. Here, several of the speakers at that conference answer questions posed by Nature Medicine. PMID:26646495

  14. Animal models of age related macular degeneration

    PubMed Central

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  15. Aging, frailty and age-related diseases.

    PubMed

    Fulop, T; Larbi, A; Witkowski, J M; McElhaney, J; Loeb, M; Mitnitski, A; Pawelec, G

    2010-10-01

    The concept of frailty as a medically distinct syndrome has evolved based on the clinical experience of geriatricians and is clinically well recognizable. Frailty is a nonspecific state of vulnerability, which reflects multisystem physiological change. These changes underlying frailty do not always achieve disease status, so some people, usually very elderly, are frail without a specific life threatening illness. Current thinking is that not only physical but also psychological, cognitive and social factors contribute to this syndrome and need to be taken into account in its definition and treatment. Together, these signs and symptoms seem to reflect a reduced functional reserve and consequent decrease in adaptation (resilience) to any sort of stressor and perhaps even in the absence of extrinsic stressors. The overall consequence is that frail elderly are at higher risk for accelerated physical and cognitive decline, disability and death. All these characteristics associated with frailty can easily be applied to the definition and characterization of the aging process per se and there is little consensus in the literature concerning the physiological/biological pathways associated with or determining frailty. It is probably true to say that a consensus view would implicate heightened chronic systemic inflammation as a major contributor to frailty. This review will focus on the relationship between aging, frailty and age-related diseases, and will highlight possible interventions to reduce the occurrence and effects of frailty in elderly people. PMID:20559726

  16. Physics of Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon

    2009-11-01

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer's disease, and Parkinson's disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. In this talk I will discuss a model of non-equilibrium cluster growth that we have developed for studying the formation and growth of lipofuscin in AMD [K.I. Mazzitello, C.M. Arizmendi, Fereydoon Family, H. E. Grossniklaus, Physical Review E (2009)]. I will also present an overview of our theoretical and computational efforts in modeling some other aspects of the physics of AMD, including CNV and the breakdown of Bruch's membrane [Ongoing collaboration with Abbas Shirinifard and James A. Glazier, Biocomplexity Institute and Department of Physics, Indiana University, Y. Jiang, Los Alamos, and Hans E. Grossniklaus, Department of Ophthalmology, Emory University].

  17. Mechanisms of age-related macular degeneration

    PubMed Central

    Ambati, Jayakrishna; Fowler, Benjamin J.

    2012-01-01

    Age-related macular degeneration (AMD), a progressive condition that is untreatable in up to 90% of patients, is a leading cause of blindness in the elderly worldwide. The two forms of AMD, wet and dry, are classified based on the presence or absence of blood vessels that have disruptively invaded the retina, respectively. A detailed understanding of the molecular mechanisms underlying wet AMD has led to several robust FDA-approved therapies. In contrast, there are not any approved treatments for dry AMD. In this review, we provide insight into the critical effector pathways that mediate each form of disease. The interplay of immune and vascular systems for wet AMD, and the proliferating interest in hunting for gene variants to explain AMD pathogenesis, are placed in the context of the latest clinical and experimental data. Emerging models of dry AMD pathogenesis are presented, with a focus on DICER1 deficit and the toxic accumulation of retinal debris. A recurring theme that spans most aspects of AMD pathogenesis is defective immune modulation in the classically immune-privileged ocular haven. Interestingly, the latest advances in AMD research highlight common molecular disease pathways with other common neurodegenerations. Finally, the therapeutic potential of intervening at known mechanisms of AMD pathogenesis is discussed. PMID:22794258

  18. Age related degradation in operating nuclear plants

    SciTech Connect

    Hermann, R.A.; Davis, J.A.; Banic, M.J.

    1995-12-01

    The aging issues being addressed for today`s operating commercial nuclear power plants encompass a wide spectrum of components, complexities, and reasons for concern. Issues include such things as the intergranular stress corrosion cracking (IGSCC) of boiling water reactor (BWR) internals, the degradation of pressurized water reactor (PWR) Alloy 600 components by primary water stress corrosion cracking (PWSCC) to those associated with significant portions of piping systems, such as service water systems. a discussion of the regulatory activity and action associated with the above issues is provided. Proactive NRC/Industry programs for inspection and repair or replacement of affected components are essential for continued operation of these nuclear reactors. These programs are also essential as licensees consider license extensions for their facilities. These plants are licensed for 40 years and can be granted an extension for an additional 20 years of operation if all of the NRC rules and regulations are met. Proper handling of potential age related problems will be a key consideration in the granting of a license extension.

  19. Statistical physics of age related macular degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, H. E.

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer disease and Parkinson disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin in the aging RPE. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the RPE the larger ones become fixed and grow by aggregation.

  20. Association of Age Related Macular Degeneration and Age Related Hearing Impairment

    PubMed Central

    Ghasemi, Hassan; Pourakbari, Malihe Shahidi; Entezari, Morteza; Yarmohammadi, Mohammad Ebrahim

    2016-01-01

    Purpose: To evaluate the association between age-related macular degeneration (ARMD) and sensory neural hearing impairment (SHI). Methods: In this case-control study, hearing status of 46 consecutive patients with ARMD were compared with 46 age-matched cases without clinical ARMD as a control group. In all patients, retinal involvements were confirmed by clinical examination, fluorescein angiography (FA) and optical coherence tomography (OCT). All participants were examined with an otoscope and underwent audiological tests including pure tone audiometry (PTA), speech reception threshold (SRT), speech discrimination score (SDS), tympanometry, reflex tests and auditory brainstem response (ABR). Results: A significant (P = 0.009) association was present between ARMD, especially with exudative and choroidal neovascularization (CNV) components, and age-related hearing impairment primarily involving high frequencies. Patients had higher SRT and lower SDS against anticipated presbycusis than control subjects. Similar results were detected in exudative, CNV and scar patterns supporting an association between late ARMD with SRT and SDS abnormalities. ABR showed significantly prolonged wave I and IV latency times in ARMD (P = 0.034 and 0.022, respectively). Average latency periods for wave I in geographic atrophy (GA) and CNV, and that for wave IV in drusen patterns of ARMD were significantly higher than controls (P = 0.030, 0.007 and 0.050, respectively). Conclusion: The association between ARMD and age-related SHI may be attributed to common anatomical components such as melanin in these two sensory organs. PMID:27195086

  1. Age-Related Changes in the Misinformation Effect.

    ERIC Educational Resources Information Center

    Sutherland, Rachel; Hayne, Harlene

    2001-01-01

    Two experiments examined relation between age-related changes in retention and age-related changes in the misinformation effect. Found large age-related retention differences when participants were interviewed immediately and after 1 day, but after 6 weeks, differences were minimal. Exposure to misleading information increased commission errors.…

  2. The Marmoset as a Model of Aging and Age-Related Diseases

    PubMed Central

    Tardif, Suzette D.; Mansfield, Keith G.; Ratnam, Rama; Ross, Corinna N.; Ziegler, Toni E.

    2013-01-01

    The common marmoset (Callithrix jacchus) is poised to become a standard nonhuman primate aging model. With an average lifespan of 5 to 7 years and a maximum lifespan of 16.5 years, marmosets are the shortest-lived anthropoid primates. They display age-related changes in pathologies that mirror those seen in humans, such as cancer, amyloidosis, diabetes, and chronic renal disease. They also display predictable age-related differences in lean mass, calf circumference, circulating albumin, hemoglobin, and hematocrit. Features of spontaneous sensory and neurodegenerative change—for example, reduced neurogenesis, β-amyloid deposition in the cerebral cortex, loss of calbindin D28k binding, and evidence of presbycusis—appear between the ages of 7 and 10 years. Variation among colonies in the age at which neurodegenerative change occurs suggests the interesting possibility that marmosets could be specifically managed to produce earlier versus later occurrence of degenerative conditions associated with differing rates of damage accumulation. In addition to the established value of the marmoset as a model of age-related neurodegenerative change, this primate can serve as a model of the integrated effects of aging and obesity on metabolic dysfunction, as it displays evidence of such dysfunction associated with high body weight as early as 6 to 8 years of age. PMID:21411858

  3. Age-related consequences of childhood obesity.

    PubMed

    Kelsey, Megan M; Zaepfel, Alysia; Bjornstad, Petter; Nadeau, Kristen J

    2014-01-01

    The severity and frequency of childhood obesity has increased significantly over the past three to four decades. The health effects of increased body mass index as a child may significantly impact obese youth as they age. However, many of the long-term outcomes of childhood obesity have yet to be studied. This article examines the currently available longitudinal data evaluating the effects of childhood obesity on adult outcomes. Consequences of obesity include an increased risk of developing the metabolic syndrome, cardiovascular disease, type 2 diabetes and its associated retinal and renal complications, nonalcoholic fatty liver disease, obstructive sleep apnea, polycystic ovarian syndrome, infertility, asthma, orthopedic complications, psychiatric disease, and increased rates of cancer, among others. These disorders can start as early as childhood, and such early onset increases the likelihood of early morbidity and mortality. Being obese as a child also increases the likelihood of being obese as an adult, and obesity in adulthood also leads to obesity-related complications. This review outlines the evidence for childhood obesity as a predictor of adult obesity and obesity-related disorders, thereby emphasizing the importance of early intervention to prevent the onset of obesity in childhood. PMID:24434909

  4. Age-related consequences of childhood obesity.

    PubMed

    Kelsey, Megan M; Zaepfel, Alysia; Bjornstad, Petter; Nadeau, Kristen J

    2014-01-01

    The severity and frequency of childhood obesity has increased significantly over the past three to four decades. The health effects of increased body mass index as a child may significantly impact obese youth as they age. However, many of the long-term outcomes of childhood obesity have yet to be studied. This article examines the currently available longitudinal data evaluating the effects of childhood obesity on adult outcomes. Consequences of obesity include an increased risk of developing the metabolic syndrome, cardiovascular disease, type 2 diabetes and its associated retinal and renal complications, nonalcoholic fatty liver disease, obstructive sleep apnea, polycystic ovarian syndrome, infertility, asthma, orthopedic complications, psychiatric disease, and increased rates of cancer, among others. These disorders can start as early as childhood, and such early onset increases the likelihood of early morbidity and mortality. Being obese as a child also increases the likelihood of being obese as an adult, and obesity in adulthood also leads to obesity-related complications. This review outlines the evidence for childhood obesity as a predictor of adult obesity and obesity-related disorders, thereby emphasizing the importance of early intervention to prevent the onset of obesity in childhood.

  5. Age-Related Neurochemical Changes in the Vestibular Nuclei.

    PubMed

    Smith, Paul F

    2016-01-01

    There is evidence that the normal aging process is associated with impaired vestibulo-ocular reflexes (VOR) and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa's ganglion and the vestibular nucleus complex (VNC), it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarizes and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics. PMID:26973593

  6. Age-related macular degeneration: Evidence of a major gene

    SciTech Connect

    Bhatt, S.; Warren, C.; Yang, H.

    1994-09-01

    Age-related macular degeneration is a major cause of blindness in developing countries. It remains a very poorly understood disorder. Although environmental and genetic factors have been implicated in its pathogenesis, none have been firmly implicated. The purpose of this study was to use pedigree analysis to evaluate the possible role of a major gene as a determinant of familial aggregation. Information was collected regarding occupation, smoking, sun exposure, associated medical problems and family history. 50 probands with age-related macular degeneration (ARMD) and 39 age, race and sex-matched controls were included in the study. In the ARMD group 15/50 (30%) of probands reported a positive family history; 22 out of 222 first degree relatives over age 60 were reported to be affected. In the control groups, none of the 138 first degree relatives over age 50 had a history of ARMD. This difference is statistically significant (p = 0.0003), indicating that genetic factors may play an important role in the pathogenesis of ARMD. In the ARMD group more siblings as compared to parents (16/127 vs. 5/82) were affected. 5/50 (10%) of the ARMD probands also gave a history of a second degree relative affected with ARMD, compared to none known among the relatives of controls. Data from 50 pedigrees were analyzed by complex segregation analysis under a class A regressive logistic model using the REGD program implemented in the SAGE package. Preliminary results allow rejection of a polygenic model and suggest there is a major gene for ARMD in these families. The inheritance model most compatible with the observed familial aggregation is autosomal recessive. In conclusion, these results are suggestive of a major gene effect in the etiology of ARMD. Identification of a major gene effect is a first step to further pursue linkage analysis and to search for the gene(s) involved in the causation of ARMD.

  7. Genetic risk factors and age-related macular degeneration (AMD)

    PubMed Central

    Mousavi, Maryam; Armstrong, Richard A.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of blindness in individuals older than 65 years of age. It is a multifactorial disorder and identification of risk factors enables individuals to make lifestyle choices that may reduce the risk of disease. Collaboration between geneticists, ophthalmologists, and optometrists suggests that genetic risk factors play a more significant role in AMD than previously thought. The most important genes are associated with immune system modulation and the complement system, e.g., complement factor H (CFH), factor B (CFB), factor C3, and serpin peptidase inhibitor (SERPING1). Genes associated with membrane transport, e.g., ATP-binding cassette protein (ABCR) and voltage-dependent calcium channel gamma 3 (CACNG3), the vascular system, e.g., fibroblast growth factor 2 (FGF2), fibulin-5, lysyl oxidase-like gene (LOXL1) and selectin-P (SELP), and with lipid metabolism, e.g., apolipoprotein E (APOE) and hepatic lipase (LIPC) have also been implicated. In addition, several other genes exhibit some statistical association with AMD, e.g., age-related maculopathy susceptibility protein 2 (ARMS2) and DNA excision repair protein gene (ERCC6) but more research is needed to establish their significance. Modifiable risk factors for AMD should be discussed with patients whose lifestyle and/or family history place them in an increased risk category. Furthermore, calculation of AMD risk using current models should be recommended as a tool for patient education. It is likely that AMD management in future will be increasingly influenced by assessment of genetic risk as such screening methods become more widely available.

  8. Age-Related Neurochemical Changes in the Vestibular Nuclei

    PubMed Central

    Smith, Paul F.

    2016-01-01

    There is evidence that the normal aging process is associated with impaired vestibulo-ocular reflexes (VOR) and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa’s ganglion and the vestibular nucleus complex (VNC), it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarizes and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics. PMID:26973593

  9. Age-related elemental change in bones

    NASA Astrophysics Data System (ADS)

    Wang, C.; Eisa, M. H.; Jin, W.; Shen, H.; Mi, Y.; Gao, J.; Zhou, Y.; Yao, H.; Zhao, Y.

    2008-04-01

    To investigate age dependence of the bone element contents and structure, lumbar and femur from Sprague-Dawley (SD) rats were chosen for their more susceptibility to fracture. These rats were divided into to 5 age groups: 1, 4, 7, 11 and 25 month-age, corresponding human beings from the young to the old. The elements contents were detected by external Proton Induced X-ray emission (PIXE) technique. X-ray Absorption Fine Structure (XAFS) method was also applied to obtain information about calcium (Ca) and phosphor (P) structure. It was found that Ca content, Ca/P ratio, valance state of Ca and P and their coordinate structure remains unaltered with age variance, whereas the content of strontium (Sr) was significantly decreasing. Sr concentration may provide a new parameter for diagnosis of bone disorder.

  10. Nanoneuromedicines for Degenerative, Inflammatory, and Infectious Nervous System Diseases

    PubMed Central

    Gendelman, Howard E.; Anantharam, Vellareddy; Bronich, Tatiana; Ghaisas, Shivani; Jin, Huajun; Kanthasamy, Anumantha G.; Liu, Xinming; McMillan, JoEllyn; Mosley, R. Lee; Narasimhan, Balaji; Mallapragada, Surya K.

    2015-01-01

    Interest in nanoneuromedicine has grown rapidly due to the immediate need for improved biomarkers and therapies for psychiatric, developmental, traumatic, inflammatory, infectious and degenerative nervous system disorders. These, in whole or in part, are a significant societal burden due to growth in numbers of affected people and in disease severity. Lost productivity of the patient and his or her caregiver, and the emotional and financial burden cannot be overstated. The need for improved health care, treatment and diagnostics are immediate. A means to such an end is nanotechnology. Indeed, recent developments of health-care enabling nanotechnologies and nanomedicines range from biomarker discovery including neuroimaging to therapeutic applications for degenerative, inflammatory and infectious disorders of the nervous system. This review focuses on the current and future potential of the field to positively affect clinical outcomes. PMID:25645958

  11. [Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis].

    PubMed

    Machalińska, Anna

    2013-01-01

    Age-related macular degeneration is the leading cause of irreversible visual impairment and disability among the elderly in developed countries. There is compelling evidence that atherosclerosis and age-related macular degeneration share a similar pathogenic process. The association between atherosclerosis and age-related macular degeneration has been inferred from histological, biochemical and epidemiological studies. Many published data indicate that drusen are similar in molecular composition to plaques in atherosclerosis. Furthermore, a great body of evidence has emerged over the past decade that implicates the chronic inflammatory processes in the pathogenesis and progression of both disorders. We speculate that vascular atherosclerosis and age-related macular degeneration may represent different manifestations of the same disease induced by a pathologic tissue response to the damage caused by oxidative stress and local ischemia. In this review, we characterise in detail a strong association between age-related macular degeneration and atherosclerosis development, and we postulate the hypothesis that age-related macular degeneration is a local manifestation of a systemic disease. This provides a new approach for understanding the aspects of pathogenesis and might improve the prevention and treatment of both diseases which both result from ageing of the human body.

  12. Parabiosis for the study of age-related chronic disease

    PubMed Central

    Eggel, Alexander; Wyss-Coray, Tony

    2014-01-01

    Summary Modern medicine wields the power to treat large numbers of diseases and injuries most of us would have died from just a hundred years ago. In view of this tremendous achievement, it can seem as if progress has slowed, and we have been unable to impact the most devastating diseases of our time. Chronic diseases of age such as cardiovascular disease, diabetes, osteoarthritis, or Alzheimer’s disease turn out to be of a complexity that may require transformative ideas and paradigms to understand and treat them. Parabiosis, which mimics aspects of the naturally occurring shared blood supply in conjoined twins in humans and certain animals, may just have the power to be such a transformative experimental paradigm. Forgotten and now shunned in many countries, it has contributed to major breakthroughs in tumor biology, endocrinology, and transplantation research in the past century, and a set of new studies in the US and Britain report stunning advances in stem cell biology and tissue regeneration using parabiosis between young and old mice. We review here briefly the history of parabiosis and discuss its utility to study physiological and pathophysiological processes. We argue that parabiosis is a technique that should enjoy wider acceptance and application, and that policies should be revisited especially if one is to study complex age-related, chronic disorders. PMID:24496774

  13. Oxidative modification of proteins: age-related changes.

    PubMed

    Chakravarti, Bulbul; Chakravarti, Deb N

    2007-01-01

    Aging is a complex biological phenomenon which involves progressive loss of different physiological functions of various tissues of living organisms. It is the inevitable fate of life and is a major risk factor for death and different pathological disorders. Based on a wide variety of studies performed in humans as well as in various animal models and microbial systems, reactive oxygen species (ROS) are believed to play a key role in the aging process. The production of ROS is influenced by cellular metabolic activities as well as environmental factors. ROS can react with all major biological macromolecules such as carbohydrates, nucleic acids, lipids, and proteins. Since, in general, proteins are the key molecules that play the ultimate role in various structural and functional aspects of living organisms, this review will focus on the age-related oxidative modifications of proteins as well as on mechanism for removal or repair of the oxidized proteins. The topics covered include protein oxidation as a marker of oxidative stress, experimental evidence indicating the role of ROS in protein oxidation, protein carbonyl content, enzymatic degradation of oxidized proteins, and effects of caloric restriction on protein oxidation in the context of aging. Finally, we will discuss different strategies which have been or can be undertaken to slow down the oxidative damage of proteins and the aging process.

  14. Adiponectin deficiency exacerbates age-related hearing impairment.

    PubMed

    Tanigawa, T; Shibata, R; Ouchi, N; Kondo, K; Ishii, M; Katahira, N; Kambara, T; Inoue, Y; Takahashi, R; Ikeda, N; Kihara, S; Ueda, H; Murohara, T

    2014-04-24

    Obesity-related disorders are closely associated with the development of age-related hearing impairment (ARHI). Adiponectin (APN) exerts protective effects against obesity-related conditions including endothelial dysfunction and atherosclerosis. Here, we investigated the impact of APN on ARHI. APN-knockout (APN-KO) mice developed exacerbation of hearing impairment, particularly in the high frequency range, compared with wild-type (WT) mice. Supplementation with APN prevented the hearing impairment in APN-KO mice. At 2 months of age, the cochlear blood flow and capillary density of the stria vascularis (SV) were significantly reduced in APN-KO mice as compared with WT mice. APN-KO mice also showed a significant increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells in the organ of Corti in the cochlea at 2 months of age. At the age of 6 months, hair cells were lost at the organ of Corti in APN-KO mice. In cultured auditory HEI-OC1 cells, APN reduced apoptotic activity under hypoxic conditions. Clinically, plasma APN levels were significantly lower in humans with ARHI. Multiple logistic regression analysis identified APN as a significant and independent predictor of ARHI. Our observations indicate that APN has an important role in preventing ARHI.

  15. Age-related alterations in the vertebral spinous processes and intervening soft tissues: radiologic-pathologic correlation.

    PubMed

    Sartoris, D J; Resnick, D; Tyson, R; Haghighi, P

    1985-11-01

    A radiologic-pathologic correlative investigation of the normal age-related alterations in the spinous processes and intervening soft tissues was performed using cadaveric spines and both ancient and modern macerated vertebral specimens. Extreme lordosis in the cervical or lumbar spine results in spinous process apposition, formation of interspinous bursae, eburnation with osteophytosis, and creation of synovial articulations. A concomitant degenerative enthesopathy involves the supraspinous or interspinous ligamentous attachments in any spinal segment. The differential diagnosis of this phenomenon, the clinical significance of which in a given patient is controversial, includes rheumatoid and other inflammatory arthritides as well as crystal deposition disease.

  16. [Dysexecutive syndromes and degenerative diseases].

    PubMed

    Pillon, B; Czernecki, V; Dubois, B

    2004-04-01

    A dysexecutive syndrome is observed not only in frontotemporal lobar degeneration, but also in subcortical degenerative diseases, and even in Alzheimer's disease whose lesions predominate in temporoparietal associative areas. The association between a dysexecutive syndrome and various cerebral localisations may be explained by the fact that cognitive and behavioral organisation recruits anatomofunctional frontostriatal and frontoparietal circuits. Both animal experimentation and human clinical observation argue in favour of a functional continuity and complementarity among these loops. The prefrontal cortex would be particularly needed in new situations, to inhibit old programs of action not adapted to the present context and to elaborate new ones; the basal ganglia would be rather required by the repetition of the situation to progressively transform the new program in routine. If we refer to Shallice model, we can hypothesize that optimal executive functions require the preservation not only of the Supervisory Attentional System, mainly dependent on the prefrontal cortex, but also of the Contention Scheduling, recruiting the basal ganglia, and of the Schemas of Action, represented in parietal and premotor areas. Therefore, the neuropsychological assessment of patients with degenerative diseases contributes to the understanding of the anatomofunctional architecture of executive functions.

  17. Diagnosis and conservative management of degenerative lumbar spondylolisthesis

    PubMed Central

    Hunter, David J.

    2007-01-01

    Degenerative spondylolisthesis (DS) is a disorder that causes the slip of one vertebral body over the one below due to degenerative changes in the spine. Lumbar DS is a major cause of spinal canal stenosis and is often related to low back and leg pain. We reviewed the symptoms, prognosis and conservative treatments for symptoms associated with DS. PubMed and MEDLINE databases (1950–2007) were searched for the key words “spondylolisthesis”, “pseudospondylolisthesis”, “degenerative spondylolisthesis”, “spinal stenosis”, “lumbar spine”, “antherolisthesis”, “posterolisthesis”, “low back pain”, and “lumbar instability”. All relevant articles in English were reviewed. Pertinent secondary references were also retrieved. The prognosis of patients with DS is favorable, however, those who suffer from neurological symptoms such as intermittent claudication or vesicorectal disorder, will most probably experience neurological deterioration if they are not operated upon. Nonoperative treatment should be the initial course of action in most cases of DS, with or without neurologic symptoms. Treatment options include use of analgesics and NSAIDs to control pain; epidural steroid injections, and physical methods such as bracing and flexion strengthening exercises. An up-to-date knowledge on diagnosis and prevention of lumbar DS can assist in determination of future research goals. Additional studies are required to establish treatment protocols for the conservative treatment of DS. PMID:18026865

  18. [Depression in Patients with Age-Related Macular Degeneration].

    PubMed

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index. PMID:26572116

  19. [Depression in Patients with Age-Related Macular Degeneration].

    PubMed

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index.

  20. Beta-Amyloid Precursor Protein (βAPP) Processing in Alzheimer's Disease (AD) and Age-Related Macular Degeneration (AMD).

    PubMed

    Zhao, Yuhai; Bhattacharjee, Surjyadipta; Jones, Brandon M; Hill, James M; Clement, Christian; Sambamurti, Kumar; Dua, Prerna; Lukiw, Walter J

    2015-08-01

    Amyloid is a generic term for insoluble, often intensely hydrophobic, fibrous protein aggregates that arise from inappropriately folded versions of naturally-occurring polypeptides. The abnormal generation and accumulation of amyloid, often referred to as amyloidogenesis, has been associated with the immune and pro-inflammatory pathology of several progressive age-related diseases of the human central nervous system (CNS) including Alzheimer's disease (AD) and age-related macular degeneration (AMD). This 'research perspective' paper reviews some of the research history, biophysics, molecular-genetics and environmental factors concerning the contribution of amyloid beta (Aβ) peptides, derived from beta-amyloid precursor protein (βAPP), to AD and AMD that suggests an extensive similarity in immune and inflammatory degenerative mechanisms between these two CNS diseases.

  1. Slowing Down: Age-Related Neurobiological Predictors of Processing Speed

    PubMed Central

    Eckert, Mark A.

    2011-01-01

    Processing speed, or the rate at which tasks can be performed, is a robust predictor of age-related cognitive decline and an indicator of independence among older adults. This review examines evidence for neurobiological predictors of age-related changes in processing speed, which is guided in part by our source based morphometry findings that unique patterns of frontal and cerebellar gray matter predict age-related variation in processing speed. These results, together with the extant literature on morphological predictors of age-related changes in processing speed, suggest that specific neural systems undergo declines and as a result slow processing speed. Future studies of processing speed – dependent neural systems will be important for identifying the etiologies for processing speed change and the development of interventions that mitigate gradual age-related declines in cognitive functioning and enhance healthy cognitive aging. PMID:21441995

  2. Meta-analysis of age-related gene expression profiles identifies common signatures of aging

    PubMed Central

    de Magalhães, João Pedro; Curado, João; Church, George M.

    2009-01-01

    Motivation: Numerous microarray studies of aging have been conducted, yet given the noisy nature of gene expression changes with age, elucidating the transcriptional features of aging and how these relate to physiological, biochemical and pathological changes remains a critical problem. Results: We performed a meta-analysis of age-related gene expression profiles using 27 datasets from mice, rats and humans. Our results reveal several common signatures of aging, including 56 genes consistently overexpressed with age, the most significant of which was APOD, and 17 genes underexpressed with age. We characterized the biological processes associated with these signatures and found that age-related gene expression changes most notably involve an overexpression of inflammation and immune response genes and of genes associated with the lysosome. An underexpression of collagen genes and of genes associated with energy metabolism, particularly mitochondrial genes, as well as alterations in the expression of genes related to apoptosis, cell cycle and cellular senescence biomarkers, were also observed. By employing a new method that emphasizes sensitivity, our work further reveals previously unknown transcriptional changes with age in many genes, processes and functions. We suggest these molecular signatures reflect a combination of degenerative processes but also transcriptional responses to the process of aging. Overall, our results help to understand how transcriptional changes relate to the process of aging and could serve as targets for future studies. Availability: http://genomics.senescence.info/uarrays/signatures.html Contact: jp@senescence.info Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19189975

  3. Progressive Bidirectional Age-Related Changes in Default Mode Network Effective Connectivity across Six Decades

    PubMed Central

    Li, Karl; Laird, Angela R.; Price, Larry R.; McKay, D. Reese; Blangero, John; Glahn, David C.; Fox, Peter T.

    2016-01-01

    The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20–29 to 70–79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging. PMID:27378909

  4. Progressive Bidirectional Age-Related Changes in Default Mode Network Effective Connectivity across Six Decades.

    PubMed

    Li, Karl; Laird, Angela R; Price, Larry R; McKay, D Reese; Blangero, John; Glahn, David C; Fox, Peter T

    2016-01-01

    The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20-29 to 70-79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging. PMID:27378909

  5. The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases.

    PubMed

    Maessen, Dionne E M; Stehouwer, Coen D A; Schalkwijk, Casper G

    2015-06-01

    The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

  6. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease

    PubMed Central

    Crosson, Bruce; McGregor, Keith M.; Nocera, Joe R.; Drucker, Jonathan H.; Tran, Stella M.; Butler, Andrew J.

    2015-01-01

    The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered. PMID:26074807

  7. Age-Related Macular Degeneration: Genetics and Biology.

    PubMed

    Kumaramanickavel, Govindasamy

    2016-01-01

    Age-related macular degeneration (AMD), widely prevalent across the globe, is a major stakeholder among adult visual morbidity and blindness, not only in the Western world but also in Asia. Several risk factors have been identified, including critical genetic factors, which were never imagined 2 decades ago. The etiopathogenesis is emerging to demonstrate that immune and complement-related inflammation pathway members chronically exposed to environmental insults could justifiably influence disease morbidity and treatment outcomes. Approximately half a dozen physiological and biochemical cascades are disrupted in the AMD disease genesis, eventually leading to the distortion and disruption of the subretinal space, subretinal pigment epithelium, and Bruch membrane, thus setting off chaos and disorder for signs and symptoms to manifest. Approximately 3 dozen genetic factors have so far been identified, including the recent ones, through powerful genomic technologies and large robust sample sizes. The noteworthy genetic variants (common and rare) are complement factor H, complement factor H-related genes 1 to 5, C3, C9, ARMS2/HTRA1, vascular endothelial growth factor A, vascular endothelial growth factor receptor 2/KDR, and rare variants (show causal link) such as TIMP3, fibrillin, COL4A3, MMP19, and MMP9. Despite the enormous amount of scientific information generated over the years, diagnostic genetic or biomarker tests are still not available for clinicians to understand the natural course of the disease and its management in a patient. However, further research in the field should reduce this gap not only by aiding the clinician but also through the possibilities of clinical intervention with complement pathway-related inhibitors entering preclinical and clinical trials in the near future. PMID:27488064

  8. Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy.

    PubMed

    Kovacs, Gabor G; Ferrer, Isidro; Grinberg, Lea T; Alafuzoff, Irina; Attems, Johannes; Budka, Herbert; Cairns, Nigel J; Crary, John F; Duyckaerts, Charles; Ghetti, Bernardino; Halliday, Glenda M; Ironside, James W; Love, Seth; Mackenzie, Ian R; Munoz, David G; Murray, Melissa E; Nelson, Peter T; Takahashi, Hitoshi; Trojanowski, John Q; Ansorge, Olaf; Arzberger, Thomas; Baborie, Atik; Beach, Thomas G; Bieniek, Kevin F; Bigio, Eileen H; Bodi, Istvan; Dugger, Brittany N; Feany, Mel; Gelpi, Ellen; Gentleman, Stephen M; Giaccone, Giorgio; Hatanpaa, Kimmo J; Heale, Richard; Hof, Patrick R; Hofer, Monika; Hortobágyi, Tibor; Jellinger, Kurt; Jicha, Gregory A; Ince, Paul; Kofler, Julia; Kövari, Enikö; Kril, Jillian J; Mann, David M; Matej, Radoslav; McKee, Ann C; McLean, Catriona; Milenkovic, Ivan; Montine, Thomas J; Murayama, Shigeo; Lee, Edward B; Rahimi, Jasmin; Rodriguez, Roberta D; Rozemüller, Annemieke; Schneider, Julie A; Schultz, Christian; Seeley, William; Seilhean, Danielle; Smith, Colin; Tagliavini, Fabrizio; Takao, Masaki; Thal, Dietmar Rudolf; Toledo, Jon B; Tolnay, Markus; Troncoso, Juan C; Vinters, Harry V; Weis, Serge; Wharton, Stephen B; White, Charles L; Wisniewski, Thomas; Woulfe, John M; Yamada, Masahito; Dickson, Dennis W

    2016-01-01

    Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of

  9. [Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

    PubMed

    Fischer, Tamás

    2015-11-15

    It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors

  10. [Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

    PubMed

    Fischer, Tamás

    2015-11-15

    It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors

  11. Low Calorie Diet Affects Aging-Related Factors

    MedlinePlus

    ... Issue Past Issues Research News From NIH Low Calorie Diet Affects Aging-Related Factors Past Issues / Summer ... learn more about the effects of sustained low-calorie diets in humans on factors affecting aging. This ...

  12. New Clues to Age-Related Hearing Loss

    MedlinePlus

    ... gov/news/fullstory_161359.html New Clues to Age-Related Hearing Loss Older people's brains have a ... the brain's ability to process speech declines with age. For the study, Alessandro Presacco and colleagues divided ...

  13. Dynamic stabilization for degenerative spondylolisthesis and lumbar spinal instability.

    PubMed

    Ohtonari, Tatsuya; Nishihara, Nobuharu; Suwa, Katsuyasu; Ota, Taisei; Koyama, Tsunemaro

    2014-01-01

    Lumbar interbody fusion is a widely accepted surgical procedure for patients with lumbar degenerative spondylolisthesis and lumbar spinal instability in the active age group. However, in elderly patients, it is often questionable whether it is truly necessary to construct rigid fixation for a short period of time. In recent years, we have been occasionally performing posterior dynamic stabilization in elderly patients with such lumbar disorders. Posterior dynamic stabilization was performed in 12 patients (6 women, 70.9 ± 5.6 years old at the time of operation) with lumbar degenerative spondylolisthesis in whom % slip was less than 20% or instability associated with lumbar disc herniation between March 2011 and March 2013. Movement occurs through the connector linked to the pedicle screw. In practice, 9 pairs of D connector system where the rod moves in the perpendicular direction alone and 8 pairs of Dynamic connector system where the connector linked to the pedicle screw rotates in the sagittal direction were installed. The observation period was 77-479 days, and the mean recovery rate of lumbar Japanese Orthopedic Association (JOA) score was 65.6 ± 20.8%. There was progression of slippage due to slight loosening in a case with lumbar degenerative spondylolisthesis, but this did not lead to exacerbation of the symptoms. Although follow-up was short, there were no symptomatic adjacent vertebral and disc disorders during this period. Posterior dynamic stabilization may diminish the development of adjacent vertebral or disc disorders due to lumbar interbody fusion, especially in elderly patients, and it may be a useful procedure that facilitates decompression and ensures a certain degree of spinal stabilization.

  14. Stereotypic behaviors in degenerative dementias.

    PubMed

    Prioni, S; Fetoni, V; Barocco, F; Redaelli, V; Falcone, C; Soliveri, P; Tagliavini, F; Scaglioni, A; Caffarra, P; Concari, L; Gardini, S; Girotti, F

    2012-11-01

    Stereotypies are simple or complex involuntary/unvoluntary behaviors, common in fronto-temporal dementia (FTD), but not studied in other types of degenerative dementias. The aim was to investigate stereotypy frequency and type in patients with FTD, Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and Parkinson's disease with dementia (PDD) in a multicenter observational study; and to investigate the relation of stereotypies to cognitive, behavioral and motor impairment. One hundred fifty-five consecutive outpatients (45 AD, 40 FTD, 35 PSP and 35 PDD) were studied in four hospitals in northern Italy. Stereotypies were examined by the five-domain Stereotypy Rating Inventory. Cognition was examined by the Mini Mental State and Frontal Assessment Battery, neuropsychiatric symptoms by the Neuropsychiatric Inventory, and motor impairment and invalidity by the Unified Parkinson's Disease Rating Scale part III, and activities of daily living. Stereotypies were present in all groups. FTD and PDD had the greatest frequency of one-domain stereotypies; FTD also had the greatest frequency of two-or-more domain stereotypies; movement stereotypies were the most common stereotypies in all groups. AD patients had fewer stereotypies than the other groups. Stereotypies are not exclusive to FTD, but are also fairly common in PSP and PDD, though less so in AD. Stereotypies may be underpinned by dysfunctional striato-frontal circuits, known to be damaged in PSP and PDD, as well as FTD.

  15. Network strategies to understand the aging process and help age-related drug design

    PubMed Central

    2009-01-01

    Recent studies have demonstrated that network approaches are highly appropriate tools for understanding the extreme complexity of the aging process. Moreover, the generality of the network concept helps to define and study the aging of technological and social networks and ecosystems, which may generate novel concepts for curing age-related diseases. The current review focuses on the role of protein-protein interaction networks (inter-actomes) in aging. Hubs and inter-modular elements of both interactomes and signaling networks are key regulators of the aging process. Aging induces an increase in the permeability of several cellular compartments, such as the cell nucleus, introducing gross changes in the representation of network structures. The large overlap between aging genes and genes of age-related major diseases makes drugs that aid healthy aging promising candidates for the prevention and treatment of age-related diseases, such as cancer, atherosclerosis, diabetes and neurodegenerative disorders. We also discuss a number of possible research options to further explore the potential of the network concept in this important field, and show that multi-target drugs (representing 'magic-buckshots' instead of the traditional 'magic bullets') may become an especially useful class of age-related drugs in the future. PMID:19804610

  16. Network strategies to understand the aging process and help age-related drug design.

    PubMed

    Simkó, Gábor I; Gyurkó, Dávid; Veres, Dániel V; Nánási, Tibor; Csermely, Peter

    2009-01-01

    Recent studies have demonstrated that network approaches are highly appropriate tools for understanding the extreme complexity of the aging process. Moreover, the generality of the network concept helps to define and study the aging of technological and social networks and ecosystems, which may generate novel concepts for curing age-related diseases. The current review focuses on the role of protein-protein interaction networks (inter-actomes) in aging. Hubs and inter-modular elements of both interactomes and signaling networks are key regulators of the aging process. Aging induces an increase in the permeability of several cellular compartments, such as the cell nucleus, introducing gross changes in the representation of network structures. The large overlap between aging genes and genes of age-related major diseases makes drugs that aid healthy aging promising candidates for the prevention and treatment of age-related diseases, such as cancer, atherosclerosis, diabetes and neurodegenerative disorders. We also discuss a number of possible research options to further explore the potential of the network concept in this important field, and show that multi-target drugs (representing 'magic-buckshots' instead of the traditional 'magic bullets') may become an especially useful class of age-related drugs in the future.

  17. The Critical Need to Promote Research of Aging and Aging-related Diseases to Improve Health and Longevity of the Elderly Population

    PubMed Central

    Jin, Kunlin; Simpkins, James W.; Ji, Xunming; Leis, Miriam; Stambler, Ilia

    2015-01-01

    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. PMID:25657847

  18. Parainflammation, chronic inflammation, and age-related macular degeneration.

    PubMed

    Chen, Mei; Xu, Heping

    2015-11-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration.

  19. [Some aspects regarding degenerative mitral valvular lesions encountered in medical practice].

    PubMed

    Ionescu, Simona Daniela; Sandru, V; Artenie, R; Manea, Paloma; Rezuş, C; Burdujan, Alina; Hrustovici, A; Cosovanu, A

    2003-01-01

    In the last years, the degenerative valvular heart diseases have the tendency to equalize in frequency the rheumatismal valvular diseases. The maximum attention has been paid on the degenerative aortic stenosis as being a lesion with maximum frequency and a severe evolution. This study, given on the 18391 admissions in the period 1997-2001, is a retrospective analyse and it is concerned with the degenerative mitral valvular lesions. Of the 223 patients with degenerative valvular heart lesions, 139 patients (62.3%) had degenerative aortic stenosis and 96 patients (38.5%) were diagnosed with degenerative mitral valvular lesions from which 30 patients have had no association with aortic valvular lesions while 66 patients have had such an association. The pointed out types of mitral lesions were: the mitral insufficiency in 59 patients, the mitral annular calcification without hemodynamic disease in 19 patients, the mitral stenosis in 9 patients and the mitral disease in 9 patients, too. The women was affected nearly 1.7 times more frequent than the men, with a maximum average age greater with four years for women but with a low minimal average age at 60 years for women and 52 years for men. The detailed analyse of this 96 cases had shown the presence of a cholesterol value over 200 mg/dl in 50 patients (52%), the diabetic mellitus of type II in 12 patients (12.5%), an association with HTA in 42 patients (43.7%), the cardiac insufficiency in 68 patients (70.8%), a permanent atrial fibrillation in 24 patients (25%), the chronical myocardiac infarct in 19 patients (19.7%) and disorders in the transmission of stimuli in 8 patients (8.3%). The degenerative mitral valvular lesions had occurred more and more frequently realizing more complex features under the mitral insufficiency predominance. Its frequent association with the degenerative valvular lesions determines the evolutive and therapeutic particularities that are dominated by the high gravity prognostic.

  20. [Some aspects of degenerative mitral valve lesions encountered in medical practice].

    PubMed

    Ionescu, Simona Daniela; Artenie, R; Rezuş, C; Manea, Paloma; Sandru, V; Burdujan, Alina; Cosovanu, A

    2004-01-01

    In recent years, degenerative valvular heart diseases have the tendency to be equal in frequency with rheumatic valvular diseases. The maximum attention has been paid on the degenerative aortic stenosis as being a lesion with maximum frequency and a severe evolution. This study, given on the 18,391 admissions in the period 1997-2001, is a retrospective analysis and it is concerned with the degenerative mitral valvular lesions. Of the 223 patients with degenerative valvular heart lesions, 139 patients (62.3%) had degenerative aortic stenosis and 96 patients (38.5%) were diagnosed with degenerative mitral valvular lesions from which 30 patients have had no association with aortic valvular lesions while 66 patients have had such an association. The pointed out types of mitral lesions were: the mitral insufficiency in 59 patients, the mitral annular calcification without hemodynamic disease in 19 patients, the mitral stenosis in 9 patients and the mitral disease in 9 patients, too. The women were affected nearly 1.7 times more frequent than the men, with a maximum average age greater with four years for women but with a low minimal average age at 60 years for women and 52 years for men. The detailed analysis of this 96 cases had shown the presence of a cholesterol value over 200 mg/dl in 50 patients (52%), the diabetes mellitus of type II in 12 patients (12.5%), an association with HTA in 42 patients (43.7%), the cardiac insufficiency in 68 patients (70.8%), a permanent atrial fibrillation in 24 patients (25%), chronic myocardial infarct in 19 patients (19.7%) and disorders in the transmission of stimuli in 8 patients (8.3%). The degenerative mitral valvular lesions had occurred more and more frequently realizing more complex features under the mitral insufficiency predominance. Its frequent association with the degenerative valvular lesions determines the evolutive and therapeutic particulars that are dominated by the high gravity prognostic.

  1. [The age-related macular degeneration as a vascular disease/part of systemic vasculopathy: contributions to its pathogenesis].

    PubMed

    Fischer, Tamás

    2015-03-01

    The wall of blood vessels including those in choroids may be harmed by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic impacts (risk factors), which may trigger a protracted response, the so-called host defense response. As a consequence, pathological changes resulting in vascular injury (e. g. atherosclerosis, age-related macular degeneration) may be evolved. Risk factors can also act directly on the endothelium through an increased production of reactive oxygen species promoting an endothelial activation, which leads to endothelial dysfunction, the onset of vascular disease. Thus, endothelial dysfunction is a link between the harmful stimulus and vascular injury; any kind of harmful stimuli may trigger the defensive chain that results in inflammation that may lead to vascular injury. It has been shown that even early age-related macular degeneration is associated with the presence of diffuse arterial disease and patients with early age-related macular degeneration demonstrate signs of systemic and retinal vascular alterations. Chronic inflammation, a feature of AMD, is tightly linked to diseases associated with ED: AMD is accompanied by a general inflammatory response, in the form of complement system activation, similar to that observed in degenerative vascular diseases such as atherosclerosis. All these facts indicate that age-related macular degeneration may be a vascular disease (or part of a systemic vasculopathy). This recognition could have therapeutic implications because restoration of endothelial dysfunction may prevent the development or improve vascular disease resulting in prevention or improvement of age-related macular degeneration as well.

  2. Pathophysiology of ageing, longevity and age related diseases

    PubMed Central

    Bürkle, Alexander; Caselli, Graziella; Franceschi, Claudio; Mariani, Erminia; Sansoni, Paolo; Santoni, Angela; Vecchio, Giancarlo; Witkowski, Jacek M; Caruso, Calogero

    2007-01-01

    On April 18, 2007 an international meeting on Pathophysiology of Ageing, Longevity and Age-Related Diseases was held in Palermo, Italy. Several interesting topics on Cancer, Immunosenescence, Age-related inflammatory diseases and longevity were discussed. In this report we summarize the most important issues. However, ageing must be considered an unavoidable end point of the life history of each individual, nevertheless the increasing knowledge on ageing mechanisms, allows envisaging many different strategies to cope with, and delay it. So, a better understanding of pathophysiology of ageing and age-related disease is essential for giving everybody a reasonable chance for living a long and enjoyable final part of the life. PMID:17683521

  3. Age-related differences in human skin proteoglycans

    PubMed Central

    Carrino, David A; Calabro, Anthony; Darr, Aniq B; Dours-Zimmermann, Maria T; Sandy, John D; Zimmermann, Dieter R; Sorrell, J Michael; Hascall, Vincent C; Caplan, Arnold I

    2011-01-01

    Previous work has shown that versican, decorin and a catabolic fragment of decorin, termed decorunt, are the most abundant proteoglycans in human skin. Further analysis of versican indicates that four major core protein species are present in human skin at all ages examined from fetal to adult. Two of these are identified as the V0 and V1 isoforms, with the latter predominating. The other two species are catabolic fragments of V0 and V1, which have the amino acid sequence DPEAAE as their carboxyl terminus. Although the core proteins of human skin versican show no major age-related differences, the glycosaminoglycans (GAGs) of adult skin versican are smaller in size and show differences in their sulfation pattern relative to those in fetal skin versican. In contrast to human skin versican, human skin decorin shows minimal age-related differences in its sulfation pattern, although, like versican, the GAGs of adult skin decorin are smaller than those of fetal skin decorin. Analysis of the catabolic fragments of decorin from adult skin reveals the presence of other fragments in addition to decorunt, although the core proteins of these additional decorin catabolic fragments have not been identified. Thus, versican and decorin of human skin show age-related differences, versican primarily in the size and the sulfation pattern of its GAGs and decorin in the size of its GAGs. The catabolic fragments of versican are detected at all ages examined, but appear to be in lower abundance in adult skin compared with fetal skin. In contrast, the catabolic fragments of decorin are present in adult skin, but are virtually absent from fetal skin. Taken together, these data suggest that there are age-related differences in the catabolism of proteoglycans in human skin. These age-related differences in proteoglycan patterns and catabolism may play a role in the age-related changes in the physical properties and injury response of human skin. PMID:20947661

  4. Age-related decline in emotional prosody discrimination: acoustic correlates.

    PubMed

    Mitchell, Rachel L C; Kingston, Rachel A

    2014-01-01

    It is now accepted that older adults have difficulty recognizing prosodic emotion cues, but it is not clear at what processing stage this ability breaks down. We manipulated the acoustic characteristics of tones in pitch, amplitude, and duration discrimination tasks to assess whether impaired basic auditory perception coexisted with our previously demonstrated age-related prosodic emotion perception impairment. It was found that pitch perception was particularly impaired in older adults, and that it displayed the strongest correlation with prosodic emotion discrimination. We conclude that an important cause of age-related impairment in prosodic emotion comprehension exists at the fundamental sensory level of processing.

  5. Palatal and Oromandibular Tremor Secondary to Degenerative Olivary Hypertrophy After Ependymoma Surgery.

    PubMed

    Lozano-Ros, Alberto; Miranda-Acuña, Jahir A; Hidalgo-de la Cruz, Milagros; Fernández-García, Pilar; Massot-Tarrús, Andreu; García-Domínguez, José M

    2016-09-01

    Palatal tremor (PT) is a rare movement disorder that involves pharynx, tongue, and other facial muscles. Symptomatic PT is due to lesions on the dentate-rubro-olivary pathways. We present an illustrative case of PT due to degenerative olivary hypertrophy after ependymoma surgery. PMID:27564077

  6. PPARα agonist, fenofibrate, ameliorates age-related renal injury.

    PubMed

    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Kim, Hyung Wook; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2016-08-01

    The kidney ages quickly compared with other organs. Expression of senescence markers reflects changes in the energy metabolism in the kidney. Two important issues in aging are mitochondrial dysfunction and oxidative stress. Peroxisome proliferator-activated receptor α (PPARα) is a member of the ligand-activated nuclear receptor superfamily. PPARα plays a major role as a transcription factor that regulates the expression of genes involved in various processes. In this study, 18-month-old male C57BL/6 mice were divided into two groups, the control group (n=7) and the fenofibrate-treated group (n=7) was fed the normal chow plus fenofibrate for 6months. The PPARα agonist, fenofibrate, improved renal function, proteinuria, histological change (glomerulosclerosis and tubular interstitial fibrosis), inflammation, and apoptosis in aging mice. This protective effect against age-related renal injury occurred through the activation of AMPK and SIRT1 signaling. The activation of AMPK and SIRT1 allowed for the concurrent deacetylation and phosphorylation of their target molecules and decreased the kidney's susceptibility to age-related changes. Activation of the AMPK-FOXO3a and AMPK-PGC-1α signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Our results suggest that activation of PPARα and AMPK-SIRT1 signaling may have protective effects against age-related renal injury. Pharmacological targeting of PPARα and AMPK-SIRT1 signaling molecules may prevent or attenuate age-related pathological changes in the kidney. PMID:27130813

  7. Nutritional antioxidants and age-related cataract and maculopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Loss of vision is the second greatest, next to death, fear among the elderly. Age-related cataract (ARC) and maculopathy (ARM) are two major causes of blindness worldwide. There are several important reasons to study relationships between risk for ARC/ARM and nutrition: (1) because it is likely that...

  8. [Impact of thymic function in age-related immune deterioration].

    PubMed

    Ferrando-Martínez, Sara; de la Fuente, Mónica; Guerrero, Juan Miguel; Leal, Manuel; Muñoz-Fernández, M Ángeles

    2013-01-01

    Age-related biological deterioration also includes immune system deterioration and, in consequence, a rise in the incidence and prevalence of infections and cancers, as well as low responses to vaccination strategies. Out of all immune cell subsets, T-lymphocytes seem to be involved in most of the age-related defects. Since T-lymphocytes mature during their passage through the thymus, and the thymus shows an age-related process of atrophy, thymic regression has been proposed as the triggering event of this immune deterioration in elderly people. Historically, it has been accepted that the young thymus sets the T-lymphocyte repertoire during the childhood, whereupon atrophy begins until the elderly thymus is a non-functional evolutionary trace. However, a rising body of knowledge points toward the thymus functioning during adulthood. In the elderly, higher thymic function is associated with a younger immune system, while thymic function failure is associated with all-cause mortality. Therefore, any new strategy focused on the improvement of the elderly quality of life, especially those trying to influence the immune system, should take into account, together with peripheral homeostasis, thymus function as a key element in slowing down age-related decline.

  9. Age-Related Differences in Idiom Production in Adulthood

    ERIC Educational Resources Information Center

    Conner, Peggy S.; Hyun, Jungmoon; O'Connor Wells, Barbara; Anema, Inge; Goral, Mira; Monereau-Merry, Marie-Michelle; Rubino, Daniel; Kuckuk, Raija; Obler, Loraine K.

    2011-01-01

    To investigate whether idiom production was vulnerable to age-related difficulties, we asked 40 younger (ages 18-30) and 40 older healthy adults (ages 60-85) to produce idiomatic expressions in a story-completion task. Younger adults produced significantly more correct idiom responses (73%) than did older adults (60%). When older adults generated…

  10. Age-Related Factors in Second Language Acquisition.

    ERIC Educational Resources Information Center

    Twyford, Charles William

    The convergence of several lines of psycholinguistic and sociolinguistic research suggests possible explanations for age-related influences on language acquisition. These factors, which include cognitive development, sociocultural context, affective factors, and language input, can be helpful to language educators. By being alert to the cognitive…

  11. A Context for Teaching Aging-Related Public Policy.

    ERIC Educational Resources Information Center

    Brown, David K.

    1999-01-01

    Describes two points of view regarding age-related public programs (Medicaid, Medicare, Social Security): that of devolutionists who would curtail them and safety netters who maintain the government's role is indispensable. Uses Relative Deprivation theory as a framework for teaching public policy about aging. (SK)

  12. Age-Related Differences in the Production of Textual Descriptions

    ERIC Educational Resources Information Center

    Marini, Andrea; Boewe, Anke; Caltagirone, Carlo; Carlomagno, Sergio

    2005-01-01

    Narratives produced by 69 healthy Italian adults were analyzed for age-related changes of microlinguistic, macrolinguistic and informative aspects. The participants were divided into five age groups (20-24, 25-39, 40-59, 60-74, 75-84). One single-picture stimulus and two cartoon sequences were used to elicit three stories per subject. Age-related…

  13. Managed care implications of age-related ocular conditions.

    PubMed

    Cardarelli, William J; Smith, Roderick A

    2013-05-01

    The economic costs of age-related ocular diseases and vision loss are increasing rapidly as our society ages. In addition to the direct costs of treating age-related eye diseases, elderly persons with vision loss are at significantly increased risk for falls and fractures, experiencing social isolation, and suffering from an array of comorbid medical conditions compared with individuals with normal vision. Recent studies estimate the total economic burden (direct and indirect costs) of adult vision impairment in the United States at $51.4 billion. This figure is expected to increase as the baby boomer generation continues to age. While a number of highly effective new therapies have caused a paradigm shift in the management of several major age-related ocular diseases in recent years, these treatments come at a substantial cost. This article reviews the economic burdens and treatment-related costs of 4 major ocular diseases of aging-glaucoma, age-related macular degeneration, diabetic retinopathy, and dry eye disease-and the implications for managed care.

  14. Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

    2012-01-01

    Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

  15. The Experience of Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Wong, Elaine Y. H.; Guymer, Robyn H.; Hassell, Jennifer B.; Keeffe, Jill E.

    2004-01-01

    This qualitative article describes the impact of age-related macular degeneration (ARMD) among 15 participants: how a person makes sense of ARMD, the effect of ARMD on the person's quality of life, the psychological disturbances associated with the limitations of ARMD, and the influence of ARMD on social interactions. Such in-depth appreciation of…

  16. Nutritional influences on epigenetics and age-related disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutritional epigenetics has emerged as a novel mechanism underlying gene–diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modu...

  17. Age-Related Differences in Moral Identity across Adulthood

    ERIC Educational Resources Information Center

    Krettenauer, Tobias; Murua, Lourdes Andrea; Jia, Fanli

    2016-01-01

    In this study, age-related differences in adults' moral identity were investigated. Moral identity was conceptualized a context-dependent self-structure that becomes differentiated and (re)integrated in the course of development and that involves a broad range of value-orientations. Based on a cross-sectional sample of 252 participants aged 14 to…

  18. Neuroanatomical Substrates of Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Salthouse, Timothy A.

    2011-01-01

    There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the…

  19. Nutritional modulation of age-related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated wi...

  20. Age-Related Health Stereotypes and Illusory Correlation

    ERIC Educational Resources Information Center

    Madey, Scott F.; Chasteen, Alison L.

    2004-01-01

    This experiment investigated how age-related health stereotypes affect people's judgments of younger and older patients' medical compliance. Previous research has shown that stereotypes of young adults include healthy components, but stereotypes of older adults include both healthy and unhealthy components (Hummert, 1990). We predicted that…

  1. Photo-damage, photo-protection and age-related macular degeneration.

    PubMed

    Marquioni-Ramella, Melisa D; Suburo, Angela M

    2015-09-26

    Age-related macular degeneration (AMD) is a degenerative retinal disease that causes blindness in people 60-65 years and older, with the highest prevalence appearing in people 90 years-old or more. Epidemiological estimates indicate that the number of cases is increasing, and will almost double in the next 20 years. Preventive measures require precise etiological knowledge. This is quite difficult, since AMD is a multifactorial condition with intricate relationships between causes and risk factors. In this review, we describe the impact of light on the structure and physiology of the retina and the pigment epithelium, taking into account the continuous exposure to natural and artificial light sources along the life of an individual. A large body of experimental evidence demonstrates the toxic effects of some lighting conditions on the retina and the pigment epithelium, and consensus exists about the importance of photo-oxidation phenomena in the causality chain between light and retinal damage. Here, we analyzed the transmission of light to the retina, and compared the aging human macula in healthy and diseased retinas, as shown by histology and non-invasive imaging systems. Finally, we have compared the putative retinal photo-sensitive molecular structures that might be involved in the genesis of AMD. The relationship between these compounds and retinal damage supports the hypothesis of light as an important initiating cause of AMD.

  2. Comparison of Informal Care Time and Costs in Different Age-Related Dementias: A Review

    PubMed Central

    Costa, Nadège; Ferlicoq, Laura; Derumeaux-Burel, Hélène; Rapp, Thomas; Garnault, Valérie; Gillette-Guyonnet, Sophie; Andrieu, Sandrine; Vellas, Bruno; Lamure, Michel; Grand, Alain; Molinier, Laurent

    2013-01-01

    Objectives. Age-related dementia is a progressive degenerative brain syndrome whose prevalence increases with age. Dementias cause a substantial burden on society and on families who provide informal care. This study aims to review the relevant papers to compare informal care time and costs in different dementias. Methods. A bibliographic search was performed on an international medical literature database (MEDLINE). All studies which assessed the social economic burden of different dementias were selected. Informal care time and costs were analyzed in three care settings by disease stages. Results. 21 studies met our criteria. Mean informal care time was 55.73 h per week for Alzheimer disease and 15.8 h per week for Parkinson disease (P = 0.0076), and the associated mean annual informal costs were $17,492 versus $3,284, respectively (P = 0.0393). Conclusion. There is a lack of data about informal care time and costs among other dementias than AD or PD. Globally, AD is the most costly in terms of informal care costs than PD, $17,492 versus $3,284, respectively. PMID:23509789

  3. Photo-damage, photo-protection and age-related macular degeneration.

    PubMed

    Marquioni-Ramella, Melisa D; Suburo, Angela M

    2015-09-26

    Age-related macular degeneration (AMD) is a degenerative retinal disease that causes blindness in people 60-65 years and older, with the highest prevalence appearing in people 90 years-old or more. Epidemiological estimates indicate that the number of cases is increasing, and will almost double in the next 20 years. Preventive measures require precise etiological knowledge. This is quite difficult, since AMD is a multifactorial condition with intricate relationships between causes and risk factors. In this review, we describe the impact of light on the structure and physiology of the retina and the pigment epithelium, taking into account the continuous exposure to natural and artificial light sources along the life of an individual. A large body of experimental evidence demonstrates the toxic effects of some lighting conditions on the retina and the pigment epithelium, and consensus exists about the importance of photo-oxidation phenomena in the causality chain between light and retinal damage. Here, we analyzed the transmission of light to the retina, and compared the aging human macula in healthy and diseased retinas, as shown by histology and non-invasive imaging systems. Finally, we have compared the putative retinal photo-sensitive molecular structures that might be involved in the genesis of AMD. The relationship between these compounds and retinal damage supports the hypothesis of light as an important initiating cause of AMD. PMID:26198091

  4. Melatonin in Retinal Physiology and Pathology: The Case of Age-Related Macular Degeneration

    PubMed Central

    Reiter, Russel J.; Kaarniranta, Kai

    2016-01-01

    Melatonin, an indoleamine, is synthesized mainly in the pineal gland in a circadian fashion, but it is produced in many other organs, including the retina, which seems to be especially important as the eye is a primary recipient of circadian signals. Melatonin displays strong antioxidative properties, which predispose it to play a protective role in many human pathologies associated with oxidative stress, including premature aging and degenerative disease. Therefore, melatonin may play a role in age-related macular degeneration (AMD), a disease affecting photoreceptors, and retinal pigment epithelium (RPE) with an established role of oxidative stress in its pathogenesis. Several studies have shown that melatonin could exert the protective effect against damage to RPE cells evoked by reactive oxygen species (ROS), but it has also been reported to increase ROS-induced damage to photoreceptors and RPE. Melatonin behaves like synthetic mitochondria-targeted antioxidants, which concentrate in mitochondria at relatively high levels; thus, melatonin may prevent mitochondrial damage in AMD. The retina contains telomerase, an enzyme implicated in maintaining the length of telomeres, and oxidative stress inhibits telomere synthesis, while melatonin overcomes this effect. These features support considering melatonin as a preventive and therapeutic agent in the treatment of AMD.

  5. Immune Responses in Age Related Macular Degeneration and a possible Long Term Therapeutic Strategy for Prevention

    PubMed Central

    Nussenblatt, Robert B.; Lee, Richard W.J.; Chew, Emily; Wei, Lai; Liu, Baoying; Sen, Nida; Dick, Andrew D.; Ferris, Frederick L.

    2014-01-01

    Purpose To describe the immune alterations associated with, age related macular degeneration (AMD). Based on these findings, to offer an approach to possibly prevent the expression of late disease. Design Perspective Methods Review of the existing literature dealing with epidemiology, models, and immunologic findings in patients. Results Significant genetic associations have been identified and reported, but environmentally induced (including epigenetic) changes are also an important consideration. Immune alterations include a strong interleukin-17 family signature as well as marked expression of these molecules in the eye. Oxidative stress as well as other homeostatic altering mechanisms occurs throughout life. With this immune dysregulation there is a rationale for considering immunotherapy. Indeed immunotherapy has been shown to affect the late stages of AMD. Conclusion Immune dysregulation appears to be an underlying alteration in AMD as in other diseases thought to be degenerative and due to aging. Parainflammation and immunosensescence may importantly contribute to the development of disease. The role of complement factor H still needs to be better defined but in light of its association with ocular inflammatory conditions such as sarcoidosis, it does not appear to be unique to AMD but rather may be a marker for retinal pigment epithelium function. With the strong interleukin-17 family signature and the need to treat early on in the disease process, oral tolerance may be considered to prevent disease progression. PMID:24709810

  6. Age-related macular degeneration: a target for nanotechnology derived medicines

    PubMed Central

    Birch, David G; Liang, Fong Qi

    2007-01-01

    Despite the fact that the retina is a fairly accessible portion of the central nervous system, there are virtually no treatments for early age-related macular degeneration (AMD). AMD is a degenerative retinal disease that causes progressive loss of central vision and is the leading cause of irreversible vision loss and legal blindness in individuals over the age of 50. Both environmental and genetic components play a role in its development. AMD is a multifactorial disease with characteristics that include drusen, hyperpigmentation and/or hypopigmentation of the retinal pigment epithelium (RPE), geographic atrophy and, in a subset of patients, late-stage choroidal neovascularization (CNV). Drugs that inhibit vascular endothelial growth factor (VEGF) have proven effective in treating late-stage CNV, but optimal means of drug delivery remains to be determined. Microscopic particles, whose size is on the nanometer scale, show considerable promise for drug delivery to the retina, for gene therapy, and for powering prosthetic “artificial retinas.” This article summarizes the pathophysiology of AMD stressing potential applications from nanotechnology. PMID:17722514

  7. Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis.

    PubMed

    O'Conor, Christopher J; Ramalingam, Sendhilnathan; Zelenski, Nicole A; Benefield, Halei C; Rigo, Isaura; Little, Dianne; Wu, Chia-Lung; Chen, Di; Liedtke, Wolfgang; McNulty, Amy L; Guilak, Farshid

    2016-01-01

    Osteoarthritis (OA) is a progressive degenerative disease of articular cartilage and surrounding tissues, and is associated with both advanced age and joint injury. Biomechanical factors play a critical role in the onset and progression of OA, yet the mechanisms through which physiologic or pathologic mechanical signals are transduced into a cellular response are not well understood. Defining the role of mechanosensory pathways in cartilage during OA pathogenesis may yield novel strategies or targets for the treatment of OA. The transient receptor potential vanilloid 4 (TRPV4) ion channel transduces mechanical loading of articular cartilage via the generation of intracellular calcium ion transients. Using tissue-specific, inducible Trpv4 gene-targeted mice, we demonstrate that loss of TRPV4-mediated cartilage mechanotransduction in adulthood reduces the severity of aging-associated OA. However, loss of chondrocyte TRPV4 did not prevent OA development following destabilization of the medial meniscus (DMM). These results highlight potentially distinct roles of TRPV4-mediated cartilage mechanotransduction in age-related and post-traumatic OA, and point to a novel disease-modifying strategy to therapeutically target the TRPV4-mediated mechanotransduction pathway for the treatment of aging-associated OA. PMID:27388701

  8. Melatonin in Retinal Physiology and Pathology: The Case of Age-Related Macular Degeneration

    PubMed Central

    Reiter, Russel J.; Kaarniranta, Kai

    2016-01-01

    Melatonin, an indoleamine, is synthesized mainly in the pineal gland in a circadian fashion, but it is produced in many other organs, including the retina, which seems to be especially important as the eye is a primary recipient of circadian signals. Melatonin displays strong antioxidative properties, which predispose it to play a protective role in many human pathologies associated with oxidative stress, including premature aging and degenerative disease. Therefore, melatonin may play a role in age-related macular degeneration (AMD), a disease affecting photoreceptors, and retinal pigment epithelium (RPE) with an established role of oxidative stress in its pathogenesis. Several studies have shown that melatonin could exert the protective effect against damage to RPE cells evoked by reactive oxygen species (ROS), but it has also been reported to increase ROS-induced damage to photoreceptors and RPE. Melatonin behaves like synthetic mitochondria-targeted antioxidants, which concentrate in mitochondria at relatively high levels; thus, melatonin may prevent mitochondrial damage in AMD. The retina contains telomerase, an enzyme implicated in maintaining the length of telomeres, and oxidative stress inhibits telomere synthesis, while melatonin overcomes this effect. These features support considering melatonin as a preventive and therapeutic agent in the treatment of AMD. PMID:27688828

  9. Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis

    PubMed Central

    O’Conor, Christopher J.; Ramalingam, Sendhilnathan; Zelenski, Nicole A.; Benefield, Halei C.; Rigo, Isaura; Little, Dianne; Wu, Chia-Lung; Chen, Di; Liedtke, Wolfgang; McNulty, Amy L.; Guilak, Farshid

    2016-01-01

    Osteoarthritis (OA) is a progressive degenerative disease of articular cartilage and surrounding tissues, and is associated with both advanced age and joint injury. Biomechanical factors play a critical role in the onset and progression of OA, yet the mechanisms through which physiologic or pathologic mechanical signals are transduced into a cellular response are not well understood. Defining the role of mechanosensory pathways in cartilage during OA pathogenesis may yield novel strategies or targets for the treatment of OA. The transient receptor potential vanilloid 4 (TRPV4) ion channel transduces mechanical loading of articular cartilage via the generation of intracellular calcium ion transients. Using tissue-specific, inducible Trpv4 gene-targeted mice, we demonstrate that loss of TRPV4-mediated cartilage mechanotransduction in adulthood reduces the severity of aging-associated OA. However, loss of chondrocyte TRPV4 did not prevent OA development following destabilization of the medial meniscus (DMM). These results highlight potentially distinct roles of TRPV4-mediated cartilage mechanotransduction in age-related and post-traumatic OA, and point to a novel disease-modifying strategy to therapeutically target the TRPV4-mediated mechanotransduction pathway for the treatment of aging-associated OA. PMID:27388701

  10. Antibody therapies and their challenges in the treatment of age-related macular degeneration.

    PubMed

    Volz, Cornelia; Pauly, Diana

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the western world. This multifactorial disease results from the combined contributions of age, environment and genetic predisposition. Antibody-based treatment of late-stage neovascular AMD with inhibitors of vascular endothelial growth factor has had great success, which is now the goal for currently untreatable AMD manifestations. The existence of an immune-privileged environment in the eye supports the feasibility of localized antibody therapy. Many different antibodies against various targets are being developed for the treatment of AMD, which reflects the etiological complexity of the disease. This review provides an overview of 19 potential therapeutic antibodies targeting angiogenesis, the complement system, inflammation or amyloid beta deposition in the eye. It summarizes the immunoglobulin structure, the specific target and study outcomes for each approach. The latter include beneficial results or adverse effects in AMD models and patients. Finally, this article discusses the challenges in the development of antibody-based drugs to treat degenerative processes in the posterior eye. In spite of these difficulties, to date, the following four antibodies have overcome the technical and preclinical hurdles and are being tested in active clinical studies: Lampalizumab, Sonepcizumab, GSK933776 and LFG316. We conclude that, while there are some antibody-based drugs that have made it into clinical practice, a successful transfer from bench to beside is still pending for many promising approaches.

  11. Age-Related Changes in 1/f Neural Electrophysiological Noise

    PubMed Central

    Kramer, Mark A.; Case, John; Lepage, Kyle Q.; Tempesta, Zechari R.; Knight, Robert T.; Gazzaley, Adam

    2015-01-01

    Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15–53 years) and scalp EEG data from healthy younger (20–30 years) and older (60–70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <−1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging. SIGNIFICANCE STATEMENT Understanding the neurobiological origins of age-related cognitive decline is of critical scientific, medical, and public health importance, especially considering the rapid aging of the world's population. We find, in two separate human studies, that 1/f electrophysiological noise increases with aging. In addition, we observe that this age-related 1/f noise statistically mediates age-related working memory decline. These results significantly add to this understanding and contextualize a long-standing problem in cognition by encapsulating age-related cognitive decline within a neurocomputational model of 1/f noise

  12. Age-Related Changes in 1/f Neural Electrophysiological Noise.

    PubMed

    Voytek, Bradley; Kramer, Mark A; Case, John; Lepage, Kyle Q; Tempesta, Zechari R; Knight, Robert T; Gazzaley, Adam

    2015-09-23

    Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15-53 years) and scalp EEG data from healthy younger (20-30 years) and older (60-70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <-1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging. Significance statement: Understanding the neurobiological origins of age-related cognitive decline is of critical scientific, medical, and public health importance, especially considering the rapid aging of the world's population. We find, in two separate human studies, that 1/f electrophysiological noise increases with aging. In addition, we observe that this age-related 1/f noise statistically mediates age-related working memory decline. These results significantly add to this understanding and contextualize a long-standing problem in cognition by encapsulating age-related cognitive decline within a neurocomputational model of 1/f noise-induced deficits in

  13. Age Related Differences of Executive Functioning Problems in Everyday Life of Children and Adolescents in the Autism Spectrum

    ERIC Educational Resources Information Center

    van den Bergh, Sanne F. W. M.; Scheeren, Anke M.; Begeer, Sander; Koot, Hans M.; Geurts, Hilde M.

    2014-01-01

    Numerous studies investigated executive functioning (EF) problems in people with autism spectrum disorders (ASD) using laboratory EF tasks. As laboratory task performances often differ from real life observations, the current study focused on EF in everyday life of 118 children and adolescents with ASD (6-18 years). We investigated age-related and…

  14. Susceptibility genes and pharmacogenetics in ocular inflammatory disorders.

    PubMed

    Liu, Baoying; Sen, H Nida; Nussenblatt, Robert

    2012-10-01

    Ocular inflammatory disorders encompass uveitis, scleritis, keratitis, and other ocular diseases where inflammation may play a role. Although age-related macular degeneration (AMD) is clinically characterized by degenerative changes in the macula, accumulating evidence suggests that inflammation plays an important role in its pathogenesis. Pharmacogenetics is the study of the influence of genetic variation and its effects on drug efficacy or toxicity. There are no pharmacogenetic studies in uveitis and very few in AMD therapies. In this review, the authors describe the susceptibility genes related to uveitis and AMD and the important advances in pharmacogenetic research in relation to AMD and uveitis therapy. They propose polygenic and composite models of treatment responses to fulfill individualized drug therapy in intraocular inflammatory disorders. PMID:22974049

  15. Stem cell transplantation improves aging-related diseases

    PubMed Central

    Ikehara, Susumu; Li, Ming

    2014-01-01

    Aging is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. The number of patients with age-associated diseases such as type 2 diabetes mellitus (T2DM), osteoporosis, Alzheimer's disease (AD), Parkinson's disease, atherosclerosis, and cancer has increased recently. Aging-related diseases are related to a deficiency of the immune system, which results from an aged thymus and bone marrow cells. Intra bone marrow-bone marrow transplantation (IBM-BMT) is a useful method to treat intractable diseases. This review summarizes findings that IBM-BMT can improve and treat aging-related diseases, including T2DM, osteoporosis and AD, in animal models. PMID:25364723

  16. Veterans have less age-related cognitive decline.

    PubMed

    McLay, R N; Lyketsos, C G

    2000-08-01

    Military service involves exposure to a number of stresses, both psychological and physical. On the other hand, military personnel generally maintain excellent fitness, and veterans have increased access to education and health care. The overall effect on age-related cognitive decline, whether for good or ill, of having served in the armed forces has not been investigated previously. In this study, we examined a diverse population of 208 veterans and 1,216 civilians followed as part of the Epidemiologic Catchment Area Study in 1981, 1982, and 1993 to 1996. We examined change in Mini-Mental State Examination (MMSE) score after a median of 11.5 years. Veterans were found to have significantly less decrease in MMSE scores at follow-up even after sex, race, and education were taken into account. These results suggest an overall positive effect of military service on the rate of age-related cognitive decline. PMID:10957857

  17. Age-related cochlear hair cell loss in the chinchilla.

    PubMed

    Bhattacharyya, T K; Dayal, V S

    1985-01-01

    The spiral organ of the chinchilla was studied by the surface-preparation technique in four different age groups: 1 month, 6 months, 1 year, and 4 years, to assess age-related hair cell loss. Decrease in hair cell population is linearly related to age, and damage rate of outer hair cells is greater than that of inner hair cells. The mean percentage of damaged total outer hair cells was 0.60%, 1.16%, 1.71%, and 7.07% in animals in 1 month, 6 months, 1 year, and 4 years of age, respectively. Outer hair cell loss was greatest in the apex of the cochlea and, of these cells, the outermost row was the most affected. Damage to inner hair cells also increases with age. Age-related apical cochlear cell loss in the chinchilla is comparable to that observed in other laboratory animals. PMID:3970507

  18. Ageism, age relations, and garment industry work in Montreal.

    PubMed

    McMullin, J A; Marshall, V W

    2001-02-01

    This study examined the complexities of age relations at work. Garment workers believed that their fate was linked to ageism and that their work experience was discounted by management. Managers wanted to be rid of older workers because they commanded higher wages than younger workers. The issue was cost reduction, and age was implicated unintendedly. Still, managers seemed to use stereotypical images to discourage older workers and they did not organize work routines to facilitate the adaptation of them. Instead, they subcontracted the easy jobs, relying on the experience of the older employees for difficult work while not adapting the workplace. Theoretically, the authors argue that ageism and age discrimination can best be understood through a recognition of the importance of structured age relations and human agency.

  19. Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases

    PubMed Central

    Zhou, Ren-Peng; Wu, Xiao-Shan; Wang, Zhi-Sen; Xie, Ya-Ya; Ge, Jin-Fang; Chen, Fei-Hu

    2016-01-01

    Degenerative diseases often strike older adults and are characterized by progressive deterioration of cells, eventually leading to tissue and organ degeneration for which limited effective treatment options are currently available. Acid-sensing ion channels (ASICs), a family of extracellular H+-activated ligand-gated ion channels, play critical roles in physiological and pathological conditions. Aberrant activation of ASICs is reported to regulate cell apoptosis, differentiation and autophagy. Accumulating evidence has highlighted a dramatic increase and activation of ASICs in degenerative disorders, including multiple sclerosis, Parkinson’s disease, Huntington’s disease, intervertebral disc degeneration and arthritis. In this review, we have comprehensively discussed the critical roles of ASICs and their potential utility as therapeutic targets in degenerative diseases. PMID:27493834

  20. Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases.

    PubMed

    Zhou, Ren-Peng; Wu, Xiao-Shan; Wang, Zhi-Sen; Xie, Ya-Ya; Ge, Jin-Fang; Chen, Fei-Hu

    2016-08-01

    Degenerative diseases often strike older adults and are characterized by progressive deterioration of cells, eventually leading to tissue and organ degeneration for which limited effective treatment options are currently available. Acid-sensing ion channels (ASICs), a family of extracellular H(+)-activated ligand-gated ion channels, play critical roles in physiological and pathological conditions. Aberrant activation of ASICs is reported to regulate cell apoptosis, differentiation and autophagy. Accumulating evidence has highlighted a dramatic increase and activation of ASICs in degenerative disorders, including multiple sclerosis, Parkinson's disease, Huntington's disease, intervertebral disc degeneration and arthritis. In this review, we have comprehensively discussed the critical roles of ASICs and their potential utility as therapeutic targets in degenerative diseases. PMID:27493834

  1. Smoking and Age-Related Macular Degeneration: Review and Update

    PubMed Central

    Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Pons-Vázquez, Sheila; Pinazo-Durán, M. Dolores; Gómez-Ulla, Francisco; Arévalo, J. Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

    2013-01-01

    Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health. PMID:24368940

  2. Age-related changes in ultra-triathlon performances

    PubMed Central

    2012-01-01

    Background The age-related decline in performance has been investigated in swimmers, runners and triathletes. No study has investigated the age-related performance decline in ultra-triathletes. The purpose of this study was to analyse the age-related declines in swimming, cycling, running and overall race time for both Triple Iron ultra-triathlon (11.4-km swimming, 540-km cycling and 126.6-km running) and Deca Iron ultra-triathlon (38-km swimming, 1,800-km cycling and 420-km running). Methods The age and performances of 423 male Triple Iron ultra-triathletes and 119 male Deca Iron ultra-triathletes were analysed from 1992 to 2010 using regression analyses and ANOVA. Results The mean age of the finishers was significantly higher for Deca Iron ultra-triathletes (41.3 ± 3.1 years) compared to a Triple Iron ultra-triathletes (38.5 ± 3.3 years) (P < 0.05). For both ultra-distances, the fastest overall race times were achieved between the ages of 25 and 44 years. Deca Iron ultra-triathletes achieved the same level of performance in swimming and cycling between 25 and 54 years of age. Conclusions The magnitudes of age-related declines in performance in the three disciplines of ultra-triathlon differ slightly between Triple and Deca Iron ultra-triathlon. Although the ages of Triple Iron ultra-triathletes were on average younger compared to Deca Iron ultra-triathletes, the fastest race times were achieved between 25 and 44 years for both distances. Further studies should investigate the motivation and training of ultra-triathletes to gain better insights in ultra-triathlon performance. PMID:23849327

  3. Hhip haploinsufficiency sensitizes mice to age-related emphysema.

    PubMed

    Lao, Taotao; Jiang, Zhiqiang; Yun, Jeong; Qiu, Weiliang; Guo, Feng; Huang, Chunfang; Mancini, John Dominic; Gupta, Kushagra; Laucho-Contreras, Maria E; Naing, Zun Zar Chi; Zhang, Li; Perrella, Mark A; Owen, Caroline A; Silverman, Edwin K; Zhou, Xiaobo

    2016-08-01

    Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip(+/-)), we observed increased lung compliance and spontaneous emphysema in Hhip(+/-) mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip(+/-) vs. Hhip(+/+) mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip(+/-) mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip(+/-) mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip(+/-) mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip. PMID:27444019

  4. Later developments: molecular keys to age-related memory impairment.

    PubMed

    Barad, Mark

    2003-01-01

    Age-related memory impairment, a cognitive decline not clearly related to any gross pathology, is progressive and widespread in the population, although not universal. While the mechanisms of learning and memory remain incompletely understood, the study of their molecular mechanisms is already yielding promising approaches toward therapy for such "normal" declines in the efficiency of learning. This review presents the rationale and results for two such approaches. One approach, partial inhibition of the type IV cAMP specific phosphodiesterase, appears to act indirectly. Although little evidence supports an age-related decline in this system, considerable evidence indicates that this approach can facilitate the transition from short-term to long-term memory and thus counterbalance defects in long-term memory, which may be due to other causes. A second approach, inhibition of l-type voltage gated calcium channels (LVGCCs) may be a specific corrective for a molecular pathology of aging, as substantial evidence indicates that an ongoing increase occurs throughout the lifespan in the density of these channels in hippocampal pyramidal cells, with a concomitant reduction in cellular excitability. Because LVGCCs are also crucial to extinction, a paradigm of inhibitory learning, age-related memory impairment may be an unfortunate side effect of a developmental process necessary to the maturation of the ability to suppress inappropriate behavior, an interpretation consistent with the antagonistic pleiotropy theory of aging.

  5. Age related alterations of adrenoreceptor activity in erythrocyte membrane.

    PubMed

    Lomsadze, G; Khetsuriani, R; Arabuli, M; Intskirveli, N; Sanikidze, T

    2011-06-01

    The aim of the study was the investigation of age-related functional alterations of adrenoreceptors and the effect of agonist and antagonist drugs on age related adrenoreceptor activity in erythrocyte membrane. The impact of isopropanol and propanol on functional activity β- adrenergic receptors in red blood cell membrane were studied in 50 practically healthy men--volunteers. (I group--75-89 years old, II group--22-30 years old). The EPR signals S1 and S2 were registered in red blood cell membrane samples after incubation with isopropanol and propanol respectively. It was found that decreasing sensitivity (functional activity) of red blood cells membrane adrenoreceptors comes with aging (S1oldage-related hypertension, heart failure, type II diabetes and other diseases, The findings suggests that the erythrocyte could be a new therapeutic marker in the treatment different diseases.

  6. Telomere length variations in aging and age-related diseases.

    PubMed

    Rizvi, Saliha; Raza, Syed Tasleem; Mahdi, Farzana

    2014-01-01

    Telomeres are gene sequences present at chromosomal ends and are responsible for maintaining genome integrity. Telomere length is maximum at birth and decreases progressively with advancing age and thus is considered as a biomarker of chronological aging. This age associated decrease in the length of telomere is linked to various ageing associated diseases like diabetes, hypertension, Alzheimer's disease, cancer etc. and their associated complications. Telomere length is a result of combined effect of oxidative stress, inflammation and repeated cell replication on it, and thus forming an association between telomere length and chronological aging and related diseases. Thus, decrease in telomere length was found to be important in determining both, the variations in longevity and age-related diseases in an individual. Ongoing and progressive research in the field of telomere length dynamics has proved that aging and age-related diseases apart from having a synergistic effect on telomere length were also found to effect telomere length independently also. Here a short description about telomere length variations and its association with human aging and age-related diseases is reviewed.

  7. Adverse environmental conditions influence age-related innate immune responsiveness

    PubMed Central

    May, Linda; van den Biggelaar, Anita HJ; van Bodegom, David; Meij, Hans J; de Craen, Anton JM; Amankwa, Joseph; Frölich, Marijke; Kuningas, Maris; Westendorp, Rudi GJ

    2009-01-01

    Background- The innate immune system plays an important role in the recognition and induction of protective responses against infectious pathogens, whilst there is increasing evidence for a role in mediating chronic inflammatory diseases at older age. Despite indications that environmental conditions can influence the senescence process of the adaptive immune system, it is not known whether the same holds true for the innate immune system. Therefore we studied whether age-related innate immune responses are similar or differ between populations living under very diverse environmental conditions. Methods- We compared cross-sectional age-related changes in ex vivo innate cytokine responses in a population living under affluent conditions in the Netherlands (age 20–68 years old, n = 304) and a population living under adverse environmental conditions in Ghana (age 23–95 years old, n = 562). Results- We found a significant decrease in LPS-induced Interleukin (IL)-10 and Tumor Necrosis Factor (TNF) production with age in the Dutch population. In Ghana a similar age-related decline in IL-10 responses to LPS, as well as to zymosan, or LPS plus zymosan, was observed. TNF production, however, did not show an age-associated decline, but increased significantly with age in response to co-stimulation with LPS and zymosan. Conclusion- We conclude that the decline in innate cytokine responses is an intrinsic ageing phenomenon, while pathogen exposure and/or selective survival drive pro-inflammatory responses under adverse living conditions. PMID:19480711

  8. Soybean β-Conglycinin Prevents Age-Related Hearing Impairment.

    PubMed

    Tanigawa, Tohru; Shibata, Rei; Kondo, Kazuhisa; Katahira, Nobuyuki; Kambara, Takahiro; Inoue, Yoko; Nonoyama, Hiroshi; Horibe, Yuichiro; Ueda, Hiromi; Murohara, Toyoaki

    2015-01-01

    Obesity-related complications are associated with the development of age-related hearing impairment. β-Conglycinin (β-CG), one of the main storage proteins in soy, offers multiple health benefits, including anti-obesity and anti-atherosclerotic effects. Here, to elucidate the potential therapeutic application of β-CG, we investigated the effect of β-CG on age-related hearing impairment. Male wild-type mice (age 6 months) were randomly divided into β-CG-fed and control groups. Six months later, the body weight was significantly lower in β-CG-fed mice than in the controls. Consumption of β-CG rescued the hearing impairment observed in control mice. Cochlear blood flow also increased in β-CG-fed mice, as did the expression of eNOS in the stria vascularis (SV), which protects vasculature. β-CG consumption also ameliorated oxidative status as assessed by 4-HNE staining. In the SV, lipofuscin granules of marginal cells and vacuolar degeneration of microvascular pericytes were decreased in β-CG-fed mice, as shown by transmission electron microscopy. β-CG consumption prevented loss of spiral ganglion cells and reduced the frequencies of lipofuscin granules, nuclear invaginations, and myelin vacuolation. Our observations indicate that β-CG ameliorates age-related hearing impairment by preserving cochlear blood flow and suppressing oxidative stress.

  9. The impact of base excision DNA repair in age-related neurodegenerative diseases.

    PubMed

    Leandro, Giovana S; Sykora, Peter; Bohr, Vilhelm A

    2015-06-01

    The aging process and several age-related neurodegenerative disorders have been linked to elevated levels of DNA damage induced by ROS and deficiency in DNA repair mechanisms. DNA damage induced by ROS is a byproduct of cellular respiration and accumulation of damage over time, is a fundamental aspect of a main theory of aging. Mitochondria have a pivotal role in generating cellular oxidative stress, and mitochondrial dysfunction has been associated with several diseases. DNA base excision repair is considered the major pathway for repair of oxidized bases in DNA both in the nuclei and in mitochondria, and in neurons this mechanism is particularly important because non-diving cells have limited back-up DNA repair mechanisms. An association between elevated oxidative stress and a decrease in BER is strongly related to the aging process and has special relevance in age-related neurodegenerative diseases. Here, we review the role of DNA repair in aging, focusing on the implications of the DNA base excision repair pathways and how alterations in expression of these DNA repair proteins are related to the aging process and to age-related neurodegenerative diseases.

  10. Identification of MOAG-4/SERF as a regulator of age-related proteotoxicity.

    PubMed

    van Ham, Tjakko J; Holmberg, Mats A; van der Goot, Annemieke T; Teuling, Eva; Garcia-Arencibia, Moises; Kim, Hyun-eui; Du, Deguo; Thijssen, Karen L; Wiersma, Marit; Burggraaff, Rogier; van Bergeijk, Petra; van Rheenen, Jeroen; Jerre van Veluw, G; Hofstra, Robert M W; Rubinsztein, David C; Nollen, Ellen A A

    2010-08-20

    Fibrillar protein aggregates are the major pathological hallmark of several incurable, age-related, neurodegenerative disorders. These aggregates typically contain aggregation-prone pathogenic proteins, such as amyloid-beta in Alzheimer's disease and alpha-synuclein in Parkinson's disease. It is, however, poorly understood how these aggregates are formed during cellular aging. Here we identify an evolutionarily highly conserved modifier of aggregation, MOAG-4, as a positive regulator of aggregate formation in C. elegans models for polyglutamine diseases. Inactivation of MOAG-4 suppresses the formation of compact polyglutamine aggregation intermediates that are required for aggregate formation. The role of MOAG-4 in driving aggregation extends to amyloid-beta and alpha-synuclein and is evolutionarily conserved in its human orthologs SERF1A and SERF2. MOAG-4/SERF appears to act independently from HSF-1-induced molecular chaperones, proteasomal degradation, and autophagy. Our results suggest that MOAG-4/SERF regulates age-related proteotoxicity through a previously unexplored pathway, which will open up new avenues for research on age-related, neurodegenerative diseases.

  11. Age-related structural and functional changes in the cochlear nucleus.

    PubMed

    Frisina, Robert D; Walton, Joseph P

    2006-01-01

    Presbycusis - age-related hearing loss - is a key communication disorder and chronic medical condition of our aged population. The cochlear nucleus is the major site of projections from the auditory portion of the inner ear. Relative to other levels of the peripheral and central auditory systems, relatively few studies have been conducted examining age-related changes in the cochlear nucleus. The neurophysiological investigations suggest declines in glycine-mediated inhibition, reflected in increased firing rates in cochlear nucleus neurons from old animals relative to young adults. Biochemical investigations of glycine inhibition in the cochlear nucleus are consistent with the functional aging declines of this inhibitory neurotransmitter system that affect complex sound processing. Anatomical reductions in neurons of the cochlear nucleus and their output pathways can occur due to aging changes in the brain, as well as due to age-dependent plasticity of the cochlear nucleus in response to the age-related loss of inputs from the cochlea, particularly from the basal, high-frequency regions. Novel preventative and curative biomedical interventions in the future aimed at alleviating the hearing loss that comes with age, will likely emanate from increasing our knowledge and understanding of its neural and molecular bases. To the extent that this sensory deficit resides in the central auditory system, including the cochlear nucleus, future neural therapies will be able to improve hearing in the elderly.

  12. Prevalence of Age-Related Changes in Ovine Lumbar Intervertebral Discs during Computed Tomography and Magnetic Resonance Imaging.

    PubMed

    Nisolle, Jean-François; Bihin, Benoît; Kirschvink, Nathalie; Neveu, Fabienne; Clegg, Peter; Dugdale, Alexandra; Wang, Xiaoqing; Vandeweerd, Jean-Michel

    2016-01-01

    Ovine models are used to study intervertebral disc (IVD) degeneration. The objective of the current study was to assess the naturally occurring age-related changes of the IVD that can be diagnosed by CT and MRI in the lumbar spine of sheep. We used CT and T2-weighted MR images to score the IVD (L6S1 to L1L2) in 41 sheep (age, 6 mo to 11 y) that were euthanized for reasons not related to musculoskeletal disease. T2 mapping and measurement of T2 time of L6S1 to L2L3 were performed in 22 of the sheep. Degenerative changes manifested as early as 2 y of age and occurred at every IVD level. Discs were more severely damaged in older sheep. The age effect of the L6S1 IVD was larger than the average age effect for the other IVD. The current study provides evidence that lesions similar to those encountered in humans can be identified by CT and MRI in lumbar spine of sheep. Ideally, research animals should be assessed at the initiation of preclinical trials to determine the extent of prevalent degenerative changes. The ovine lumbosacral disc seems particularly prone to degeneration and might be a favorable anatomic site for studying IVD degeneration.

  13. Prevalence of Age-Related Changes in Ovine Lumbar Intervertebral Discs during Computed Tomography and Magnetic Resonance Imaging.

    PubMed

    Nisolle, Jean-François; Bihin, Benoît; Kirschvink, Nathalie; Neveu, Fabienne; Clegg, Peter; Dugdale, Alexandra; Wang, Xiaoqing; Vandeweerd, Jean-Michel

    2016-01-01

    Ovine models are used to study intervertebral disc (IVD) degeneration. The objective of the current study was to assess the naturally occurring age-related changes of the IVD that can be diagnosed by CT and MRI in the lumbar spine of sheep. We used CT and T2-weighted MR images to score the IVD (L6S1 to L1L2) in 41 sheep (age, 6 mo to 11 y) that were euthanized for reasons not related to musculoskeletal disease. T2 mapping and measurement of T2 time of L6S1 to L2L3 were performed in 22 of the sheep. Degenerative changes manifested as early as 2 y of age and occurred at every IVD level. Discs were more severely damaged in older sheep. The age effect of the L6S1 IVD was larger than the average age effect for the other IVD. The current study provides evidence that lesions similar to those encountered in humans can be identified by CT and MRI in lumbar spine of sheep. Ideally, research animals should be assessed at the initiation of preclinical trials to determine the extent of prevalent degenerative changes. The ovine lumbosacral disc seems particularly prone to degeneration and might be a favorable anatomic site for studying IVD degeneration. PMID:27538861

  14. A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration.

    PubMed

    Schmidt-Erfurth, Ursula; Waldstein, Sebastian M

    2016-01-01

    Neovascular age-related macular degeneration (AMD) has undergone substantial break-throughs in diagnostic as well as therapeutic respect, with optical coherence tomography (OCT) allowing to identify disease morphology in great detail, and intravitreal anti-vascular endothelial growth factor therapy providing unprecedented benefit. However, these two paths have yet not been combined in an optimal way, real-world outcomes are inferior to expectations, and disease management is largely inefficient in the real-world setting. This dilemma can be solved by identification of valid biomarkers relevant for visual function, disease activity and prognosis, which can provide solid guidance for therapeutic management on an individual level as well as on the population base. Qualitative and quantitative morphological features obtained by advanced OCT provide novel insight into exudative and degenerative stages of neovascular AMD. However, conclusions from structure/function correlations evolve differently from previous paradigms. While central retinal thickness was used as biomarker for guiding retreatment management in clinical trials and practice, fluid localization in different compartments offers superior prognostic value: Intraretinal cystoid fluid has a negative impact on visual acuity and is considered as degenerative when persisting through the initial therapeutic interval. Subretinal fluid is associated with superior visual benefit and a lower rate of progression towards geographic atrophy. Detachment of the retinal pigment epithelium was identified as most pathognomonic biomarker, often irresponsive to therapy and responsible for visual decline during a pro-re-nata regimen. Alterations of neurosensory tissue are usually associated with irreversible loss of functional elements and a negative prognosis. Novel OCT technologies offer crucial insight into corresponding changes at the level of the photoreceptor--retinal pigment epithelial--choriocapillary unit, identifying

  15. A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration.

    PubMed

    Schmidt-Erfurth, Ursula; Waldstein, Sebastian M

    2016-01-01

    Neovascular age-related macular degeneration (AMD) has undergone substantial break-throughs in diagnostic as well as therapeutic respect, with optical coherence tomography (OCT) allowing to identify disease morphology in great detail, and intravitreal anti-vascular endothelial growth factor therapy providing unprecedented benefit. However, these two paths have yet not been combined in an optimal way, real-world outcomes are inferior to expectations, and disease management is largely inefficient in the real-world setting. This dilemma can be solved by identification of valid biomarkers relevant for visual function, disease activity and prognosis, which can provide solid guidance for therapeutic management on an individual level as well as on the population base. Qualitative and quantitative morphological features obtained by advanced OCT provide novel insight into exudative and degenerative stages of neovascular AMD. However, conclusions from structure/function correlations evolve differently from previous paradigms. While central retinal thickness was used as biomarker for guiding retreatment management in clinical trials and practice, fluid localization in different compartments offers superior prognostic value: Intraretinal cystoid fluid has a negative impact on visual acuity and is considered as degenerative when persisting through the initial therapeutic interval. Subretinal fluid is associated with superior visual benefit and a lower rate of progression towards geographic atrophy. Detachment of the retinal pigment epithelium was identified as most pathognomonic biomarker, often irresponsive to therapy and responsible for visual decline during a pro-re-nata regimen. Alterations of neurosensory tissue are usually associated with irreversible loss of functional elements and a negative prognosis. Novel OCT technologies offer crucial insight into corresponding changes at the level of the photoreceptor--retinal pigment epithelial--choriocapillary unit, identifying

  16. The Aging of the Global Population: The Changing Epidemiology of Disease and Spinal Disorders.

    PubMed

    Fehlings, Michael G; Tetreault, Lindsay; Nater, Anick; Choma, Ted; Harrop, James; Mroz, Tom; Santaguida, Carlo; Smith, Justin S

    2015-10-01

    The global population is currently undergoing an upward shift in its age structure due to decreasing fertility rates and increasing life expectancy. As a result, clinicians worldwide will be required to manage an increasing number of spinal disorders specific to the elderly and the aging of the spine. Elderly individuals pose unique challenges to health care systems and to spinal physicians as these patients typically have an increased number of medical comorbidities, reduced bone density mass, more severe spinal degeneration and a greater propensity to falls. In anticipation of the aging of the population, we undertook this project to heighten physicians' awareness of age-related spinal disorders, including geriatric odontoid fractures, central cord syndrome, osteoporotic compression fractures, degenerative cervical myelopathy, lumbar spinal stenosis and degenerative spinal deformity. This introductory article provides an overview of the changing demographics of the global population; discusses the age-related alterations that may occur to the spine; and summarizes the purpose and contents of this focus issue. PMID:26378347

  17. D-penicillamine Induced Degenerative Dermopathy

    PubMed Central

    Khandpur, Sujay; Jain, Naresh; Singla, Shweta; Chatterjee, Priti; Behari, Madhuri

    2015-01-01

    D-penicillamine interferes with elastin and collagen metabolism and produces several cutaneous and multi-systemic side-effects. We present two cases of Wilson's disease who on long-term penicillamine therapy developed drug-induced degenerative dermopathy manifesting as skin fragility over pressure sites and cutis laxa-like changes. PMID:26288416

  18. Age-related degradation of Westinghouse 480-volt circuit breakers

    SciTech Connect

    Subudhi, M.; Shier, W.; MacDougall, E. )

    1990-07-01

    An aging assessment of Westinghouse DS-series low-voltage air circuit breakers was performed as part of the Nuclear Plant Aging Research (NPAR) program. The objectives of this study are to characterize age-related degradation within the breaker assembly and to identify maintenance practices to mitigate their effect. Since this study has been promulgated by the failures of the reactor trip breakers at the McGuire Nuclear Station in July 1987, results relating to the welds in the breaker pole lever welds are also discussed. The design and operation of DS-206 and DS-416 breakers were reviewed. Failure data from various national data bases were analyzed to identify the predominant failure modes, causes, and mechanisms. Additional operating experiences from one nuclear station and two industrial breaker-service companies were obtained to develop aging trends of various subcomponents. The responses of the utilities to the NRC Bulletin 88-01, which discusses the center pole lever welds, were analyzed to assess the final resolution of failures of welds in the reactor trips. Maintenance recommendations, made by the manufacturer to mitigate age-related degradation were reviewed, and recommendations for improving the monitoring of age-related degradation are discussed. As described in Volume 2 of this NUREG, the results from a test program to assess degradation in breaker parts through mechanical cycling are also included. The testing has characterized the cracking of center-pole lever welds, identified monitoring techniques to determine aging in breakers, and provided information to augment existing maintenance programs. Recommendations to improve breaker reliability using effective maintenance, testing, and inspection programs are suggested. 13 refs., 21 figs., 8 tabs.

  19. Age-related changes in the meibomian gland.

    PubMed

    Nien, Chyong Jy; Paugh, Jerry R; Massei, Salina; Wahlert, Andrew J; Kao, Winston W; Jester, James V

    2009-12-01

    The purpose of this study was to characterize the age-related changes of the mouse meibomian gland. Eyelids from adult C57Bl/6 mice at 2, 6, 12 and 24 months of age were stained with specific antibodies against peroxisome proliferator activated receptor gamma (PPARgamma) to identify differentiating meibocytes, Oil Red O (ORO) to identify lipid, Ki67 nuclear antigen to identify cycling cells, B-lymphocyte-induced maturation protein-1 (Blimp1) to identify potential stem cells and CD45 to identify immune cells. Meibomian glands from younger mice (2 and 6 months) showed cytoplasmic and perinuclear staining with anti-PPARgamma antibodies with abundant ORO staining of small, intracellular lipid droplets. Meibomian glands from older mice (12 and 24 months) showed only nuclear PPARgamma localization with less ORO staining and significantly reduced acinar tissue (p < 0.04). Acini of older mice also showed significantly reduced (p < 0.004) numbers of Ki67 stained nuclei. While Blimp1 appeared to diffusely stain the superficial ductal epithelium, isolated cells were occasionally stained within the meibomian gland duct and acini of older mice that also stained with CD45 antibodies, suggesting the presence of infiltrating plasmacytoid cells. These findings suggest that there is altered PPARgamma receptor signaling in older mice that may underlie changes in cell cycle entry/proliferation, lipid synthesis and gland atrophy during aging. These results are consistent with the hypothesis that mouse meibomian glands undergo age-related changes similar to those identified in humans and may be used as a model for age-related meibomian gland dysfunction.

  20. Age-Related Deterioration of Rod Vision in Mice

    PubMed Central

    Kolesnikov, Alexander V.; Fan, Jie; Crouch, Rosalie K.; Kefalov, Vladimir J.

    2010-01-01

    Even in healthy individuals, aging leads to deterioration in visual acuity, contrast sensitivity, visual field, and dark adaptation. Little is known about the neural mechanisms that drive the age-related changes of the retina and more specifically of photoreceptors. According to one hypothesis, the age-related deterioration in rod function is due to the limited availability of 11-cis-retinal for rod pigment formation. To determine how aging affects rod photoreceptors and to test the retinoid deficiency hypothesis, we compared the morphological and functional properties of rods of adult and aged B6D2F1/J mice. We found that the number of rods and the length of their outer segments were significantly reduced in 2.5 year-old mice compared to 4 month-old animals. Aging also resulted in a 2-fold reduction in the total level of opsin in the retina. Behavioral tests revealed that scotopic visual acuity and contrast sensitivity were decreased by 2-fold in aged mice, and rod ERG recordings demonstrated reduced amplitudes of both a- and b-waves. Sensitivity of aged rods determined from single-cell recordings was also decreased by 1.5-fold, corresponding to not more than 1% free opsin in these photoreceptors, and kinetic parameters of dim flash response were not altered. Notably, the rate of rod dark adaptation was unaffected by age. Thus, our results argue against age-related deficiency of 11-cis-retinal in the B6D2F1/J mouse rod visual cycle. Surprisingly, the level of cellular dark noise was increased in aged rods providing an alternative mechanism for their desensitization. PMID:20720130

  1. Age-related differences in updating working memory.

    PubMed

    Van der Linden, M; Brédart, S; Beerten, A

    1994-02-01

    Age-related differences in updating working memory were investigated in two experiments using a running memory task. In the first experiment, the task of the young and elderly subjects was to watch strings of four to 10 consonants and then to recall serially the four most recent items. Results revealed no age effect. A second experiment was then carried out using a memory load that was close to memory span: lists of six to 12 consonants were presented and subjects had to recall the last six items. Age interacted with list length but not with serial position. This dissociation is discussed in terms of Baddeley's (1986) model.

  2. [Diagnostic Criteria for Atrophic Age-related Macular Degeneration].

    PubMed

    Takahashi, Kanji; Shiraga, Fumio; Ishida, Susumu; Kamei, Motohiro; Yanagi, Yasuo; Yoshimura, Nagahisa

    2015-10-01

    Diagnostic criteria for dry age-related macular degeneration is described. Criteria include visual acuity, fundscopic findings, diagnostic image findings, exclusion criteria and classification of severity grades. Essential findings to make diagnosis as "geographic atrophy" are, 1) at least 250 μm in diameter, 2) round/oval/cluster-like or geographic in shape, 3) sharp delineation, 4) hypopigmentation or depigmentation in retinal pigment epithelium, 5) choroidal vessels are more visible than in surrounding area. Severity grades were classified as mild, medium and severe by relation of geographic atrophy to the fovea and attendant findings. PMID:26571627

  3. Effects of Vitreomacular Adhesion on Age-Related Macular Degeneration

    PubMed Central

    Kang, Eui Chun; Koh, Hyoung Jun

    2015-01-01

    Herein, we review the association between vitreomacular adhesion (VMA) and neovascular age-related macular degeneration (AMD). Meta-analyses have shown that eyes with neovascular AMD are twice as likely to have VMA as normal eyes. VMA in neovascular AMD may induce inflammation, macular traction, decrease in oxygenation, sequestering of vascular endothelial growth factor (VEGF), and other cytokines or may directly stimulate VEGF production. VMA may also interfere with the treatment effects of anti-VEGF therapy, which is the standard treatment for neovascular AMD, and releasing VMA can improve the treatment response to anti-VEGF treatment in neovascular AMD. We also reviewed currently available methods of relieving VMA. PMID:26425354

  4. [Glaucoma and age-related macular degeneration intricacy].

    PubMed

    Valtot, F

    2008-07-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness among the elderly in Western nations. Age is also a well-known and well-evidenced risk factor for glaucoma. With increasing longevity and the rising prevalence of older people around the world, more and more patients will have glaucoma and AMD. Clinical evaluation of these patients still poses problems for clinicians. It is very important to order the right tests at the right time to distinguish glaucomatous defects from those caused by retinal lesions, because appropriate therapy has a beneficial effect on slowing or halting damage. PMID:18957915

  5. Age-Related Macular Degeneration: Advances in Management and Diagnosis

    PubMed Central

    Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.

    2015-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

  6. Squalamine lactate for exudative age-related macular degeneration.

    PubMed

    Connolly, Brian; Desai, Avinash; Garcia, Charles A; Thomas, Edgar; Gast, Michael J

    2006-09-01

    Squalamine lactate inhibits angiogenesis by a long-lived, intracellular mechanism of action. The drug is taken up into activated endothelial cells through caveolae, small invaginations in the cellular membrane. Subsequently, the drug binds to and "chaperones" calmodulin to an intracellular membrane compartment and blocks angiogenesis at several levels. A series of basic investigations, preclinical studies, and human clinical trials have begun to establish the proof of concept, efficacy, and safety parameters for use of squalamine lactate as a therapeutic agent for exudative age-related macular degeneration and several types of malignancies. PMID:16935213

  7. Exploring age-related brain degeneration in meditation practitioners.

    PubMed

    Luders, Eileen

    2014-01-01

    A growing body of research suggests that meditation practices are associated with substantial psychological as well as physiological benefits. In searching for the biological mechanisms underlying the beneficial impact of meditation, studies have revealed practice-induced alterations of neurotransmitters, brain activity, and cognitive abilities, just to name a few. These findings not only imply a close link between meditation and brain structure, but also suggest possible modulating effects of meditation on age-related brain atrophy. Given that normal aging is associated with significant loss of brain tissue, meditation-induced growth and/or preservation might manifest as a seemingly reduced brain age in meditators (i.e., cerebral measures characteristic of younger brains). Surprisingly, there are only three published studies that have addressed the question of whether meditation diminishes age-related brain degeneration. This paper reviews these three studies with respect to the brain attributes studied, the analytical strategies applied, and the findings revealed. The review concludes with an elaborate discussion on the significance of existing studies, implications and directions for future studies, as well as the overall relevance of this field of research.

  8. Age-related changes to the production of linguistic prosody

    NASA Astrophysics Data System (ADS)

    Barnes, Daniel R.

    The production of speech prosody (the rhythm, pausing, and intonation associated with natural speech) is critical to effective communication. The current study investigated the impact of age-related changes to physiology and cognition in relation to the production of two types of linguistic prosody: lexical stress and the disambiguation of syntactically ambiguous utterances. Analyses of the acoustic correlates of stress: speech intensity (or sound-pressure level; SPL), fundamental frequency (F0), key word/phrase duration, and pause duration revealed that both young and older adults effectively use these acoustic features to signal linguistic prosody, although the relative weighting of cues differed by group. Differences in F0 were attributed to age-related physiological changes in the laryngeal subsystem, while group differences in duration measures were attributed to relative task complexity and the cognitive-linguistic load of these respective tasks. The current study provides normative acoustic data for older adults which informs interpretation of clinical findings as well as research pertaining to dysprosody as the result of disease processes.

  9. Age-Related Deficits in Reality Monitoring of Action Memories

    PubMed Central

    McDaniel, Mark A.; Lyle, Keith B.; Butler, Karin M.; Dornburg, Courtney C.

    2008-01-01

    We describe three theoretical accounts of age-related increases in falsely remembering that imagined actions were performed (Thomas & Bulevich, 2006). To investigate these accounts and further explore age-related changes in reality monitoring of action memories, we used a new paradigm in which actions were (a) imagined-only (b) actually performed, or (c) both imagined and performed. Older adults were more likely than younger adults to misremember the source of imagined-only actions, with older adults’ more often specifying that the action was imagined and also that it was performed. For both age groups, as repetitions of the imagined-only events increased, illusions that the actions were only performed decreased. These patterns suggest that both older and younger adults utilize qualitative characteristics when making reality-monitoring judgments and that repeated imagination produces richer records of both sensory details and cognitive operations. However, sensory information derived from imagination appears to be more similar to that derived from performance for older than younger adults. PMID:18808253

  10. Age-Related Loss of Muscle Mass and Strength

    PubMed Central

    Goldspink, Geoffrey

    2012-01-01

    Age-related muscle wasting and increased frailty are major socioeconomic as well as medical problems. In the quest to extend quality of life it is important to increase the strength of elderly people sufficiently so they can carry out everyday tasks and to prevent them falling and breaking bones that are brittle due to osteoporosis. Muscles generate the mechanical strain that contributes to the maintenance of other musculoskeletal tissues, and a vicious circle is established as muscle loss results in bone loss and weakening of tendons. Molecular and proteomic approaches now provide strategies for preventing age-related muscle wasting. Here, attention is paid to the role of the GH/IGF-1 axis and the special role of the IGFI-Ec (mechano growth factor/MGF) which is derived from the IGF-I gene by alternative splicing. During aging MGF levels decline but when administered MGF activates the muscle satellite (stem) cells that “kick start” local muscle repair and induces hypertrophy. PMID:22506111

  11. Age-related preferences and age weighting health benefits.

    PubMed

    Tsuchiya, A

    1999-01-01

    This paper deals with the relevance of age in the paradigm of quality adjusted life years (QALYs). The first section outlines two rationales for incorporating age weights into QALYs. One of them is based on efficiency concerns; and the other on equity concerns. Both of these are theoretical constructs. The main purpose of this paper is to examine the extent of published empirical support for such age weighting. The second section is a brief survey of nine empirical studies that elicited age-related preferences from the general public. Six of these quantified the strength of the preferences, and these are discussed in more detail in the third section. The analysis distinguishes three kinds of age-related preference: productivity ageism, utilitarian ageism and egalitarian ageism. The relationship between them and their relevance to the two different rationales for age weighting are then explored. It is concluded that, although there is strong prima facie evidence of public support for both types of age weighting, the empirical evidence to support any particular set of weights is at present weak. PMID:10048783

  12. Auditory white noise reduces age-related fluctuations in balance.

    PubMed

    Ross, J M; Will, O J; McGann, Z; Balasubramaniam, R

    2016-09-01

    Fall prevention technologies have the potential to improve the lives of older adults. Because of the multisensory nature of human balance control, sensory therapies, including some involving tactile and auditory noise, are being explored that might reduce increased balance variability due to typical age-related sensory declines. Auditory white noise has previously been shown to reduce postural sway variability in healthy young adults. In the present experiment, we examined this treatment in young adults and typically aging older adults. We measured postural sway of healthy young adults and adults over the age of 65 years during silence and auditory white noise, with and without vision. Our results show reduced postural sway variability in young and older adults with auditory noise, even in the absence of vision. We show that vision and noise can reduce sway variability for both feedback-based and exploratory balance processes. In addition, we show changes with auditory noise in nonlinear patterns of sway in older adults that reflect what is more typical of young adults, and these changes did not interfere with the typical random walk behavior of sway. Our results suggest that auditory noise might be valuable for therapeutic and rehabilitative purposes in older adults with typical age-related balance variability. PMID:27495013

  13. Complement, a target for therapy in inflammatory and degenerative diseases.

    PubMed

    Morgan, B Paul; Harris, Claire L

    2015-12-01

    The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies.

  14. Defining Alzheimer as a common age-related neurodegenerative process not inevitably leading to dementia.

    PubMed

    Ferrer, Isidro

    2012-04-01

    Since the description by Alois Alzheimer, more than 50 years have passed during which senile dementia and pre-senile dementia have been considered Alzheimer disease (AD) on the basis of their common neuropathological and clinical manifestations. AD now covers pre-senile dementia, senile dementia, mild cognitive impairment and pre-clinical AD, all of them within the context of AD-related pathology. However, there is still a gray area between normal aging with AD-related pathology and AD. Here it is proposed that Alzheimer (or alzheimer) is an age-related neurodegenerative process distinguished from normal aging by the presence of senile plaques and neurofibrillary tangles. Alzheimer affects about 80% of individuals aged 65 years but dementia only occurs in a small percentage of individuals at this age; prevalence of dementia in Alzheimer increases to 25% in individuals aged 80 years. The concepts derived from the β-amyloid hypothesis support β-amyloid as a conductor in the pathogenesis of familial AD and as a prodding factor in sporadic AD. Moreover, seeding of β-amyloid and truncated tau explains incorporation, enhancement and perpetuation of AD-related changes. Therefore, the earliest Alzheimer changes confined to selected regions are the first grounds and the main risk factor for developing dementia. The term Alzheimer embraces this assumption and likens its meaning to other degenerative biological processes, such as atherosclerosis, that may eventually progress to disease. In this context, the first stages of Alzheimer should be considered as primary targets of therapeutic intervention in order to prevent progression to diseased states.

  15. Dietary and behavioral interventions protect against age related activation of caspase cascades in the canine brain.

    PubMed

    Snigdha, Shikha; Berchtold, Nicole; Astarita, Giuseppe; Saing, Tommy; Piomelli, Daniele; Cotman, Carl W

    2011-01-01

    Lifestyle interventions such as diet, exercise, and cognitive training represent a quietly emerging revolution in the modern approach to counteracting age-related declines in brain health. Previous studies in our laboratory have shown that long-term dietary supplementation with antioxidants and mitochondrial cofactors (AOX) or behavioral enrichment with social, cognitive, and exercise components (ENR), can effectively improve cognitive performance and reduce brain pathology of aged canines, including oxidative damage and Aβ accumulation. In this study, we build on and extend our previous findings by investigating if the interventions reduce caspase activation and ceramide accumulation in the aged frontal cortex, since caspase activation and ceramide accumulation are common convergence points for oxidative damage and Aβ, among other factors associated with the aged and AD brain. Aged beagles were placed into one of four treatment groups: CON--control environment/control diet, AOX--control environment/antioxidant diet, ENR--enriched environment/control diet, AOX/ENR--enriched environment/antioxidant diet for 2.8 years. Following behavioral testing, brains were removed and frontal cortices were analyzed to monitor levels of active caspase 3, active caspase 9 and their respective cleavage products such as tau and semaphorin7a, and ceramides. Our results show that levels of activated caspase-3 were reduced by ENR and AOX interventions with the largest reduction occurring with combined AOX/ENR group. Further, reductions in caspase-3 correlated with reduced errors in a reversal learning task, which depends on frontal cortex function. In addition, animals treated with an AOX arm showed reduced numbers of cells expressing active caspase 9 or its cleavage product semaphorin 7A, while ENR (but not AOX) reduced ceramide levels. Overall, these data demonstrate that lifestyle interventions curtail activation of pro-degenerative pathways to improve cellular health and are the

  16. Factors Associated With Age-related Hearing Impairment: A Retrospective Cohort Study.

    PubMed

    Moon, Il Joon; Byun, Hayoung; Woo, Sook-Young; Gwak, Geum-Youn; Hong, Sung Hwa; Chung, Won-Ho; Cho, Yang-Sun

    2015-10-01

    Age-related hearing impairment (ARHI) is a complex degenerative disease in the elderly. As multiple factors interact during the development of ARHI, it is important to elucidate the major influencing factors to understand and prevent ARHI. We aimed to identify risk factors associated with the development of ARHI with a retrospective cohort from 2001 to 2010. The records of the adult subjects over 40 years of age who consecutively underwent a comprehensive health checkup including pure-tone audiometry at the Health Promotion Center were reviewed. During this period, 1560 subjects who underwent pure-tone audiometry more than twice, had no other otologic diseases, and were followed-up more than 2 years were included. A pure-tone average (PTA: 0.5, 1, 2, 4 kHz) was calculated. Development of ARHI was defined as a PTA at follow-up more than 10 dB greater than the baseline PTA. Times to the first development of ARHI were investigated. Overall, 12.7% of subjects developed ARHI within the first 4 years. High blood ionized calcium (hazard ratio [HR] 0.084), albumin (HR 0.239), systolic blood pressure (HR 0.577), thyroid hormone (T3) (HR 0.593), and alpha fetoprotein levels (HR 0.883) were associated with decreased hazard for the development of ARHI. In contrast, high blood high-density lipoprotein (HR 2.105), uric acid (HR 1.684), total protein (HR 1.423), and total bilirubin levels (HR 1.220) were potential risk factors for the development of ARHI. Development of ARHI is common among the aged population, and a variety of factors may interact during this process. The results of this study can be used for counseling of adults at high-risk of developing ARHI with regard to regular audiological check-up.

  17. Age-related priming effects in social judgments.

    PubMed

    Hess, T M; McGee, K A; Woodburn, S M; Bolstad, C A

    1998-03-01

    Two experiments investigated adult age differences in the impact of previously activated (and thus easily accessible) trait-related information on judgments about people. The authors hypothesized that age-related declines in the efficiency of controlled processing mechanisms during adulthood would be associated with increased susceptibility to judgment biases associated with such information. In each study, different-aged adults made impression judgments about a target, and assimilation of these judgments to trait constructs activated in a previous, unrelated task were examined. Consistent with the authors' hypotheses, older adults were likely to form impressions that were biased toward the primed trait constructs. In contrast, younger adults exhibited greater awareness of the primed information and were more likely to correct for its perceived influence, especially when distinctive contextual cues regarding the source of the primes were available. PMID:9533195

  18. Age-related differences in multiple task monitoring.

    PubMed

    Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

    2014-01-01

    Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

  19. Age-related changes in human vitreous structure.

    PubMed

    Sebag, J

    1987-01-01

    Changes in vitreous structure that occur with aging are important in the pathogenesis of vitreous liquefaction (synchisis senilis), vitreous detachment, and retinal disease. Vitreous morphology was studied in 59 human eyes post-mortem using dark-field horizontal slit illumination of the entire dissected vitreous. In many individuals younger than 30 years, the vitreous was homogeneous in structure. Middle-aged individuals had macroscopic fibers in the central vitreous, which coursed anteroposteriorly and inserted into the vitreous base and the vitreous cortex, posteriorly. During senescence, the vitreous volume was reduced, the vitreous body was collapsed (syneresis), and the fibers were thickened, tortuous, and surrounded by liquid vitreous. This sequence of age-related changes probably results from a progressive reorganization of the hyaluronic acid and collagen molecular networks. Characterization of the molecular events underlying these changes will elucidate the mechanisms of the phenomena of synchisis, syneresis, and detachment, and may provide methods with which to prevent or induce vitreous detachment prophylactically.

  20. Sex- and age-related differences in mathematics.

    PubMed

    Rustemeyer, Ruth; Fischer, Natalie

    2005-08-01

    This study examined sex differences and age-related changes in mathematics based on Eccles's 1985 expectancy-value model of "achievement-related choices" and Dweck's 1986 motivation-process model. We have assessed motivational variables and performance in mathematics for youth in Grades 5, 7, and 9 in a German comprehensive secondary school. Significant sex differences in Grades 7 and 9 were observed even when school marks were controlled for. Furthermore, the results indicated differences between Grade 7 and Grade 9 on most of the motivational variables. Older students show a less favorable motivational pattern. Our results give evidence of the importance of motivational encouragement in mathematics classes, especially for girls and low achieving learners. PMID:16279324

  1. Age-Related Differences in Multiple Task Monitoring

    PubMed Central

    Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

    2014-01-01

    Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age. PMID:25215609

  2. Gene-Diet Interactions in Age-Related Macular Degeneration.

    PubMed

    Rowan, Sheldon; Taylor, Allen

    2016-01-01

    Age-related macular degeneration (AMD) is a prevalent blinding disease, accounting for roughly 50 % of blindness in developed nations. Very significant advances have been made in terms of discovering genetic susceptibilities to AMD as well as dietary risk factors. To date, nutritional supplementation is the only available treatment option for the dry form of the disease known to slow progression of AMD. Despite an excellent understanding of genes and nutrition in AMD, there is remarkably little known about gene-diet interactions that may identify efficacious approaches to treat individuals. This review will summarize our current understanding of gene-diet interactions in AMD with a focus on animal models and human epidemiological studies.

  3. Age-related responses to mild restraint in the rat.

    PubMed

    Rattner, B A; Michael, S D; Altland, P D

    1983-11-01

    Immature, postpubertal, young adult, and middle-aged rats were lightly restrained for 4 h. Relative to untreated controls, restraint uniformly reduced body weight and plasma luteinizing hormone concentration and elevated plasma corticosterone concentration in all age groups. However, restraint increased activities of plasma alanine and aspartate aminotransferase, creatine phosphokinase, and fructose-diphosphate aldolase in only immature and middle-aged animals. This age-related release of tissue enzymes is hypothesized to reflect enhanced responsiveness to catecholamines in immature rats, and possible ischemia related to diminished vasodilatory activity in middle-aged rats. On the basis of these changes, tolerance to restraint in postpubertal and young adults appears to be slightly greater than that of immature and middle-aged rats.

  4. A Revised Hemodynamic Theory of Age-Related Macular Degeneration.

    PubMed

    Gelfand, Bradley D; Ambati, Jayakrishna

    2016-08-01

    Age-related macular degeneration (AMD) afflicts one out of every 40 individuals worldwide, causing irreversible central blindness in millions. The transformation of various tissue layers within the macula in the retina has led to competing conceptual models of the molecular pathways, cell types, and tissues responsible for the onset and progression of AMD. A model that has persisted for over 6 decades is the hemodynamic, or vascular theory of AMD progression, which states that vascular dysfunction of the choroid underlies AMD pathogenesis. Here, we re-evaluate this hypothesis in light of recent advances on molecular, anatomic, and hemodynamic changes underlying choroidal dysfunction in AMD. We propose an updated, detailed model of hemodynamic dysfunction as a mechanism of AMD development and progression. PMID:27423265

  5. Molecular pathology of age-related macular degeneration

    PubMed Central

    Ding, Xiaoyan; Patel, Mrinali; Chan, Chi-Chao

    2009-01-01

    Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. Although the etiology and pathogenesis of AMD remain largely unclear, a complex interaction of genetic and environmental factors is thought to exist. AMD pathology is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium, and Bruch’s membrane, as well as, in some cases, alterations in choroidal capillaries. Recent research on the genetic and molecular underpinnings of AMD brings to light several basic molecular pathways and pathophysiological processes that might mediate AMD risk, progression, and/or response to therapy. This review summarizes, in detail, the molecular pathological findings in both humans and animal models, including genetic variations in CFH, CX3CR1, and ARMS2/HtrA1, as well as the role of numerous molecules implicated in inflammation, apoptosis, cholesterol trafficking, angiogenesis, and oxidative stress. PMID:19026761

  6. Radiation Therapy for Neovascular Age-related Macular Degeneration

    SciTech Connect

    Kishan, Amar U.; Modjtahedi, Bobeck S.; Morse, Lawrence S.; Lee, Percy

    2013-03-01

    In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity.

  7. Targeting MAPK Signaling in Age-Related Macular Degeneration

    PubMed Central

    Kyosseva, Svetlana V.

    2016-01-01

    Age-related macular degeneration (AMD) is a major cause of irreversible blindness affecting elderly people in the world. AMD is a complex multifactorial disease associated with demographic, genetics, and environmental risk factors. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in the pathogenesis of AMD. The mitogen-activated protein kinase (MAPK) signaling pathways are activated by diverse extracellular stimuli, including growth factors, mitogens, hormones, cytokines, and different cellular stressors such as oxidative stress. They regulate cell proliferation, differentiation, survival, and apoptosis. This review addresses the novel findings from human and animal studies on the relationship of MAPK signaling with AMD. The use of specific MAPK inhibitors may represent a potential therapeutic target for the treatment of this debilitating eye disease. PMID:27385915

  8. Complement factor H polymorphism and age-related macular degeneration.

    PubMed

    Edwards, Albert O; Ritter, Robert; Abel, Kenneth J; Manning, Alisa; Panhuysen, Carolien; Farrer, Lindsay A

    2005-04-15

    Age-related macular degeneration (AMD) is a common, late-onset, and complex trait with multiple risk factors. Concentrating on a region harboring a locus for AMD on 1q25-31, the ARMD1 locus, we tested single-nucleotide polymorphisms for association with AMD in two independent case-control populations. Significant association (P = 4.95 x 10(-10)) was identified within the regulation of complement activation locus and was centered over a tyrosine-402 --> histidine-402 protein polymorphism in the gene encoding complement factor H. Possession of at least one histidine at amino acid position 402 increased the risk of AMD 2.7-fold and may account for 50% of the attributable risk of AMD.

  9. The Neural Consequences of Age-Related Hearing Loss.

    PubMed

    Peelle, Jonathan E; Wingfield, Arthur

    2016-07-01

    During hearing, acoustic signals travel up the ascending auditory pathway from the cochlea to auditory cortex; efferent connections provide descending feedback. In human listeners, although auditory and cognitive processing have sometimes been viewed as separate domains, a growing body of work suggests they are intimately coupled. Here, we review the effects of hearing loss on neural systems supporting spoken language comprehension, beginning with age-related physiological decline. We suggest that listeners recruit domain general executive systems to maintain successful communication when the auditory signal is degraded, but that this compensatory processing has behavioral consequences: even relatively mild levels of hearing loss can lead to cascading cognitive effects that impact perception, comprehension, and memory, leading to increased listening effort during speech comprehension. PMID:27262177

  10. Age-related differences in arithmetic strategy sequential effects.

    PubMed

    Lemaire, Patrick

    2016-03-01

    In this article, I review a series of new findings concerning how age-related changes in strategic variations are modulated by sequential effects. Sequential effects refer to how strategy selection and strategy execution on current problems are influenced by which strategy is used on immediately preceding problems. Two sequential effects during strategy selection (i.e., strategy revisions and strategy perseverations) and during strategy execution (i.e., strategy switch costs and modulations of poorer strategy effects) are presented. I also discuss how these effects change with age during adulthood. These phenomena are important, as they shed light on arithmetic processes and how these processes change with age during adulthood. In particular, they speak to the role of executive control while participants select and execute arithmetic strategies. Finally, I discuss the implications of sequential effects for theories of strategies and of arithmetic.

  11. Age-related macular degeneration and the complement system.

    PubMed

    Khandhadia, S; Cipriani, V; Yates, J R W; Lotery, A J

    2012-02-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. It is a complex multifactorial disease, and despite new advances in treatment, many patients still succumb to visual impairment. The complement pathway has been implicated in the pathogenesis of many diseases, and recently variants in several genes encoding complement pathway proteins have been associated with AMD. Complement proteins have been found in histological specimens of eyes with AMD. Altered levels of both intrinsic complement proteins and activated products have been found in the circulation of patients with AMD. Complement activation may be triggered by oxidative stress, resulting from retinal exposure to incoming light; indeed an inter-play between these two pathological processes seems to exist. Finally, complement inhibitors are currently being evaluated in clinical trials. This article reviews the role of the complement system in AMD, and the potential of complement inhibition in preventing the devastating blindness resulting from this disease.

  12. The Neural Consequences of Age-Related Hearing Loss.

    PubMed

    Peelle, Jonathan E; Wingfield, Arthur

    2016-07-01

    During hearing, acoustic signals travel up the ascending auditory pathway from the cochlea to auditory cortex; efferent connections provide descending feedback. In human listeners, although auditory and cognitive processing have sometimes been viewed as separate domains, a growing body of work suggests they are intimately coupled. Here, we review the effects of hearing loss on neural systems supporting spoken language comprehension, beginning with age-related physiological decline. We suggest that listeners recruit domain general executive systems to maintain successful communication when the auditory signal is degraded, but that this compensatory processing has behavioral consequences: even relatively mild levels of hearing loss can lead to cascading cognitive effects that impact perception, comprehension, and memory, leading to increased listening effort during speech comprehension.

  13. Is running associated with degenerative joint disease

    SciTech Connect

    Panush, R.S.; Schmidt, C.; Caldwell, J.R.; Edwards, N.L.; Longley, S.; Yonker, R.; Webster, E.; Nauman, J.; Stork, J.; Pettersson, H.

    1986-03-07

    Little information is available regarding the long-term effects, if any, of running on the musculoskeletal system. The authors compared the prevalence of degenerative joint disease among 17 male runners with 18 male nonrunners. Running subjects (53% marathoners) ran a mean of 44.8 km (28 miles)/wk for 12 years. Pain and swelling of hips, knees, ankles and feet and other musculoskeletal complaints among runners were comparable with those among nonrunners. Radiologic examinations (for osteophytes, cartilage thickness, and grade of degeneration) also were without notable differences among groups. They did not find an increased prevalence of osteoarthritis among the runners. Our observations suggest that long-duration, high-mileage running need to be associated with premature degenerative joint disease in the lower extremities.

  14. Dietary folate improves age-related decreases in lymphocyte function.

    PubMed

    Field, Catherine J; Van Aerde, Arne; Drager, Kelly L; Goruk, Susan; Basu, Tapan

    2006-01-01

    Although low folate status is thought to be fairly common in the older population, its implication on immunity has not been adequately investigated. Using 11-month-old and 23-month-old male rats (Fisher 344), the present study was undertaken to examine the modifying effects of feeding a control diet (NIH-07) supplemented with folate (35.7 mg/kg) for 3 weeks on the immune cells of spleen and mesenteric lymph node (MLN) origin. The serum concentrations of folate along with vitamin B(12) were elevated in response to the folate supplementation (P<.05). These results were accompanied by an improved proliferative response (stimulation index) to mitogens in both the spleen and MLNs (P<.05). The proportion of T cells in the MLNs, but not in the spleen, was significantly increased in rats fed a diet supplemented with folate. In the spleen, the folate-supplemented diet prevented the age-associated decrease (P<.05) in the production of interferon (IFN)alpha by unstimulated cells and the decrease in T-helper (Th)1/Th2-type response after stimulation with phorbol myristate acetate and ionomycin. In the MLNs, on the other hand, the folate-supplemented diet failed to influence any age-related increase in interleukin (IL)-2, tumor necrosis factor alpha and IFNgamma following stimulation but did result in a significantly increased production of IL-4 (P<.05). Overall, this study provides data suggesting that aging is associated with changes in the proportion of T cells, the ability of immune cells to proliferate and the production of cytokines after stimulation. Supplementing a folate-sufficient diet with additional folate improves proliferative response to mitogens, the distribution of T cells in the MLNs and the age-related changes in cytokine production in the spleen. These results suggest that the dietary folate requirement may be higher in the older population than in the younger population to support immune functions.

  15. Age-related vascular stiffening: causes and consequences

    PubMed Central

    Kohn, Julie C.; Lampi, Marsha C.; Reinhart-King, Cynthia A.

    2015-01-01

    Arterial stiffening occurs with age and is closely associated with the progression of cardiovascular disease. Stiffening is most often studied at the level of the whole vessel because increased stiffness of the large arteries can impose increased strain on the heart leading to heart failure. Interestingly, however, recent evidence suggests that the impact of increased vessel stiffening extends beyond the tissue scale and can also have deleterious microscale effects on cellular function. Altered extracellular matrix (ECM) architecture has been recognized as a key component of the pre-atherogenic state. Here, the underlying causes of age-related vessel stiffening are discussed, focusing on age-related crosslinking of the ECM proteins as well as through increased matrix deposition. Methods to measure vessel stiffening at both the macro- and microscale are described, spanning from the pulse wave velocity measurements performed clinically to microscale measurements performed largely in research laboratories. Additionally, recent work investigating how arterial stiffness and the changes in the ECM associated with stiffening contributed to endothelial dysfunction will be reviewed. We will highlight how changes in ECM protein composition contribute to atherosclerosis in the vessel wall. Lastly, we will discuss very recent work that demonstrates endothelial cells (ECs) are mechano-sensitive to arterial stiffening, where changes in stiffness can directly impact EC health. Overall, recent studies suggest that stiffening is an important clinical target not only because of potential deleterious effects on the heart but also because it promotes cellular level dysfunction in the vessel wall, contributing to a pathological atherosclerotic state. PMID:25926844

  16. Age-related modifications in neural cardiovascular control.

    PubMed

    Ferrari, A U

    1992-09-01

    Integrated cardiovascular responses to a range of different stimuli, as well as the overall, spontaneously occurring variability in blood pressure and heart rate, undergo complex changes with aging. A general trend is that homeostatic control mechanisms lose part of their ability to modulate heart rate and to buffer the concomitant blood pressure variations; the two phenomena are possibly linked by a cause-effect relationship. A detailed analysis of the age-related changes in the major reflex systems reveals a clear-cut impairment in arterial baroreceptor control of the heart rate, but much less pronounced changes in its control of blood pressure, on the other hand, both the hemodynamic and humoral components of the cardiopulmonary reflex appear to be markedly attenuated. The experimental evidence of the mechanisms underlying these changes is still largely incomplete, and it appears that the gaps will have to be filled by a systematic, detailed analysis, i.e., that no generalizations or extrapolations will be possible. Indeed, the data available so far indicate that the age-related alterations are highly non-uniform, some functions undergoing a definite impairment but others being much better preserved and some being even enhanced; thus aging is by no means associated with a generalized decline in cardiovascular functions and should instead be viewed as a complex, highly selective process. These peculiar biological features of the aging phenomena merit further investigation in both the cardiovascular and the other organ systems, in order to verify the possibility that currently unrecognized homeostatic potentials in the elderly subject may be exploited to advance his/her clinical management in health and disease.

  17. Age-Related Tissue Stiffening: Cause and Effect

    PubMed Central

    Sherratt, Michael J.

    2013-01-01

    Significance Tissue elasticity is severely compromised in aging skin, lungs, and blood vessels. In the vascular and pulmonary systems, respectively, loss of mechanical function is linked to hypertension, which in turn is a risk factor for heart and renal failure, stroke, and aortic aneurysms, and to an increased risk of mortality as a result of acute lung infections. Recent Advances Although cellular mechanisms were thought to play an important role in mediating tissue aging, the reason for the apparent sensitivity of elastic fibers to age-related degradation remained unclear. We have recently demonstrated that compared with type I collagen, a key component of the elastic fiber system, the cysteine-rich fibrillin microfibril is highly susceptible to direct UV exposure in a cell-free environment. We hypothesized therefore that, as a consequence of both their remarkable longevity and cysteine-rich composition, many elastic fiber-associated components will be susceptible to the accumulation of damage by both direct UV radiation and reactive oxygen species-mediated oxidation. Critical Issues Although elastic fiber remodeling is a common feature of aging dynamic tissues, the inaccessibility of most human tissues has hampered attempts to define the molecular causes. Clinical Care Relevance Although, currently, the localized repair of damaged elastic fibers may be effected by the topical application of retinoids and some cosmetic products, future studies may extend the application of systemic transforming growth factor β antagonists, which can prevent cardiovascular remodeling in murine Marfan syndrome, to aging humans. Acellular mechanisms may be key mediators of elastic fiber remodeling and hence age-related tissue stiffening. PMID:24527318

  18. [Actualities regarding the degenerative valvular heart].

    PubMed

    Ionescu, Simona Daniela; Sandru, V; Burdujan, Alina

    2002-01-01

    The degenerative valvular heart disease became prioritary from the epidemiological point of view by contrast with the rheumatismal one, as a consequence of the increase of the economic standard and of average life expectancy. The calcific aortic stenosis is the most frequently encountered among the valvular heart lesions. Since the history of this disease is not well known, many efforts have been made in order to research all its aspects from the etiology to therapeutical and prophylactic methods.

  19. Degenerative mitral valve regurgitation: best practice revolution

    PubMed Central

    Adams, David H.; Rosenhek, Raphael; Falk, Volkmar

    2010-01-01

    Degenerative mitral valve disease often leads to leaflet prolapse due to chordal elongation or rupture, and resulting in mitral valve regurgitation. Guideline referral for surgical intervention centres primarily on symptoms and ventricular dysfunction. The recommended treatment for degenerative mitral valve disease is mitral valve reconstruction, as opposed to valve replacement with a bioprosthetic or mechanical valve, because valve repair is associated with improved event free survival. Recent studies have documented a significant number of patients are not referred in a timely fashion according to established guidelines, and when they are subjected to surgery, an alarming number of patients continue to undergo mitral valve replacement. The debate around appropriate timing of intervention for asymptomatic severe mitral valve regurgitation has put additional emphasis on targeted surgeon referral and the need to ensure a very high rate of mitral valve repair, particularly in the non-elderly population. Current clinical practice remains suboptimal for many patients, and this review explores the need for a ‘best practice revolution’ in the field of degenerative mitral valve regurgitation. PMID:20624767

  20. Aging-associated formaldehyde-induced norepinephrine deficiency contributes to age-related memory decline.

    PubMed

    Mei, Yufei; Jiang, Chun; Wan, You; Lv, Jihui; Jia, Jianping; Wang, Xiaomin; Yang, Xu; Tong, Zhiqian

    2015-08-01

    A norepinephrine (NE) deficiency has been observed in aged rats and in patients with Alzheimer's disease and is thought to cause cognitive disorder. Which endogenous factor induces NE depletion, however, is largely unknown. In this study, we investigated the effects of aging-associated formaldehyde (FA) on the inactivation of NE in vitro and in vivo, and on memory behaviors in rodents. The results showed that age-related DNA demethylation led to hippocampal FA accumulation, and when this occurred, the hippocampal NE content was reduced in healthy male rats of different ages. Furthermore, biochemical analysis revealed that FA rapidly inactivated NE in vitro and that an intrahippocampal injection of FA markedly reduced hippocampal NE levels in healthy adult rats. Unexpectedly, an injection of FA (at a pathological level) or 6-hydroxydopamine (6-OHDA, a NE depletor) can mimic age-related NE deficiency, long-term potentiation (LTP) impairments, and spatial memory deficits in healthy adult rats. Conversely, an injection of NE reversed age-related deficits in both LTP and memory in aged rats. In agreement with the above results, the senescence-accelerated prone 8 (SAMP8) mice also exhibited a severe deficit in LTP and memory associated with a more severe NE deficiency and FA accumulation, when compared with the age-matched, senescence-resistant 1 (SAMR1) mice. Injection of resveratrol (a natural FA scavenger) or NE into SAMP8 mice reversed FA accumulation and NE deficiency and restored the magnitude of LTP and memory. Collectively, these findings suggest that accumulated FA is a critical endogenous factor for aging-associated NE depletion and cognitive decline.

  1. Red ginseng delays age-related hearing and vestibular dysfunction in C57BL/6 mice.

    PubMed

    Tian, Chunjie; Kim, Yeon Ju; Lim, Hye Jin; Kim, Young Sun; Park, Hun Yi; Choung, Yun-Hoon

    2014-09-01

    Since Korean red ginseng (KRG) has been proven to protect against gentamicin-induced vestibular and hearing dysfunction, the effects of KRG on age-related inner ear disorder in C57BL/6 mice were investigated. While age-related hearing loss was detected at the age of 6months (32kHz) and 9months (16kHz) in the control group, it was significantly delayed (p<0.05) in the 150mg/kg KRG-treated group. Vestibular dysfunction was observed in the tail-hanging and swimming tests, with significantly different severity scores and swimming times detected between the control and 150mg/kg KRG-treated group at the age of 12months (p<0.05). Mice treated with 500mg/kg KRG exhibited irritability and aggravated inner ear dysfunction. Histological observation supported the findings of hearing and vestibular function defects. In conclusion, C57BL/6 mice showed early-onset hearing loss and progressive vestibular dysfunction with aging, which were delayed by treatment with 150mg/kg KRG. However, 500mg/kg KRG treatment may induce aggressive behavior. PMID:24952098

  2. Age-related motor dysfunction and neuropathology in a transgenic mouse model of multiple system atrophy.

    PubMed

    Fernagut, P O; Meissner, W G; Biran, M; Fantin, M; Bassil, F; Franconi, J M; Tison, F

    2014-03-01

    Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a progressive degeneration of the striatonigral, olivo-ponto-cerebellar, and autonomic systems. Glial cytoplasmic inclusions (GCIs) containing alpha-synuclein represent the hallmark of MSA and are recapitulated in mice expressing alpha-synuclein in oligodendrocytes. To assess if oligodendroglial expression of human wild-type alpha-synuclein in mice (proteolipid promoter, PLP-SYN) could be associated with age-related deficits, PLP-SYN and wild-type mice were assessed for motor function, brain morphometry, striatal levels of dopamine and metabolites, dopaminergic loss, and distribution of GCIs. PLP-SYN displayed age-related impairments on a beam-traversing task. MRI revealed a significantly smaller brain volume in PLP-SYN mice at 12 months, which further decreased at 18 months together with increased volume of ventricles and cortical atrophy. The distribution of GCIs was reminiscent of MSA with a high burden in the basal ganglia. Mild dopaminergic cell loss was associated with decreased dopamine turnover at 18 months. These data indicate that PLP-SYN mice may recapitulate some of the progressive features of MSA and deliver endpoints for the evaluation of therapeutic strategies.

  3. Protective effect of myostatin gene deletion on aging-related muscle metabolic decline.

    PubMed

    Chabi, B; Pauly, M; Carillon, J; Carnac, G; Favier, F B; Fouret, G; Bonafos, B; Vanterpool, F; Vernus, B; Coudray, C; Feillet-Coudray, C; Bonnieu, A; Lacan, D; Koechlin-Ramonatxo, C

    2016-06-01

    While myostatin gene deletion is a promising therapy to fight muscle loss during aging, this approach induces also skeletal muscle metabolic changes such as mitochondrial deficits, redox alteration and increased fatigability. In the present study, we evaluated the effects of aging on these features in aged wild-type (WT) and mstn knockout (KO) mice. Moreover, to determine whether an enriched-antioxidant diet may be useful to prevent age-related disorders, we orally administered to the two genotypes a melon concentrate rich in superoxide dismutase for 12 weeks. We reported that mitochondrial functional abnormalities persisted (decreased state 3 and 4 of respiration; p<0.05) in skeletal muscle from aged KO mice; however, differences with WT mice were attenuated at old age in line with reduced difference on running endurance between the two genotypes. Interestingly, we showed an increase in glutathione levels, associated with lower lipid peroxidation levels in KO muscle. Enriched antioxidant diet reduced the aging-related negative effects on maximal aerobic velocity and running limit time (p<0.05) in both groups, with systemic adaptations on body weight. The redox status and the hypertrophic phenotype appeared to be beneficial to KO mice, mitigating the effect of aging on the skeletal muscle metabolic remodeling.

  4. [Non-pharmacologic therapy of age-related macular degeneration, based on the etiopathogenesis of the disease].

    PubMed

    Fischer, Tamás

    2015-07-12

    It has a great therapeutic significance that the disorder of the vascular endothelium, which supplies the affected ocular structures, plays a major role in the development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfuncition and age-related macular degeneration is accompanied by a general inflammatory response. The vascular wall including those in chorioids may be activated by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic and genetic factors causing a protracted host defence response with a consequent vascular damage, which leads to age-related macular degeneration. Based on this concept, age-related macular degeneration is a local manifestation of the systemic vascular disease. This recognition should have therapeutic implications because restoration of endothelial dysfunction can stabilize the condition of chronic vascular disease including age-related macular degeneration, as well. Restoration of endothelial dysfunction by non-pharmacological or pharmacological interventions may prevent the development or improve endothelial dysfunction resulting in prevention or improvement of age-related macular degeneration. Non-pharmacological interventions which may have beneficial effect in endothelial dysfunction include (1) smoking cessation; (2) reduction of increased body weight; (3) adequate physical activity; (4) appropriate diet (a) proper dose of flavonoids, polyphenols and kurcumin; (b) omega-3 long-chain polyunsaturated fatty acids: docosahexaenoic acid and eicosapentaenoic acid; (c) carotenoids, lutein and zeaxanthins), (d) management of dietary glycemic index, (e) caloric restriction, and (5) elimination of stressful lifestyle. Non-pharmacological interventions should be preferable even if medicaments are also used for the treatment of endothelial dysfunction.

  5. Progress on retinal image analysis for age related macular degeneration.

    PubMed

    Kanagasingam, Yogesan; Bhuiyan, Alauddin; Abràmoff, Michael D; Smith, R Theodore; Goldschmidt, Leonard; Wong, Tien Y

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50 years in the developed countries. The number is expected to increase by ∼1.5 fold over the next ten years due to an increase in aging population. One of the main measures of AMD severity is the analysis of drusen, pigmentary abnormalities, geographic atrophy (GA) and choroidal neovascularization (CNV) from imaging based on color fundus photograph, optical coherence tomography (OCT) and other imaging modalities. Each of these imaging modalities has strengths and weaknesses for extracting individual AMD pathology and different imaging techniques are used in combination for capturing and/or quantification of different pathologies. Current dry AMD treatments cannot cure or reverse vision loss. However, the Age-Related Eye Disease Study (AREDS) showed that specific anti-oxidant vitamin supplementation reduces the risk of progression from intermediate stages (defined as the presence of either many medium-sized drusen or one or more large drusen) to late AMD which allows for preventative strategies in properly identified patients. Thus identification of people with early stage AMD is important to design and implement preventative strategies for late AMD, and determine their cost-effectiveness. A mass screening facility with teleophthalmology or telemedicine in combination with computer-aided analysis for large rural-based communities may identify more individuals suitable for early stage AMD prevention. In this review, we discuss different imaging modalities that are currently being considered or used for screening AMD. In addition, we look into various automated and semi-automated computer-aided grading systems and related retinal image analysis techniques for drusen, geographic atrophy and choroidal neovascularization detection and/or quantification for measurement of AMD severity using these imaging modalities. We also review the existing telemedicine studies which

  6. The role of glucocorticoids in aging and age-related pharmacotherapy.

    PubMed

    Goudochnikov, V I

    2011-01-01

    Recently we have evaluated the role of glucocorticoids (GC) and other stress hormones in the pathogeny of age-related diseases. In order to perform this evaluation, we considered the DOHaD paradigm discussing long-term effects of adverse perinatal factors. In the present work, a part of the data collected previously was used for analyzing the role of GC in aging, as well as in age-related pharmacotherapy. The data were gathered in various databases, preferably in English, during the last 25-30 years. Although some authors suggest that GC can be considered as hormones of aging, the majority of investigators are quite careful in this respect. Nevertheless, it appears that the role of GC in various stages of ontogeny and transitions between them is well established. Besides, there are a lot of data that confirm a contribution of GC to the phenomena of perinatal programming/imprinting of adult diseases. What for the relationship between GC and aging, some studies confirm its existence, at least partially. Having analyzed the dynamics of morbidity and mortality of age-related diseases, we concluded on the absence of evidence in favor of unique general scheme of aging, where GC could play a role. However, in a rather paradoxal mode it was demonstrated that GC participate, at least indirectly, in the mechanisms of action of various drugs used for the treatment of cardiometabolic disorders (beta-blockers, angiotensin antagonists, some oral hypoglycemic agents) and neuropsychiatric diseases (antidepressants, antipsychotic agents, benzodiazepines and some anticonvulsive medicines), as well as in the effects of toxic agents (for example, drugs of abuse, including caffeine). Using the concept of hormesis, we discuss a reason for frequent utilization of these drugs, and not GC or their antagonists, in age-related pharmacotherapy. The caution is suggested in considering the essential function of GC in aging. Nevertheless, due to existence of theory that connects GC with aging

  7. THE ENERGY-REDOX AXIS IN AGING AND AGE-RELATED NEURODEGENERATION

    PubMed Central

    Yap, Li-Peng; Garcia, Jerome V.; Han, Derick; Cadenas, Enrique

    2009-01-01

    Decrease in mitochondrial energy-transducing capacity is a feature of the aging process that accompanies redox alterations, such as increased generation of mitochondrial oxidants, altered GSH status, and increased protein oxidation. The decrease in mitochondrial energy-transducing capacity and altered redox status should be viewed as a concerted process that embodies the mitochondrial energy – redox axis and is linked through various mechanisms including: (a) an inter-convertible reducing equivalents pool (i.e., NAD(P)+/NAD(P)H) and (b) redox-mediated protein post-translational modifications involved in energy metabolism. The energy–redox axis provides the rationale for therapeutic approaches targeted to each or both component(s) of the axis that effectively preserves or improve mitochondrial function and that have implications for aging and age-related neurodegenerative disorders. PMID:19716388

  8. One-step labeling of degenerative neurons in unfixed brain tissue samples using Fluoro-Jade C.

    PubMed

    Gu, Qiang; Schmued, Larry C; Sarkar, Sumit; Paule, Merle G; Raymick, Bryan

    2012-06-30

    Neurodegeneration is the underlying cause of a vast majority of neurological disorders and often a result of brain trauma, stroke, or neurotoxic insult. Here we describe a simple method for labeling degenerating neurons in unfixed brain tissue samples. This method could provide a new avenue for identifying and harvesting degenerative neurons from unfixed brain tissues for subsequent molecular analyses.

  9. Age-related changes in deformability of human erythrocytes.

    PubMed

    Sutera, S P; Gardner, R A; Boylan, C W; Carroll, G L; Chang, K C; Marvel, J S; Kilo, C; Gonen, B; Williamson, J R

    1985-02-01

    The present study was designed to further the characterization of age-related changes in the deformability of human erythrocytes. The top (approximately young) and bottom (approximately old) 10% fractions of density-separated red cells from ten normal donors were subjected to graded levels of shear stress in a rheoscope. Measurements were made of steady-state elongation (cells tank treading in a state of dynamic equilibrium) and the time course of shape recovery following abrupt cessation of shear. In parallel with the rheologic experiments, several physical and chemical properties were assayed to determine correlates of mechanical properties. These included mean cell volume, mean corpuscular hemoglobin concentration, type A1 hemoglobin, glucosylation of membrane proteins, and membrane phospholipid and protein concentration. The microrheologic observations revealed that only about 90% of the old cells retained their capacity to tank tread. However, the tank-treading cells elongated less than their younger counterparts at corresponding levels of shear stress, thus demonstrating a reduced level of deformability. Further analysis of the data indicates that increases in membrane viscosity and elastic modulus along with a significant loss in excess surface area contribute to the limitation of the ability of the older cells to change shape.

  10. Aging-related differences in chondrocyte viscoelastic properties.

    PubMed

    Steklov, Nikolai; Srivastava, Ajay; Sung, K L P; Chen, Peter C; Lotz, Martin K; D'Lima, Darryl D

    2009-06-01

    The biomechanical properties of articular cartilage change profoundly with aging. These changes have been linked with increased potential for cartilage degeneration and osteoarthritis. However, less is known about the change in biomechanical properties of chondrocytes with increasing age. Cell stiffness can affect mechanotransduction pathways and may alter cell function. We measured aging-related changes in the biomechanical properties of chondrocytes. Human chondrocytes were isolated from knee articular cartilage within 48 hours after death or from osteochondral specimens obtained from knee arthroplasty. Cells were divided into two age groups: between 18 and 35 years (18 - 35); and greater than 55 years (55+) of age. The 55+ group was further subdivided based on visual grade of osteoarthritis: normal (N) or osteoarthritic (OA). The viscoelastic properties of the cell were measured using the previously described micropipette cell aspiration technique. The equilibrium modulus, instantaneous modulus, and apparent viscosity were significantly higher in the 55+ year age group than in the 18 - 35 age group. On the other hand, no differences were found in the equilibrium modulus, instantaneous modulus, or apparent viscosity between the N and OA groups. The increase in cell stiffness can be attributed to altered mechanical properties of the cell membrane, the cytoplasm, or the cytoskeleton. Increased stiffness has been reported in osteoarthritic chondrocytes, which in turn has been attributed to the actin cytoskeleton. A similar mechanism may be responsible for our finding of increased stiffness in aging chondrocytes. With advancing age, changes in the biomechanical properties of the cell could alter molecular and biochemical responses.

  11. Age-Related Macular Degeneration: A Scientometric Analysis

    PubMed Central

    Ramin, Shahrokh; Soheilian, Masoud; Habibi, Gholamreza; Ghazavi, Roghayeh; Gharebaghi, Reza; Heidary, Fatemeh

    2015-01-01

    Age-related macular degeneration (ARMD) is a major cause of central blindness among working aged adults across the world. Systematic research planning on any subject, including ARMD is in need of solid data regarding previous efforts in this field and to identify the gaps in the research. This study aimed to elucidate the most important trends, directions, and gap in this subject. The data extracted from the Institute for Scientific Information were used to perform a bibliometric analysis of the scientific productions (1993–2013) about ARMD. Specific parameters related to ARMD were analyzed to obtain a view of the topic’s structure, history, and document relationships. Additionally, the trends and authors in the most influential publications were analyzed. The number of articles in this field was found constantly increasing. Most highly cited articles addressed genetic epidemiology and clinical research topics in this field. During the past 3 years, there has been a trend toward biomarker research. Through performing the first scientometric survey on ARMD research, we analyzed the characteristics of papers and the trends in scientific production. We also identified some of the critical gaps in the current research efforts that would help in large-scale research strategic planning. PMID:26060829

  12. Promising new treatments for neovascular age-related macular degeneration.

    PubMed

    Michels, Stephan; Schmidt-Erfurth, Ursula; Rosenfeld, Philip J

    2006-07-01

    Angiogenesis, the growth of new blood vessels from existing blood vessels, is responsible for vision loss in a variety of ophthalmic diseases. In neovascular age-related macular degeneration (AMD), the leading cause for legal blindness in many industrialised countries, abnormal blood vessels grow in the macula and cause blindness. There are a number of factors important in the angiogenic cascade but VEGF-A has been implicated in recent years as the major factor responsible for neovascular and exudative diseases of the eye. Numerous antiangiogenic drugs are in development but anti-VEGF drugs have shown great promise in treating neovascular AMD and other ocular diseases, and many of these drugs have been adopted from oncology where antiangiogenic therapy is gaining wide acceptance. For the first time in neovascular AMD, anti-VEGF drugs have brought the hope of vision improvement to a significant proportion of patients. This review provides an overview on angiogenic mechanisms, potential antiangiogenic treatment strategies and different antiangiogenic drugs with special focus on neovascular AMD.

  13. Radiation therapy for neovascular age-related macular degeneration

    PubMed Central

    Petrarca, Robert; Jackson, Timothy L

    2011-01-01

    Antivascular endothelial growth factor (anti-VEGF) therapies represent the standard of care for most patients presenting with neovascular (wet) age-related macular degeneration (neovascular AMD). Anti-VEGF drugs require repeated injections and impose a considerable burden of care, and not all patients respond. Radiation targets the proliferating cells that cause neovascular AMD, including fibroblastic, inflammatory, and endothelial cells. Two new neovascular AMD radiation treatments are being investigated: epimacular brachytherapy and stereotactic radiosurgery. Epimacular brachytherapy uses beta radiation, delivered to the lesion via a pars plana vitrectomy. Stereotactic radiosurgery uses low voltage X-rays in overlapping beams, directed onto the lesion. Feasibility data for epimacular brachytherapy show a greatly reduced need for anti-VEGF therapy, with a mean vision gain of 8.9 ETDRS letters at 12 months. Pivotal trials are underway (MERLOT, CABERNET). Preliminary stereotactic radiosurgery data suggest a mean vision gain of 8 to 10 ETDRS letters at 12 months. A large randomized sham controlled stereotactic radiosurgery feasibility study is underway (CLH002), with pivotal trials to follow. While it is too early to conclude on the safety and efficacy of epimacular brachytherapy and stereotactic radiosurgery, preliminary results are positive, and these suggest that radiation offers a more durable therapeutic effect than intraocular injections. PMID:21311657

  14. Review of nutrient actions on age-related macular degeneration.

    PubMed

    Zampatti, Stefania; Ricci, Federico; Cusumano, Andrea; Marsella, Luigi Tonino; Novelli, Giuseppe; Giardina, Emiliano

    2014-02-01

    The actions of nutrients and related compounds on age-related macular degeneration (AMD) are explained in this review. The findings from 80 studies published since 2003 on the association between diet and supplements in AMD were reviewed. Antioxidants and other nutrients with an effect on AMD susceptibility include carotenoids (lutein and zeaxanthin, β-carotene), vitamins (vitamin A, E, C, D, B), mineral supplements (zinc, copper, selenium), dietary fatty acids [monounsaturated fatty acids, polyunsaturated fatty acids (PUFA both omega-3 PUFA and omega-6 PUFA), saturated fatty acids and cholesterol], and dietary carbohydrates. The literature revealed that many of these antioxidants and nutrients exert a protective role by functioning synergistically. Specifically, the use of dietary supplements with targeted actions can provide minimal benefits on the onset or progression of AMD; however, this does not appear to be particularly beneficial in healthy people. Furthermore, some supplements or nutrients have demonstrated discordant effects on AMD in some studies. Since intake of dietary supplements, as well as exposure to damaging environmental factors, is largely dependent on population habits (including dietary practices) and geographical localization, an overall healthy diet appears to be the best strategy in reducing the risk of developing AMD. As of now, the precise mechanism of action of certain nutrients in AMD prevention remains unclear. Thus, future studies are required to examine the effects that nutrients have on AMD and to determine which factors are most strongly correlated with reducing the risk of AMD or preventing its progression. PMID:24461310

  15. Age-related changes in skin topography and microcirculation.

    PubMed

    Li, Li; Mac-Mary, Sophie; Marsaut, David; Sainthillier, Jean Marie; Nouveau, Stéphanie; Gharbi, Tijani; de Lacharriere, Olivier; Humbert, Philippe

    2006-03-01

    Skin topography and microvasculature undergo characteristic changes with age. Although several non-invasive bioengineering methods are currently available to measure them quantitatively, few publications have referred to their relationship with age in different anatomical sites. This study was carried out to observe the age-related changes of the skin topography and skin microcirculation. The microrelief was assessed with special processing software from scanning by interference fringe profilometry of silicone replicas performed on two sites (volar forearm and back of hand) on 50 female volunteers (aged 20-74 years who consisted of ten probands in each decade). The superficial vascular network of both sites was assessed by videocapillaroscopy, and the subpapillary vascular plexus was studied with laser Doppler flowmetry. Skin color, which is affected by blood flow, was observed by colorimeter. The skin roughness and the mean height between peak and valley increased with age. There were statistically significant differences between the evaluated sites. This study also shows that the capillary loops in the dermal papillae decrease but the subpapillary plexus increase with age. The interference fringe profilometry associated with videocapillaroscopy may be useful and accurate to measure the efficacy of medical or cosmetic products to delay skin aging.

  16. Age related microsatellite instability in T cells from healthy individuals.

    PubMed

    Krichevsky, Svetlana; Pawelec, Graham; Gural, Alexander; Effros, Rita B; Globerson, Amiela; Yehuda, Dina Ben; Yehuda, Arie Ben

    2004-04-01

    Many immune functions decline with age and may jeopardize the elderly, as illustrated, for example by the significantly higher mortality rate from influenza in old age. Although innate and humoral immunity are affected by aging, it is the T cell compartment, which manifests most alterations. The mechanisms behind these alterations are still unclear, and several explanations have been offered including thymic involution and Telomere attrition leading to cell senescence. Age related accumulation of mutations has been documented and could serve as an additional mechanism of T cell dysfunction. One effective repair mechanism capable of rectifying errors in DNA replications is the mismatch repair (MMR) system. We previously reported a comparative examination of individual DNA samples from blood cells obtained at 10 year intervals from young and old subjects. We showed significantly higher rates of microsatellite instability (MSI), an indicator of MMR dysfunction in older subjects, compared to young. In the present study we confirm this result, using direct automated sequencing and in addition, we demonstrate that as CD8 lymphocytes from aged individuals, undergo repeated population doublings (PDs) in culture, they develop MSI. CD4 clones that also undergo repeated PDs in culture develop significant MSI as well. Elucidation of this previously unexplored facet of lymphocyte dynamics in relation to aging may help identify novel mechanisms of immunosenescence and pathways that could serve as targets for interventions to restore immune function.

  17. The Theory Behind the Age-Related Positivity Effect

    PubMed Central

    Reed, Andrew E.; Carstensen, Laura L.

    2012-01-01

    The “positivity effect” refers to an age-related trend that favors positive over negative stimuli in cognitive processing. Relative to their younger counterparts, older people attend to and remember more positive than negative information. Since the effect was initially identified and the conceptual basis articulated (Mather and Carstensen, 2005) scores of independent replications and related findings have appeared in the literature. Over the same period, a number of investigations have failed to observe age differences in the cognitive processing of emotional material. When findings are considered in theoretical context, a reliable pattern of evidence emerges that helps to refine conceptual tenets. In this article we articulate the operational definition and theoretical foundations of the positivity effect and review the empirical evidence based on studies of visual attention, memory, decision making, and neural activation. We conclude with a discussion of future research directions with emphasis on the conditions where a focus on positive information may benefit and/or impair cognitive performance in older people. PMID:23060825

  18. The Chromospheric Activity-Age Relation for M Dwarf Stars

    NASA Astrophysics Data System (ADS)

    Silvestri, N. M.; Oswalt, T. D.; Hawley, S. L.

    2000-12-01

    We present preliminary results from our study in which we use moderate resolution spectroscopy to determine the correlation between the chromospheric activity and age of M dwarf stars in wide binary systems. We have observed ~50 M dwarf stars from our sample with the Apache Point Observatory 3.5-m telescope. We measure the ratio of Hα luminosity to the bolometric luminosity (LHα /Lbol) of the M dwarf---a measure of activity that is proven to correlate well with age. This project is unique in that it will extend the chromospheric activity-age relation of low-mass main sequence stars beyond the ages provided by cluster methods. The ages so determined are also independent of the uncertainties in cluster age determinations. The technique has the potential to improve by at least a factor of two the precision and the range over which ages can currently be determined for main sequence stars. Work on this project is supported by the NASA Graduate Student Researchers Program grant NGT-50290 (N.M.S.).

  19. Age related changes in steroid receptors on cultured lung fibroblasts

    SciTech Connect

    Barile, F.A.; Bienkowski, R.S.

    1986-03-05

    The number of high affinity glucocorticoid receptors (Ro) on human fetal lung fibroblasts decreases as the cells age in vitro, and it has been suggested that these cell systems may be useful models of age-related changes in vivo. They examined the relation between change in Ro with in vitro aging and donor age. Confluent monolayers of lung fibroblasts at various population doubling levels (PDL), were incubated with (/sup 3/H)-dexamethasone ((/sup 3/H)Dex) either alone or with excess (.01 mM) Dex. Specific binding was calculated as the difference between radioactivity in cells incubated with and without unlabeled Dex; Scatchard plots were used to analyze the data. Ro, measured as fmol (/sup 3/H)Dex/10/sup 6/ cells, for two lines of human fetal cells (HFL-1 and MRC-5) decreased with increasing age in vitro. However, human newborn (CRL-1485) and adult (CCL-201) cells and fetal rabbit cells (FAB-290), showed increases in Ro with continuous passage. For each cell line, the affinity constant (K/sub d/) did not change significantly with passage. They conclude that the direction of changes in steroid receptor levels on cells aging in vitro is influenced by donor age and species. Caution should be used in applying results obtained from model systems to aging organisms.

  20. Age-related neural changes in autobiographical remembering and imagining.

    PubMed

    Addis, Donna Rose; Roberts, Reece P; Schacter, Daniel L

    2011-11-01

    Numerous neuroimaging studies have revealed that in young adults, remembering the past and imagining the future engage a common core network. Although it has been observed that older adults engage a similar network during these tasks, it is unclear whether or not they activate this network in a similar manner to young adults. Young and older participants completed two autobiographical tasks (imagining future events and recalling past events) in addition to a semantic-visuospatial control task. Spatiotemporal Partial Least Squares analyses examined whole brain patterns of activity across both the construction and elaboration of autobiographical events. These analyses revealed that that both age groups activated a similar network during the autobiographical tasks. However, some key age-related differences in the activation of this network emerged. During the construction of autobiographical events, older adults showed less activation relative to younger adults, in regions supporting episodic detail such as the medial temporal lobes and the precuneus. Later in the trial, older adults showed differential recruitment of medial and lateral temporal regions supporting the elaboration of autobiographical events, and possibly reflecting an increased role of conceptual information when older adults describe their pasts and their futures.

  1. eNOS-uncoupling in age-related erectile dysfunction.

    PubMed

    Johnson, J M; Bivalacqua, T J; Lagoda, G A; Burnett, A L; Musicki, B

    2011-01-01

    Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH(4)) on erectile function in the aged rats. Male Fischer 344 'young' (4-month-old) and 'aged' (19-month-old) rats were treated with a BH(4) precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS production, but did not affect eNOS uncoupling in the penis of aged rats. These findings suggest that aging induces eNOS uncoupling in the penis, resulting in increased oxidative stress and ED. PMID:21289638

  2. eNOS-uncoupling in age-related erectile dysfunction

    PubMed Central

    Johnson, JM; Bivalacqua, TJ; Lagoda, GA; Burnett, AL; Musicki, B

    2011-01-01

    Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH4) on erectile function in the aged rats. Male Fischer 344 ‘young’ (4-month-old) and ‘aged’ (19-month-old) rats were treated with a BH4 precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS production, but did not affect eNOS uncoupling in the penis of aged rats. These findings suggest that aging induces eNOS uncoupling in the penis, resulting in increased oxidative stress and ED. PMID:21289638

  3. Age-related hearing loss increases cross-modal distractibility.

    PubMed

    Puschmann, Sebastian; Sandmann, Pascale; Bendixen, Alexandra; Thiel, Christiane M

    2014-10-01

    Recent electrophysiological studies have provided evidence that changes in multisensory processing in auditory cortex cannot only be observed following extensive hearing loss, but also in moderately hearing-impaired subjects. How the reduced auditory input affects audio-visual interactions is however largely unknown. Here we used a cross-modal distraction paradigm to investigate multisensory processing in elderly participants with an age-related high-frequency hearing loss as compared to young and elderly subjects with normal hearing. During the experiment, participants were simultaneously presented with independent streams of auditory and visual input and were asked to categorize either the auditory or visual information while ignoring the other modality. Unisensory sequences without any cross-modal input served as control conditions to assure that all participants were able to perform the task. While all groups performed similarly in these unisensory conditions, hearing-impaired participants showed significantly increased error rates when confronted with distracting cross-modal stimulation. This effect could be observed in both the auditory and the visual task. Supporting these findings, an additional regression analysis indicted that the degree of high-frequency hearing loss significantly modulates cross-modal visual distractibility in the auditory task. These findings provide new evidence that already a moderate sub-clinical hearing loss, a common phenomenon in the elderly population, affects the processing of audio-visual information.

  4. Modifiable risk factors for age-related macular degeneration.

    PubMed

    Guymer, Robyn H; Chong, Elaine Wei-Tinn

    2006-05-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in Australia and other Western countries. As there is no cure for AMD, and treatments to stop its progression have met with limited success, there is an interest in identifying modifiable risk factors to prevent or slow disease progression. To date, smoking is the only proven modifiable risk factor for AMD. Other factors under study include (i) cardiovascular risk factors such as hypertension, body mass index, and atherosclerosis; and (ii) dietary risk factors including fat and antioxidant intake, but so far these studies have produced conflicting results. Dietary fat in relation to AMD has recently attracted media attention. Despite very limited work supporting an association between vegetable fat and AMD, widespread publicity advocating margarine as a cause of AMD and encouraging use of butter instead has caused confusion and anxiety among sufferers of AMD and the general public, as well as concern among health professionals. The antioxidant carotenoids--lutein and zeaxanthin--found in dark green or yellow vegetables exist in high concentrations in the macula and are hypothesised to play a protective role. Of nine controlled trials of supplementation with carotenoids and other antioxidants, three suggested that various combinations of antioxidants and carotenoids were protective. While a low-fat diet rich in dark green and yellow vegetables is advocated in general, any specific recommendations regarding certain fats or antioxidant supplementation and AMD are not based on consistent findings at this stage. PMID:16646746

  5. Eye Conditions in Older Adults: Age-Related Macular Degeneration.

    PubMed

    Iroku-Malize, Tochi; Kirsch, Scott

    2016-06-01

    Age-related macular degeneration (AMD) causes a progressive loss of photoreceptors in the macula. It is the most common cause of legal blindness in the United States, and some form of AMD is thought to affect more than 9 million individuals. Risk factors include older age, smoking, dyslipidemia, obesity, white race, female sex, and a family history of AMD. There are two types of advanced AMD: nonexudative (dry or geographic atrophy) and exudative (wet or neovascular). Both cause progressive central vision loss with intact peripheral vision. Nonexudative AMD accounts for 80% to 90% of all advanced cases, and more than 90% of patients with severe vision loss have exudative AMD. On ophthalmoscopic examination, early findings include drusen (ie, yellow deposits in the retina). Prominent choroidal vessels, subretinal edema, and/or hemorrhage are seen in wet AMD. Regular eye examinations, visual field testing, fluorescein angiography, and optical coherence tomography are used for diagnosis and to guide management. There is no specific therapy for dry AMD, but antioxidant supplementation may be helpful. Intravitreal injection of a vascular endothelial growth factor inhibitor is the treatment of choice for wet AMD. Optical aids and devices can help to maximize function for patients with AMD. PMID:27348529

  6. Age-related carbonyl stress and erythrocyte membrane protein carbonylation.

    PubMed

    Li, Guolin; Liu, Li; Hu, Hui; Zhao, Qiong; Xie, Fuxia; Chen, Keke; Liu, Shenglin; Chen, Yaqin; Shi, Wang; Yin, Dazhong

    2010-01-01

    Reactive carbonyl species (RCS) have been widely used as indicators of oxidative stress. However, the associations of carbonyl stress with aging process and biochemical alteration of erythrocyte are still poorly understood. Fresh blood samples in vacutainer tubes containing sodium heparinate were obtained from 874 volunteers who were divided into young, adult and old groups based on their age. Plasma RCS and thiols concentrations between different age groups and erythrocyte membrane protein carbonylation in the adult group were detected within 24h of the blood sampling. Results showed that the plasma thiols concentration decreased gradually during aging process, and the p-values between all three groups are less than 0.05. The plasma RCS concentration in different age groups showed a nonlinear association with age. The levels in the young group were slightly higher than the adult group (not significant) and lower than the old group (p < 0.01). The protein carbonylation of erythrocyte membrane was positively correlated with plasma RCS concentration (p < 0.01), but not plasma thiols concentration. We conclude that higher levels of RCS, not lower levels of thiols, in plasma are a direct risk factor for the protein carbonylation of erythrocyte membrane. Owing to the decrease of thiols levels and increase of RCS levels during aging process, a shift from RCS-related redox allostasis to carbonyl stress would contribute to age-related biological dysfunction and even aging process.

  7. Seven New Loci Associated with Age-Related Macular Degeneration

    PubMed Central

    2013-01-01

    Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate understanding of AMD biology and help design new therapies, we executed a collaborative genomewide association study, examining >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 genomic loci associated with AMD with p<5×10−8 and enriched for genes involved in regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include 7 loci reaching p<5×10−8 for the first time, near the genes COL8A1/FILIP1L, IER3/DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9/MIR548A2, and B3GALTL. A genetic risk score combining SNPs from all loci displayed similar good ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD. PMID:23455636

  8. Defining the boundary: age-related changes in childhood amnesia.

    PubMed

    Tustin, Karen; Hayne, Harlene

    2010-09-01

    Childhood amnesia refers to the inability of adults to recall events that occurred during their infancy and early childhood. Although it is generally assumed that children and adolescents also experience childhood amnesia, with limited exceptions, most empirical research on the phenomenon has focused exclusively on adults. Here, we developed a new Timeline procedure to directly compare the early memories reported by children, adolescents, and adults. Overall, the proportion of memories reported before the age of 3 years was greater for the children and adolescents relative to the adults. In addition, the single earliest memory reported by children and adolescents was at a younger age than that reported by adults. In fact, the earliest memories reported by the children and adolescents, but not the adults, were significantly younger than the traditional 3 (1/2)-year-old boundary of childhood amnesia. Regardless of the age of the rememberer, participants' early memories had the same episodic characteristics. We conclude that the boundary and the density of childhood amnesia may increase over the course of human development and that age-related changes in basic memory mechanisms make an important contribution to our understanding of the source of childhood amnesia.

  9. Epigenetic modification of PKMζ rescues aging-related cognitive impairment.

    PubMed

    Chen, Chen; Meng, Shi-Qiu; Xue, Yan-Xue; Han, Ying; Sun, Cheng-Yu; Deng, Jia-Hui; Chen, Na; Bao, Yan-Ping; Zhang, Fei-Long; Cao, Lin-Lin; Zhu, Wei-Guo; Shi, Jie; Song, Wei-Hong; Lu, Lin

    2016-03-01

    Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue.

  10. Age-Related Macular Degeneration: A Scientometric Analysis.

    PubMed

    Ramin, Shahrokh; Soheilian, Masoud; Habibi, Gholamreza; Ghazavi, Roghayeh; Gharebaghi, Reza; Heidary, Fatemeh

    2015-01-01

    Age-related macular degeneration (ARMD) is a major cause of central blindness among working aged adults across the world. Systematic research planning on any subject, including ARMD is in need of solid data regarding previous efforts in this field and to identify the gaps in the research. This study aimed to elucidate the most important trends, directions, and gap in this subject. The data extracted from the Institute for Scientific Information were used to perform a bibliometric analysis of the scientific productions (1993-2013) about ARMD. Specific parameters related to ARMD were analyzed to obtain a view of the topic's structure, history, and document relationships. Additionally, the trends and authors in the most influential publications were analyzed. The number of articles in this field was found constantly increasing. Most highly cited articles addressed genetic epidemiology and clinical research topics in this field. During the past 3 years, there has been a trend toward biomarker research. Through performing the first scientometric survey on ARMD research, we analyzed the characteristics of papers and the trends in scientific production. We also identified some of the critical gaps in the current research efforts that would help in large-scale research strategic planning. PMID:26060829

  11. Age-related impairment of mesenchymal progenitor cell function.

    PubMed

    Stolzing, Alexandra; Scutt, Andrew

    2006-06-01

    In most mesenchymal tissues a subcompartment of multipotent progenitor cells is responsible for the maintenance and repair of the tissue following trauma. With increasing age, the ability of tissues to repair themselves is diminished, which may be due to reduced functional capacity of the progenitor cells. The purpose of this study was to investigate the effect of aging on rat mesenchymal progenitor cells. Mesenchymal progenitor cells were isolated from Wistar rats aged 3, 7, 12 and 56 weeks. Viability, capacity for differentiation and cellular aging were examined. Cells from the oldest group accumulated raised levels of oxidized proteins and lipids and showed decreased levels of antioxidative enzyme activity. This was reflected in decreased fibroblast colony-forming unit (CFU-f) numbers, increased levels of apoptosis and reduced proliferation and potential for differentiation. These data suggest that the reduced ability to maintain mesenchymal tissue homeostasis in aged mammals is not purely due to a decline in progenitor cells numbers but also to a loss of progenitor functionality due to the accumulation of oxidative damage, which may in turn be a causative factor in a number of age-related pathologies such as arthritis, tendinosis and osteoporosis.

  12. Age-Related Macular Degeneration: A Scientometric Analysis.

    PubMed

    Ramin, Shahrokh; Soheilian, Masoud; Habibi, Gholamreza; Ghazavi, Roghayeh; Gharebaghi, Reza; Heidary, Fatemeh

    2015-01-01

    Age-related macular degeneration (ARMD) is a major cause of central blindness among working aged adults across the world. Systematic research planning on any subject, including ARMD is in need of solid data regarding previous efforts in this field and to identify the gaps in the research. This study aimed to elucidate the most important trends, directions, and gap in this subject. The data extracted from the Institute for Scientific Information were used to perform a bibliometric analysis of the scientific productions (1993-2013) about ARMD. Specific parameters related to ARMD were analyzed to obtain a view of the topic's structure, history, and document relationships. Additionally, the trends and authors in the most influential publications were analyzed. The number of articles in this field was found constantly increasing. Most highly cited articles addressed genetic epidemiology and clinical research topics in this field. During the past 3 years, there has been a trend toward biomarker research. Through performing the first scientometric survey on ARMD research, we analyzed the characteristics of papers and the trends in scientific production. We also identified some of the critical gaps in the current research efforts that would help in large-scale research strategic planning.

  13. Nutritional Risk Factors for Age-Related Macular Degeneration

    PubMed Central

    Ersoy, Lebriz; Lechanteur, Yara T.; Hoyng, Carel B.; Kirchhof, Bernd; den Hollander, Anneke I.

    2014-01-01

    Purpose. To evaluate the role of nutritional factors, serum lipids, and lipoproteins in late age-related macular degeneration (late AMD). Methods. Intake of red meat, fruit, fish, vegetables, and alcohol, smoking status, and body mass index (BMI) were ascertained questionnaire-based in 1147 late AMD cases and 1773 controls from the European Genetic Database. Serum levels of lipids and lipoproteins were determined. The relationship between nutritional factors and late AMD was assessed using logistic regression. Based on multivariate analysis, area-under-the-curve (AUC) was calculated by receiver-operating-characteristics (ROC). Results. In a multivariate analysis, besides age and smoking, obesity (odds ratio (OR): 1.44, P = 0.014) and red meat intake (daily: OR: 2.34, P = 8.22 × 10−6; 2–6x/week: OR: 1.67, P = 7.98 × 10−5) were identified as risk factors for developing late AMD. Fruit intake showed a protective effect (daily: OR: 0.52, P = 0.005; 2–6x/week: OR: 0.58, P = 0.035). Serum lipid and lipoprotein levels showed no significant association with late AMD. ROC for nutritional factors, smoking, age, and BMI revealed an AUC of 0.781. Conclusion. Red meat intake and obesity were independently associated with increased risk for late AMD, whereas fruit intake was protective. A better understanding of nutritional risk factors is necessary for the prevention of AMD. PMID:25101280

  14. Breed- and age-related differences in canine mammary tumors.

    PubMed

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-04-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted. PMID:27127342

  15. Endocrine causes of age-related bone loss and osteoporosis.

    PubMed

    Riggs, B Lawrence

    2002-01-01

    Women have an early postmenopausal phase of rapid bone loss that lasts for 5-10 years after menopause, whereas both ageing women and men have a slow continuous phase of bone loss that lasts indefinitely. In women, the rapid phase is mediated mainly by loss of the direct restraining effect of oestrogen on bone cell function, whereas the slow phase is mediated mainly by the loss of oestrogen action on extraskeletal calcium homeostasis leading to net calcium wasting and secondary hyperparathyroidism. Because elderly men have low serum bioavailable oestrogen and testosterone levels, and because recent data suggest that oestrogen is the main sex steroid regulating bone metabolism in men, oestrogen deficiency may also be the principal cause of bone loss in elderly men. Decreased bone formation contributes to bone loss in both genders and may be caused by a decreased production of growth hormone and IGF1 as well as oestrogen and testosterone deficiency. Other changes in endocrine secretion, although present in the elderly, seem less important in the pathophysiology of age-related bone loss and osteoporosis. PMID:11855691

  16. Prevalence of age-related macular degeneration among the elderly

    PubMed Central

    Rasoulinejad, Seyed Ahmad; Zarghami, Amin; Hosseini, Seyed Reza; Rajaee, Neda; Rasoulinejad, Seyed Elahe; Mikaniki, Ebrahim

    2015-01-01

    Background: Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in elderly population in the developing countries. Previous epidemiological studies revealed various potential modifiable risk factors for this disease. The purpose of this study was to evaluate the prevalence of AMD among elderly living in Babol, North of Iran. Methods: The study population of this cross-sectional study came from the Amirkola Health and Ageing Project (AHAP), the first comprehensive cohort study of the health of people aged 60 years and over in Amirkola, North of Iran. The prevalence of AMD was estimated and its risk was determined using logistic regression analysis (LRA) with regard to variables such as smoking, hyperlipidemia, hypertension and diabetes. Results: Five hundred and five participants with mean age of 71.55±5.9 (ranged 60-89) years entered the study. The prevalence of AMD was 17.6%. There was a significant association between AMD and smoking (P<0.001) but no association was seen with AMD and age, level of education, history of hyperlipidemia, hypertension and diabetes. Multiple LRAs revealed that smoking increased AMD by odds ratio of 5.03 (95% confidence interval 2.47-10.23 p<0.001) as compared to nonsmokers Conclusion: According to our findings, the prevalence of AMD was relatively high and smoking increased the risk of AMD in the elderly population. PMID:26644880

  17. Age-Related Changes in Demand–Withdraw Communication Behaviors

    PubMed Central

    Holley, Sarah R.; Haase, Claudia M.; Levenson, Robert W.

    2013-01-01

    Demand–withdraw communication is a set of conflict-related behaviors in which one partner blames or pressures while the other partner withdraws or avoids. The present study examined age-related changes in these behaviors longitudinally over the course of later life stages. One hundred twenty-seven middle-aged and older long-term married couples were observed at 3 time points across 13 years as they engaged in a conversation about an area of relationship conflict. Husbands’ and wives’ demand–withdraw behaviors (i.e., blame, pressure, withdrawal, avoidance) were objectively rated by trained coders at each time point. Data were analyzed using dyad-level latent growth curve models in a structural equation modeling framework. For both husbands and wives, the results showed a longitudinal pattern of increasing avoidance behavior over time and stability in all other demand and withdraw behaviors. This study supports the notion that there is an important developmental shift in the way that conflict is handled in later life. PMID:23913982

  18. Breed- and age-related differences in canine mammary tumors

    PubMed Central

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-01-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted. PMID:27127342

  19. Eye Conditions in Older Adults: Age-Related Macular Degeneration.

    PubMed

    Iroku-Malize, Tochi; Kirsch, Scott

    2016-06-01

    Age-related macular degeneration (AMD) causes a progressive loss of photoreceptors in the macula. It is the most common cause of legal blindness in the United States, and some form of AMD is thought to affect more than 9 million individuals. Risk factors include older age, smoking, dyslipidemia, obesity, white race, female sex, and a family history of AMD. There are two types of advanced AMD: nonexudative (dry or geographic atrophy) and exudative (wet or neovascular). Both cause progressive central vision loss with intact peripheral vision. Nonexudative AMD accounts for 80% to 90% of all advanced cases, and more than 90% of patients with severe vision loss have exudative AMD. On ophthalmoscopic examination, early findings include drusen (ie, yellow deposits in the retina). Prominent choroidal vessels, subretinal edema, and/or hemorrhage are seen in wet AMD. Regular eye examinations, visual field testing, fluorescein angiography, and optical coherence tomography are used for diagnosis and to guide management. There is no specific therapy for dry AMD, but antioxidant supplementation may be helpful. Intravitreal injection of a vascular endothelial growth factor inhibitor is the treatment of choice for wet AMD. Optical aids and devices can help to maximize function for patients with AMD.

  20. Mechanism of Inflammation in Age-Related Macular Degeneration

    PubMed Central

    Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

  1. Caspase-2 Deficiency Enhances Aging-Related Traits in Mice

    PubMed Central

    Zhang, Yingpei; Padalecki, Susan S; Chaudhuri, Asish R; Waal, Eric De; Goins, Beth A; Grubbs, Barry; Ikeno, Yuji; Richardson, Arlan; Mundy, Gregory R; Herman, Brian

    2007-01-01

    Alteration of apoptotic activity has been observed in a number of tissues in aging mammals, but it remains unclear whether and/or how apoptosis may affect aging. Caspase-2 is a member of the cysteine protease family that plays a critical role in apoptosis. To understand the impact of compromised apoptosis function on mammalian aging, we conducted a comparative study on caspase-2 deficient mice and their wild-type littermates with a specific focus on the aging-related traits at advanced ages. We found that caspase-2 deficiency enhanced a number of traits commonly seen in premature aging animals. Loss of caspase-2 was associated with shortened maximum lifespan, impaired hair growth, increased bone loss, and reduced body fat content. In addition, we found that the livers of caspase-2 deficient mice had higher levels of oxidized proteins than those of age-matched wild-type mice, suggesting that caspase-2 deficiency compromised the animal's ability to clear oxidatively damaged cells. Collectively, these results suggest that caspase-2 deficiency affects aging in the mice. This study thus demonstrates for the first time that disruption of a key apoptotic gene has a significant impact on aging. PMID:17188333

  2. Epigenetic modification of PKMζ rescues aging-related cognitive impairment

    PubMed Central

    Chen, Chen; Meng, Shi-Qiu; Xue, Yan-Xue; Han, Ying; Sun, Cheng-Yu; Deng, Jia-Hui; Chen, Na; Bao, Yan-Ping; Zhang, Fei-Long; Cao, Lin-Lin; Zhu, Wei-Guo; Shi, Jie; Song, Wei-Hong; Lu, Lin

    2016-01-01

    Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue. PMID:26926225

  3. Promising new treatments for neovascular age-related macular degeneration.

    PubMed

    Michels, Stephan; Schmidt-Erfurth, Ursula; Rosenfeld, Philip J

    2006-07-01

    Angiogenesis, the growth of new blood vessels from existing blood vessels, is responsible for vision loss in a variety of ophthalmic diseases. In neovascular age-related macular degeneration (AMD), the leading cause for legal blindness in many industrialised countries, abnormal blood vessels grow in the macula and cause blindness. There are a number of factors important in the angiogenic cascade but VEGF-A has been implicated in recent years as the major factor responsible for neovascular and exudative diseases of the eye. Numerous antiangiogenic drugs are in development but anti-VEGF drugs have shown great promise in treating neovascular AMD and other ocular diseases, and many of these drugs have been adopted from oncology where antiangiogenic therapy is gaining wide acceptance. For the first time in neovascular AMD, anti-VEGF drugs have brought the hope of vision improvement to a significant proportion of patients. This review provides an overview on angiogenic mechanisms, potential antiangiogenic treatment strategies and different antiangiogenic drugs with special focus on neovascular AMD. PMID:16787141

  4. Age-related macular degeneration: experimental and emerging treatments

    PubMed Central

    Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D

    2009-01-01

    Purpose: This essay reviews the experimental treatments and new imaging modalities that are currently being explored by investigators to help treat patients with age-related macular degeneration (AMD). Design: Interpretative essay. Methods: Literature review and interpretation. Results: Experimental treatments to preserve vision in patients with exudative AMD include blocking vascular endothelial growth factor (VEGF), binding VEGF, and modulating the VEGF receptors. Investigators are also attempting to block signal transduction with receptor tyrosine kinase inhibitors. Experimental treatments for non-exudative AMD include agents that target inflammation, oxidative stress, and implement immune-modulation. The effectiveness of these newer pharmacologic agents has the potential to grow exponentially when used in combination with new and improved imaging modalities that can help identify disease earlier and follow treatment response more precisely. Conclusion: With a better understanding, at the genetic and molecular level, of AMD and the development of superior imaging modalities, investigators are able to offer treatment options that may offer unprecedented visual gains while reducing the need for repetitive treatments. PMID:19668561

  5. The impact of sleep on age-related sarcopenia: Possible connections and clinical implications.

    PubMed

    Piovezan, Ronaldo D; Abucham, Julio; Dos Santos, Ronaldo Vagner Thomatieli; Mello, Marco Tulio; Tufik, Sergio; Poyares, Dalva

    2015-09-01

    Sarcopenia is a geriatric condition that comprises declined skeletal muscle mass, strength and function, leading to the risk of multiple adverse outcomes, including death. Its pathophysiology involves neuroendocrine and inflammatory factors, unfavorable nutritional habits and low physical activity. Sleep may play a role in muscle protein metabolism, although this hypothesis has not been studied extensively. Reductions in duration and quality of sleep and increases in prevalence of circadian rhythm and sleep disorders with age favor proteolysis, modify body composition and increase the risk of insulin resistance, all of which have been associated with sarcopenia. Data on the effects of age-related slow-wave sleep decline, circadian rhythm disruptions and obstructive sleep apnea (OSA) on hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG), somatotropic axes, and glucose metabolism indicate that sleep disorder interventions may affect muscle loss. Recent research associating OSA with the risk of conditions closely related to the sarcopenia process, such as frailty and sleep quality impairment, indirectly suggest that sleep can influence skeletal muscle decline in the elderly. Several protein synthesis and degradation pathways are mediated by growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, cortisol and insulin, which act on the cellular and molecular levels to increase or reestablish muscle fiber, strength and function. Age-related sleep problems potentially interfere intracellularly by inhibiting anabolic hormone cascades and enhancing catabolic pathways in the skeletal muscle. Specific physical exercises combined or not with nutritional recommendations are the current treatment options for sarcopenia. Clinical studies testing exogenous administration of anabolic hormones have not yielded adequate safety profiles. Therapeutic approaches targeting sleep disturbances to normalize circadian rhythms and sleep homeostasis may

  6. The impact of sleep on age-related sarcopenia: Possible connections and clinical implications.

    PubMed

    Piovezan, Ronaldo D; Abucham, Julio; Dos Santos, Ronaldo Vagner Thomatieli; Mello, Marco Tulio; Tufik, Sergio; Poyares, Dalva

    2015-09-01

    Sarcopenia is a geriatric condition that comprises declined skeletal muscle mass, strength and function, leading to the risk of multiple adverse outcomes, including death. Its pathophysiology involves neuroendocrine and inflammatory factors, unfavorable nutritional habits and low physical activity. Sleep may play a role in muscle protein metabolism, although this hypothesis has not been studied extensively. Reductions in duration and quality of sleep and increases in prevalence of circadian rhythm and sleep disorders with age favor proteolysis, modify body composition and increase the risk of insulin resistance, all of which have been associated with sarcopenia. Data on the effects of age-related slow-wave sleep decline, circadian rhythm disruptions and obstructive sleep apnea (OSA) on hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG), somatotropic axes, and glucose metabolism indicate that sleep disorder interventions may affect muscle loss. Recent research associating OSA with the risk of conditions closely related to the sarcopenia process, such as frailty and sleep quality impairment, indirectly suggest that sleep can influence skeletal muscle decline in the elderly. Several protein synthesis and degradation pathways are mediated by growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, cortisol and insulin, which act on the cellular and molecular levels to increase or reestablish muscle fiber, strength and function. Age-related sleep problems potentially interfere intracellularly by inhibiting anabolic hormone cascades and enhancing catabolic pathways in the skeletal muscle. Specific physical exercises combined or not with nutritional recommendations are the current treatment options for sarcopenia. Clinical studies testing exogenous administration of anabolic hormones have not yielded adequate safety profiles. Therapeutic approaches targeting sleep disturbances to normalize circadian rhythms and sleep homeostasis may

  7. Developing Cellular Therapies for Retinal Degenerative Diseases

    PubMed Central

    Bharti, Kapil; Rao, Mahendra; Hull, Sara Chandros; Stroncek, David; Brooks, Brian P.; Feigal, Ellen; van Meurs, Jan C.; Huang, Christene A.; Miller, Sheldon S.

    2014-01-01

    Biomedical advances in vision research have been greatly facilitated by the clinical accessibility of the visual system, its ease of experimental manipulation, and its ability to be functionally monitored in real time with noninvasive imaging techniques at the level of single cells and with quantitative end-point measures. A recent example is the development of stem cell–based therapies for degenerative eye diseases including AMD. Two phase I clinical trials using embryonic stem cell–derived RPE are already underway and several others using both pluripotent and multipotent adult stem cells are in earlier stages of development. These clinical trials will use a variety of cell types, including embryonic or induced pluripotent stem cell–derived RPE, bone marrow– or umbilical cord–derived mesenchymal stem cells, fetal neural or retinal progenitor cells, and adult RPE stem cells–derived RPE. Although quite distinct, these approaches, share common principles, concerns and issues across the clinical development pipeline. These considerations were a central part of the discussions at a recent National Eye Institute meeting on the development of cellular therapies for retinal degenerative disease. At this meeting, emphasis was placed on the general value of identifying and sharing information in the so-called “precompetitive space.” The utility of this behavior was described in terms of how it could allow us to remove road blocks in the clinical development pipeline, and more efficiently and economically move stem cell–based therapies for retinal degenerative diseases toward the clinic. Many of the ocular stem cell approaches we discuss are also being used more broadly, for nonocular conditions and therefore the model we develop here, using the precompetitive space, should benefit the entire scientific community. PMID:24573369

  8. Auditory sensitivity and the outer hair cell system in the CBA mouse model of age-related hearing loss.

    PubMed

    Frisina, Robert D; Zhu, Xiaoxia

    2010-06-01

    Age-related hearing loss is a highly prevalent sensory disorder, from both the clinical and animal model perspectives. Understanding of the neurophysiologic, structural, and molecular biologic bases of age-related hearing loss will facilitate development of biomedical therapeutic interventions to prevent, slow, or reverse its progression. Thus, increased understanding of relationships between aging of the cochlear (auditory portion of the inner ear) hair cell system and decline in overall hearing ability is necessary. The goal of the present investigation was to test the hypothesis that there would be correlations between physiologic measures of outer hair cell function (otoacoustic emission levels) and hearing sensitivity (auditory brainstem response thresholds), starting in middle age. For the CBA mouse, a useful animal model of age-related hearing loss, it was found that correlations between these two hearing measures occurred only for high sound frequencies in middle age. However, in old age, a correlation was observed across the entire mouse range of hearing. These findings have implications for improved early detection of progression of age-related hearing loss in middle-aged mammals, including mice and humans, and distinguishing peripheral etiologies from central auditory system decline.

  9. Differences in age-related effects on brain volume in Down syndrome as compared to Williams syndrome and typical development

    PubMed Central

    2014-01-01

    Background Individuals with Down Syndrome (DS) are reported to experience early onset of brain aging. However, it is not well understood how pre-existing neurodevelopmental effects versus neurodegenerative processes might be contributing to the observed pattern of brain atrophy in younger adults with DS. The aims of the current study were to: (1) to confirm previous findings of age-related changes in DS compared to adults with typical development (TD), (2) to test for an effect of these age-related changes in a second neurodevelopmental disorder, Williams syndrome (WS), and (3) to identify a pattern of regional age-related effects that are unique to DS. Methods High-resolution T1-weighted MRI of the brains of subjects with DS, WS, and TD controls were segmented, and estimates of regional brain volume were derived using FreeSurfer. A general linear model was employed to test for age-related effects on volume between groups. Secondary analyses in the DS group explored the relationship between brain volume and neuropsychological tests and APOE. Results Consistent with previous findings, the DS group showed significantly greater age-related effects relative to TD controls in total gray matter and in regions of the orbitofrontal cortex and the parietal cortex. Individuals with DS also showed significantly greater age-related effects on volume of the left and right inferior lateral ventricles (LILV and RILV, respectively). There were no significant differences in age-related effects on volume when comparing the WS and TD groups. In the DS group, cognitive tests scores measuring signs of dementia and APOE ϵ4 carrier status were associated with LILV and RILV volume. Conclusions Individuals with DS demonstrated a unique pattern of age-related effects on gray matter and ventricular volume, the latter of which was associated with dementia rating scores in the DS group. Results may indicate that early onset of brain aging in DS is primarily due to DS

  10. DEGENERATIVE STENOSIS OF THE LUMBAR SPINE

    PubMed Central

    Zylbersztejn, Sérgio; Spinelli, Leandro de Freitas; Rodrigues, Nilson Rodinei; Werlang, Pablo Mariotti; Kisaki, Yorito; Rios, Aldemar Roberto Mieres; Bello, Cesar Dall

    2015-01-01

    This paper presents an update on degenerative stenosis of the lumbar spine, which is a common pathological condition among patients over the age of 65 years. The anamnesis and physical examination need to be precise, since radiography often only provides indirect signs. Magnetic resonance imaging is necessary if the symptoms persist. The treatment for lumbar stenosis is a matter of controversy. However, there seems to be some benefit from surgical treatment rather than conservative treatment, such that surgery brings improvements in symptoms and functions for a period of up to two years. PMID:27042635

  11. Age-Related Susceptibility of Turkeys to Enteric Viruses.

    PubMed

    Awe, Olusegun O; Kang, Kyung-il; Ibrahim, Mahmoud; Ali, Ahmed; Elaish, Mohamed; Saif, Yehia M; Lee, Chang-Won

    2015-06-01

    Several different enteric viruses have been identified as the causes of gastrointestinal infections in poultry. Enteric virus infections are well characterized in poults, but limited studies have been conducted in older birds. The susceptibility of 2-, 7-, 12-, 30-, and 52-wk-old turkeys to turkey coronavirus (TCoV) and turkey astrovirus (TAstV) was evaluated, as well as the effect of combined infection of TAstV and TCoV in 2-wk-old poults and turkey hens. From cloacal swabs and intestines, TCoV was consistently detected by reverse transcriptase-PCR throughout the experimental period (1-21 days postinoculation [DPI]) from all age groups. In contrast, the last detection point of TAstV gradually decreased to 21, 16, and 12 DPI in birds inoculated at 2, 7, and 12 wk of age, respectively, and viral RNA was rarely detected from cloacal swabs or intestinal contents in turkey hens within 3 DPI. Infection with TAstV alone did not affect body weight in poults or egg production in hens. The combined infection of TAstV and TCoV did not induce more severe clinical signs and pathology than the TCoV infection alone. However, a severe prolonged decrease in egg production (about 50%) was observed in turkey hens in the combined infection group compared with a transient egg production drop in the TCoV-infected hens alone. The underlying mechanism regarding the age-related TAstV susceptibility and the pathogenesis of the TAstV and TCoV coinfection in layer hens needs to be further elucidated. PMID:26473670

  12. Heterogeneity in age-related white matter changes.

    PubMed

    Schmidt, Reinhold; Schmidt, Helena; Haybaeck, Johannes; Loitfelder, Marisa; Weis, Serge; Cavalieri, Margherita; Seiler, Stephan; Enzinger, Christian; Ropele, Stefan; Erkinjuntti, Timo; Pantoni, Leonardo; Scheltens, Philip; Fazekas, Franz; Jellinger, Kurt

    2011-08-01

    White matter changes occur endemically in routine magnetic resonance imaging (MRI) scans of elderly persons. MRI appearance and histopathological correlates of white matter changes are heterogeneous. Smooth periventricular hyperintensities, including caps around the ventricular horns, periventricular lining and halos are likely to be of non-vascular origin. They relate to a disruption of the ependymal lining with subependymal widening of the extracellular space and have to be differentiated from subcortical and deep white matter abnormalities. For the latter a distinction needs to be made between punctate, early confluent and confluent types. Although punctate white matter lesions often represent widened perivascular spaces without substantial ischemic tissue damage, early confluent and confluent lesions correspond to incomplete ischemic destruction. Punctate abnormalities on MRI show a low tendency for progression, while early confluent and confluent changes progress rapidly. The causative and modifying pathways involved in the occurrence of sporadic age-related white matter changes are still incompletely understood, but recent microarray and genome-wide association approaches increased the notion of pathways that might be considered as targets for therapeutic intervention. The majority of differentially regulated transcripts in white matter lesions encode genes associated with immune function, cell cycle, proteolysis, and ion transport. Genome-wide association studies identified six SNPs mapping to a locus on chromosome 17q25 to be related to white matter lesion load in the general population. We also report first and preliminary data that demonstrate apolipoprotein E (ApoE) immunoreactivity in white matter lesions and support epidemiological findings indicating that ApoE is another factor possibly related to white matter lesion occurrence. Further insights come from modern MRI techniques, such as diffusion tensor and magnetization transfer imaging, as they

  13. Age-related changes in the Brazilian woman's smile.

    PubMed

    Correia, Luiza Nayara Almeida Lyra; Reis, Silvia Augusta Braga; Conti, Ana Claudia de Castro Ferreira; Capelozza Filho, Leopoldino; Almeida-Pedrin, Renata Rodrigues

    2016-01-01

    The aim of this research was to evaluate age-related changes in the smile of Brazilian women. The sample consisted of 249 Brazilian women who had not undergone previous orthodontic treatment or facial surgery. They were divided into four groups, according to age: G1 (20-29), G2 (30-39), G3 (40-49) and G4 (50 or older). Standardized front view photographs were taken while smiling and at rest. Measurements were evaluated by ANOVA and post-hoc Tukey. The Chi-square test was applied for qualitative variables. Upper lip thickness at rest and exposure of upper incisors on smiling decreased with age. Most individuals (60.9%) exhibited a medium smile. High smiles were more often seen in G1 (45%) and less frequently in G4 (18.8%), whereas the opposite occurred with the low smile, i.e., G4 (21.9%) and G1 (6.7%). Variations among the groups were observed in the transverse exposure of the teeth on smiling. In G1 and G3, there was a balance between tooth exposures, so that the teeth were exposed as far as the premolars and/or molars. Most of the women (56.3%) in G2 exposed their teeth as far as the first molars on smiling, whereas most of those (40.6%) in G4 exposed their teeth only as far as the first premolars on smiling. As age increased, there was decreased exposure of the upper incisors, decreased upper lip thickness and lower exposure of teeth vertically and transversely.

  14. Genetic and Environmental Factors in Age-Related Hearing Impairment.

    PubMed

    Momi, Sukhleen K; Wolber, Lisa E; Fabiane, Stella Maris; MacGregor, Alex J; Williams, Frances M K

    2015-08-01

    Age-related hearing impairment (ARHI) is a common condition with complex etiology but a recognized genetic component. Heritability estimates for pure tone audiogram-determined hearing ability lie in the range 26-75%. The speech-in-noise (SIN) auditory test, however, may be better at encapsulating ARHI symptoms, particularly the diminished ability to segregate environmental sounds into comprehendible auditory streams. As heritability of SIN has not previously been reported, we explored the genetic and environmental contributions to ARHI determined by SIN in 2,076 twins (87.8% female) aged 18-87 (mean age 54.4). SIN was found to be significantly heritable (A, unadjusted for age=40%; 95% confidence intervals, CI=32%-47%). With age adjustment, heritability fell (A=25%; 95% CI=16-33%), and a relatively strong influence of environmental exposure unshared within twin siblings was identified (E=75%). To explore the environmental aspects further, we assessed the influence of diet (through the Food Frequency Questionnaire, FFQ), smoking (through self-report and cotinine metabolite levels) and alcohol intake (through the FFQ). A negative influence of high cholesterol diet was observed after adjustment (p=.037). A protective effect of raised serum high-density lipoprotein (HDL) cholesterol levels was observed after adjustment (p=.004). This study is the first assessment of the genetic and environmental influence on SIN perception. The findings suggest SIN is less heritable than pure tone audiogram (PTA) ability and highly influenced by the environment unique to each twin. Furthermore, a possible role of dietary fat in the etiology of ARHI is highlighted.

  15. Gene Therapy for Age-Related Macular Degeneration.

    PubMed

    Constable, Ian Jeffery; Blumenkranz, Mark Scott; Schwartz, Steven D; Barone, Sam; Lai, Chooi-May; Rakoczy, Elizabeth Piroska

    2016-01-01

    The purpose of this article was to evaluate safety and signals of efficacy of gene therapy with subretinal rAAV.sFlt-1 for wet age-related macular degeneration (wet AMD). A phase 1 dose-escalating single-center controlled unmasked human clinical trial was followed up by extension of the protocol to a phase 2A single-center trial. rAAV.sFlt-1 vector was used to deliver a naturally occurring anti-vascular endothelial growth factor agent, sFlt-1, into the subretinal space. In phase 1, step 1 randomized 3 subjects to low-dose rAAV.sFlt-1 (1 × 10 vector genomes) and 1 subject to the control arm; step 2 randomized an additional 3 subjects to treatment with high-dose rAAV.sFlt-1 (1 × 10 vector genomes) and 1 subject to the control arm. Follow-up studies demonstrated that rAAV.sFlt-1 was well tolerated with a favorable safety profile in these elderly subjects with wet AMD. Subretinal injection was highly reproducible, and no drug-related adverse events were reported. Procedure-related adverse events were mild and self-resolving. Two phakic patients developed cataract and underwent cataract surgery. Four of the 6 patients responded better than the small control group in this study and historical controls in terms of maintaining vision and a relatively dry retina with zero ranibizumab retreatments per annum. Two patients required 1 ranibizumab injection over the 52-week follow-up period. rAAV.sFlt-1 gene therapy may prove to be a potential adjunct or alternative to conventional intravitreal injection for patients with wet AMD by providing extended delivery of a naturally occurring antiangiogenic protein. PMID:27488071

  16. Neuropharmacology of depression in aging and age-related diseases.

    PubMed

    Gareri, Pietro; De Fazio, Pasquale; De Sarro, Giovambattista

    2002-02-01

    Depression in the elderly is nowadays a predominant health care problem, mainly due to the progressive aging of the population. It results from psychosocial stress, polypathology, as well as some biochemical changes which occur in the aged brain and can lead to cognitive impairments, increased symptoms from medical illness, higher utilization of health care services and increased rates of suicide and non-suicide mortality. Depression may be also caused by a various number of drugs currently administered; this is remarkable especially in elderly people, where polypathology is often associated with polypharmacotherapy. However, the pathogenesis of geriatric depression is not well understood; major depression may arise from dysfunction of the limbic-hypothalamic-pituitary-adrenal axis. Some clinical observations also suggest that striato-frontal dysfunction is associated with late life depression. A number of hypotheses have been made, focusing that mood disturbances are probably linked to a disturbed central metabolism of monoamines 5-hydroxytryptamine, noradrenaline and dopamine; however most of this knowledge is derived from animal models. Parkinson's and Alzheimer's diseases are age-related diseases associated to decreased activity or brain lesions in the orbital frontal cortex and basal ganglia. These observations lead to the hypothesis that the dysfunction of one or more of the cortical basal ganglia-thalamic neuronal loops are involved in the pathophysiology of primary and secondary depression. This dysfunction may be mediated by decreased serotonin release and probably, also by reduction in serotonin receptors. Development of novel approaches such as dynamic brain imaging methods, together with indirect knowledge coming from the effects of new antidepressants, will increase the understanding of neurochemistry of depression in old age. PMID:12039452

  17. The Age-Related Orientational Changes of Human Semicircular Canals

    PubMed Central

    Lyu, Hui-Ying; Chen, Ke-Guang; Yin, Dong-Ming; Hong, Juan; Yang, Lin; Zhang, Tian-Yu; Dai, Pei-Dong

    2016-01-01

    Objectives Some changes are found in the labyrinth anatomy during postnatal development. Although the spatial orientation of semicircular canals was thought to be stable after birth, we investigated the age-related orientational changes of human semicircular canals during development. Methods We retrospectively studied the computed tomography (CT) images of both ears of 76 subjects ranged from 1 to 70 years old. They were divided into 4 groups: group A (1–6 years), group B (7–12 years), group C (13–18 years), and group D (>18 years). The anatomical landmarks of the inner ear structures were determined from CT images. Their coordinates were imported into MATLAB software for calculating the semicircular canals orientation, angles between semicircular canal planes and the jugular bulb (JB) position. Differences between age groups were analyzed using multivariate statistics. Relationships between variables were analyzed using Pearson analysis. Results The angle between the anterior semicircular canal plane and the coronal plane, and the angle between the horizontal semicircular canal plane and the coronal plane were smaller in group D than those in group A (P<0.05). The JB position, especially the anteroposterior position of right JB, correlated to the semicircular canals orientation (P<0.05). However, no statistically significant differences in the angles between ipsilateral canal planes among different age groups were found. Conclusion The semicircular canals had tendencies to tilt anteriorly simultaneously as a whole with age. The JB position correlated to the spatial arrangement of semicircular canals, especially the right JB. Our calculation method helps detect developmental and pathological changes in vestibular anatomy. PMID:27090280

  18. Glycolysis in Patients with Age-Related Macular Degeneration

    PubMed Central

    Yokosako, Kanako; Mimura, Tatsuya; Funatsu, Hideharu; Noma, Hidetaka; Goto, Mari; Kamei, Yuko; Kondo, Aki; Matsubara, Masao

    2014-01-01

    Purpose: Retinal adenosine triphosphate is mainly produced via glycolysis, so inhibition of glycolysis may promote the onset and progression of age-related macular degeneration (AMD). When glycolysis is inhibited, pyruvate is metabolized by lactic acid fermentation instead of entering the mitochondrial tricarboxylic acid (TCA) cycle. We measured urinary pyruvate and lactate levels in patients with AMD. Methods: Eight patients with typical AMD (tAMD group) and 9 patients with polypoidal choroidal vasculopathy (PCV group) were enrolled. Urinary levels of pyruvate, lactate, α-hydroxybutyrate, and β-hydroxybutyrate were measured in all patients. Results: The mean urinary levels of pyruvate and lactate were 8.0 ± 2.8 and 7.5 ± 8.3 μg/mg creatinine (reference values: 0.5-6.6 and 0.0-1.6), respectively, with the mean increase over the reference value being 83.6 ± 51.1% and 426.5 ± 527.8%, respectively. In 12 patients (70.6%), the lactate/pyruvate ratio was above the reference range. Urinary levels of α-hydroxybutyrate and β-hydroxybutyrate were decreased by -31.9 ± 15.2% and -33.1 ± 17.5% compared with the mean reference values. There were no significant differences of any of these glycolysis metabolites between the tAMD and PCV groups. Multivariate analysis revealed that none of the variables tested, including patient background factors (age, hypertension, diabetes, hyperlipidemia, cerebrovascular disease, alcohol, smoking, visual acuity, and AMD phenotype), were significantly associated with the lactate/pyruvate ratio. Conclusion: A high lactate/pyruvate ratio is a well-known marker of mitochondrial impairment, and it indicates poor oxidative function in AMD. Our results suggest that increased lactate levels may be implicated in the pathogenesis of AMD. PMID:25191529

  19. Age-related decline in global form suppression.

    PubMed

    Wiegand, Iris; Finke, Kathrin; Töllner, Thomas; Starman, Kornelija; Müller, Hermann J; Conci, Markus

    2015-12-01

    Visual selection of illusory 'Kanizsa' figures, an assembly of local elements that induce the percept of a whole object, is facilitated relative to configurations composed of the same local elements that do not induce a global form--an instance of 'global precedence' in visual processing. Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global-local task requiring selection of either a 'global' Kanizsa- or a 'local' non-Kanizsa configuration (in the presence of the respectively other configuration) by analyzing event-related lateralizations (ERLs). Behaviorally, older participants showed a more pronounced global-precedence effect. Electrophysiologically, this effect was accompanied by an early (150-225 ms) 'positivity posterior contralateral' (PPC), which was elicited for older, but not younger, participants, when the target was a non-Kanizsa configuration and the Kanizsa figure a distractor (rather than vice versa). In addition, timing differences in the subsequent (250-500 ms) posterior contralateral negativity (PCN) indicated that attentional resources were allocated faster to Kanizsa, as compared to non-Kanizsa, targets in both age groups, while the allocation of spatial attention seemed to be generally delayed in older relative to younger age. Our results suggest that the enhanced global-local asymmetry in the older age group originated from less effective suppression of global distracter forms on early processing stages--indicative of older observers having difficulties with disengaging from a global default selection mode and switching to the required local state of attentional resolution. PMID:26498865

  20. Individual and age-related variation in chromatic contrast adaptation

    PubMed Central

    Elliott, Sarah L.; Werner, John S.; Webster, Michael A.

    2012-01-01

    Precortical color channels are tuned primarily to the LvsM (stimulation of L and M cones varied, but S cone stimulation held constant) or SvsLM (stimulation of S cones varied, but L and M cone stimulation held constant) cone-opponent (cardinal) axes, but appear elaborated in the cortex to form higher-order mechanisms tuned to both cardinal and intermediate directions. One source of evidence for these higher-order mechanisms has been the selectivity of color contrast adaptation for noncardinal directions, yet the degree of this selectivity has varied widely across the small sample of observers tested in previous studies. This study explored the possible bases for this variation, and in particular tested whether it reflected age-related changes in the distribution or tuning of color mechanisms. Observers included 15 younger (18–22 years of age) and 15 older individuals (66–82), who adapted to temporal modulations along one of four chromatic axes (two cardinal and two intermediate axes) and then matched the hue and contrast of test stimuli lying along eight different directions in the equiluminant plane. All observers exhibited aftereffects that were selective for both the cardinal and intermediate directions, although selectivity was weaker for the intermediate axes. The degree of selectivity increased with the magnitude of adaptation for all axes, and thus adaptation strength alone may account for much of the variance in selectivity among observers. Older observers showed a stronger magnitude of adaptation thus, surprisingly, more conspicuous evidence for higher-order mechanisms. For both age groups the aftereffects were well predicted by response changes in chromatic channels with linear spectral sensitivities, and there was no evidence for weakened channel tuning with aging. The results suggest that higher-order mechanisms may become more exposed in observers or conditions in which the strength of adaptation is greater, and that both chromatic contrast

  1. New Treatment Greatly Improves Prognosis for Patients with AMD (Age-Related Macular Degeneration)

    MedlinePlus

    ... turn JavaScript on. Feature: Age-related Macular Degeneration New Treatment Greatly Improves Prognosis for Patients with AMD ... Eye Institute Photo Courtesy of: NEI In a new study of nearly 650 people with age-related ...

  2. Imaging of genetic and degenerative disorders primarily causing Parkinsonism.

    PubMed

    Brooks, David J

    2016-01-01

    In this chapter the structural and functional imaging changes associated with both genetic causes of Parkinson's disease and the sporadic condition are reviewed. The role of imaging for supporting diagnosis and detecting subclinical disease is discussed and the potential use and drawbacks of using imaging biomarkers for monitoring disease progression are debated. Additionally, the use of imaging for differentiating atypical parkinsonian syndromes from Parkinson's disease is presented. PMID:27432680

  3. Common cell biologic and biochemical changes in aging and age-related diseases of the eye: Toward new therapeutic approaches to age-related ocular diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reviews of information about age related macular degeneration (AMD), cataract, and glaucoma make it apparent that while each eye tissue has its own characteristic metabolism, structure and function, there are common perturbations to homeostasis that are associated with age-related dysfunction. The c...

  4. Oxidative stress, innate immunity, and age-related macular degeneration

    PubMed Central

    Shaw, Peter X.; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

    2016-01-01

    Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have

  5. Age-related alterations in retinal neurovascular and inflammatory transcripts

    PubMed Central

    Van Kirk, Colleen A.; VanGuilder, Heather D.; Young, Megan; Farley, Julie A.; Sonntag, William E.

    2011-01-01

    factor [Pedf]) displayed patterns of expression dissimilar to that previously demonstrated with diabetes. Conclusions The commonalities in retinal age-related and diabetes-induced molecular alterations provide support for the hypothesis that diabetes and aging engage some common para-inflammatory processes. However, these results also demonstrate that while the retinal genomic response to diabetes and aging share commonalities, they are not superimposable phenotypes. The observed changes in retinal gene expression provide further evidence of retinal alterations in neurovascular and inflammatory processes across the adult rat lifespan; this is indicative of para-inflammation that may contribute to the functional impairments that occur with advanced age. The data also suggest the potential for an additive effect of aging and diabetes in the development of diabetic complications. PMID:21633715

  6. A twin study on age-related macular degeneration.

    PubMed Central

    Meyers, S M

    1994-01-01

    A prospective twin study on age-related macular degeneration (AMD) recruited 83 monozygotic pairs, 28 dizygotic pairs, and one triplet set from 1986 through 1993. Zygosity was determined by genetic testing of red cell markers, HLA antigens, or specific DNA loci. There were no twin pairs in which I collected data on only one twin. To decrease ascertainment bias, after 1991 the recruitment notice did not mention AMD, and I did not ask about a history of eye disease before the eye examination. Because of this, twin pairs recruited from 1986 through 1991 were statistically analyzed separately from those after January 1, 1992. From 1986 through 1991, 23 twin pairs were recruited; 11 monozygotic and 2 dizygotic pairs had nonAMD retinal changes or no retinal abnormalities, 9 monozygotic pairs with AMD were all concordant, and 1 dizygotic pair was discordant for basal laminar drusen. The concordance rate of AMD did not differ significantly between monozygotic and dizygotic twin pairs (P = .10) for 1986 through 1991. In 1992 and 1993, 88 twin pairs and one triplet set were recruited; 49 monozygotic and 19 dizygotic pairs had nonAMD retinal changes or no retinal abnormalities, 14 monozygotic pairs with AMD were all concordant, and 2 of 7 dizygotic pairs were concordant for AMD. The nonidentical triplets (1 with and 2 without AMD) were categorized as one of the discordant dizygotic pairs in the statistical evaluation. In nontwin age-matched (within 2 or 5 years of age) or age- and sex-matched sibling pairs the concordance rate of AMD ranged from 16% to 25%. The concordance rate of AMD was significantly higher in monozygotic than in dizygotic twins (P = .001) for 1992 and 1993. The concordance rate was higher for monozygotic twin pairs recruited in 1992 and 1993 than in any of the four subsets of nontwin age-method or age- and sex-matched sibling pairs (P < .0001). Overall, from 1986 through 1993, 23 of 23 monozygotic and 2 of 8 dizygotic twin pairs were concordant for AMD

  7. [Age-related Macular Degeneration in the Japanese].

    PubMed

    Yoshimura, Nagahisa

    2016-03-01

    Age-related macular degeneration (AMD) in the Japanese often shows different clinical features from those described in Caucasians. For example, we often observe choroidal neovascularization (CNV) in elderly patients without drusen in the fundus. The high incidence of polypoidal choroidal vasculopathy (PCV) in AMD among Japanese is well-known. The reason why such differences occur in clinical manifestations of AMD has been one of my main interests. In this review article, I will discuss the characteristics of AMD in the Japanese population, as found in our recent study. I. Prevalence and clinical characteristics of AMD in the Japanese population. Cohort studies are important to determine the prevalence and incidence of diseases. In Japan, cohort studies began to be carried out rather late compared with Western countries. Although good cohort studies from Japan are reported in the literature, the size of the cohorts was not sufficiently large to determine the prevalence of AMD. However, a recent meta-analysis of Asian cohorts has shown that the prevalence of late AMD in Asians is not different from that reported in Caucasians. On the other hand, the prevalence of early AMD appears lower in the Japanese than in Caucasians. Recently, we have published the results of the Nagahama Cohort study. In this cohort study, we found a high prevalence of drusen. It seems that the incidence of dry AMD is likely to increase among Japanese. In Japan, most retina specialists classify AMD into three categories : typical AMD, PCV, and retinal angiomatous proliferation (RAP). However, there are no definite diagnostic criteria to distinguish between the three conditions. To compare the clinical features of Japanese and Western cases of AMD, and to determine the incidence of the three types of AMD, we exchanged data about 100 consecutive cases between Kyoto University and Centre d'Ophtalmologie de Paris, France. Interestingly, the diagnoses made by the two institutes were not always in

  8. [Age-related Macular Degeneration in the Japanese].

    PubMed

    Yoshimura, Nagahisa

    2016-03-01

    Age-related macular degeneration (AMD) in the Japanese often shows different clinical features from those described in Caucasians. For example, we often observe choroidal neovascularization (CNV) in elderly patients without drusen in the fundus. The high incidence of polypoidal choroidal vasculopathy (PCV) in AMD among Japanese is well-known. The reason why such differences occur in clinical manifestations of AMD has been one of my main interests. In this review article, I will discuss the characteristics of AMD in the Japanese population, as found in our recent study. I. Prevalence and clinical characteristics of AMD in the Japanese population. Cohort studies are important to determine the prevalence and incidence of diseases. In Japan, cohort studies began to be carried out rather late compared with Western countries. Although good cohort studies from Japan are reported in the literature, the size of the cohorts was not sufficiently large to determine the prevalence of AMD. However, a recent meta-analysis of Asian cohorts has shown that the prevalence of late AMD in Asians is not different from that reported in Caucasians. On the other hand, the prevalence of early AMD appears lower in the Japanese than in Caucasians. Recently, we have published the results of the Nagahama Cohort study. In this cohort study, we found a high prevalence of drusen. It seems that the incidence of dry AMD is likely to increase among Japanese. In Japan, most retina specialists classify AMD into three categories : typical AMD, PCV, and retinal angiomatous proliferation (RAP). However, there are no definite diagnostic criteria to distinguish between the three conditions. To compare the clinical features of Japanese and Western cases of AMD, and to determine the incidence of the three types of AMD, we exchanged data about 100 consecutive cases between Kyoto University and Centre d'Ophtalmologie de Paris, France. Interestingly, the diagnoses made by the two institutes were not always in

  9. Imaging of degenerative spine disease--the state of the art.

    PubMed

    Sasiadek, Marek J; Bladowska, Joanna

    2012-01-01

    The authors review the current state of imaging of degenerative spinal disease (DSD), which is one of the most common disorders in humans. The most important definitions as well as short descriptions of the etiopathology and clinical presentation of DSD are provided first, followed by an overview of conventional and advanced imaging methods that are used in DSD. The authors then discuss in detail the imaging patterns of particular types of degenerative changes. Finally, the current imaging algorithm in DSD is presented. The imaging method of choice is magnetic resonance, including advanced techniques--especially diffusion tensor imaging. Other imaging methods (plain radiography, computed tomography, vascular studies, scintigraphy, positron emission tomography, discography) play a supplementary role ).

  10. The role of omega-3 and micronutrients in age-related macular degeneration.

    PubMed

    Querques, Giuseppe; Souied, Eric H

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the United States, Europe, and other developed countries. Although the pathogenesis of AMD remains unclear, current evidence suggests a multifactorial aetiology. Nutrition may play an important role in the development and progression of AMD. There have been several epidemiological studies suggesting that omega-3 fatty acids could have a protective role in AMD, but a beneficial effect remains to be demonstrated in randomized controlled trials. There also exists a substantial body of evidence suggesting that protection against AMD may be provided by specific micronutrients (vitamins and minerals and antioxidants). The identification of risk factors for the development and progression of AMD is of particular importance for understanding the origins of the disorder and for establishing strategies for its prevention. We examine the relationship between dietary omega-3 intake and the incidence and progression of AMD, as well as the role of omega-3 supplementation in the prevention of the disorder, and also explore the role of other micronutrients in AMD.

  11. MRI Evaluation of Lumbar Disc Degenerative Disease

    PubMed Central

    Patel, Rupal; Mehta, Chetan; Patel, Narrotam

    2015-01-01

    Introduction: Lower back pain secondary to degenerative disc disease is a condition that affects young to middle-aged persons with peak incidence at approximately 40 y. MRI is the standard imaging modality for detecting disc pathology due to its advantage of lack of radiation, multiplanar imaging capability, excellent spinal soft-tissue contrast and precise localization of intervertebral discs changes. Aims and Objective: To evaluate the characterization, extent, and changes associated with the degenerative lumbar disc disease by Magnetic Resonance Imaging. Study Design: Cross-sectional and observational study. Materials and Methods: A total 109 patients of the lumbar disc degeneration with age group between 17 to 80 y were diagnosed & studied on 1.5 Tesla Magnetic Resonance Imaging machine. MRI findings like lumbar lordosis, Schmorl’s nodes, decreased disc height, disc annular tear, disc herniation, disc bulge, disc protrusion and disc extrusion were observed. Narrowing of the spinal canal, lateral recess and neural foramen with compression of nerve roots observed. Ligamentum flavum thickening and facetal arthropathy was observed. Result: Males were more commonly affected in Degenerative Spinal Disease & most of the patients show loss of lumbar lordosis. Decreased disc height was common at L5-S1 level. More than one disc involvement was seen per person. L4 – L5 disc was the most commonly involved. Annular disc tear, disc herniation, disc extrusion, narrowing of spinal canal, narrowing of lateral recess, compression of neural foramen, ligamentum flavum thickening and facetal arthropathy was common at the L4 –L5 disc level. Disc buldge was common at L3 – L4 & L4 – L5 disc level. Posterior osteophytes are common at L3 - L4 & L5 –S1 disc level. L1- L2 disc involvement and spondylolisthesis are less common. Conclusion: Lumbar disc degeneration is the most common cause of low back pain. Plain radiograph can be helpful in visualizing gross anatomic changes in

  12. What associates Charles Bonnet syndrome with age-related macular degeneration?

    PubMed

    Vojniković, Bozo; Radeljak, Sanja; Dessardo, Sandro; Zarković-Palijan, Tija; Bajek, Goran; Linsak, Zeljko

    2010-04-01

    Charles Bonnet syndrome (CBS) is a condition related to patients with visual loss due to age related macular degeneration or glaucoma that are having complex visual hallucinations. The CBS was first described by Swiss physician Charles Bonnet in 1760. Affected patients, who are otherwise mentally healthy people with significant visual loss, have vivid, complex recurrent visual hallucinations (VHs). One characteristic of these hallucinations is that they usually are "Lilliputian hallucinations" as patients experience micropsia (hallucinations in which the characters or objects are distorted and much smaller than normal). The prevalence of Charles Bonnet Syndrome has been reported to be between 10% and 40%; a recent Australian study has found the prevalence to be 17.5%. The high incidence of non-reported CBS is thought to be as a result of patient's fear to report the symptoms as they could be labeled as mentally insane since those type of visual hallucinations could be found in variety of psychiatric and neurological disorders such as drug or alcohol abuse (delirium tremens), Alice in Wonderland syndrome (AIWS), psychosis, schizophrenia, dementia, narcolepsy, epilepsy, Parkinson disease, brain tumors, migraine, as well as, in long term sleep deprivation. VHs can also be presented as the initial sign of the Epstein-Barr virus infection in infectious mononucleosis. Patients who suffer from CBS usually possess insight into the unreality of their visual experiences, which are commonly pleasant but may sometimes cause distress. The hallucinations consist of well-defined, organized, and clear images over which the subject has little control. It is believed that they represent release phenomena due to deafferentiation of the visual association areas of the cerebral cortex, leading to a form of phantom vision. Cognitive defects, social isolation, and sensory deprivation have also been implicated in the etiology of this condition. This study was conducted on 350 patients

  13. What associates Charles Bonnet syndrome with age-related macular degeneration?

    PubMed

    Vojniković, Bozo; Radeljak, Sanja; Dessardo, Sandro; Zarković-Palijan, Tija; Bajek, Goran; Linsak, Zeljko

    2010-04-01

    Charles Bonnet syndrome (CBS) is a condition related to patients with visual loss due to age related macular degeneration or glaucoma that are having complex visual hallucinations. The CBS was first described by Swiss physician Charles Bonnet in 1760. Affected patients, who are otherwise mentally healthy people with significant visual loss, have vivid, complex recurrent visual hallucinations (VHs). One characteristic of these hallucinations is that they usually are "Lilliputian hallucinations" as patients experience micropsia (hallucinations in which the characters or objects are distorted and much smaller than normal). The prevalence of Charles Bonnet Syndrome has been reported to be between 10% and 40%; a recent Australian study has found the prevalence to be 17.5%. The high incidence of non-reported CBS is thought to be as a result of patient's fear to report the symptoms as they could be labeled as mentally insane since those type of visual hallucinations could be found in variety of psychiatric and neurological disorders such as drug or alcohol abuse (delirium tremens), Alice in Wonderland syndrome (AIWS), psychosis, schizophrenia, dementia, narcolepsy, epilepsy, Parkinson disease, brain tumors, migraine, as well as, in long term sleep deprivation. VHs can also be presented as the initial sign of the Epstein-Barr virus infection in infectious mononucleosis. Patients who suffer from CBS usually possess insight into the unreality of their visual experiences, which are commonly pleasant but may sometimes cause distress. The hallucinations consist of well-defined, organized, and clear images over which the subject has little control. It is believed that they represent release phenomena due to deafferentiation of the visual association areas of the cerebral cortex, leading to a form of phantom vision. Cognitive defects, social isolation, and sensory deprivation have also been implicated in the etiology of this condition. This study was conducted on 350 patients

  14. Plasminogen activator inhibitor 1, fibroblast apoptosis resistance, and aging-related susceptibility to lung fibrosis.

    PubMed

    Huang, Wen-Tan; Akhter, Hasina; Jiang, Chunsun; MacEwen, Mark; Ding, Qiang; Antony, Veena; Thannickal, Victor John; Liu, Rui-Ming

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fatal lung disorder with unknown cause and no effective treatment. The incidence of and mortality from IPF increase with age, suggesting that advanced age is a major risk factor for IPF. The mechanism underlying the increased susceptibility of the elderly to IPF, however, is unknown. In this study, we show for the first time that the protein level of plasminogen activator inhibitor 1 (PAI-1), a protease inhibitor which plays an essential role in the control of fibrinolysis, was significantly increased with age in mouse lung homogenate and lung fibroblasts. Upon bleomycin challenge, old mice experienced augmented PAI-1 induction and lung fibrosis as compared to young mice. Most interestingly, we show that fewer (myo)fibroblasts underwent apoptosis and more (myo)fibroblasts with increased level of PAI-1 accumulated in the lung of old than in young mice after bleomycin challenge. In vitro studies further demonstrate that fibroblasts isolated from lungs of old mice were resistant to H2O2 and tumor necrosis factor alpha-induced apoptosis and had augmented fibrotic responses to TGF-β1, compared to fibroblasts isolated from young mice. Inhibition of PAI-1 activity with a PAI-1 inhibitor, on the other hand, eliminated the aging-related apoptosis resistance and TGF-β1 sensitivity in isolated fibroblasts. Moreover, we show that knocking down PAI-1 in human lung fibroblasts with PAI-1 siRNA significantly increased their sensitivity to apoptosis and inhibited their responses to TGF-β1. Together, the results suggest that increased PAI-1 expression may underlie the aging-related sensitivity to lung fibrosis in part by protecting fibroblasts from apoptosis.

  15. [Age-related cognitive impairment: conceptual changes and diagnostic strategies].

    PubMed

    Annoni, Jean-Marie; Chouiter, Leila; Démonet, Jean-François

    2016-04-20

    The actual field of dementia encompasses also the pre-symptomatic phase, which may evolve for decades. Early detection and appropriate diagnosis decrease patient's and family's anxiety, improve patient's global care and allow better legal patient's protection. General Practitioners have at hand several available tools to screen a neurocognitive disorder, with up to 80% of sensitivity and specificity, to complete their clinical evaluation. An accurate diagnosis requires then a complete medical, neurological neuropsychological and neuroradiological evaluation in a Memory Clinic. Other investigations, such as functional cerebral imagery and spinal tap can be critical in unusual situations. Despite mood improvement after diagnostic announcement, increased suicidal risk in the 3 first months should be screened. PMID:27276719

  16. Age related changes in gut physiology and nutritional status.

    PubMed Central

    Lovat, L B

    1996-01-01

    Few gastrointestinal functions decline to an important extent as a result of old age alone and there is little clinical evidence that significant malnutrition occurs in any normal elderly person as a result of the aging process itself. Nevertheless, decreased gastrointestinal reserve makes older people highly sensitive to minor insults and decompensation can rapidly occur. Drugs appreciably affect taste sensation, which is already blunted and psychological as well as physical disability can have a major impact on appetite. Malabsorption can be caused by gastric hypochlorhydria with small bowel bacterial overgrowth and while gastrointestinal dysmotility can be caused by subclinical hypothyroidism, it can improve in response to physical exercise. Evidence is now mounting that thorough investigation of gastrointestinal disturbances in elderly patients coupled with intensive nutritional support can make a very real impact on their outcome. Gastroenterologists should therefore seek out and actively treat gastrointestinal disorders in the elderly and not just ascribe them to old age. PMID:8675079

  17. Age-Related Psychophysical Changes and Low Vision

    PubMed Central

    Dagnelie, Gislin

    2013-01-01

    When considering the burden of visual impairment on aging individuals and society at large, it is important to bear in mind that vision changes are a natural aspect of aging. In this article, we consider vision changes that are part of normal aging, the prevalence of abnormal vision changes caused by disorders of the visual system, and the anticipated incidence and impact of visual impairment as the US population ages. We then discuss the services available to reduce the impact of vision loss, and the extent to which those services can and should be improved, not only to be better prepared for the anticipated increase in low vision over the coming decades, but also to increase the awareness of interactions between visual impairment and comorbidities that are common among the elderly. Finally, we consider how to promote improved quality, availability, and acceptance of low vision care to lessen the impact of visual impairment on individuals, and its burden on society. PMID:24335074

  18. Mechanism of Inflammation in Age-Related Macular Degeneration: An Up-to-Date on Genetic Landmarks

    PubMed Central

    Parmeggiani, Francesco; Sorrentino, Francesco S.; Romano, Mario R.; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Nadai, Katia; Bonomo Roversi, Elia; Franceschelli, Paola; Sebastiani, Adolfo

    2013-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment among people over 50 years of age, accounting for up to 50% of all cases of legal blindness in Western countries. Although the aging represents the main determinant of AMD, it must be considered a multifaceted disease caused by interactions among environmental risk factors and genetic backgrounds. Mounting evidence and/or arguments document the crucial role of inflammation and immune-mediated processes in the pathogenesis of AMD. Proinflammatory effects secondary to chronic inflammation (e.g., alternative complement activation) and heterogeneous types of oxidative stress (e.g., impaired cholesterol homeostasis) can result in degenerative damages at the level of crucial macular structures, that is photoreceptors, retinal pigment epithelium, and Bruch's membrane. In the most recent years, the association of AMD with genes, directly or indirectly, involved in immunoinflammatory pathways is increasingly becoming an essential core for AMD knowledge. Starting from the key basic-research notions detectable at the root of AMD pathogenesis, the present up-to-date paper reviews the best-known and/or the most attractive genetic findings linked to the mechanisms of inflammation of this complex disease. PMID:24369445

  19. Neuromuscular exercise as treatment of degenerative knee disease.

    PubMed

    Ageberg, Eva; Roos, Ewa M

    2015-01-01

    Exercise is recommended as first-line treatment of degenerative knee disease. Our hypothesis is that neuromuscular exercise is feasible and at least as effective as traditionally used strength or aerobic training but aims to target more closely the sensorimotor deficiencies and functional instability associated with the degenerative knee disease than traditionally used training methods.

  20. Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD)

    ClinicalTrials.gov

    2016-10-20

    Macular Degeneration; Age-Related Maculopathies; Age-Related Maculopathy; Maculopathies, Age-Related; Maculopathy, Age-Related; Retinal Degeneration; Retinal Neovascularization; Gene Therapy; Therapy, Gene; Eye Diseases

  1. Is age-related macular degeneration a manifestation of systemic disease? New prospects for early intervention and treatment.

    PubMed

    Cheung, C M G; Wong, T Y

    2014-08-01

    Age-related macular degeneration (AMD) is a common vision-threatening condition affecting the elderly. AMD shares common risk factors and processes, including vascular and inflammatory pathways, with many systemic disorders. Associations have been reported between AMD and hypertension, cardiovascular disease, cerebrovascular disease, dyslipidaemia, chronic kidney disease and neurodegenerative disorders. An increasing amount of evidence suggests that individuals with AMD are also at risk of systemic diseases such as stroke. In this review, we summarize the latest evidence to support the notion that AMD is an ocular manifestation of systemic disease processes, and discuss the potential systemic side effects of ocular AMD therapy of which general physicians should be aware. Recent genetic discoveries and understanding of the pathogenic pathways in AMD in relation to systemic disorders are also highlighted.

  2. Degenerative disease of the lumbar spine.

    PubMed

    Kovacs, F M; Arana, E

    2016-04-01

    In the last 25 years, scientific research has brought about drastic changes in the concept of low back pain and its management. Most imaging findings, including degenerative changes, reflect anatomic peculiarities or the normal aging process and turn out to be clinically irrelevant; imaging tests have proven useful only when systemic disease is suspected or when surgery is indicated for persistent spinal cord or nerve root compression. The radiologic report should indicate the key points of nerve compression, bypassing inconsequential findings. Many treatments have proven inefficacious, and some have proven counterproductive, but they continue to be prescribed because patients want them and there are financial incentives for doing them. Following the guidelines that have proven effective for clinical management improves clinical outcomes, reduces iatrogenic complications, and decreases unjustified and wasteful healthcare expenditures. PMID:26872873

  3. Degenerative disease of the lumbar spine.

    PubMed

    Kovacs, F M; Arana, E

    2016-04-01

    In the last 25 years, scientific research has brought about drastic changes in the concept of low back pain and its management. Most imaging findings, including degenerative changes, reflect anatomic peculiarities or the normal aging process and turn out to be clinically irrelevant; imaging tests have proven useful only when systemic disease is suspected or when surgery is indicated for persistent spinal cord or nerve root compression. The radiologic report should indicate the key points of nerve compression, bypassing inconsequential findings. Many treatments have proven inefficacious, and some have proven counterproductive, but they continue to be prescribed because patients want them and there are financial incentives for doing them. Following the guidelines that have proven effective for clinical management improves clinical outcomes, reduces iatrogenic complications, and decreases unjustified and wasteful healthcare expenditures.

  4. Degenerative meniscus: Pathogenesis, diagnosis, and treatment options

    PubMed Central

    Howell, Richard; Kumar, Neil S; Patel, Nimit; Tom, James

    2014-01-01

    The symptomatic degenerative meniscus continues to be a source of discomfort for a significant number of patients. With vascular penetration of less than one-third of the adult meniscus, healing potential in the setting of chronic degeneration remains low. Continued hoop and shear stresses upon the degenerative meniscus results in gross failure, often in the form of complex tears in the posterior horn and midbody. Patient history and physical examination are critical to determine the true source of pain, particularly with the significant incidence of simultaneous articular pathology. Joint line tenderness, a positive McMurray test, and mechanical catching or locking can be highly suggestive of a meniscal source of knee pain and dysfunction. Radiographs and magnetic resonance imaging are frequently utilized to examine for osteoarthritis and to verify the presence of meniscal tears, in addition to ruling out other sources of pain. Non-operative therapy focused on non-steroidal anti-inflammatory drugs and physical therapy may be able to provide pain relief as well as improve mechanical function of the knee joint. For patients refractory to conservative therapy, arthroscopic partial meniscectomy can provide short-term gains regarding pain relief, especially when combined with an effective, regular physiotherapy program. Patients with clear mechanical symptoms and meniscal pathology may benefit from arthroscopic partial meniscectomy, but surgery is not a guaranteed success, especially with concomitant articular pathology. Ultimately, the long-term outcomes of either treatment arm provide similar results for most patients. Further study is needed regarding the short and long-term outcomes regarding conservative and surgical therapy, with a particular focus on the economic impact of treatment as well. PMID:25405088

  5. Alzheimer’s Disease and Age-Related Memory Decline (Preclinical)

    PubMed Central

    Terry, Alvin V.; Callahan, Patrick M.; Hall, Brandon; Webster, Scott J.

    2011-01-01

    An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer’s disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as “Mild Cognitive Impairment” (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD, MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy, adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory

  6. A review of creatine supplementation in age-related diseases: more than a supplement for athletes.

    PubMed

    Smith, Rachel N; Agharkar, Amruta S; Gonzales, Eric B

    2014-01-01

    Creatine is an endogenous compound synthesized from arginine, glycine and methionine. This dietary supplement can be acquired from food sources such as meat and fish, along with athlete supplement powders. Since the majority of creatine is stored in skeletal muscle, dietary creatine supplementation has traditionally been important for athletes and bodybuilders to increase the power, strength, and mass of the skeletal muscle. However, new uses for creatine have emerged suggesting that it may be important in preventing or delaying the onset of neurodegenerative diseases associated with aging. On average, 30% of muscle mass is lost by age 80, while muscular weakness remains a vital cause for loss of independence in the elderly population. In light of these new roles of creatine, the dietary supplement's usage has been studied to determine its efficacy in treating congestive heart failure, gyrate atrophy, insulin insensitivity, cancer, and high cholesterol. In relation to the brain, creatine has been shown to have antioxidant properties, reduce mental fatigue, protect the brain from neurotoxicity, and improve facets/components of neurological disorders like depression and bipolar disorder. The combination of these benefits has made creatine a leading candidate in the fight against age-related diseases, such as Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, long-term memory impairments associated with the progression of Alzheimer's disease, and stroke. In this review, we explore the normal mechanisms by which creatine is produced and its necessary physiology, while paying special attention to the importance of creatine supplementation in improving diseases and disorders associated with brain aging and outlining the clinical trials involving creatine to treat these diseases.

  7. Magnetic resonance imaging assessment of degenerative cervical myelopathy: a review of structural changes and measurement techniques.

    PubMed

    Nouri, Aria; Martin, Allan R; Mikulis, David; Fehlings, Michael G

    2016-06-01

    Degenerative cervical myelopathy encompasses a spectrum of age-related structural changes of the cervical spine that result in static and dynamic injury to the spinal cord and collectively represent the most common cause of myelopathy in adults. Although cervical myelopathy is determined clinically, the diagnosis requires confirmation via imaging, and MRI is the preferred modality. Because of the heterogeneity of the condition and evolution of MRI technology, multiple techniques have been developed over the years in an attempt to quantify the degree of baseline severity and potential for neurological recovery. In this review, these techniques are categorized anatomically into those that focus on bone, ligaments, discs, and the spinal cord. In addition, measurements for the cervical spine canal size and sagittal alignment are also described briefly. These tools have resulted collectively in the identification of numerous useful parameters. However, the development of multiple techniques for assessing the same feature, such as cord compression, has also resulted in a number of challenges, including introducing ambiguity in terms of which methods to use and hindering effective comparisons of analysis in the literature. In addition, newer techniques that use advanced MRI are emerging and providing exciting new tools for assessing the spinal cord in patients with degenerative cervical myelopathy.

  8. Magnetic resonance imaging assessment of degenerative cervical myelopathy: a review of structural changes and measurement techniques.

    PubMed

    Nouri, Aria; Martin, Allan R; Mikulis, David; Fehlings, Michael G

    2016-06-01

    Degenerative cervical myelopathy encompasses a spectrum of age-related structural changes of the cervical spine that result in static and dynamic injury to the spinal cord and collectively represent the most common cause of myelopathy in adults. Although cervical myelopathy is determined clinically, the diagnosis requires confirmation via imaging, and MRI is the preferred modality. Because of the heterogeneity of the condition and evolution of MRI technology, multiple techniques have been developed over the years in an attempt to quantify the degree of baseline severity and potential for neurological recovery. In this review, these techniques are categorized anatomically into those that focus on bone, ligaments, discs, and the spinal cord. In addition, measurements for the cervical spine canal size and sagittal alignment are also described briefly. These tools have resulted collectively in the identification of numerous useful parameters. However, the development of multiple techniques for assessing the same feature, such as cord compression, has also resulted in a number of challenges, including introducing ambiguity in terms of which methods to use and hindering effective comparisons of analysis in the literature. In addition, newer techniques that use advanced MRI are emerging and providing exciting new tools for assessing the spinal cord in patients with degenerative cervical myelopathy. PMID:27246488

  9. [Treatment of exudative age-related macular degeneration].

    PubMed

    Yuzawa, M

    2000-12-01

    I PROPHYLACTIC TREATMENT: We followed 75 eyes contralateral to eyes with exudative age-related macular degeneration (AMD), using indocyanine green angiography (IA), for more than one year. Hyperfluorescent areas in the late phase of IA were seen in 19 eyes at the initial examination, and in 25 eyes during follow-up. Exudative AMD developed in 9 of the 25 eyes. Using timetable analysis, we estimated that 11% of these 27 eyes developed AMD within one year and 55% within three years. The hyperfluorescent areas seen on IA appeared to be latent choroidal neovascularization (CNV) under the retinal pigment epithelium. We propose that photocoagulation aimed at hyperfluorescent areas should be considered in such cases. We performed prophylactic laser photocoagulation in 21 eyes, which were then followed up for at least six months. These eyes all had 10 or more serous drusen within 1,500 microns of the fovea and did not show hyperfluorescence, suggesting latent CNV in the late phase of IA. The majority or a small fraction of the serous drusen disappeared in 48% and 18% of the 21 eyes, respectively. CNV appeared adjacent to the laser scar in one eye (5%). Judging from these results, it is important to establish a method of definitively abolishing drusen and preventing the development of CNV. II TREATMENT OF CNV: Of 229 eyes which showed occult CNV in fluorescein angiography (FA), 124 eyes (54%) showed classic CNV outside the fovea on IA. One hundred and two of the 124 eyes (45%) underwent laser photocoagulation. We evaluated indocyanine green guided laser photocoagulation of extrafoveal CNV in 139 eyes. The success rate was 81% at 3 months after laser photocoagulation. This was estimated using timetable analyses to have decreased to 78% at one year and 71% at three years. Eighty percent of successfully treated eyes showed maintained or improved visual acuity. These results did not differ significantly from those obtained with laser photocoagulation based on FA findings. When

  10. [Sex Specificity in Age-Related Thyroid Hormone Responsiveness].

    PubMed

    Suzuki, Satoru

    2016-01-01

    Similar to other systems, the endocrine system is affected by aging. Thyroid hormone, the action of which is affected by many factors, has been shown to be associated with longevity. The most useful marker for assessment of the thyroid hormone action is the TSH level. Although age and sex are believed to modify the pituitary set point or response to the free thyroid hormone concentration, the precise age- and sex-dependent responses to thyroid hormone have yet to be reported. In this lecture, molecular aspects of resistance to thyroid hormone are initially overviewed. After presentation of the evidence that the TSH-thyroid hormone axis is evolutionarily modified, and that negative feedback mechanisms may start to play roles in homeostatic regulation at the time of delivery, the rationale of age-dependent thyroid hormone resistance is introduced. To assess the age- and sex-dependent resistance to thyroid hormone, the index is provided by the formula based on the relationship between thyroid hormone and TSH levels. The index is calculated by the results of thyroid function tests obtained from the two individual clinical groups. From the results, there were negative relationships between the free T3 resistance index and age in males of both groups, while there were no apparent relationships in females. These findings indicate that there is a male-specific response to thyroid hormone with aging. Furthermore, the specific features of the response may not be affected by environmental factors such as the presence of disorders or medical treatments. PMID:27192800

  11. Models for preclinical studies in aging-related disorders: One is not for all

    PubMed Central

    Santulli, Gaetano; Borras, Consuelo; Bousquet, Jean; Calzà, Laura; Cano, Antonio; Illario, Maddalena; Franceschi, Claudio; Liotta, Giuseppe; Maggio, Marcello; Molloy, William D.; Montuori, Nunzia; O’Caoimh, Rónán; Orfila, Francesc; Rauter, Amelia P.; Santoro, Aurelia; Iaccarino, Guido

    2015-01-01

    Preclinical studies are essentially based on animal models of a particular disease. The primary purpose of preclinical efficacy studies is to support generalization of treatment–effect relationships to human subjects. Researchers aim to demonstrate a causal relationship between an investigational agent and a disease-related phenotype in such models. Numerous factors can muddle reliable inferences about such cause-effect relationships, including biased outcome assessment due to experimenter expectations. For instance, responses in a particular inbred mouse might be specific to the strain, limiting generalizability. Selecting well-justified and widely acknowledged model systems represents the best start in designing preclinical studies, especially to overcome any potential bias related to the model itself. This is particularly true in the research that focuses on aging, which carries unique challenges, mainly attributable to the fact that our already long lifespan makes designing experiments that use people as subjects extremely difficult and largely impractical. PMID:27042427

  12. Age-related macular degeneration and coronary heart disease: evaluation of genetic and environmental associations.

    PubMed

    Keilhauer, Claudia N; Fritsche, Lars G; Guthoff, Rainer; Haubitz, Imme; Weber, Bernhard H

    2013-02-01

    An association between coronary heart disease (CHD) and age-related macular degeneration (AMD) has long been postulated but results from epidemiological case-control studies, and genetic analyses have been ambiguous. In this study we illuminate the association between AMD and CHD with respect to genetic and environmental risk factors, age of disease onset and AMD subgroups. AMD patients (n = 1036) and age-matched control subjects (n = 412) between 68 and 95 years of age were included in the case-control study. A medical history of CHD, cerebral stroke and arterial hypertension was determined for each individual. The assessment of interacting factors included the current use of systemic medications and smoking habits. Analysis of AMD associated genetic variants included frequent polymorphisms at the complement factor H (CFH, MIM 134370) gene (rs1061170 [p.Y402H], rs800292 [p.I62V]), the complement factor H-related 3 (CFHR3, MIM 605336)/complement factor H-related 1 (CFHR1, MIM 134371) locus (rs6677604; proxy for ΔCFHR3/CFHR1; r(2) = 0.97) as well as the age-related maculopathy susceptibility 2 (ARMS2, MIM 611313) gene (rs10490924 [p.A69S]). Logistic regression identified a significant positive association of AMD with AMD-risk variants in CFH, ARMS2, and smoking ≥ 20 packs/year. A history of CHD and the current use of antihyperuricemic agents were inversely associated with the disease. Significantly fewer patients with rs6677604 nonrisk genotype A/A regularly used statins. ARMS2:p.A69S risk variant was significantly associated with exsudative AMD. AMD patients with risk variants at rs1061170 (CFH:p.Y402H) and ARMS2 and smokers (≥20 packs/year) were significantly earlier affected by AMD than those carrying the non-risk variants at each locus. Our data support three major conclusions. First, the age of AMD onset is significantly influenced by genetic and environmental risk factors. Second, in support of previous reports we also show that the ARMS2 rs10490924:T

  13. Management of Neovascular Age-Related Macular Degeneration in Clinical Practice: Initiation, Maintenance, and Discontinuation of Therapy

    PubMed Central

    Keane, Pearse A.; Tufail, Adnan; Patel, Praveen J.

    2011-01-01

    Neovascular age-related macular degeneration (AMD) is a leading cause of irreversible visual loss in elderly populations. In recent years, pharmacological inhibition of vascular endothelial growth factor (VEGF), via intravitreal injection of ranibizumab (Lucentis) or bevacizumab (Avastin), has offered the first opportunity to improve visual outcomes in patients diagnosed with this disorder. In this paper, we provide recommendations on how bevacizumab and ranibizumab may be best applied in current clinical practice, with an emphasis on their underlying pharmacology and efficacy. In addition, we review current guidelines for the initiation, maintenance, and discontinuation of anti-VEGF therapies, as well as emerging treatment strategies and future directions in the field. PMID:22174995

  14. Long-term caloric restriction in mice may prevent age-related learning impairment via suppression of apoptosis.

    PubMed

    Ma, Lina; Wang, Rong; Dong, Wen; Li, Yun; Xu, Baolei; Zhang, Jingshuang; Zhao, Zhiwei

    2016-12-15

    Caloric restriction (CR) is the most reliable intervention to extend lifespan and prevent age-related disorders in various species from yeast to rodents. However, the underlying mechanisms have not yet been clearly defined. Therefore, we aimed to identify the underlying mechanisms of long-term CR on age-related learning impairment in C57/BL mice. Thirty six-week-old male C57/BL mice were randomly divided into three groups: normal control group (NC group, n=10), high energy group (HE group, n=10), and CR group (n=10). After 10 months, the Morris water maze test was performed to monitor learning abilities. Western blotting, immunohistochemistry and real-time polymerase chain reaction were used to monitor changes in protein and mRNA levels associated with apoptosis-related proteins in the hippocampus. The average escape latency was lower in the CR group compared with the NC group, and the average time taken to first cross the platform in the CR group was significantly shorter than the HE group. Both Bcl-2 protein and mRNA expression levels in the CR group were significantly higher than those of the NC group and HE group. The expression of Bax, Caspase-3 and PARP protein in the CR group was significantly lower than the NC group. Our findings demonstrate that long-term CR may prevent age-related learning impairments via suppressing apoptosis in mice. PMID:27452805

  15. Age-related intra-axonal accumulation of neurofilaments in the dorsal column nuclei of the cat brainstem: a light and electron microscopic immunohistochemical study.

    PubMed

    Zhang, J H; Sampogna, S; Morales, F R; Chase, M H

    1998-06-29

    In the present study, we examined the age-related intra-axonal accumulation of neurofilaments in the dorsal column nuclei of the cat by using immunohistochemical techniques combined with light and electron microscopy. Light microscopic analysis revealed oval or circular immunostained structures in the dorsal column nuclei of old cats. These immunostained structures were not observed in the material obtained from adult controls. Under the electron microscope, it was discovered that the immunostained structures were greatly enlarged axons with disrupted myelin sheaths. These enlarged axons contained massive accumulations of neurofilaments, some mitochondria, vacuoles and dense granules. The abnormalities of the myelin sheaths included the breaking of myelin at several locations, a splitting and ballooning in the myelin lamellae of the sheath and a distended periaxonal space between the axon and myelin sheaths. These ultrastructural changes resembled the degenerative alterations that have been observed in the axons of human and animals suffering from a number of pathological conditions, including giant axonal neuropathy and toxic neuropathy. Therefore, severely altered axons with intra-axonal accumulation of neurofilaments appear to reflect chronic degenerative changes that are a component of the aging process. PMID:9666164

  16. Effects of physical training on age-related balance and postural control.

    PubMed

    Lelard, T; Ahmaidi, S

    2015-11-01

    In this paper, we review the effects of physical activity on balance performance in the elderly. The increase in the incidence of falls with age reflects the disorders of balance-related to aging. We are particularly interested in age-related changes in the balance control system as reflected in different static and dynamic balance tests. We report the results of studies demonstrating the beneficial effects of physical activity on postural balance. By comparing groups of practitioners of different physical activities, it appears that these effects on postural control depend on the type of activity and the time of practice. Thus, we have focused in the present review on "proprioceptive" and "strength" activities. Training programs offering a combination of several activities have demonstrated beneficial effects on the incidence of falls, and we present and compare the effects of these two types of training activities. It emerges that there are differential effects of programs of activities: while all activities improve participants' confidence in their ability, the "proprioceptive" activities rather improve performance in static tasks, while "strength" activities tend to improve performance in dynamic tasks. These effects depend on the targeted population and will have a greater impact on the frailest subjects. The use of new technologies in the form of "exergames" may also be proposed in home-based exercises.

  17. Age-related changes in conjunctive visual search in children with and without ASD.

    PubMed

    Iarocci, Grace; Armstrong, Kimberly

    2014-04-01

    Visual-spatial strengths observed among people with autism spectrum disorder (ASD) may be associated with increased efficiency of selective attention mechanisms such as visual search. In a series of studies, researchers examined the visual search of targets that share features with distractors in a visual array and concluded that people with ASD showed enhanced performance on visual search tasks. However, methodological limitations, the small sample sizes, and the lack of developmental analysis have tempered the interpretations of these results. In this study, we specifically addressed age-related changes in visual search. We examined conjunctive visual search in groups of children with (n = 34) and without ASD (n = 35) at 7-9 years of age when visual search performance is beginning to improve, and later, at 10-12 years, when performance has improved. The results were consistent with previous developmental findings; 10- to 12-year-old children were significantly faster visual searchers than their 7- to 9-year-old counterparts. However, we found no evidence of enhanced search performance among the children with ASD at either the younger or older ages. More research is needed to understand the development of visual search in both children with and without ASD.

  18. Automated age-related macular degeneration classification in OCT using unsupervised feature learning

    NASA Astrophysics Data System (ADS)

    Venhuizen, Freerk G.; van Ginneken, Bram; Bloemen, Bart; van Grinsven, Mark J. J. P.; Philipsen, Rick; Hoyng, Carel; Theelen, Thomas; Sánchez, Clara I.

    2015-03-01

    Age-related Macular Degeneration (AMD) is a common eye disorder with high prevalence in elderly people. The disease mainly affects the central part of the retina, and could ultimately lead to permanent vision loss. Optical Coherence Tomography (OCT) is becoming the standard imaging modality in diagnosis of AMD and the assessment of its progression. However, the evaluation of the obtained volumetric scan is time consuming, expensive and the signs of early AMD are easy to miss. In this paper we propose a classification method to automatically distinguish AMD patients from healthy subjects with high accuracy. The method is based on an unsupervised feature learning approach, and processes the complete image without the need for an accurate pre-segmentation of the retina. The method can be divided in two steps: an unsupervised clustering stage that extracts a set of small descriptive image patches from the training data, and a supervised training stage that uses these patches to create a patch occurrence histogram for every image on which a random forest classifier is trained. Experiments using 384 volume scans show that the proposed method is capable of identifying AMD patients with high accuracy, obtaining an area under the Receiver Operating Curve of 0:984. Our method allows for a quick and reliable assessment of the presence of AMD pathology in OCT volume scans without the need for accurate layer segmentation algorithms.

  19. [Age-related changes in the rat lacrimal gland: specific morphology and unknown nature].

    PubMed

    Gancharova, O S; Manskikh, V N

    2014-01-01

    The rat lacrimal apparatus includes several glands; among them, the exorbital gland plays the central role. Its parenchyma and stroma undergo prominent morphologic changes with age. The parenchymal transformation includes metaplasia of some of its acini and their turning into Harderian gland-like structures (harderization), accumulation of gland ducts ("ductularization"), and morphologic dysplasia-cytomegaly, karyomegaly, and'cell and nuclearpolymorphism in the other part of acini. All these transformations are hormone-dependent andsex-specific: theyoften appear in males. On the final stages of age-related transformations, the lacrimal gland tissue is morphologically similar to the neoplasm and has neoplastic morphology but no other features of a tumor. Therefore, the rat lacrimal gland is an interesting object to study tissue and cell atypia. In the rat glandular stroma, lymphocytic infiltration and fibrosis appear with age; these changes are similar to processes taking place in human lacrimal apparatus involved in the pathogenesis of senile dry eye syndrome. The spontaneous changes in the rat lacrimal gland, predominantly in male rats, can be used as a model of the human lacrimal apparatus disorders.

  20. Progress and prospects in human genetic research into age-related hearing impairment.

    PubMed

    Uchida, Yasue; Sugiura, Saiko; Sone, Michihiko; Ueda, Hiromi; Nakashima, Tsutomu

    2014-01-01

    Age-related hearing impairment (ARHI) is a complex, multifactorial disorder that is attributable to confounding intrinsic and extrinsic factors. The degree of impairment shows substantial variation between individuals, as is also observed in the senescence of other functions. This individual variation would seem to refute the stereotypical view that hearing deterioration with age is inevitable and may indicate that there is ample scope for preventive intervention. Genetic predisposition could account for a sizable proportion of interindividual variation. Over the past decade or so, tremendous progress has been made through research into the genetics of various forms of hearing impairment, including ARHI and our knowledge of the complex mechanisms of auditory function has increased substantially. Here, we give an overview of recent investigations aimed at identifying the genetic risk factors involved in ARHI and of what we currently know about its pathophysiology. This review is divided into the following sections: (i) genes causing monogenic hearing impairment with phenotypic similarities to ARHI; (ii) genes involved in oxidative stress, biologic stress responses, and mitochondrial dysfunction; and (iii) candidate genes for senescence, other geriatric diseases, and neurodegeneration. Progress and prospects in genetic research are discussed.

  1. Recent Patents on Emerging Therapeutics for the Treatment of Glaucoma, Age Related Macular Degeneration and Uveitis

    PubMed Central

    Vadlapudi, Aswani Dutt; Patel, Ashaben; Cholkar, Kishore; Mitra, Ashim K.

    2014-01-01

    Advancements in the field and rising interest among pharmaceutical researchers have led to the development of new molecules with enhanced therapeutic activity. Design of new drugs which can target a particular pathway and/or explore novel targets is of immense interest to ocular pharmacologists worldwide. Delivery of suitable pharmacologically active agents at proper dose (within the therapeutic window) to the target tissues without any toxicity to the healthy ocular tissues still remain an elusive task. Moreover, the presence of static and dynamic barriers to drug absorption including the corneal epithelium (lipophilic), corneal and scleral stroma (hydrophilic), conjunctival lymphatics, choroidal vasculature and the blood-ocular barriers also pose a significant challenge for achieving therapeutic drug concentrations at the target site. Although many agents are currently available, new compounds are being introduced for treating various ocular diseases. Deeper understanding of the etiology and complex mechanisms associated with the disease condition would aid in the development of potential therapeutic candidates. Novel small molecules as well as complex biotechnology derived macromolecules with superior efficacy, safety and tolerability are being developed. Therefore, this review article provides an overview of existing drugs, treatment options, advances in emerging therapeutics and related recent patents for the treatment of ocular disorders such as glaucoma, age related macular degeneration (AMD) and uveitis. PMID:25414810

  2. Age-Related Cognitive Deficits In Rhesus Monkeys Mirror Human Deficits on an Automated Test Battery

    PubMed Central

    Nagahara, Alan H.; Bernot, Tim; Tuszynski, Mark H.

    2010-01-01

    Aged non-human primates are a valuable model for gaining insight into mechanisms underlying neural decline with aging and during the course of neurodegenerative disorders. Behavioral studies are a valuable component of aged primate models, but are difficult to perform, time consuming, and often of uncertain relevance to human cognitive measures. We now report findings from an automated cognitive test battery in aged primates using equipment that is identical, and tasks that are similar, to those employed in human aging and Alzheimer’s disease studies. Young (7.1 ± 0.8 years) and aged (23.0 ± 0.5 years) rhesus monkeys underwent testing on a modified version of the Cambridge Automated Neuropsychological Test Battery (CANTAB), examining cognitive performance on separate tasks that sample features of visuospatial learning, spatial working memory, discrimination learning, and skilled motor performance. We find selective cognitive impairments among aged subjects in visuospatial learning and spatial working memory, but not in delayed recall of previously learned discriminations. Aged monkeys also exhibit slower speed in skilled motor function. Thus, aged monkeys behaviorally characterized on a battery of automated tests reveal patterns of age-related cognitive impairment that mirror in quality and severity those of aged humans, and differ fundamentally from more severe patterns of deficits observed in Alzheimer’s Disease. PMID:18760505

  3. Low Vision Depression Prevention Trial in Age-Related Macular Degeneration

    PubMed Central

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Massof, Robert W.; Leiby, Benjamin E.; Ho, Allen C.; Tasman, William S.

    2014-01-01

    Purpose To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD). Design Single-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months. Participants Patients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188). Interventions Before randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. Main Outcome Measures The Diagnostic and Statistical Manual IV defined depressive disorder based on the Patient Health Questionnaire-9 (primary outcome), Activities Inventory, National Eye Institute Vision Function Questionnaire–25 plus Supplement (NEI-VFQ), and NEI-VFQ quality of life (secondary outcomes). Results At 4 months, 11 BA+LVR subjects (12.6%) and 18 ST+LVR subjects (23.4%) developed a depressive disorder (relative risk [RR], 0.54; 95% CI, 0.27–1.06; P = 0.067). In planned adjusted analyses the RR was 0.51 (95% CI, 0.27–0.98; P = 0.04). A mediational analysis suggested that BA+LVR prevented depression to the extent that it enabled subjects to remain socially engaged. In addition, BA+LVR was associated with greater improvements in functional vision than ST+LVR, although there was no significant between-group difference. There was no significant change or between-group difference in quality of life. Conclusions An integrated mental health and low vision intervention halved the incidence of depressive disorders relative to standard outpatient LVR in patients with AMD. As the population ages, the number of persons with AMD and the adverse effects of comorbid

  4. Gender Associated Lipid and Apolipoprotein Profile in Patients with Age-Related Macular Degeneration

    PubMed Central

    Majkic-Singh, Nada T.; Stankovic, Sanja S.; Kosanovic-Jakovic, Natalija G.; Zoric, Lepsa D.; Radosavljevic, Aleksandra P.; Terzic, Dragana D.; Stojanovic, Jecka Z.

    2011-01-01

    The role of lipid parameters disorder in the development of age-related macular degeneration (AMD) is unclear. The aim of this study was to analyze lipid profile in these patients and to test the influence of gender on lipid profile of AMD patients, especially in the early and late form of the disease. 82 patients with AMD (mean age 70.3 yrs) and 80 age-matched control subjects were included in this study. Serum lipid and apolipoproteiin levels were determined using standardized methods. AMD patients had significantly higher values of total cholesterol (P=0.000), HDL-cholesterol (P=0.0003) and LDL-cholesterol (P=0.000) compared to control group. Significantly higher values of apo A1 (P=0.039), apo E (P=0.002), total-cholesterol (P=0.000), LDL-chol. (P=0.026), total HDL-chol (P=0.000), HDL3-chol. (P=0.005) and non-HDL-cholesterol (P=0.029) were found in female AMD patients compared to males with AMD. Females with the advanced form of the disease had significantly higher total cholesterol (P=0.006), HDL-C (P=0.004), non HDL-C (P=0.05) and apo E (P=0.014) compared to males with the same form of the disease. There is a significant disorder of lipid parameters in AMD patients especially in females. More severe forms of AMD are followed by the increase of atherogenic lipoproteins and apolipoproteins, and females have higher values of these parameters compared to males with the same form of AMD.

  5. Operative Management of Lumbar Degenerative Disc Disease

    PubMed Central

    Lee, Yu Chao; Osti, Orso Lorenzo

    2016-01-01

    Lumbar degenerative disc disease is extremely common. Current evidence supports surgery in carefully selected patients who have failed non-operative treatment and do not exhibit any substantial psychosocial overlay. Fusion surgery employing the correct grafting and stabilization techniques has long-term results demonstrating successful clinical outcomes. However, the best approach for fusion remains debatable. There is some evidence supporting the more complex, technically demanding and higher risk interbody fusion techniques for the younger, active patients or patients with a higher risk of non-union. Lumbar disc arthroplasty and hybrid techniques are still relatively novel procedures despite promising short-term and mid-term outcomes. Long-term studies demonstrating superiority over fusion are required before these techniques may be recommended to replace fusion as the gold standard. Novel stem cell approaches combined with tissue engineering therapies continue to be developed in expectation of improving clinical outcomes. Results with appropriate follow-up are not yet available to indicate if such techniques are safe, cost-effective and reliable in the long-term. PMID:27559465

  6. Operative Management of Lumbar Degenerative Disc Disease.

    PubMed

    Lee, Yu Chao; Zotti, Mario Giuseppe Tedesco; Osti, Orso Lorenzo

    2016-08-01

    Lumbar degenerative disc disease is extremely common. Current evidence supports surgery in carefully selected patients who have failed non-operative treatment and do not exhibit any substantial psychosocial overlay. Fusion surgery employing the correct grafting and stabilization techniques has long-term results demonstrating successful clinical outcomes. However, the best approach for fusion remains debatable. There is some evidence supporting the more complex, technically demanding and higher risk interbody fusion techniques for the younger, active patients or patients with a higher risk of non-union. Lumbar disc arthroplasty and hybrid techniques are still relatively novel procedures despite promising short-term and mid-term outcomes. Long-term studies demonstrating superiority over fusion are required before these techniques may be recommended to replace fusion as the gold standard. Novel stem cell approaches combined with tissue engineering therapies continue to be developed in expectation of improving clinical outcomes. Results with appropriate follow-up are not yet available to indicate if such techniques are safe, cost-effective and reliable in the long-term. PMID:27559465

  7. Degenerative lumbar spinal stenosis and its imposters: three case studies

    PubMed Central

    Ammendolia, Carlo

    2014-01-01

    Degenerative lumbar spinal stenosis causing neurogenic claudicaton is a common condition impacting walking ability in older adults. There are other highly prevalent conditions in this patient population that have similar signs and symptoms and cause limited walking ability. The purpose of this study is to highlight the diagnostic challenges using three case studies of older adults who present with limited walking ability who have imaging evidence of degenerative lumbar spinal stenosis. PMID:25202160

  8. Mechanistically linking age-related diseases and dietary carbohydrate via autophagy and the ubiquitin proteolytic systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological data indicate that consuming diets that deliver sugar to the blood rapidly (called high glycemic index, GI) is associated with enhanced risk for age-related diseases such as cardiovascular disease, type 2 diabetes, cataract and age-related macular degeneration (AMD). These debilities...

  9. College Students' Attitudes towards Age-Related Changes in Physical Appearance.

    ERIC Educational Resources Information Center

    Kanter, Allison; Agliata, Daniel; Tantleff-Dunn, Stacey

    The aim of this study was to identify factors associated with young adults' concerns about age related changes in body image and their anticipated impact on psychosocial functioning. One hundred and sixty-seven college students completed the Body Image and Aging Survey, designed to assess age related issues in body image, the Peer Dieting Survey,…

  10. Experience-Based Mitigation of Age-Related Performance Declines: Evidence from Air Traffic Control

    ERIC Educational Resources Information Center

    Nunes, Ashley; Kramer, Arthur F.

    2009-01-01

    Previous research has found age-related deficits in a variety of cognitive processes. However, some studies have demonstrated age-related sparing on tasks where individuals have substantial experience, often attained over many decades. Here, the authors examined whether decades of experience in a fast-paced demanding profession, air traffic…

  11. The relationship of major American dietary patterns to age-related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We hypothesized that major American dietary patterns are associated with age-related macular degeneration (AMD) risk. This was a cross-sectional study with 8,103 eyes from 4,088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into control (n=2,739), early ...

  12. Lack of serotonin1B receptor expression leads to age-related motor dysfunction, early onset of brain molecular aging and reduced longevity

    PubMed Central

    Sibille, E; Su, J; Leman, S; Le Guisquet, AM; Ibarguen-Vargas, Y; Joeyen-Waldorf, J; Glorioso, C; Tseng, GC; Pezzone, M; Hen, R; Belzung, C

    2008-01-01

    Normal aging of the brain differs from pathological conditions and is associated with increased risk for psychiatric and neurological disorders. In addition to its role in the etiology and treatment of mood disorders, altered serotonin (5-HT) signaling is considered a contributing factor to aging; however, no causative role has been identified in aging. We hypothesized that a deregulation of the 5-HT system would reveal its contribution to age-related processes and investigated behavioral and molecular changes throughout adult life in mice lacking the regulatory presynaptic 5-HT1B receptor (5-HT1BR), a candidate gene for 5-HT-mediated age-related functions. We show that the lack of 5-HT1BR (Htr1bKO mice) induced an early age-related motor decline and resulted in decreased longevity. Analysis of life-long transcriptome changes revealed an early and global shift of the gene expression signature of aging in the brain of Htr1bKO mice. Moreover, molecular changes reached an apparent maximum effect at 18-months in Htr1bKO mice, corresponding to the onset of early death in that group. A comparative analysis with our previous characterization of aging in the human brain revealed a phylogenetic conservation of age-effect from mice to humans, and confirmed the early onset of molecular aging in Htr1bKO mice. Potential mechanisms appear independent of known central mechanisms (Bdnf, inflammation), but may include interactions with previously identified age-related systems (IGF-1, sirtuins). In summary, our findings suggest that the onset of age-related events can be influenced by altered 5-HT function, thus identifying 5-HT as a modulator of brain aging, and suggesting age-related consequences to chronic manipulation of 5-HT. PMID:17420766

  13. A Study of the Association Between Sleep Bruxism, Low Quality of Sleep, and Degenerative Changes of the Temporomandibular Joint.

    PubMed

    Dias, Glaucia Marques; Bonato, Letícia Ladeira; Guimarães, Josemar Parreira; Silva, Jesca Neftali Nogueira; Ferreira, Luciano Ambrosio; Grossmann, Eduardo; Carvalho, Antonio Carlos Pires

    2015-11-01

    The aim of this study was to evaluate the presence of degenerative bone changes of the temporomandibular joint (TMJ) in individuals suffering from sleep bruxism (SB), associating these characteristics with the quality of sleep. For this, we followed the International Classification of Sleep Disorders for the diagnosis of SB, in addition to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) for the classification of TMD and cone beam computed tomography. It was found that 97.7% of the individuals with bruxism had at least 1 RDC/TMD group III diagnosis, 75.6% of the subjects considered their sleep quality as poor, and the largest group (23%) had centric bruxism. There was no significant association between the pattern of sleep quality (P = 0.36), the type of SB (P = 0.277), and the presence of degenerative changes of the TMJ. Regardless of the quality of sleep and the type of bruxism presented, the prevalence of degenerative bone disorders was high (67%) among women with a mean age of 46 years and a clinical diagnosis of SB.

  14. Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

    PubMed Central

    He, Liang; Kernogitski, Yelena; Kulminskaya, Irina; Loika, Yury; Arbeev, Konstantin G.; Loiko, Elena; Bagley, Olivia; Duan, Matt; Yashkin, Arseniy; Ukraintseva, Svetlana V.; Kovtun, Mikhail; Yashin, Anatoliy I.; Kulminski, Alexander M.

    2016-01-01

    the expression of nearby genes. Our mediation analyses suggest that the effects of some SNPs are mediated by specific endophenotypes. In conclusion, these findings indicate that loci with pleiotropic effects on age-related disorders tend to be enriched in genes involved in underlying mechanisms potentially related to nervous, cardiovascular and immune system functions, stress resistance, inflammation, ion channels and hematopoiesis, supporting the hypothesis of shared pathological role of infection, and inflammation in chronic age-related diseases. PMID:27790247

  15. Defining the inherent stability of degenerative spondylolisthesis: a systematic review.

    PubMed

    Simmonds, Andrea M; Rampersaud, Y Raja; Dvorak, Marcel F; Dea, Nicolas; Melnyk, Angela D; Fisher, Charles G

    2015-08-01

    OBJECT A range of surgical options exists for the treatment of degenerative lumbar spondylolisthesis (DLS). The chosen technique inherently depends on the stability of the DLS. Despite a substantial body of literature dedicated to the outcome analysis of numerous DLS procedures, no consensus has been reached on defining or classifying the disorder with respect to stability or the role that instability should play in a treatment algorithm. The purpose of this study was to define grades of stability and to develop a guide for deciding on the optimal approach in surgically managing patients with DLS. METHODS The authors conducted a qualitative systematic review of clinical or biomechanical analyses evaluating the stability of and surgical outcomes for DLS for the period from 1990 to 2013. Research focused on nondegenerative forms of spondylolisthesis or spinal stenosis without associated DLS was excluded. The primary extracted results were clinical and radiographic parameters indicative of DLS instability. RESULTS The following preoperative parameters are predictors of stability in DLS: restabilization signs (disc height loss, osteophyte formation, vertebral endplate sclerosis, and ligament ossification), no disc angle change or less than 3 mm of translation on dynamic radiographs, and the absence of low-back pain. The validity and magnitude of each parameter's contribution can only be determined through appropriately powered prospective evaluation in the future. Identifying these parameters has allowed for the creation of a preliminary DLS instability classification (DSIC) scheme based on the preoperative assessment of DLS stability. CONCLUSIONS Spinal stability is an important factor to consider in the evaluation and treatment of patients with DLS. Qualitative assessment of the best available evidence revealed clinical and radiographic parameters for the creation of the DSIC, a decision aid to help surgeons develop a method of preoperative evaluation to better

  16. Picking a bone with WISP1 (CCN4): new strategies against degenerative joint disease

    PubMed Central

    Maiese, Kenneth

    2016-01-01

    As the world’s population continues to age, it is estimated that degenerative joint disease disorders such as osteoarthritis will impact at least 130 million individuals throughout the globe by the year 2050. Advanced age, obesity, genetics, gender, bone density, trauma, and a poor level of physical activity can lead to the onset and progression of osteoarthritis. However, factors that lead to degenerative joint disease and involve gender, genetics, epigenetic mechanisms, and advanced age are not within the control of an individual. Furthermore, current therapies including pain management, improved nutrition, and regular programs for exercise do not lead to the resolution of osteoarthritis. As a result, new avenues for targeting the treatment of osteoarthritis are desperately needed. Wnt1 inducible signaling pathway protein 1 (WISP1), a matricellular protein and a downstream target of the wingless pathway Wnt1, is one such target to consider that governs cellular protection, stem cell proliferation, and tissue regeneration in a number of disorders including bone degeneration. However, increased WISP1 expression also has been associated with the progression of osteoarthritis. WISP1 has an intricate relationship with a number of proliferative and protective pathways that include phosphoinositide 3-kinase (PI 3-K), protein kinase B (Akt), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin -6 (IL-6), transforming growth factor-β, matrix metalloproteinase, small non-coding ribonucleic acids (RNAs), sirtuin silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), and the mechanistic target of rapamycin (mTOR). Taken together, this complex association WISP1 holds with these signaling pathways necessitates a fine biological regulation of WISP1 activity that can offset the progression of degenerative joint disease, but not limit the cellular protective capabilities of the WISP1 pathway. PMID:26893943

  17. [The genetic variability of complement system in pathogenesis of age-related macular degeneration].

    PubMed

    Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Dziedzina, Sylwia; Sanak, Marek

    2015-01-01

    Age-related macular degeneration is the leading cause of irreversible central vision impairment in people aged over 50 in developed countries. Age-related macular degeneration is a complex disease derived from environmental, immune and genetic factors. The complement pathway has been implicated in the pathogenesis of many diseases. Recently, variants in several genes, such as complement H (CFH), complement factor B (CFB), complement 2 (C2), and complement 3 (C3), encoding complement pathway proteins, have been identified as associated with age-related macular degeneration. However, the associations between these genes and age-related macular degeneration varied due to genetic variation within populations and various ethnics groups. The strongest association was found between the age-related macular degeneration and SNP Y402H rs 1061170 variant of CFH gene, which is present in 30% to 50% of age-related macular degeneration patients in Caucasian population and which is a risk factor for the development of age-related macular degeneration. Cohort studies showed that polymorphism Arg102Gly (SNP rs 2230199) of C3 protein could serve as a high-risk genetic marker for the development of age-related macular degeneration. Other rare variants of C3 (Lys155Gln, Lys65Gln, Arg735Trp, Ser1619Arg), may also be associated with a high incidence of age-related macular degeneration in some ethnic groups. A protective haplotype of variants E318D and IVS10 in the C2 gene as well as L9H and R320 in the BF were associated with age-related macular degeneration but only in Caucasians. The genetic findings in age-related macular degeneration patients stress the importance of detailed phenotyping to identify age-related macular degeneration subtypes, which may be associated with the presence of different polymorphisms and various environmental risk factors in any population. Further studies may be helpful to improve the effectiveness of prophylaxis and therapeutic options in age-related

  18. Genetic evidence for common pathways in human age-related diseases.

    PubMed

    Johnson, Simon C; Dong, Xiao; Vijg, Jan; Suh, Yousin

    2015-10-01

    Aging is the single largest risk factor for chronic disease. Studies in model organisms have identified conserved pathways that modulate aging rate and the onset and progression of multiple age-related diseases, suggesting that common pathways of aging may influence age-related diseases in humans as well. To determine whether there is genetic evidence supporting the notion of common pathways underlying age-related diseases, we analyzed the genes and pathways found to be associated with five major categories of age-related disease using a total of 410 genomewide association studies (GWAS). While only a small number of genes are shared among all five disease categories, those found in at least three of the five major age-related disease categories are highly enriched for apoliprotein metabolism genes. We found that a more substantial number of gene ontology (GO) terms are shared among the 5 age-related disease categories and shared GO terms include canonical aging pathways identified in model organisms, such as nutrient-sensing signaling, translation, proteostasis, stress responses, and genome maintenance. Taking advantage of the vast amount of genetic data from the GWAS, our findings provide the first direct evidence that conserved pathways of aging simultaneously influence multiple age-related diseases in humans as has been demonstrated in model organisms.

  19. Stemming the Degeneration: IVD Stem Cells and Stem Cell Regenerative Therapy for Degenerative Disc Disease

    PubMed Central

    Sivakamasundari, V; Lufkin, Thomas

    2013-01-01

    The intervertebral disc (IVD) is immensely important for the integrity of vertebral column function. The highly specialized IVD functions to confer flexibility and tensile strength to the spine and endures various types of biomechanical force. Degenerative disc disease (DDD) is a prevalent musculoskeletal disorder and is the major cause of low back pain and includes the more severe degenerative lumbar scoliosis, disc herniation and spinal stenosis. DDD is a multifactorial disorder whereby an imbalance of anabolic and catabolic factors, or alterations to cellular composition, or biophysical stimuli and genetic background can all play a role in its genesis. However, our comprehension of IVD formation and theetiology of disc degeneration (DD) are far from being complete, hampering efforts to formulate appropriate therapies to tackle DD. Knowledge of the stem cells and various techniques to manipulate and direct them to particular fates have been promising in adopting a stem-cell based regenerative approach to DD. Moreover, new evidence on the residence of stem/progenitor cells within particular IVD niches has emerged holding promise for future therapeutic applications. Existing issues pertaining to current therapeutic approaches are also covered in this review. PMID:23951558

  20. Redox Signaling as a Therapeutic Target to Inhibit Myofibroblast Activation in Degenerative Fibrotic Disease

    PubMed Central

    Berger, Peter; Zenzmaier, Christoph

    2014-01-01

    Degenerative fibrotic diseases encompass numerous systemic and organ-specific disorders. Despite their associated significant morbidity and mortality, there is currently no effective antifibrotic treatment. Fibrosis is characterized by the development and persistence of myofibroblasts, whose unregulated deposition of extracellular matrix components disrupts signaling cascades and normal tissue architecture leading to organ failure and death. The profibrotic cytokine transforming growth factor beta (TGFβ) is considered the foremost inducer of fibrosis, driving myofibroblast differentiation in diverse tissues. This review summarizes recent in vitro and in vivo data demonstrating that TGFβ-induced myofibroblast differentiation is driven by a prooxidant shift in redox homeostasis. Elevated NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H2O2) supported by concomitant decreases in nitric oxide (NO) signaling and reactive oxygen species scavengers are central factors in the molecular pathogenesis of fibrosis in numerous tissues and organs. Moreover, complex interplay between NOX4-derived H2O2 and NO signaling regulates myofibroblast differentiation. Restoring redox homeostasis via antioxidants or NOX4 inactivation as well as by enhancing NO signaling via activation of soluble guanylyl cyclases or inhibition of phosphodiesterases can inhibit and reverse myofibroblast differentiation. Thus, dysregulated redox signaling represents a potential therapeutic target for the treatment of wide variety of different degenerative fibrotic disorders. PMID:24701562

  1. Age-related changes in mesenchymal stem cells identified using a multi-omics approach.

    PubMed

    Peffers, M J; Collins, J; Fang, Y; Goljanek-Whysall, K; Rushton, M; Loughlin, J; Proctor, C; Clegg, P D

    2016-01-01

    Mesenchymal stem cells (MSC) are capable of multipotent differentiation into connective tissues and as such are an attractive source for autologous cell-based treatments for many clinical diseases and injuries. Ageing is associated with various altered cellular phenotypes coupled with a variety of transcriptional, epigenetic and translational changes. Furthermore, the regeneration potential of MSCs is reduced with increasing age and is correlated with changes in cellular functions. This study used a systems biology approach to investigate the transcriptomic (RNASeq), epigenetic (miRNASeq and DNA methylation) and protein alterations in ageing MSCs in order to understand the age-related functional and biological variations, which may affect their applications to regenerative medicine. We identified no change in expression of the cellular senescence markers. Alterations were evident at both the transcriptional and post-transcriptional level in a number of transcription factors. There was enrichment in genes involved in developmental disorders at mRNA and differential methylated loci (DML) level. Alterations in energy metabolism were apparent at the DML and protein level. The microRNA miR-199b-5p, whose expression was reduced in old MSCs, had predicted gene targets involved in energy metabolism and cell survival. Additionally, enrichment of DML and proteins in cell survival was evident. Enrichment in metabolic processes was revealed at the protein level and in genes identified as undergoing alternate splicing. Overall, an altered phenotype in MSC ageing at a number of levels implicated roles for inflamm-ageing and mitochondrial ageing. Identified changes represent novel insights into the ageing process, with implications for stem cell therapies in older patients. PMID:26853623

  2. A Novel Source of Methylglyoxal and Glyoxal in Retina: Implications for Age-Related Macular Degeneration

    PubMed Central

    Yoon, Kee Dong; Yamamoto, Kazunori; Ueda, Keiko; Zhou, Jilin; Sparrow, Janet R.

    2012-01-01

    Aging of retinal pigment epithelial (RPE) cells of the eye is marked by accumulations of bisretinoid fluorophores; two of the compounds within this lipofuscin mixture are A2E and all-trans-retinal dimer. These pigments are implicated in pathological mechanisms involved in some vision-threatening disorders including age-related macular degeneration (AMD). Studies have shown that bisretinoids are photosensitive compounds that undergo photooxidation and photodegradation when irradiated with short wavelength visible light. Utilizing ultra performance liquid chromatography (UPLC) with electrospray ionization mass spectrometry (ESI-MS) we demonstrate that photodegradation of A2E and all-trans-retinal dimer generates the dicarbonyls glyoxal (GO) and methylglyoxal (MG), that are known to modify proteins by advanced glycation endproduct (AGE) formation. By extracellular trapping with aminoguanidine, we established that these oxo-aldehydes are released from irradiated A2E-containing RPE cells. Enzyme-linked immunosorbant assays (ELISA) revealed that the substrate underlying A2E-containing RPE was AGE-modified after irradiation. This AGE deposition was suppressed by prior treatment of the cells with aminoguanidine. AGE-modification causes structural and functional impairment of proteins. In chronic diseases such as diabetes and atherosclerosis, MG and GO modify proteins by non-enzymatic glycation and oxidation reactions. AGE-modified proteins are also components of drusen, the sub-RPE deposits that confer increased risk of AMD onset. These results indicate that photodegraded RPE bisretinoid is likely to be a previously unknown source of MG and GO in the eye. PMID:22829938

  3. High Resolution Topography of Age-Related Changes in Non-Rapid Eye Movement Sleep Electroencephalography.

    PubMed

    Sprecher, Kate E; Riedner, Brady A; Smith, Richard F; Tononi, Giulio; Davidson, Richard J; Benca, Ruth M

    2016-01-01

    Sleeping brain activity reflects brain anatomy and physiology. The aim of this study was to use high density (256 channel) electroencephalography (EEG) during sleep to characterize topographic changes in sleep EEG power across normal aging, with high spatial resolution. Sleep was evaluated in 92 healthy adults aged 18-65 years old using full polysomnography and high density EEG. After artifact removal, spectral power density was calculated for standard frequency bands for all channels, averaged across the NREM periods of the first 3 sleep cycles. To quantify topographic changes with age, maps were generated of the Pearson's coefficient of the correlation between power and age at each electrode. Significant correlations were determined by statistical non-parametric mapping. Absolute slow wave power declined significantly with increasing age across the entire scalp, whereas declines in theta and sigma power were significant only in frontal regions. Power in fast spindle frequencies declined significantly with increasing age frontally, whereas absolute power of slow spindle frequencies showed no significant change with age. When EEG power was normalized across the scalp, a left centro-parietal region showed significantly less age-related decline in power than the rest of the scalp. This partial preservation was particularly significant in the slow wave and sigma bands. The effect of age on sleep EEG varies substantially by region and frequency band. This non-uniformity should inform the design of future investigations of aging and sleep. This study provides normative data on the effect of age on sleep EEG topography, and provides a basis from which to explore the mechanisms of normal aging as well as neurodegenerative disorders for which age is a risk factor.

  4. High Resolution Topography of Age-Related Changes in Non-Rapid Eye Movement Sleep Electroencephalography

    PubMed Central

    Sprecher, Kate E.; Riedner, Brady A.; Smith, Richard F.; Tononi, Giulio; Davidson, Richard J.; Benca, Ruth M.

    2016-01-01

    Sleeping brain activity reflects brain anatomy and physiology. The aim of this study was to use high density (256 channel) electroencephalography (EEG) during sleep to characterize topographic changes in sleep EEG power across normal aging, with high spatial resolution. Sleep was evaluated in 92 healthy adults aged 18–65 years old using full polysomnography and high density EEG. After artifact removal, spectral power density was calculated for standard frequency bands for all channels, averaged across the NREM periods of the first 3 sleep cycles. To quantify topographic changes with age, maps were generated of the Pearson’s coefficient of the correlation between power and age at each electrode. Significant correlations were determined by statistical non-parametric mapping. Absolute slow wave power declined significantly with increasing age across the entire scalp, whereas declines in theta and sigma power were significant only in frontal regions. Power in fast spindle frequencies declined significantly with increasing age frontally, whereas absolute power of slow spindle frequencies showed no significant change with age. When EEG power was normalized across the scalp, a left centro-parietal region showed significantly less age-related decline in power than the rest of the scalp. This partial preservation was particularly significant in the slow wave and sigma bands. The effect of age on sleep EEG varies substantially by region and frequency band. This non-uniformity should inform the design of future investigations of aging and sleep. This study provides normative data on the effect of age on sleep EEG topography, and provides a basis from which to explore the mechanisms of normal aging as well as neurodegenerative disorders for which age is a risk factor. PMID:26901503

  5. Who should have surgery for degenerative spondylolisthesis?

    PubMed Central

    Pearson, Adam M.; Lurie, Jon D.; Tosteson, Tor D.; Zhao, Wenyan; Abdu, William A.; Weinstein, James N.

    2013-01-01

    Study Design Combined prospective randomized controlled trial and observational cohort study of degenerative spondylolisthesis (DS) with an as-treated analysis. Objective To determine modifiers of the treatment effect (TE) of surgery (the difference between surgical and nonoperative outcomes) for DS using subgroup analysis. Summary of Background Data SPORT demonstrated a positive surgical TE for DS at the group level. However, individual characteristics may affect TE. Methods DS patients were treated with either surgery (n=395) or nonoperative care (n=206) and were analyzed according to treatment received. Fifty-five baseline variables were used to define subgroups for calculating the time-weighted average TE for the Oswestry Disability Index (ODI) over 4 years (TE=ΔODIsurgery-ΔODInonoperative). Variables with significant subgroup-by-treatment interactions (p<0.05) were simultaneously entered into a multivariate model to select independent TE predictors. Results All analyzed subgroups that included at least 50 patients improved significantly more with surgery than with nonoperative treatment (p<0.05). Multivariate analyses demonstrated that age ≤ 67 (TE −15.7 vs. −11.8 for age>67, p=0.014); female gender (TE −15.6 vs. −11.2 for males, p=0.01); the absence of stomach problems (TE −15.2 vs. −11.3 for those with stomach problems, p=0.035); neurogenic claudication (TE −15.3 vs. −9.0 for those without claudication, p=0.004); reflex asymmetry (TE −17.3 vs. −13.0 for those without asymmetry, p=0.016); opioid use (TE −18.4 vs. −11.7 for those not using opioids, p<0.001); not taking antidepressants (TE −14.5 vs. −5.4 for those on antidepressants, p=0.014); dissatisfaction with symptoms (TE −14.5 vs. −8.3 for those satisfied or neutral, p=0.039); and anticipating a high likelihood of improvement with surgery (TE −14.8 vs. −5.1 for anticipating a low likelihood of improvement with surgery, p=0.019) were independently associated with

  6. Maternal inflammation linearly exacerbates offspring age-related changes of spatial learning and memory, and neurobiology until senectitude.

    PubMed

    Li, Xue-Wei; Cao, Lei; Wang, Fang; Yang, Qi-Gang; Tong, Jing-Jing; Li, Xue-Yan; Chen, Gui-Hai

    2016-06-01

    Maternal inflammation during pregnancy can elevate the risk of neurodegenerative disorders in offspring. However, how it affects age-related impairments of spatial learning and memory and changes in the neurobiological indictors in the offspring in later adulthood is still elusive. In this study, the CD-1 mice with maternal gestational inflammation due to receiving lipopolysaccharide (LPS, i.p. 50 or 25μg/kg) were divided into 3-, 12-, 18-, and 22-month-old groups. The spatial learning and memory were evaluated using a six-radial arm water maze and the levels of presynaptic proteins (synaptotagmin-1 and syntaxin-1) and histone acetylation (H3K9ac and H4K8ac) in the dorsal hippocampus were detected using the immunohistochemical method. The results indicated that there were significant age-related impairments of spatial learning and memory, decreased levels of H4K8ac, H3K9ac, and syntaxin-1, and increased levels of synaptotagmin-1 in the offspring mice from 12 months old to 22 months old compared to the same-age controls. Maternal LPS treatment significantly exacerbated the offspring impairments of spatial learning and memory, the reduction of H3K9ac, H4K8ac, and syntaxin-1, and the increment of synaptotagmin-1 from 12 months old to 22 months old compared to the same-age control groups. The changes in the neurobiological indicators significantly correlated with the impairments of spatial learning and memory. Furthermore, this correlation, besides the age and LPS-treatment effects, also showed a dose-dependent effect. Our results suggest that maternal inflammation during pregnancy could exacerbate age-related impairments of spatial learning and memory, and neurobiochemical indicators in the offspring CD-1 mice from midlife to senectitude.

  7. The Bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularization

    PubMed Central

    Smith, Richard S.; John, Simon W. M.; Zabeleta, Adriana; Davisson, Muriel T.; Hawes, Norman L.; Chang, Bo

    2000-01-01

    Ocular neovascularization is the leading cause of blindness in developed countries and often causes rapid loss of vision in age-related macular degeneration. Acute visual loss is most often due to hemorrhage from new vessels that have extended from the choroid into the subretinal space. Growth of abnormal vessels beneath the retina in this condition is known as subretinal neovascularization (SRN). Age-related animal models of macular degeneration and SRN have not been described. Current animal models of SRN depend on chemical or physical stimuli to initiate growth of subretinal vessels. The genes responsible for age-related human macular degeneration with SRN have not been firmly identified. We report an angiogenic phenotype in Bst/+ mice that is age-related, clinically evident, and resembles human SRN. This represents a spontaneous, genetically determined model of SRN. Bst/+ mice offer the possibility of exploring the molecular mechanisms of SRN without the need for exogenous agents. PMID:10681427

  8. Aging Changes in Retinal Microglia and their Relevance to Age-related Retinal Disease.

    PubMed

    Ma, Wenxin; Wong, Wai T

    2016-01-01

    Age-related retinal diseases, such as age-related macular degeneration (AMD) and glaucoma, contain features of chronic retinal inflammation that may promote disease progression. However, the relationship between aging and neuroinflammation is unclear. Microglia are long-lived, resident immune cells of the retina, and mediate local neuroinflammatory reactions. We hypothesize that aging changes in microglia may be causally linked to neuroinflammatory changes underlying age-dependent retinal diseases. Here, we review the evidence for (1) how the retinal microglial phenotype changes with aging, (2) the factors that drive microglial aging in the retina, and (3) aging-related changes in microglial gene expression. We examine how these aspects of microglial aging changes may relate to pathogenic mechanisms of immune dysregulation driving the progression of age-related retinal disease. These relationships can highlight microglial aging as a novel target for the prevention and treatment of retinal disease.

  9. From mind wandering to involuntary retrieval: Age-related differences in spontaneous cognitive processes.

    PubMed

    Maillet, David; Schacter, Daniel L

    2016-01-01

    The majority of studies that have investigated the effects of healthy aging on cognition have focused on age-related differences in voluntary and deliberately engaged cognitive processes. Yet many forms of cognition occur spontaneously, without any deliberate attempt at engaging them. In this article we review studies that have assessed age-related differences in four such types of spontaneous thought processes: mind-wandering, involuntary autobiographical memory, intrusive thoughts, and spontaneous prospective memory retrieval. These studies suggest that older adults exhibit a reduction in frequency of both mind-wandering and involuntary autobiographical memory, whereas findings regarding intrusive thoughts have been more mixed. Additionally, there is some preliminary evidence that spontaneous prospective memory retrieval may be relatively preserved in aging. We consider the roles of age-related differences in cognitive resources, motivation, current concerns and emotional regulation in accounting for these findings. We also consider age-related differences in the neural correlates of spontaneous cognitive processes.

  10. Age-related differences in neurotoxicity produced by organophosphorus and N-methyl carbamate pesticides

    EPA Science Inventory

    Potential pesticide effects in infants and toddlers have received much attention in the scientific literature and the public media, including the concern for increased response to acute or shortterm exposures. Age-related differences in the acute neurotoxicity of acetylcholinest...

  11. AGE-RELATED GENE EXPRESSION CHANGES IN HUMAN SKIN FIBROBLASTS INDUCED BY MMS

    EPA Science Inventory

    Age-Related Gene Expression Changes In Human Skin Fibroblasts Induced By methyl methanesulfonate. Geremy W. Knapp, Alan H. Tennant, and Russell D. Owen. Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, U. S. Environmental Prote...

  12. Controlled processes account for age-related decrease in episodic memory.

    PubMed

    Vanderaspoilden, Valérie; Adam, Stéphane; der Linden, Martial Van; Morais, José

    2007-05-01

    A decrease in controlled processes has been proposed to be responsible for age-related episodic memory decline. We used the Process Dissociation Procedure, a method that attempts to estimate the contribution of controlled and automatic processes to cognitive performance, and entered both estimates in regression analyses. Results indicate that only controlled processes explained a great part of the age-related variance in a word recall task, especially when little environmental support was offered. PMID:16860766

  13. Altered Hippocampal Transcript Profile Accompanies an Age-Related Spatial Memory Deficit in Mice

    ERIC Educational Resources Information Center

    Verbitsky, Miguel; Yonan, Amanda L.; Malleret, Gael; Kandel, Eric R.; Gilliam, T. Conrad; Pavlidis, Paul

    2004-01-01

    We have carried out a global survey of age-related changes in mRNA levels in the 57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged…

  14. To unite or divide: mitochondrial dynamics in the murine outer retina that preceded age related photoreceptor loss

    PubMed Central

    Kam, Jaimie Hoh; Jeffery, Glen

    2015-01-01

    Mitochondrial function declines with age and is associated with age-related disorders and cell death. In the retina this is critical as photoreceptor energy demands are the greatest in the body and aged cell loss large (~30%). But mitochondria can fuse or divide to accommodate changing demands. We explore ageing mitochondrial dynamics in young (1 month) and old (12 months) mouse retina, investigating changes in mitochondrial fission (Fis1) and fusion (Opa1) proteins, cytochrome C oxidase (COX III), which reflects mitochondrial metabolic status, and heat shock protein 60 (Hsp60) that is a mitochondrial chaperon for protein folding. Western blots showed each protein declined with age. However, within this, immunostaining revealed increases of around 50% in Fis1 and Opa1 in photoreceptor inner segments (IS). Electron microscope analysis revealed mitochondrial fragmentation with age and marked changes in morphology in IS, consistent with elevated dynamics. COX III declined by approximately 30% in IS, but Hsp60 reductions were around 80% in the outer plexiform layer. Our results are consistent with declining mitochondrial metabolism. But also with increased photoreceptor mitochondrial dynamics that differ from other retinal regions, perhaps reflecting attempts to maintain function. These changes are the platform for age related photoreceptor loss initiated after 12 months. PMID:26393878

  15. Characteristics of age-related behavioral changes in senescence-accelerated mouse SAMP8 and SAMP10.

    PubMed

    Miyamoto, M

    1997-01-01

    Senescence-Accelerated Mouse (SAM), a murine model of accelerated senescence, has been established by Takeda et al. (1981). SAM consists of senescence-accelerated-prone mouse (SAMP) and senescence-accelerated-resistant mouse (SAMR), the latter of which shows normal aging characteristics. In 1991 there were eight different substrains in the P-series, which commonly exhibited accelerated aging with a shortened life span (Takeda et al., 1991). Among the P-series, we have found that SAMP8 mice show significant impairments in a variety of learning tasks when compared with SAMR1 mice (Miyamoto et al., 1986). Further studies suggest that SAMP8 exhibits an age-related emotional disorder characterized by reduced anxiety-like behavior (Miyamoto et al., 1992). On the other hand, it has been shown that SAMP10 exhibits brain atrophy and learning impairments in an avoidance task (Shimada et al., 1992, 1993). Here, characteristics of age-related deficits in learning and memory, changes in emotional behavior, and abnormality of circadian rhythms in SAMP8 and SAMP10 mice are described. In the experiments, SAMP8/Ta (SAMP8), SAMP10/(/)Ta (SAMP10) and SAMR1TA (SAMR1) reared under specific pathogen-free conditions at Takeda Chemical Industries were used. PMID:9088911

  16. Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons

    PubMed Central

    Zhu, Xiaoxia; Walton, Joseph P.

    2016-01-01

    Age-related hearing loss (ARHL) -presbycusis - is the most prevalent neurodegenerative disease and number one communication disorder of our aged population; and affects hundreds of millions of people worldwide. Its prevalence is close to that of cardiovascular disease and arthritis, and can be a precursor to dementia. The auditory perceptual dysfunction is well understood, but knowledge of the biological bases of ARHL is still somewhat lacking. Surprisingly, there are no FDA-approved drugs for treatment. Based on our previous studies of human subjects, where we discovered relations between serum aldosterone levels and the severity of ARHL, we treated middle age mice with aldosterone, which normally declines with age in all mammals. We found that hearing thresholds and suprathreshold responses significantly improved in the aldosterone-treated mice compared to the non-treatment group. In terms of cellular and molecular mechanisms underlying this therapeutic effect, additional experiments revealed that spiral ganglion cell survival was significantly improved, mineralocorticoid receptors were upregulated via post-translational protein modifications, and age-related intrinsic and extrinsic apoptotic pathways were blocked by the aldosterone therapy. Taken together, these novel findings pave the way for translational drug development towards the first medication to prevent the progression of ARHL. PMID:27667674

  17. The Digital Ageing Atlas: integrating the diversity of age-related changes into a unified resource.

    PubMed

    Craig, Thomas; Smelick, Chris; Tacutu, Robi; Wuttke, Daniel; Wood, Shona H; Stanley, Henry; Janssens, Georges; Savitskaya, Ekaterina; Moskalev, Alexey; Arking, Robert; de Magalhães, João Pedro

    2015-01-01

    Multiple studies characterizing the human ageing phenotype have been conducted for decades. However, there is no centralized resource in which data on multiple age-related changes are collated. Currently, researchers must consult several sources, including primary publications, in order to obtain age-related data at various levels. To address this and facilitate integrative, system-level studies of ageing we developed the Digital Ageing Atlas (DAA). The DAA is a one-stop collection of human age-related data covering different biological levels (molecular, cellular, physiological, psychological and pathological) that is freely available online (http://ageing-map.org/). Each of the >3000 age-related changes is associated with a specific tissue and has its own page displaying a variety of information, including at least one reference. Age-related changes can also be linked to each other in hierarchical trees to represent different types of relationships. In addition, we developed an intuitive and user-friendly interface that allows searching, browsing and retrieving information in an integrated and interactive fashion. Overall, the DAA offers a new approach to systemizing ageing resources, providing a manually-curated and readily accessible source of age-related changes.

  18. The Digital Ageing Atlas: integrating the diversity of age-related changes into a unified resource

    PubMed Central

    Craig, Thomas; Smelick, Chris; Tacutu, Robi; Wuttke, Daniel; Wood, Shona H.; Stanley, Henry; Janssens, Georges; Savitskaya, Ekaterina; Moskalev, Alexey; Arking, Robert; de Magalhães, João Pedro

    2015-01-01

    Multiple studies characterizing the human ageing phenotype have been conducted for decades. However, there is no centralized resource in which data on multiple age-related changes are collated. Currently, researchers must consult several sources, including primary publications, in order to obtain age-related data at various levels. To address this and facilitate integrative, system-level studies of ageing we developed the Digital Ageing Atlas (DAA). The DAA is a one-stop collection of human age-related data covering different biological levels (molecular, cellular, physiological, psychological and pathological) that is freely available online (http://ageing-map.org/). Each of the >3000 age-related changes is associated with a specific tissue and has its own page displaying a variety of information, including at least one reference. Age-related changes can also be linked to each other in hierarchical trees to represent different types of relationships. In addition, we developed an intuitive and user-friendly interface that allows searching, browsing and retrieving information in an integrated and interactive fashion. Overall, the DAA offers a new approach to systemizing ageing resources, providing a manually-curated and readily accessible source of age-related changes. PMID:25232097

  19. Age-related differences in brain activity in the subsequent memory paradigm: a meta-analysis.

    PubMed

    Maillet, David; Rajah, M Natasha

    2014-09-01

    Healthy aging is associated with declines in episodic memory. This reduction is thought to be due in part to age-related differences in encoding-related processes. In the current study, we performed an activation likelihood estimation meta-analysis of functional magnetic resonance imaging (fMRI) studies assessing age-related differences in the neural correlates of episodic encoding. Only studies using the subsequent memory paradigm were included. We found age-related under-recruitment of occipital and fusiform cortex, but over-recruitment in a set of regions including bilateral middle/superior frontal gyri, anterior medial frontal gyrus, precuneus and left inferior parietal lobe. We demonstrate that all of the regions consistently over-recruited by older adults during successful encoding exhibit either direct overlap, or occur in close vicinity to regions consistently involved in unsuccessful encoding in young adults. We discuss the possibility that this overall pattern of age-related differences represents an age-related shift in focus: away from perceptual details, and toward evaluative and personal thoughts and feelings during memory tasks. We discuss whether these age-related differences in brain activation benefit performance in older adults, and additional considerations.

  20. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    PubMed

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration.

  1. Age-related Hearing Loss: GABA, Nicotinic Acetylcholine and NMDA Receptor Expression Changes in Spiral Ganglion Neurons of the Mouse

    PubMed Central

    Tang, Xiaolan; Zhu, Xiaoxia; Ding, Bo; Walton, Joseph P.; Frisina, Robert D.; Su, Jiping

    2014-01-01

    Age-related hearing loss – presbycusis – is the number one communication disorder and most prevalent neurodegenerative condition of our aged population. Although speech understanding in background noise is quite difficult for those with presbycusis, there are currently no biomedical treatments to prevent, delay or reverse this condition. A better understanding of the cochlear mechanisms underlying presbycusis will help lead to future treatments. Objectives of the present study were to investigate gamma-amino butyric acid A (GABAA) receptor subunit α1, nicotinic acetylcholine (nACh) receptor subunit β2, and N-methyl-D-aspartate (NMDA) receptor subunit NR1 mRNA and protein expression changes in spiral ganglion neurons of the CBA/CaJ mouse cochlea, that occur in age-related hearing loss, utilizing quantitative immunohistochemistry and semi-quantitative RT-PCR techniques. We found that auditory brainstem response (ABR) thresholds shifted over 40 dB from 3–48 kHz in old mice compared to young adults. DPOAE thresholds also shifted over 40 dB from 6–49 kHz in old mice, and their amplitudes were significantly decreased or absent in the same frequency range. Spiral ganglion neuron (SGN) density decreased with age in basal, middle and apical turns, and SGN density of the basal turn declined the most. A positive correlation was observed between SGN density and ABR wave 1 amplitude. mRNA and protein expression of GABAAR α1 and AChR β2 decreased with age in SGNs in the old mouse cochlea. mRNA and protein expression of NMDAR NR1 increased with age in SGNs of the old mice. These findings demonstrate that there are functionally-relevant age-related changes of GABAAR, nAChR, NMDAR expression in CBA mouse SGNs reflecting their degeneration, which may be related to functional changes in cochlear synaptic transmission with age, suggesting biological mechanisms for peripheral age-related hearing loss. PMID:24316061

  2. Computer Simulations of Loss of Organization of Neurons as a Model for Age-related Cognitive Decline

    NASA Astrophysics Data System (ADS)

    Cruz, Luis; Fengometidis, Elene; Jones, Frank; Jampani, Srinivas

    2011-03-01

    In normal aging, brains suffer from progressive cognitive decline not linked with loss of neurons common in neurodegenerative disorders such as Alzheimer's disease. However, in some brain areas neurons have lost positional organization specifically within microcolumns: arrays of interconnected neurons which may constitute fundamental computational units in the brain. This age-related loss of organization, likely a result of micron-sized random displacements in neuronal positions, is hypothesized to be a by-product of the loss of support from the surrounding medium, including dendrites. Using a dynamical model applied to virtual 3D representation of neuronal arrangements, that previously showed loss of organization in brains of cognitively tested rhesus monkeys, the relationship between these displacements and changes to the surrounding dendrite network are presented. The consequences of these displacements on the structure of the dendritic network, with possible disruptions in signal synchrony important to cognitive function, are discussed. NIH R01AG021133.

  3. Discovering novel microRNAs and age-related nonlinear changes in rat brains using deep sequencing.

    PubMed

    Yin, Lanxuan; Sun, Yubai; Wu, Jinfeng; Yan, Siyu; Deng, Zhenglu; Wang, Jun; Liao, Shenke; Yin, Dazhong; Li, Guolin

    2015-02-01

    Elucidating the molecular mechanisms of brain aging remains a significant challenge for biogerontologists. The discovery of gene regulation by microRNAs (miRNAs) has added a new dimension for examining this process; however, the full complement of miRNAs involved in brain aging is still not known. In this study, miRNA profiles of young, adult, and old rats were obtained to evaluate molecular changes during aging. High-throughput deep sequencing revealed 547 known and 171 candidate novel miRNAs that were differentially expressed among groups. Unexpectedly, miRNA expression did not decline progressively with advancing age; moreover, genes targeted by age-associated miRNAs were predicted to be involved in biological processes linked to aging and neurodegenerative diseases. These findings provide novel insight into the molecular mechanisms underlying brain aging and a resource for future studies on age-related brain disorders.

  4. Destructive discovertebral degenerative disease of the lumbar spine.

    PubMed

    Charran, A K; Tony, G; Lalam, R; Tyrrell, P N M; Tins, B; Singh, J; Eisenstein, S M; Balain, B; Trivedi, J M; Cassar-Pullicino, V N

    2012-09-01

    The uncommon variant of degenerative hip joint disease, termed rapidly progressive osteoarthritis, and highlighted by severe joint space loss and osteochondral disintegration, is well established. We present a similar unusual subset in the lumbar spine termed destructive discovertebral degenerative disease (DDDD) with radiological features of vertebral malalignment, severe disc resorption, and "bone sand" formation secondary to vertebral fragmentation. Co-existing metabolic bone disease is likely to promote the development of DDDD of the lumbar spine, which presents with back pain and sciatica due to nerve root compression by the "bone sand" in the epidural space. MRI and CT play a complimentary role in making the diagnosis.

  5. Anterior Cervical Spine Surgery for Degenerative Disease: A Review

    PubMed Central

    SUGAWARA, Taku

    Anterior cervical spine surgery is an established surgical intervention for cervical degenerative disease and high success rate with excellent long-term outcomes have been reported. However, indications of surgical procedures for certain conditions are still controversial and severe complications to cause neurological dysfunction or deaths may occur. This review is focused mainly on five widely performed procedures by anterior approach for cervical degenerative disease; anterior cervical discectomy, anterior cervical discectomy and fusion, anterior cervical corpectomy and fusion, anterior cervical foraminotomy, and arthroplasty. Indications, procedures, outcomes, and complications of these surgeries are discussed. PMID:26119899

  6. Gene Expression Changes for Antioxidants Pathways in the Mouse Cochlea: Relations to Age-related Hearing Deficits

    PubMed Central

    Tadros, Sherif F.; D'Souza, Mary; Zhu, Xiaoxia; Frisina, Robert D.

    2014-01-01

    Age-related hearing loss – presbycusis – is the number one neurodegenerative disorder and top communication deficit of our aged population. Like many aging disorders of the nervous system, damage from free radicals linked to production of reactive oxygen and/or nitrogen species (ROS and RNS, respectively) may play key roles in disease progression. The efficacy of the antioxidant systems, e.g., glutathione and thioredoxin, is an important factor in pathophysiology of the aging nervous system. In this investigation, relations between the expression of antioxidant-related genes in the auditory portion of the inner ear – cochlea, and age-related hearing loss was explored for CBA/CaJ mice. Forty mice were classified into four groups according to age and degree of hearing loss. Cochlear mRNA samples were collected and cDNA generated. Using Affymetrix® GeneChip, the expressions of 56 antioxidant-related gene probes were analyzed to estimate the differences in gene expression between the four subject groups. The expression of Glutathione peroxidase 6, Gpx6; Thioredoxin reductase 1, Txnrd1; Isocitrate dehydrogenase 1, Idh1; and Heat shock protein 1, Hspb1; were significantly different, or showed large fold-change differences between subject groups. The Gpx6, Txnrd1 and Hspb1 gene expression changes were validated using qPCR. The Gpx6 gene was upregulated while the Txnrd1 gene was downregulated with age/hearing loss. The Hspb1 gene was found to be downregulated in middle-aged animals as well as those with mild presbycusis, whereas it was upregulated in those with severe presbycusis. These results facilitate development of future interventions to predict, prevent or slow down the progression of presbycusis. PMID:24587312

  7. Gene expression changes for antioxidants pathways in the mouse cochlea: relations to age-related hearing deficits.

    PubMed

    Tadros, Sherif F; D'Souza, Mary; Zhu, Xiaoxia; Frisina, Robert D

    2014-01-01

    Age-related hearing loss - presbycusis - is the number one neurodegenerative disorder and top communication deficit of our aged population. Like many aging disorders of the nervous system, damage from free radicals linked to production of reactive oxygen and/or nitrogen species (ROS and RNS, respectively) may play key roles in disease progression. The efficacy of the antioxidant systems, e.g., glutathione and thioredoxin, is an important factor in pathophysiology of the aging nervous system. In this investigation, relations between the expression of antioxidant-related genes in the auditory portion of the inner ear - cochlea, and age-related hearing loss was explored for CBA/CaJ mice. Forty mice were classified into four groups according to age and degree of hearing loss. Cochlear mRNA samples were collected and cDNA generated. Using Affymetrix® GeneChip, the expressions of 56 antioxidant-related gene probes were analyzed to estimate the differences in gene expression between the four subject groups. The expression of Glutathione peroxidase 6, Gpx6; Thioredoxin reductase 1, Txnrd1; Isocitrate dehydrogenase 1, Idh1; and Heat shock protein 1, Hspb1; were significantly different, or showed large fold-change differences between subject groups. The Gpx6, Txnrd1 and Hspb1 gene expression changes were validated using qPCR. The Gpx6 gene was upregulated while the Txnrd1 gene was downregulated with age/hearing loss. The Hspb1 gene was found to be downregulated in middle-aged animals as well as those with mild presbycusis, whereas it was upregulated in those with severe presbycusis. These results facilitate development of future interventions to predict, prevent or slow down the progression of presbycusis.

  8. Oxidative damage impact on aging and age-related diseases: drug targeting of telomere attrition and dynamic telomerase activity flirting with imidazole-containing dipeptides.

    PubMed

    Babizhayev, Mark A; Vishnyakova, Khava S; Yegorov, Yegor E

    2014-01-01

    It has been documented that telomere-associated cellular senescence may contribute to certain age-related disorders, including an increase in cancer incidence, wrinkling and diminished skin elasticity, atherosclerosis, osteoporosis, weight loss, age-related cataract, glaucoma and others. Shorter telomere length in leukocytes was associated crosssectionally with cardiovascular disorders and their risk factors, including pulse pressure and vascular aging, obesity, vascular dementia, diabetes, coronary artery disease, myocardial infarction (although not in all studies), cellular turnover and exposure to oxidative and inflammatory damage in chronic obstructive pulmonary disease. It has been proposed that telomere length may not be a strong biomarker of survival in older individuals, but it may be an informative biomarker of healthy aging. The data reveal that telomere dynamics and changes in telomerase activity are consistent elements of cellular alterations associated with changes in proliferative state and in this article these processes are consequently considered as the new therapeutic drug targets for physiological control with advanced drug delivery and nutritional formulations. In particular, the presence of highly specific correlations and early causal relationships between telomere loss in the absence of telomerase activity and replicative senescence or crisis, and from the other side, telomerase reactivation and cell immortality, point to new and important treatment strategies or the therapeutic manipulation during treatment of age related disorders and cancer. Once better controls and therapeutic treatments for aging and age-related disorders are achieved, cellular rejuvenation by manipulating telomeres and enzyme telomerase activity may reduce some of the physiological declines that accompany aging. In this work, we raise and support a therapeutic concept of using non-hydrolyzed forms of naturally occurring imidazoledipeptide based compounds carnosine and

  9. Stromal Fibroblast in Age-Related Cancer: Role in Tumorigenesis and Potential as Novel Therapeutic Target

    PubMed Central

    Elkhattouti, Abdelouahid; Hassan, Mohamed; Gomez, Christian R.

    2015-01-01

    Incidence of most common cancers increases with age due to accumulation of damage to cells and tissues. Stroma, the structure close to the basement membrane, is gaining increased attention from clinicians and researchers due to its increasingly, yet incompletely understood role in the development of age-related cancer. With advanced age, stroma generates a pro-tumorigenic microenvironment, exemplified by the senescence-associated secretory phenotype (SASP). Components of the SASP, such as cytokines, chemokines, and high energy metabolites are main drivers of age-related cancer initiation and sustain its progression. Our purpose is to provide insight into the mechanistic role of the stroma, with particular emphasis on stromal fibroblasts, on the development of age-related tumors. We also present evidence of the potential of the stroma as target for tumor therapy. Likewise, a rationale for age-related antitumor therapy targeting the stroma is presented. We expect to foster debate on the underlining basis of age-related cancer pathobiology. We also would like to promote discussion on novel stroma-based anticancer therapeutic strategies tailored to treat the elderly. PMID:26284191

  10. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.

    PubMed

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

    Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer's Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer's Disease.

  11. Age-related infertility and unexplained infertility: an intricate clinical dilemma.

    PubMed

    Somigliana, Edgardo; Paffoni, Alessio; Busnelli, Andrea; Filippi, Francesca; Pagliardini, Luca; Vigano, Paola; Vercellini, Paolo

    2016-07-01

    A diagnosis of unexplained infertility is commonly made when clinical investigations fail to identify any obvious barriers to conception. As a consequence, unexplained infertility includes several heterogeneous conditions, one being women with age-related infertility. However, the latter represent a peculiar and different situation. Women with age-related infertility may have a different prognosis and may benefit from different treatments. Unfortunately, since fecundity declines with age, discerning between unexplained infertility and age-related infertility becomes more and more difficult as the woman's age increases. In this opinion, with the use of a mathematical model we show that the rate of false positive diagnoses of unexplained infertility increases rapidly after 35 years of age. Using a threshold of 2 years of unfruitful, regular unprotected intercourse, this rate exceeds 50% in women starting pregnancy seeking after 37 years. The scenario is much worse using a threshold of 1 year. From a clinical perspective, extrapolating results obtained in a population of young women with unexplained infertility to those with age-related infertility is not justified. It is noteworthy that, if Assisted Reproductive Technologies are unable to overcome age-related infertility, the older women erroneously labeled with unexplained infertility may receive inappropriate therapies. These may expose women to unjustified risks and waste financial resources. Unfortunately, the available literature about older women is scanty and does not provide valid evidence. Randomized controlled trials aimed at identifying the most suitable clinical management of older women with a normal infertility work-up are pressingly needed. PMID:27060173

  12. Stromal Fibroblast in Age-Related Cancer: Role in Tumorigenesis and Potential as Novel Therapeutic Target.

    PubMed

    Elkhattouti, Abdelouahid; Hassan, Mohamed; Gomez, Christian R

    2015-01-01

    Incidence of most common cancers increases with age due to accumulation of damage to cells and tissues. Stroma, the structure close to the basement membrane, is gaining increased attention from clinicians and researchers due to its increasingly, yet incompletely understood role in the development of age-related cancer. With advanced age, stroma generates a pro-tumorigenic microenvironment, exemplified by the senescence-associated secretory phenotype (SASP). Components of the SASP, such as cytokines, chemokines, and high energy metabolites are main drivers of age-related cancer initiation and sustain its progression. Our purpose is to provide insight into the mechanistic role of the stroma, with particular emphasis on stromal fibroblasts, on the development of age-related tumors. We also present evidence of the potential of the stroma as target for tumor therapy. Likewise, a rationale for age-related antitumor therapy targeting the stroma is presented. We expect to foster debate on the underlining basis of age-related cancer pathobiology. We also would like to promote discussion on novel stroma-based anticancer therapeutic strategies tailored to treat the elderly. PMID:26284191

  13. Aging assessment of reactor instrumentation and protection system components. Aging-related operating experiences

    SciTech Connect

    Gehl, A.C.; Hagen, E.W.

    1992-07-01

    A study of the aging-related operating experiences throughout a five-year period (1984--1988) of six generic instrumentation modules (indicators, sensors, controllers, transmitters, annunciators, and recorders) was performed as a part of the Nuclear Plant Aging Research Program. The effects of aging from operational and environmental stressors were characterized from results depicted in Licensee Event Reports (LERs). The data are graphically displayed as frequency of events per plant year for operating plant ages from 1 to 28 years to determine aging-related failure trend patterns. Three main conclusions were drawn from this study: (1) Instrumentation and control (I&C) modules make a modest contribution to safety-significant events: 17% of LERs issued during 1984--1988 dealt with malfunctions of the six I&C modules studied, and 28% of the LERs dealing with these I&C module malfunctions were aging related (other studies show a range 25--50%); (2) Of the six modules studied, indicators, sensors, and controllers account for the bulk (83%) of aging-related failures; and (3) Infant mortality appears to be the dominant aging-related failure mode for most I&C module categories (with the exception of annunciators and recorders, which appear to fail randomly).

  14. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.

    PubMed

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

    Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer's Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer's Disease. PMID:26937969

  15. Profiling age-related epigenetic markers of stomach adenocarcinoma in young and old subjects.

    PubMed

    Kim, Byoung-Chul; Jeong, Hyoung Oh; Park, Daeui; Kim, Chul-Hong; Lee, Eun Kyeong; Kim, Dae Hyun; Im, Eunok; Kim, Nam Deuk; Lee, Sunghoon; Yu, Byung Pal; Bhak, Jong; Chung, Hae Young

    2015-01-01

    The purpose of our study is to identify epigenetic markers that are differently expressed in the stomach adenocarcinoma (STAD) condition. Based on data from The Cancer Genome Atlas (TCGA), we were able to detect an age-related difference in methylation patterns and changes in gene and miRNA expression levels in young (n = 14) and old (n = 70) STAD subjects. Our analysis identified 323 upregulated and 653 downregulated genes in old STAD subjects. We also found 76 miRNAs with age-related expression patterns and 113 differentially methylated genes (DMGs), respectively. Our further analysis revealed that significant upregulated genes (n = 35) were assigned to the cell cycle, while the muscle system process (n = 27) and cell adhesion-related genes (n = 57) were downregulated. In addition, by comparing gene and miRNA expression with methylation change, we identified that three upregulated genes (ELF3, IL1β, and MMP13) known to be involved in inflammatory responses and cell growth were significantly hypomethylated in the promoter region. We further detected target candidates for age-related, downregulated miRNAs (hsa-mir-124-3, hsa-mir-204, and hsa-mir-125b-2) in old STAD subjects. This is the first report of the results from a study exploring age-related epigenetic biomarkers of STAD using high-throughput data and provides evidence for a complex clinicopathological condition expressed by the age-related STAD progression.

  16. Mesenchymal stem cells: a revolution in therapeutic strategies of age-related diseases.

    PubMed

    Peng, Yan; Huang, Sha; Cheng, Biao; Nie, Xiaohu; Enhe, Jirigala; Feng, Changjiang; Fu, Xiaobing

    2013-01-01

    The great evolutionary biologist Theodosius Dobzhansky once said: "Nothing in biology makes sense except in the light of evolution". Aging is a complex biological phenomenon and the factors governing the process of aging and age-related diseases are only beginning to be understood, oxidative stress, telomere shortening in DNA components and genetic changes were shown to be the mainly regulating mechanisms during the recent decades. Although a considerable amount of both animal and clinical data that demonstrate the extensive and safe use of mesenchymal stromal cells (MSCs) is available, the precise summarization and identification of MSCs in age-related diseases remains a challenge. Along this line, this review discussed several typical age-related diseases for which MSCs have been proved to confer protection and put forward a hypothesis for the association among MSCs and age-related diseases from an evolutionary perspective. Above all, we hope further and more research efforts could be aroused to elucidate the role and mechanisms that MSCs involved in the age-related diseases.

  17. Nd:YAG laser in experimentally induced chronic degenerative osteoarthritis in broiler chickens: pilot study

    NASA Astrophysics Data System (ADS)

    Fortuna, Damiano; Rossi, Giacomo; Bilotta, Teresa W.; Zati, Allesandro; Cardillo, Ilaria; Venturini, Antonio; Pinna, Stefania; Serra, Christian; Masotti, Leonardo

    2002-10-01

    The Low Level Laser Therapy (LLLT) has been widely tested in arthritis disorders, but there is still some disagreement in the results, therefore in this study we have investigated High Intensity Laser Therapy (HILT). The degenerative arthritis was induced in 18 chickens by intra-articular inoculation of Freund's complete adjuvant. Clinical studies were carried out (weight increase and grades of lameness) as well as morphological (macroscopic and histological) tests and seroassay (C Reactive Protein). The Nd:YAG pulsed wave was employed. The serologic data revealed the anti-inflammatory effect on the laser, with a highly significant difference between those treated and the control group. No lesion on the skin, i.e. burn, or in depth has been observed in the Treated group. Heavyline of broiler chickens in growing age has been revealed a good animal model of O.A.. The Nd:YAG Pulsed Wave it is safe on these structures. The anti-inflammatory effect of the HILT it seems to contrast the destructive degenerative process.

  18. Nerve cell death in degenerative diseases of the central nervous system: clinical aspects.

    PubMed

    Agid, Y; Blin, J

    1987-01-01

    The origin of degenerative diseases of the central nervous system lies in genetic and acquired disorders. Analysis of the clinical characteristics of diseases affecting specific neuronal systems may help us to understand their pathogenesis. The stereotyped symptomatology characteristic of most degenerative diseases results from neuronal death in specific pathways: pyramidal tract and motor neurons in amyotrophic lateral sclerosis, nigrostriatal dopamine system in Parkinson's disease, posterior and lateral columns of the spinal cord in Friedreich's ataxia, etc. This suggests that these neurons are sensitive to pathological processes that are still unknown. Progression of the disease, whether linear or not, is slow, but it is more rapid than similar effects due to ageing. This indicates either that the environmental cause of degeneration (if it exists) is continuously present or that a vital process has been once and for all disrupted, perhaps at the level of the genome, causing insufficient production of essential proteins, or accumulation of eventually toxic metabolites. Symptoms generally appear during adulthood, i.e. after normal differentiation has taken place, and after a considerable number of neurons have already been damaged. The initiation of neuronal death precedes the appearance of the first symptoms. PMID:3556087

  19. Effects of interspinous spacers on lumbar degenerative disease.

    PubMed

    Zhou, Dong; Nong, Lu-Ming; DU, Rui; Gao, Gong-Ming; Jiang, Yu-Qing; Xu, Nan-Wei

    2013-03-01

    The present study aimed to evaluate the early effects of interspinous spacers on lumbar degenerative disease. The clinical outcomes of 23 patients with lumbar degenerative disease, treated using interspinous spacer implantation alone or combined with posterior lumbar fusion, were retrospectively studied and assessed with a visual analogue scale (VAS) and the Oswestry Disability Index (ODI). Pre-operative and post-operative interspinous distance, disc space height, foraminal width and height and segmental lordosis were determined. The early effects and complications associated with the interspinous spacers were recorded. The surgical procedures performed with the in-space treatment were easy and minimally invasive. The VAS scores and ODI were improved post-operatively compared with pre-operatively. Significant changes in the interspinous distance, disc space height, foraminal width and height and segmental lordosis were noted. In-space treatment for degenerative lumbar disease is easy and safe, with good early effects. The in-space system provides an alternative treatment for lumbar degenerative disease.

  20. 78 FR 36305 - Proposed Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-17

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  1. Bivalent separation into univalents precedes age-related meiosis I errors in oocytes

    PubMed Central

    Sakakibara, Yogo; Hashimoto, Shu; Nakaoka, Yoshiharu; Kouznetsova, Anna; Höög, Christer; Kitajima, Tomoya S.

    2015-01-01

    The frequency of chromosome segregation errors during meiosis I (MI) in oocytes increases with age. The two-hit model suggests that errors are caused by the combination of a first hit that creates susceptible crossover configurations and a second hit comprising an age-related reduction in chromosome cohesion. This model predicts an age-related increase in univalents, but direct evidence of this phenomenon as a major cause of segregation errors has been lacking. Here, we provide the first live analysis of single chromosomes undergoing segregation errors during MI in the oocytes of naturally aged mice. Chromosome tracking reveals that 80% of the errors are preceded by bivalent separation into univalents. The set of the univalents is biased towards balanced and unbalanced predivision of sister chromatids during MI. Moreover, we find univalents predisposed to predivision in human oocytes. This study defines premature bivalent separation into univalents as the primary defect responsible for age-related aneuploidy. PMID:26130582

  2. Genetics and age-related macular degeneration: a practical review for the clinician

    PubMed Central

    Schwartz, Stephen G; Hampton, Blake M; Kovach, Jaclyn L; Brantley, Milam A

    2016-01-01

    Age-related macular degeneration is a complex disease, with both genetic and environmental risk factors interacting in unknown ways. Currently, 52 gene variants within 34 loci have been significantly associated with age-related macular degeneration. Two well-studied major genes are complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2). There exist several commercially available tests that are proposed to stratify patients into high-risk and low-risk groups, as well as predict response to nutritional supplementation. However, at present, the bulk of the available peer-reviewed evidence suggests that genetic testing is more useful as a research tool than for clinical management of patients. PMID:27445455

  3. Understanding Age-Related Changes in Skeletal Muscle Metabolism: Differences Between Females and Males.

    PubMed

    Gheller, Brandon J F; Riddle, Emily S; Lem, Melinda R; Thalacker-Mercer, Anna E

    2016-07-17

    Skeletal muscle is the largest metabolic organ system in the human body. As such, metabolic dysfunction occurring in skeletal muscle impacts whole-body nutrient homeostasis. Macronutrient metabolism changes within the skeletal muscle with aging, and these changes are associated in part with age-related skeletal muscle remodeling. Moreover, age-related changes in skeletal muscle metabolism are affected differentially between males and females and are likely driven by changes in sex hormones. Intrinsic and extrinsic factors impact observed age-related changes and sex-related differences in skeletal muscle metabolism. Despite some support for sex-specific differences in skeletal muscle metabolism with aging, more research is necessary to identify underlying differences in mechanisms. Understanding sex-specific aging skeletal muscle will assist with the development of therapies to attenuate adverse metabolic and functional outcomes.

  4. Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy

    PubMed Central

    Sakellariou, Giorgos K.; Pearson, Timothy; Lightfoot, Adam P.; Nye, Gareth A.; Wells, Nicola; Giakoumaki, Ifigeneia I.; Vasilaki, Aphrodite; Griffiths, Richard D.; Jackson, Malcolm J.; McArdle, Anne

    2016-01-01

    Age-related loss of skeletal muscle mass and function is a major contributor to morbidity and has a profound effect on the quality of life of older people. The potential role of age-dependent mitochondrial dysfunction and cumulative oxidative stress as the underlying cause of muscle aging remains a controversial topic. Here we show that the pharmacological attenuation of age-related mitochondrial redox changes in muscle with SS31 is associated with some improvements in oxidative damage and mitophagy in muscles of old mice. However, this treatment failed to rescue the age-related muscle fiber atrophy associated with muscle atrophy and weakness. Collectively, these data imply that the muscle mitochondrial redox environment is not a key regulator of muscle fiber atrophy during sarcopenia but may play a key role in the decline of mitochondrial organelle integrity that occurs with muscle aging. PMID:27681159

  5. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System.

    PubMed

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-02-01

    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. PMID:25657851

  6. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System

    PubMed Central

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-01-01

    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. PMID:25657851

  7. Adverse Childhood Experiences and Adult Risk Factors for Age-Related Disease

    PubMed Central

    Danese, Andrea; Moffitt, Terrie E.; Harrington, HonaLee; Milne, Barry J.; Polanczyk, Guilherme; Pariante, Carmine M.; Poulton, Richie; Caspi, Avshalom

    2013-01-01

    Objective To understand why children exposed to adverse psychosocial experiences are at elevated risk for age-related disease, such as cardiovascular disease, by testing whether adverse childhood experiences predict enduring abnormalities in stress-sensitive biological systems, namely, the nervous, immune, and endocrine/metabolic systems. Design A 32-year prospective longitudinal study of a representative birth cohort. Setting New Zealand. Participants A total of 1037 members of the Dunedin Multidisciplinary Health and Development Study. Main Exposures During their first decade of life, study members were assessed for exposure to 3 adverse psychosocial experiences: socioeconomic disadvantage, maltreatment, and social isolation. Main Outcome Measures At age 32 years, study members were assessed for the presence of 3 age-related-disease risks: major depression, high inflammation levels (high-sensitivity C-reactive protein level >3 mg/L), and the clustering of metabolic risk biomarkers (overweight, high blood pressure, high total cholesterol, low high-density lipoprotein cholesterol, high glycated hemoglobin, and low maximum oxygen consumption levels. Results Children exposed to adverse psychosocial experiences were at elevated risk of depression, high inflammation levels, and clustering of metabolic risk markers. Children who had experienced socioeconomic disadvantage (incidence rate ratio, 1.89; 95% confidence interval, 1.36–2.62), maltreatment (1.81; 1.38–2.38), or social isolation (1.87; 1.38–2.51) had elevated age-related-disease risks in adulthood. The effects of adverse childhood experiences on age-related-disease risks in adulthood were nonredundant, cumulative, and independent of the influence of established developmental and concurrent risk factors. Conclusions Children exposed to adverse psychosocial experiences have enduring emotional, immune, and metabolic abnormalities that contribute to explaining their elevated risk for age-related disease. The

  8. Age-Related Differences in Cortical Thickness Vary by Socioeconomic Status.

    PubMed

    Piccolo, Luciane R; Merz, Emily C; He, Xiaofu; Sowell, Elizabeth R; Noble, Kimberly G

    2016-01-01

    Recent findings indicate robust associations between socioeconomic status (SES) and brain structure in children, raising questions about the ways in which SES may modify structural brain development. In general, cortical thickness and surface area develop in nonlinear patterns across childhood and adolescence, with developmental patterns varying to some degree by cortical region. Here, we examined whether age-related nonlinear changes in cortical thickness and surface area varied by SES, as indexed by family income and parental education. We hypothesized that SES disparities in age-related change may be particularly evident for language- and literacy-supporting cortical regions. Participants were 1148 typically-developing individuals between 3 and 20 years of age. Results indicated that SES factors moderate patterns of age-associated change in cortical thickness but not surface area. Specifically, at lower levels of SES, associations between age and cortical thickness were curvilinear, with relatively steep age-related decreases in cortical thickness earlier in childhood, and subsequent leveling off during adolescence. In contrast, at high levels of SES, associations between age and cortical thickness were linear, with consistent reductions across the age range studied. Notably, this interaction was prominent in the left fusiform gyrus, a region that is critical for reading development. In a similar pattern, SES factors significantly moderated linear age-related change in left superior temporal gyrus, such that higher SES was linked with steeper age-related decreases in cortical thickness in this region. These findings suggest that SES may moderate patterns of age-related cortical thinning, especially in language- and literacy-supporting cortical regions. PMID:27644039

  9. Age-Related Differences in Cortical Thickness Vary by Socioeconomic Status

    PubMed Central

    He, Xiaofu; Sowell, Elizabeth R.; Noble, Kimberly G.

    2016-01-01

    Recent findings indicate robust associations between socioeconomic status (SES) and brain structure in children, raising questions about the ways in which SES may modify structural brain development. In general, cortical thickness and surface area develop in nonlinear patterns across childhood and adolescence, with developmental patterns varying to some degree by cortical region. Here, we examined whether age-related nonlinear changes in cortical thickness and surface area varied by SES, as indexed by family income and parental education. We hypothesized that SES disparities in age-related change may be particularly evident for language- and literacy-supporting cortical regions. Participants were 1148 typically-developing individuals between 3 and 20 years of age. Results indicated that SES factors moderate patterns of age-associated change in cortical thickness but not surface area. Specifically, at lower levels of SES, associations between age and cortical thickness were curvilinear, with relatively steep age-related decreases in cortical thickness earlier in childhood, and subsequent leveling off during adolescence. In contrast, at high levels of SES, associations between age and cortical thickness were linear, with consistent reductions across the age range studied. Notably, this interaction was prominent in the left fusiform gyrus, a region that is critical for reading development. In a similar pattern, SES factors significantly moderated linear age-related change in left superior temporal gyrus, such that higher SES was linked with steeper age-related decreases in cortical thickness in this region. These findings suggest that SES may moderate patterns of age-related cortical thinning, especially in language- and literacy-supporting cortical regions. PMID:27644039

  10. The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases

    PubMed Central

    Kerch, Garry

    2015-01-01

    Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed. PMID:25871293

  11. "Older is always better": Age-related differences in vocabulary scores across 16 years.

    PubMed

    Ben-David, Boaz M; Erel, Hadas; Goy, Huiwen; Schneider, Bruce A

    2015-12-01

    Cross-sectional studies of cognitive aging compare age groups at 1 time point. It is unclear from such studies whether age-related cognitive differences remain stable across time. We present a cross-sectional investigation of vocabulary scores of 2,000 younger and older adults collected across 16 years, using the same laboratory and protocol. We found a steady decrease with year of testing and an advantage for older adults. An additive relation between age group and year of testing implied that age-related differences in vocabulary are independent of changes over time, suggesting that younger and older adults are similarly affected by changes in word usage.

  12. The potential of chitosan and its derivatives in prevention and treatment of age-related diseases.

    PubMed

    Kerch, Garry

    2015-04-01

    Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed.

  13. [Soft tissue enhancement with injectable fillers for correction of age related folds and wrinkles].

    PubMed

    Hönig, J; Fricke, M

    2005-12-01

    Injectable fillers for facial soft tissue enhancement have been developed and used for decades for the correction of age related folds and wrinkles. Many of the disadvantages of xenogenic and prior exogenous materials have been overcome with the advent of autologous and synthetic alternative materials. Autologous and synthetic injectable fillers herald a new era in the treatment of the aging face. Therefore this article will give an in-depth look at the implant choice, surgical approach, and possible complications and will provide a review of current injectable fillers for age related facial soft tissue augmentation.

  14. [Relationship between educational level and dementia: social factor and age-related chronic disease].

    PubMed

    Dartigues, J-F; Foubert-Samier, A; Helmer, C

    2013-08-01

    Dementia is an age-related chronic syndrome, whose the first cause is a neurodegenerative disease: Alzheimer's disease (AD). In spite of some controversies, educational level is now considered as a major risk factor for dementia and AD. The protective effect of a high level of education could be related to a preservation of cognitive reserve and a reinforcement of brain reserve. Moreover, subjects with a high level of education have a better access to health care and a better management of vascular risk factors. With the general improvement of the educational level, the age-related incidence of AD and dementia should decrease in the future.

  15. Improved word recognition for observers with age-related maculopathies using compensation filters

    NASA Technical Reports Server (NTRS)

    Lawton, Teri B.

    1988-01-01

    A method for improving word recognition for people with age-related maculopathies, which cause a loss of central vision, is discussed. It is found that the use of individualized compensation filters based on an person's normalized contrast sensitivity function can improve word recognition for people with age-related maculopathies. It is shown that 27-70 pct more magnification is needed for unfiltered words compared to filtered words. The improvement in word recognition is positively correlated with the severity of vision loss.

  16. Fatty old hearts: role of cardiac lipotoxicity in age-related cardiomyopathy

    PubMed Central

    Drosatos, Konstantinos

    2016-01-01

    Age-related cardiomyopathy accounts for a significant part of heart failure cases. Imbalance of the energetic equilibrium of the heart along with mitochondrial dysfunction and impaired β-adrenergic receptor signaling contributes in the aggravation of cardiac function in the elderly. In this review article, studies that correlate cardiac aging with lipotoxicity are summarized. The involvement of inhibition of peroxisome proliferator-activated receptor-α, β-adrenergic receptor desensitization, and mitochondrial dysfunction as underlying mechanisms for the lipid-driven age-related cardiomyopathy are presented with the aim to indicate potential therapeutic targets for cardiac aging. PMID:27558317

  17. A thermographic study on eyes affected by Age-related Macular Degeneration: Comparison among various forms of the pathology and analysis of risk factors

    NASA Astrophysics Data System (ADS)

    Matteoli, Sara; Finocchio, Lucia; Biagini, Ilaria; Giacomelli, Giovanni; Sodi, Andrea; Corvi, Andrea; Virgili, Gianni; Rizzo, Stanislao

    2016-05-01

    The aims of this study are to investigate (1) the ocular thermographic profiles in eyes affected by Age related Macular Degeneration (AMD) and age-matched controls to detect possible hemodynamic abnormalities that could be involved in the pathogenesis of the disease, (2) whether any risk factors associated with the disease could affect the development of a form of AMD rather than another. Thirty-four eyes with Age-Related Maculopathy (ARM), 41 eyes with dry AMD, 60 eyes affected by wet AMD, and 74 eyes with fibrotic AMD were included in the study. The control group consisted of 48 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, systemic diseases and a body temperature higher than 37.5 °C. A total of 210 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The Ocular Surface Temperature (OST) of five ocular areas was calculated by means of an image processing technique from the infrared images. Two-sample t-test, one-way ANOVA test and multivariate analysis were used for statistical analyses. ANOVA analyses showed no significant differences among AMD groups (P-value > 0.05), however, OST in AMD patients was significantly lower than in controls (P-value < 0.0001). Smokers showed higher possibility (P-value = 0.012) of developing wet AMD instead of dry AMD. Infrared thermography may be a helpful, non-invasive and not time-consuming method to be used in the management of patients with this common degenerative maculopathy.

  18. A neglected requirement for optimizing treatment of age-related osteoporosis: Replenishing the skeleton's base reservoir with net base-producing diets.

    PubMed

    Sebastian, Anthony; Frassetto, Lynda A

    2016-06-01

    Osteoporosis is a disorder of bone in which the mass of the bone is reduced and the bone's architecture at the microscopic level is disordered. Together those abnormalities predispose affected individuals to experience fractures despite only minimal trauma (i.e., fragility fractures). Age related osteoporosis is a common type of osteoporosis that occurs with aging in both men and women usually beginning after the age of peak bone mass. Research has found that the disorder can be partially reversed by reducing the net amount of acid that is produced when consuming typical Western diets. However, the amelioration that results has not been so dramatic or so consistent that physicians have adopted the procedure as part of the standard treatment for age-related osteoporosis. We propose that reducing the net acid load from the diet is not sufficient to reverse age related osteoporosis because it fails to supply base needed to restore the large amount of base in bone that had been lost by reacting with the net acid load of the diet that had been consumed for years or decades. Reducing the net acid load from the diet might be expected to have little ameliorative effect or merely slow the progression of the disorder. We hypothesize that both to restore osteoporotic bone to, or nearly to, its pre-disease state, as well as to eliminate the risk of fragility fractures, requires consuming diets that produce net amounts of base to restore the base lost from years to decades of consuming diets that produce net amounts of acid. We hypothesize also that the excess base and attendant subclinical metabolic alkalosis will both stimulate the cellular process of bone formation and suppress the cellular process of bone resorption, and thereby implement the restorative process.

  19. Evaluation of the peripherin/RDS gene as a candidate gene in families with age-related macular degeneration.

    PubMed

    Shastry, B S; Trese, M T

    1999-01-01

    Age-related macular degeneration (AMD) is a heterogeneous group of disorders and is the leading cause of blindness in the elderly. While degeneration changes in the macula can occur at any time in life, it is the most common cause of severe visual impairment with advancing age. The disease affects approximately 11 million Americans and causes loss of central vision, impairing activities such as reading. The exact cause of the disorder is not known. In this report, we studied two unrelated families having familial-type AMD, with the assumption that mutations in the peripherin/retinal degeneration slow (RDS) gene could contribute to the disease phenotype. Our extensive analyses have identified two silent mutations (84D and 106V) in one family in the same allele of exon 1 which segregated in 3 patients with AMD. However, the fourth affected individual in the same family, as well as 40 normal controls, did not contain this mutation. Further analysis of exon 2 and exon 3 in both families did not show any other sequence alterations. Since one of these silent mutations (106V) has been reported to exist in certain general populations and the other mutation (84D) failed to segregate completely in the family, it is unlikely that these mutations are pathogenic. The results of the study suggest that the peripherin/RDS gene is not a major factor responsible for AMD in the families analyzed.

  20. Mechanisms of Age-Related Decline in Memory Search across the Adult Life Span

    ERIC Educational Resources Information Center

    Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.

    2013-01-01

    Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis).…

  1. Age-Related Impairments in the Revision of Syntactic Misanalyses: Effects of Prosody

    ERIC Educational Resources Information Center

    Titone, Debra A.; Koh, Christine K.; Kjelgaard, Margaret M.; Bruce, Stephanie; Speer, Shari R.; Wingfield, Arthur

    2006-01-01

    Two experiments examined whether young and older adults differ in comprehending sentences that contain temporary syntactic closure ambiguities. Experiment 1 examined age-related differences using the Auditory Moving Window (AMW) task, in which sentences were presented in a segment-by-segment self-paced fashion. Experiment 2 examined age-related…

  2. A systematic review on zinc for the prevention and treatment of age-related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Zinc is a potential candidate for the prevention and treatment of age-related macular degeneration (AMD) due to its high concentration in the retina and role as a cofactor for antioxidant enzymes. The objective of this work was to conduct a systematic review of studies that investigated dietary inta...

  3. Correcting age-related changes in the face by use of injectable fillers and neurotoxins.

    PubMed

    Rubin, Mark G; Cox, Sue Ellen; Kaminer, Michael S; Solish, Nowell

    2014-06-01

    Many patients seeking rejuvenation treatment have readily apparent age-related changes in facial features. Others exhibit more subtle changes that nonetheless can be corrected to achieve a more youthful appearance. In the following article, four specialists in aesthetic dermatology discuss how injectable hyaluronic acid-based fillers and neurotoxins can achieve rejuvenation without surgery.

  4. Age-related differences in acute neurotoxicity produced by mevinphos, monocrotophos, dicrotophos, and phosphamidon

    EPA Science Inventory

    Age-related differences in the acute neurotoxicity of cholinesterase (ChE)-inhibiting pesticides have been well-studied for a few organophosphates, but not for many others. In this study, we directly compared dose-responses using brain and red blood cell (RBC) ChE measurements, a...

  5. Adaptation to Low Vision Caused by Age-Related Macular Degeneration: A Case Study

    ERIC Educational Resources Information Center

    Smith, Theresa Marie

    2008-01-01

    One in eight Americans aged 65 and older has an eye disease resulting in low vision, and more women than men are visually impaired, mainly because women live longer. Age-related visual impairments are an indicator of a decline in activities of daily living and self-help skills. The top eye conditions that affect older adults are macular…

  6. Age-Related Hearing Loss: Quality of Care for Quality of Life

    ERIC Educational Resources Information Center

    Li-Korotky, Ha-Sheng

    2012-01-01

    Age-related hearing loss (ARHL), known as presbycusis, is characterized by progressive deterioration of auditory sensitivity, loss of the auditory sensory cells, and central processing functions associated with the aging process. ARHL is the third most prevalent chronic condition in older Americans, after hypertension and arthritis, and is a…

  7. Nutritional interventions protect against age-related deficits in behavior: from animals to humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aged rats show impaired performance on motor and cognitive tasks. Similar changes in behavior occur in humans with age, and the development of methods to retard or reverse these age-related neuronal and behavioral deficits could increase healthy aging and decrease health care costs. In the present s...

  8. Psychosocial Intervention for Age-Related Macular Degeneration: A Pilot Project

    ERIC Educational Resources Information Center

    Wahl, Hans-Werner; Kammerer, Annette; Holz, Frank; Miller, Daniel; Becker, Stefanie; Kaspar, Roman; Himmelsbach, Ines

    2006-01-01

    This study evaluated an emotion-focused and a problem-focused intervention designed for patients with age-related macular degeneration. It found a limited decrease in depression in the emotion-focused group and an increase in active problem orientation and in adaptation to vision loss in the problem-focused group.

  9. The Psychosocial Impact of Closed-Circuit Televisions on Persons with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Huber, Jessica G.; Jutai, Jeffrey W.; Strong, J. Graham; Plotkin, Ann D.

    2008-01-01

    Closed-circuit televisions (CCTVs) are used by many elderly people who have age-related macular degeneration (AMD). The functional vision of 68 participants, which was measured immediately after they adopted CCTVs, suggested successful outcomes, but the psychosocial impact of the use of CCTVs did not peak until a month later. The findings help…

  10. Lighting Needs and Lighting Comfort During Reading with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Fosse, Per; Valberg, Arne

    2004-01-01

    This study investigated the effects of changes in luminance on the oral reading speeds of 13 participants with age-related macular degeneration (AMD) and a control group of six age-matched persons with typical vision. For the AMD participants, self-reports of light preferences were also recorded. In the AMD group, reading rates depended on light…

  11. A Qualitative Analysis of Reading Rehabilitation of Persons with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Feely, Mary; Vetere, Arlene; Myers, Lynn B.

    2007-01-01

    One of the most prevalent visual impairments of people aged 60 and older is age-related macular degeneration (AMD), which ranks third globally as a cause of visual impairment (World Health Organization, 2006). The purpose of this study was to conduct a tentative subjective assessment of eccentric viewing by persons with AMD. The authors recruited…

  12. Ability of university-level education to prevent age-related decline in emotional intelligence

    PubMed Central

    Cabello, Rosario; Navarro Bravo, Beatriz; Latorre, José Miguel; Fernández-Berrocal, Pablo

    2014-01-01

    Numerous studies have suggested that educational history, as a proxy measure of active cognitive reserve, protects against age-related cognitive decline and risk of dementia. Whether educational history also protects against age-related decline in emotional intelligence (EI) is unclear. The present study examined ability EI in 310 healthy adults ranging in age from 18 to 76 years using the Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT). We found that older people had lower scores than younger people for total EI and for the EI branches of perceiving, facilitating, and understanding emotions, whereas age was not associated with the EI branch of managing emotions. We also found that educational history protects against this age-related EI decline by mediating the relationship between age and EI. In particular, the EI scores of older adults with a university education were higher than those of older adults with primary or secondary education, and similar to those of younger adults of any education level. These findings suggest that the cognitive reserve hypothesis, which states that individual differences in cognitive processes as a function of lifetime intellectual activities explain differential susceptibility to functional impairment in the presence of age-related changes and brain pathology, applies also to EI, and that education can help preserve cognitive-emotional structures during aging. PMID:24653697

  13. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease

    PubMed Central

    Potter, Paul K.; Bowl, Michael R.; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E.; Simon, Michelle M.; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V.; Law, Gemma; MacLaren, Robert E.; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H.; Foster, Russell G.; Jackson, Ian J.; Peirson, Stuart N.; Thakker, Rajesh V.; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M.; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D. M.

    2016-01-01

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss. PMID:27534441

  14. Age-Related Changes in Duration Reproduction: Involvement of Working Memory Processes

    ERIC Educational Resources Information Center

    Baudouin, Alexia; Vanneste, Sandrine; Pouthas, Viviane; Isingrini, Michel

    2006-01-01

    The aim of the present research was to study age-related changes in duration reproduction by differentiating the working memory processes underlying this time estimation task. We compared performances of young and elderly adults in a duration reproduction task performed in simple and concurrent task conditions. Participants were also administered…

  15. Age-Related and Sex-Related Differences in Hand and Pinch Grip Strength in Adults

    ERIC Educational Resources Information Center

    Puh, Urska

    2010-01-01

    The purpose of the study was to quantify age-related changes in hand grip strength and three types of pinch grip strength (key pinch, tip pinch, and palmar pinch) among male and female participants. The study included 199 healthy participants (100 females, 99 males) aged 20-79 years, who were divided into four age groups. The Baseline Hydraulic…

  16. NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism.

    PubMed

    Park, Seongjoon; Fujishita, Chika; Komatsu, Toshimitsu; Kim, Sang Eun; Chiba, Takuya; Mori, Ryoichi; Shimokawa, Isao

    2014-12-01

    An orexigenic hormone, neuropeptide Y (NPY), plays a role not only in the hypothalamic regulation of appetite, but also in the peripheral regulation of lipid metabolism. However, the intracellular mechanisms triggered by NPY to regulate lipid metabolism are poorly understood. Here we report that NPY deficiency reduces white adipose tissue (WAT) mass and ameliorates the age-related imbalance of adipose tissue metabolism in mice. Gene expression involved in adipogenesis/lipogenesis was found to decrease, whereas proteins involved in lipolysis increased in gonadal WAT (gWAT) of NPY-knockout mice. These changes were associated with an activated SIRT1- and PPARγ-mediated pathway. Moreover, the age-related decrease of de novo lipogenesis in gWAT and thermogenesis in inguinal WAT was inhibited by NPY deficiency. Further analysis using 3T3-L1 cells showed that NPY inhibited lipolysis through the Y1 receptor and enhanced lipogenesis following a reduction in cAMP response element-binding protein (CREB) and SIRT1 protein expression. Therefore, NPY appears to act as a key regulator of adipose tissue metabolism via the CREB-SIRT1 signaling pathway. Taken together, NPY deficiency reduces adiposity and ameliorates the age-related imbalance of adipose tissue metabolism, suggesting that antagonism of NPY may be a promising target for drug development to prevent age-related metabolic diseases.

  17. Cognitive Abilities Explaining Age-Related Changes in Time Perception of Short and Long Durations

    ERIC Educational Resources Information Center

    Zelanti, Pierre S.; Droit-Volet, Sylvie

    2011-01-01

    The current study investigated how the development of cognitive abilities explains the age-related changes in temporal judgment over short and long duration ranges from 0.5 to 30 s. Children (5- and 9-year-olds) as well as adults were given a temporal bisection task with four different duration ranges: a duration range shorter than 1 s, two…

  18. Children's Recognition of Fairness and Others' Welfare in a Resource Allocation Task: Age Related Changes

    ERIC Educational Resources Information Center

    Rizzo, Michael T.; Elenbaas, Laura; Cooley, Shelby; Killen, Melanie

    2016-01-01

    The present study investigated age-related changes regarding children's (N = 136) conceptions of fairness and others' welfare in a merit-based resource allocation paradigm. To test whether children at 3- to 5-years-old and 6- to 8-years-old took others' welfare into account when dividing resources, in addition to merit and equality concerns,…

  19. Age-Related Differences in Reaction Time Task Performance in Young Children

    ERIC Educational Resources Information Center

    Kiselev, Sergey; Espy, Kimberlay Andrews; Sheffield, Tiffany

    2009-01-01

    Performance of reaction time (RT) tasks was investigated in young children and adults to test the hypothesis that age-related differences in processing speed supersede a "global" mechanism and are a function of specific differences in task demands and processing requirements. The sample consisted of 54 4-year-olds, 53 5-year-olds, 59 6-year-olds,…

  20. Age-related changes to the neural correlates of working memory which emerge after midlife

    PubMed Central

    Macpherson, Helen N.; White, David J.; Ellis, Kathryn A.; Stough, Con; Camfield, David; Silberstein, Richard; Pipingas, Andrew

    2014-01-01

    Previous research has indicated that the neural processes which underlie working memory change with age. Both age-related increases and decreases to cortical activity have been reported. This study investigated which stages of working memory are most vulnerable to age-related changes after midlife. To do this we examined age-differences in the 13 Hz steady state visually evoked potential (SSVEP) associated with a spatial working memory delayed response task. Participants were 130 healthy adults separated into a midlife (40–60 years) and an older group (61–82 years). Relative to the midlife group, older adults demonstrated greater bilateral frontal activity during encoding and this pattern of activity was related to better working memory performance. In contrast, evidence of age-related under activation was identified over left frontal regions during retrieval. Findings from this study suggest that after midlife, under-activation of frontal regions during retrieval contributes to age-related decline in working memory performance. PMID:24795625

  1. The short-wavelength mechanisms of Stiles in age-related macular degeneration.

    PubMed

    Hubschman, J P; Vola, J L; Conrath, J; Berros, P; Hougrand, F

    1998-11-01

    Clinical measurements by the increment-threshold technique of W.S. Stiles are reported in five cases of age-related macular degeneration. Measurements were made on a modified Tübingen perimeter using 1 degree, short-wavelength targets presented on a red field.

  2. Knowledge and Use of Low Vision Services Among Persons with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin J.; Maloney, Eileen K.; Rovner, Barry W.

    2005-01-01

    Visual impairment (blindness or low vision) is a leading cause of disability among older adults and is most often due to age-related macular degeneration (AMD). It is predicted that 2.95 million people will have AMD by 2020 (Eye Diseases Prevalence Research Group, 2004). Unfortunately, there is no cure for AMD, nor can lost vision be restored.…

  3. Age-related behavioral effects of methomyI in Brown Norway rats.

    EPA Science Inventory

    Methomyl is a cholinesterase-inhibiting carbamate pesticide that is used in the field on cotton and a variety of fruits and vegetables. Concerns have been raised generally about age-related differences in susceptibility to cholinesterase-inhibiting pesticides, especially for chil...

  4. Heritability of Anxious-Depressive and Withdrawn Behavior: Age-Related Changes during Adolescence

    ERIC Educational Resources Information Center

    Lamb, Diane J.; Middeldorp, Christel M.; van Beijsterveldt, Catarina E. M.; Bartels, Meike; van der Aa, Niels; Polderman, Tinca J. C.; Boomsma, Dorret I.

    2010-01-01

    Objective: To explain the differential course of anxiety and depression in individuals from childhood to adulthood by examining age-related changes in the genetic and environmental etiology of anxious and depressive symptoms. Method: A sample of 1470, 1839, and 2023 Dutch twins aged 12, 14, and 16 years reported on symptoms of anxious depression…

  5. Pentosidine Accumulation in Human Oocytes and Their Correlation to Age-Related Apoptosis

    PubMed Central

    Matsumine, Miki; Shibata, Noriyuki; Ishitani, Ken; Kobayashi, Makio; Ohta, Hiroaki

    2008-01-01

    Age-related atresia of ovarian follicles is characterized by apoptosis of the constituent cells. Recent studies have indicated that dysfunction of the proteasome and endoplasmic reticulum and subsequent apoptosis in the presence of oxidative stress have relevance to aging. The aim of this study was to assess the involvement of these processes in age-related follicular atresia. Formalin-fixed, paraffin-embedded sections of ovaries obtained at surgery from 74 women (age: 21–54 y) were examined with the terminal deoxynucleotidyl transferase-mediated, dUTP-biotin nick-end labeling (TUNEL) method and an immunohistochemical technique. Primary antibodies used in immunohistochemistry were against pentosidine, ubiquitin and caspase 12. Histological localization of these substances in oocytes was observed by light microscopy, and labeling indices of these cells were evaluated by regression analysis. Positive signals for pentosidine, ubiquitin, caspase 12, and TUNEL were detectable in oocytes of the primordial, primary and their atretic follicles. Regression analysis revealed an age-related increase in the labeling indices for pentosidine, ubiquitin, caspase 12, and TUNEL. These results suggest that pentosidine accumulation in human oocytes is related to apoptosis and increases with age. Further studies will be necessary to clarify the involvement of pentosidine accumulation, proteasome inhibition, and endoplasmic reticulum stress in age-related apoptosis of oocytes in human ovaries. PMID:18787640

  6. Shared and Unique Genetic and Environmental Influences on Aging-Related Changes in Multiple Cognitive Abilities

    ERIC Educational Resources Information Center

    Tucker-Drob, Elliot M.; Reynolds, Chandra A.; Finkel, Deborah; Pedersen, Nancy L.

    2014-01-01

    Aging-related declines occur in many different domains of cognitive function during middle and late adulthood. However, whether a global dimension underlies individual differences in changes in different domains of cognition and whether global genetic influences on cognitive changes exist is less clear. We addressed these issues by applying…

  7. Age-related clinical and microbiological characteristics of enteric fever in India.

    PubMed

    Walia, Mandeep; Gaind, Rajni; Paul, Premila; Mehta, Rajesh; Aggarwal, Pushpa; Kalaivani, Mani

    2006-10-01

    A retrospective, hospital-based study at Safdarjang Hospital, India, was undertaken between January 1999 and December 2003 to estimate age-related epidemiological, clinical and microbiological characteristics in enteric fever cases. A total of 750 blood-culture-proven cases of enteric fever were studied. The majority of cases occurred in children aged 5-12 years and 24.8% of cases were in children up to 5 years of age. Salmonella serotypes showed an age-related predilection, with paratyphoid fever more common in adults. Classically-described clinical features of the disease were comparable among patients under and above 5 years of age. Hepatomegaly, anaemia and complications in general were more frequent in children up to 5 years of age. The antimicrobial resistance pattern, irrespective of Salmonella serotype, did not reveal a statistically significant difference across age groups for the different antibiotics tested. Multidrug resistance was seen only in Salmonella enterica serotype Typhi but not in S. Paratyphi A isolates. However, resistance to nalidixic acid was comparable in both serotypes. Age-related differences of serotype isolation rates, clinical presentation and associated complications are noteworthy for better case management and policy planning. More epidemiological studies regarding reasons for age-related differential serotype patterns would enable and guide public health strategies to contain enteric fever in endemic locations. PMID:16766005

  8. The potential effects of meditation on age-related cognitive decline: a systematic review.

    PubMed

    Gard, Tim; Hölzel, Britta K; Lazar, Sara W

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline.

  9. Age-related alterations to immune parameters in Labrador retriever dogs.

    PubMed

    Blount, Daniel G; Pritchard, David I; Heaton, Paul R

    2005-12-15

    In order to assess age-related changes in the immune status of Labrador retriever dogs, leukocyte phenotypes, lymphocyte proliferative capacity, and serum antibody levels were measured in four cohorts of dogs, ranging from 2 to 10 years of age. Absolute numbers of white blood cells, lymphocytes, monocytes, granulocytes, and CD3+, CD4+, CD8+ and CD21+ lymphocytes significantly decreased with increasing age. Relative percentages of lymphocytes and CD4 cells were significantly decreased, and relative percentages of granulocytes and CD8 cells significantly increased, with age. The CD4:CD8 ratio showed a significant age-related decrease. Proliferative responses of T-cells to mitogens in whole-blood cultures either increased (Concanavalin A) or remained the same (phytohemagglutinin) with age when data was normalised to allow for differences in responding cell number. Similarly, normalised data of proliferative response to anti-CD3 stimulation together with phorbol 12-myristate 13-acetate showed an age-related increase. Serum levels of total IgA significantly increased with age whereas total IgG levels remained unchanged. These observations illustrate a significant change to a number of immune parameters with age. However, further work is required to determine whether the differences reported here are sufficient to cause overt or functional immune senescence in Labrador retriever dogs. PMID:16105688

  10. Age-related spatial working memory deficits in homing pigeons (Columba livia).

    PubMed

    Coppola, Vincent J; Hough, Gerald; Bingman, Verner P

    2014-12-01

    The hippocampus is particularly susceptible to age-related degeneration that, like hippocampal lesions, is thought to lead to age-related decline in spatial memory and navigation. Lesions to the avian hippocampal formation (HF) also result in impaired spatial memory and navigation, but the relationship between aging and HF-dependent spatial cognition is unknown. To investigate possible age-related decline in avian spatial cognition, the current study investigated spatial working memory performance in older homing pigeons (10+ years of age). Pigeons completed a behavioral procedure nearly identical to the delayed spatial, win-shift procedure in a modified radial arm maze that has been previously used to study spatial working memory in rats and pigeons. The results revealed that the older pigeons required a greater number of choices to task completion and were less accurate with their first 4 choices as compared to younger pigeons (1-2 years of age). In addition, older pigeons were more likely to adopt a stereotyped sampling strategy, which explained in part their impaired performance. To the best of our knowledge, this study is the first to demonstrate an age-related impairment of HF-dependent, spatial memory in birds. Implications and future directions of the findings are discussed.

  11. A novel radial water tread maze tracks age-related cognitive decline in mice

    PubMed Central

    Pettan-Brewer, Christina; Touch, Dylan V.; Wiley, Jesse C.; Hopkins, Heather C.; Rabinovitch, Peter S.; Ladiges, Warren C.

    2013-01-01

    There is currently no treatment and cure for age-related dementia and cognitive impairment in humans. Mice suffer from age-related cognitive decline just as people do, but assessment is challenging because of cumbersome and at times stressful performance tasks. We developed a novel radial water tread (RWT) maze and tested male C57BL/6 (B6) and C57BL/6 x Balb/c F1 (CB6F1) mice at ages 4, 12, 20, and 28 months. B6 mice showed a consistent learning experience and memory retention that gradually decreased with age. CB6F1 mice showed a moderate learning experience in the 4 and 12 month groups, which was not evident in the 20 and 28 month groups. In conclusion, CB6F1 mice showed more severe age-related cognitive impairment compared to B6 mice and might be a suitable model for intervention studies. In addition, the RWT maze has a number of operational advantages compared to currently accepted tasks and can be used to assess age-related cognition impairment in B6 and CB6F1 mice as early as 12 months of age. PMID:24106580

  12. Cortical complexity as a measure of age-related brain atrophy.

    PubMed

    Madan, Christopher R; Kensinger, Elizabeth A

    2016-07-01

    The structure of the human brain changes in a variety of ways as we age. While a sizeable literature has examined age-related differences in cortical thickness, and to a lesser degree, gyrification, here we examined differences in cortical complexity, as indexed by fractal dimensionality in a sample of over 400 individuals across the adult lifespan. While prior studies have shown differences in fractal dimensionality between patient populations and age-matched, healthy controls, it is unclear how well this measure would relate to age-related cortical atrophy. Initially computing a single measure for the entire cortical ribbon, i.e., unparcellated gray matter, we found fractal dimensionality to be more sensitive to age-related differences than either cortical thickness or gyrification index. We additionally observed regional differences in age-related atrophy between the three measures, suggesting that they may index distinct differences in cortical structure. We also provide a freely available MATLAB toolbox for calculating fractal dimensionality. PMID:27103141

  13. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    PubMed

    Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

    2016-08-18

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

  14. Guidelines for the Evaluation of Dementia and Age-Related Cognitive Change

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Dementia in its many forms is a leading cause of functional limitation among older adults worldwide and will continue to ascend in global health importance as populations continue to age and effective cures remain elusive. The following guidelines were developed for psychologists who perform evaluations of dementia and age-related cognitive…

  15. Stress Constellations and Coping Styles of Older Adults with Age-Related Visual Impairment

    ERIC Educational Resources Information Center

    Lee, Kyoung Othelia; Brennan, Mark

    2006-01-01

    Narrative data from two earlier studies of adaptation to age-related visual impairment were examined for constellations of stressors and coping styles. In the course of previous qualitative analyses, the researchers identified stress and coping codes according to behavioral, psychological, and social domains using a grounded theory approach. In…

  16. Diminishing risk for age related macular degeneration with nutrition: A current view

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies because they are more affordable...

  17. Intake of zinc and antioxidant micronutrients and early age-related maculopathy lesions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Macular degeneration, the end stage of age-related maculopathy (ARM), is the leading cause of legal blindness worldwide, and few modifiable risk factors are known. The high concentration of carotenoids in the macula, plus evidence linking oxidative stress to ARM, and carotenoids to antioxidation, ge...

  18. Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases

    PubMed Central

    Reinisalo, Mika; Kårlund, Anna; Koskela, Ali; Kaarniranta, Kai; Karjalainen, Reijo O.

    2015-01-01

    Numerous studies have highlighted the key roles of oxidative stress and inflammation in aging-related diseases such as obesity, type 2 diabetes, age-related macular degeneration (AMD), and Alzheimer's disease (AD). In aging cells, the natural antioxidant capacity decreases and the overall efficiency of reparative systems against cell damage becomes impaired. There is convincing data that stilbene compounds, a diverse group of natural defence phenolics, abundant in grapes, berries, and conifer bark waste, may confer a protective effect against aging-related diseases. This review highlights recent data helping to clarify the molecular mechanisms involved in the stilbene-mediated protection against oxidative stress. The impact of stilbenes on the nuclear factor-erythroid-2-related factor-2 (Nrf2) mediated cellular defence against oxidative stress as well as the potential roles of SQSTM1/p62 protein in Nrf2/Keap1 signaling and autophagy will be summarized. The therapeutic potential of stilbene compounds against the most common aging-related diseases is discussed. PMID:26180583

  19. Introduction to the issue regarding research regarding age related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Blindness is the second greatest fear among the elderly. Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly in most industrialized nations. AMD first compromises central high acuity vision. Subsequently, all vision may be lost. AMD is a progressive retinal d...

  20. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    PubMed

    Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

    2016-01-01

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss. PMID:27534441