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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. Biomechanics of Degenerative Spinal Disorders.

    PubMed

    Iorio, Justin A; Jakoi, Andre M; Singla, Anuj

    2016-04-01

    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

  4. Review: Axon pathology in age-related neurodegenerative disorders.

    PubMed

    Adalbert, R; Coleman, M P

    2013-02-01

    'Dying back' axon degeneration is a prominent feature of many age-related neurodegenerative disorders and is widespread in normal ageing. Although the mechanisms of disease- and age-related losses may differ, both contribute to symptoms. Here, we review recent advances in understanding axon pathology in age-related neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and glaucoma. In particular, we highlight the importance of axonal transport, autophagy, traumatic brain injury and mitochondrial quality control. We then place these disease mechanisms in the context of changes to axons and dendrites that occur during normal ageing. We discuss what makes ageing such an important risk factor for many neurodegenerative disorders and conclude that the processes of normal ageing and disease combine at the molecular, cellular or systems levels in a range of disorders to produce symptoms. Pathology identical to disease also occurs at the cellular level in most elderly individuals. Thus, normal ageing and age-related disease are inextricably linked and the term 'healthy ageing' downplays the important contributions of cellular pathology. For a full understanding of normal ageing or age-related disease we must study both processes. PMID:23046254

  5. 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

  6. Gene Risk Factors for Age-Related Brain Disorders May Affect Immune System Function

    MedlinePlus

    ... for age-related brain disorders may affect immune system function June 17, 2014 Scientists have discovered gene ... factors for age-related neurological disorders to immune system functions, such as inflammation, offers new insights into ...

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. [Age-related factors of psychopathology of impulse control disorders].

    PubMed

    Shiurkute, A

    1999-01-01

    15 children and adolescents with impulse control disorders (mean age 12.9 years) were examined. These disorders were presented as dromomania, kleptomania, aggressive-sadistic actions, tricholillomania, pyromania; a combination of different types was observed in some cases. Schizophrenia was diagnosed in 7 cases, affective disorders--in 8 patients. Independently of the nosologic unity of the disease, development of the impulse control disorders took place in affective disorders which manifested either by monopolar course (depression) (11 cases), or by bypolar attacks with unclear outlines of the phases (4 patients). Psychopathology of impulse control disorders in children and juveniles was analogous to that of the adults, however, their structure wasn't so complex and development of the phases wasn't so clear. PMID:11530454

  13. Possible therapeutic benefits of adenosine-potentiating drugs in reducing age-related degenerative disease in dogs and cats.

    PubMed

    Scaramuzzi, R J; Baker, D J

    2003-10-01

    Adenosine is a ubiquitous, biologically important molecule that is a precursor of other biologically active molecules. It also is a component of some co-factors and has distinct physiological actions in its own right. Levels are maintained by synthesis from dietary precursors and re-cycling. The daily turnover of adenosine is very high. Adenosine can act either as a hormone by binding to adenosine receptors, four adenosine receptor subtypes have been identified, and as an intracellular modulator, after transport into the cell by membrane transporter proteins. One of the principal intracellular actions of adenosine is inhibition of the enzyme phosphodiesterase. Extracellular adenosine also has specific neuromodulatory actions on dopamine and glutamate. Selective and nonselective agonists and antagonists of adenosine are available. The tasks of developing, evaluating and exploiting the therapeutic potential of these compounds is still in its infancy. Adenosine has actions in the central nervous system (CNS), heart and vascular system, skeletal muscle and the immune system and the presence of receptors suggests potential actions in the gonads and other organs. Adenosine agonists improve tissue perfusion through actions on vascular smooth muscle and erythrocyte fluidity and they can be used to improve the quality of life in aged dogs. This article reviews the therapeutic potential of adenosine-potentiating drugs in the treatment of age-related conditions in companion animals, some of which may be exacerbated by castration or spaying at an early age. PMID:14633184

  14. 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.

  15. 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

  16. 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

  17. 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. PMID:26333004

  18. Age-related changes in intrinsic function of the superior temporal sulcus in autism spectrum disorders.

    PubMed

    Alaerts, Kaat; Nayar, Kritika; Kelly, Clare; Raithel, Jessica; Milham, Michael P; Di Martino, Adriana

    2015-10-01

    Currently, the developmental trajectories of neural circuits implicated in autism spectrum disorders (ASD) are largely unknown. Here, we specifically focused on age-related changes in the functional circuitry of the posterior superior temporal sulcus (pSTS), a key hub underlying social-cognitive processes known to be impaired in ASD. Using a cross-sectional approach, we analysed resting-state functional magnetic resonance imaging (fMRI) data collected from children, adolescents and adults available through the autism brain imaging data exchange repository [n = 106 with ASD and n = 109 typical controls (TC), ages 7-30 years]. The observed age-related changes of pSTS intrinsic functional connectivity (iFC) suggest that no single developmental pattern characterizes ASD. Instead, pSTS circuitry displayed a complex developmental picture, with some functional circuits showing patterns consistent with atypical development in ASD relative to TC (pSTS-iFC with fusiform gyrus and angular gyrus) and others showing delayed maturation (pSTS-iFC with regions of the action perception network). Distinct developmental trajectories in different functional circuits in ASD likely reflect differential age-related changes in the socio-cognitive processes they underlie. Increasing insight on these mechanisms is a critical step in the development of age-specific interventions in ASD. PMID:25809403

  19. Age-related abnormalities in white matter microstructure in autism spectrum disorders

    PubMed Central

    Kleinhans, Natalia M.; Pauley, Gregory; Richards, Todd; Neuhaus, Emily; Martin, Nathalie; Corrigan, Neva M.; Shaw, Dennis W.; Estes, Annette; Dager, Stephen R.

    2012-01-01

    Abnormalities in structural and functional connectivity have been reported in autism spectrum disorders (ASD) across a wide age range. However, developmental changes in white matter microstructure are poorly understood. We used a cross-sectional design to determine whether white matter abnormalities measured using diffusion tensor imaging (DTI) were present in adolescents and adults with ASD and whether age-related changes in white matter microstructure differed between ASD and typically developing (TD) individuals. Participants included 28 individuals with ASD and 33 TD controls matched on age and IQ and assessed at one time point. Widespread decreased fractional anisotropy (FA), and increased radial diffusivity (RaD) and mean diffusivity (MD) were observed in the ASD group compared to the TD group. In addition, significant group-by-age interactions were also observed in FA, RaD, and MD in all major tracts except the brain stem, indicating that age-related changes in white matter microstructure differed between the groups. We propose that white matter microstructural changes in ASD may reflect myelination and/or other structural differences including differences in axonal density/arborization. In addition, we suggest that white matter microstuctural impairments may be normalizing during young adulthood in ASD. Future longitudinal studies that include a wider range of ages and more extensive clinical characterization will be critical for further uncovering the neurodevelopmental processes unfolding during this dynamic time in development. PMID:22902768

  20. 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

  1. 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

  2. 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

  3. Niemann-Pick C Disease Gene Mutations and Age-Related Neurodegenerative Disorders

    PubMed Central

    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

  4. 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

  5. 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

  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. 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

  9. Current concepts on spinal arthrodesis in degenerative disorders of the lumbar spine

    PubMed Central

    Lykissas, Marios G; Aichmair, Alexander

    2013-01-01

    Back pain is a common chronic disorder that represents a large burden for the health care system. There is a broad spectrum of available treatment options for patients suffering from chronic lower back pain in the setting of degenerative disorders of the lumbar spine, including both conservative and operative approaches. Lumbar arthrodesis techniques can be divided into sub-categories based on the part of the vertebral column that is addressed (anterior vs posterior). Furthermore, one has to differentiate between approaches aiming at a solid fusion in contrast to motion-sparing techniques with the proposed advantage of a reduced risk of developing adjacent disc disease. However, the field of application and long-term outcomes of these novel motion-preserving surgical techniques, including facet arthroplasty, nucleus replacement, and lumbar disc arthroplasty, need to be more precisely evaluated in long-term prospective studies. Innovative surgical treatment strategies involving minimally invasive techniques, such as lateral lumbar interbody fusion or transforaminal lumbar interbody fusion, as well as percutaneous implantation of transpedicular or transfacet screws, have been established with the reported advantages of reduced tissue invasiveness, decreased collateral damage, reduced blood loss, and decreased risk of infection. The aim of this study was to review well-established procedures for lumbar spinal fusion with the main focus on current concepts on spinal arthrodesis and motion-sparing techniques in degenerative disorders of the lumbar spine. PMID:24303453

  10. 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

  11. The role of extracellular matrix in age-related conduction disorders: a forgotten player?

    PubMed Central

    Spadaccio, Cristiano; Rainer, Alberto; Mozetic, Pamela; Trombetta, Marcella; Dion, Robert A; Barbato, Raffaele; Nappi, Francesco; Chello, Massimo

    2015-01-01

    Cardiovascular aging is a physiological process gradually leading to structural degeneration and functional loss of all the cardiac and vascular components. Conduction system is also deeply influenced by the aging process with relevant reflexes in the clinical side. Age-related arrhythmias carry significant morbidity and mortality and represent a clinical and economical burden. An important and unjustly unrecognized actor in the pathophysiology of aging is represented by the extracellular matrix (ECM) that not only structurally supports the heart determining its mechanical and functional properties, but also sends a biological signaling regulating cellular function and maintaining tissue homeostasis. At the biophysical level, cardiac ECM exhibits a peculiar degree of anisotropy, which is among the main determinants of the conductive properties of the specialized electrical conduction system. Age-associated alterations of cardiac ECM are therefore able to profoundly affect the function of the conduction system with striking impact on the patient clinical conditions. This review will focus on the ECM changes that occur during aging in the heart conduction system and on their translation to the clinical scenario. Potential diagnostic and therapeutical perspectives arising from the knowledge on ECM age-associated alterations are further discussed. PMID:25678907

  12. 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

  13. 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

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

    PubMed Central

    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

  15. 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

  16. A Heme Oxygenase-1 Transducer Model of Degenerative and Developmental Brain Disorders

    PubMed Central

    Schipper, Hyman M.; Song, Wei

    2015-01-01

    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. PMID:25761244

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

    PubMed Central

    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 PMID:27212841

  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. PMID:27212841

  19. Numeracy Skills in Patients With Degenerative Disorders and Focal Brain Lesions

    PubMed Central

    Cappelletti, Marinella; Butterworth, Brian; Kopelman, Michael

    2012-01-01

    Objective: To characterize the numerical profile of patients with acquired brain disorders. Method: We investigated numeracy skills in 76 participants—40 healthy controls and 36 patients with neurodegenerative disorders (Alzheimer dementia, frontotemporal dementia, semantic dementia, progressive aphasia) and with focal brain lesions affecting parietal, frontal, and temporal areas as in herpes simplex encephalitis (HSE). All patients were tested with the same comprehensive battery of paper-and-pencil and computerized tasks assessing numerical abilities and calculation. Degenerative and HSE patients also performed nonnumerical semantic tasks. Results: Our results, based on nonparametric group statistics as well as on the analysis of individual patients, and all highly significant, show that: (a) all patients, including those with parietal lesions—a key brain area for numeracy processing—had intact processing of number quantity; (b) patients with impaired semantic knowledge had much better preserved numerical knowledge; and (c) most patients showed impaired calculation skills, with the exception of most semantic dementia and HSE patients. Conclusion: Our results allow us, for the first time, to characterize the numeracy skills in patients with a variety of neurological conditions and to suggest that the pattern of numerical performance can vary considerably across different neurological populations. Moreover, the selective sparing of calculation skills in most semantic dementia and HSE suggest that numerical abilities are an independent component of the semantic system. Finally, our data suggest that, besides the parietal areas, other brain regions might be critical to the understanding and processing of numerical concepts. PMID:22122516

  20. 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. PMID:23269081

  1. [Degenerative disorders of the lumbar spine Total disc replacement as an alternative to lumbar fusion?].

    PubMed

    Mayer, H M

    2005-10-01

    Spinal fusion is accepted worldwide as a therapeutic option for the treatment of degenerative disorders of the lumbar spine. Because there are only few evidence-based data available supporting the usefulness of lumbar spinal fusion, its questionable benefit as well as the potential for complications are the reasons for an ongoing discussion. In recent years, total disc replacement with implants has emerged as an alternative treatment. Although early results are promising, there is still a lack of evidence-based data as well as of long-term results for this technology. This article gives a critical update on the implant systems currently in use (SB Charité, Prodisc II L, Maverick, Flexicore, Mobidisc), which all have to be considered as "first-generation" implants. Morphological and clinical sequelae of the different biomechanical properties, designs, and materials have not yet been sufficiently investigated. There is no international consensus on the indication spectrum and on the preoperative diagnosis of discogenic low back pain. The same is true for the (minimally invasive) surgical access strategies. Complication rates seem to be somewhat lower compared to spinal fusion techniques. There are no standardized revision concepts in cases of implant failure. Lumbar disc replacement has opened a new era in spinal surgery with a still unproven benefit for the patient. It is strongly recommended that these techniques should only be applied by experienced and well-trained spine surgeons. Until evidence-based data are available, all patients should be treated under scientific study conditions with close postoperative follow-up. PMID:16034627

  2. 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

  3. Specificity of transcranial sonography in parkinson spectrum disorders in comparison to degenerative cognitive syndromes

    PubMed Central

    2012-01-01

    Background Hyperechogenicity of the substantia nigra (SN+), detected by transcranial sonography (TCS), was reported as a characteristic finding in Parkinson's disease (PD), with high diagnostic accuracy values, when compared mainly to healthy controls or essential tremor (ET) group. However, some data is accumulating that the SN + could be detected in other neurodegenerative and even in non-neurodegenerative disorders too. Our aim was to estimate the diagnostic accuracy of TCS, mainly focusing on the specificity point, when applied to a range of the parkinsonian disorders, and comparing to the degenerative cognitive syndromes. Methods A prospective study was carried out at the Hospital of Lithuanian University of Health Sciences from January until September 2011. Initially, a TCS and clinical examination were performed on 258 patients and 76 controls. The General Electric Voluson 730 Expert ultrasound system was used. There were 12.8% of cases excluded with insufficient temporal bones, and 4.3% excluded with an unclear diagnosis. The studied sample consisted of the groups: PD (n = 71, 33.2%), ET (n = 58, 27.1%), PD and ET (n = 10, 4.7%), atypical parkinsonian syndromes (APS) (n = 3, 1.4%), hereditary neurodegenerative parkinsonism (HDP) (n = 3, 1.4%), secondary parkinsonism (SP) (n = 23, 10.8%), mild cognitive impairment (MCI) (n = 33, 15.4%), dementia (n = 13, 6.1%), and control (n = 71). Results There were 80.3% of PD patients at stages 1 & 2 according to Hoehn and Yahr. At the cut-off value of 0.20 cm2 of the SN+, the sensitivity for PD was 94.3% and the specificity - 63.3% (ROC analysis, AUC 0.891), in comparison to the rest of the cohort. At the cut-off value of 0.26 cm2, the sensitivity was 90% and the specificity 82.4%. The estimations for the lowest specificity for PD, in comparison to the latter subgroups (at the cut-off values of 0.20 cm2 and 0.26 cm2, respectively) were: 0% and 33.3% to APS, 33.3% and 66.7% to HDP, 34.8% and 69.6% to SP, 55.2% and 82

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

    ERIC Educational Resources Information Center

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

    2010-01-01

    The Autism Diagnostic Interview-Revised (ADI-R) was used to examine diagnostic profiles and age-related changes in autism symptoms for a group of verbal children and adolescents who had fragile X syndrome, with and without autism. After controlling for nonverbal IQ, we found statistically significant between-group differences for lifetime and…

  5. 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

  6. 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

  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. Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Disorders: Mini-open TLIF and Corrective TLIF

    PubMed Central

    HARA, Masahito; NISHIMURA, Yusuke; NAKAJIMA, Yasuhiro; UMEBAYASHI, Daisuke; TAKEMOTO, Masaya; YAMAMOTO, Yuu; HAIMOTO, Shoichi

    Minimally invasive transforaminal lumbar interbody fusion (TLIF) as a short fusion is widely accepted among the spine surgeons. However in the long fusion for degenerative kyphoscoliosis, corrective spinal fixation by an open method is thought to be frequently selected. Our objective is to study whether the mini-open TLIF and corrective TLIF contribute to the improvement of the spinal segmental and global alignment. We divided the patients who performed lumbar fixation surgery into three groups. Group 1 (G1) consisted of mini-open TLIF procedures without complication. Group 2 (G2) consisted of corrective TLIF without complication. Group 3 (G3) consisted of corrective TLIF with instrumentation-related complication postoperatively. In all groups, the lumbar lordosis (LL) highly correlated with developing surgical complications. LL significantly changed postoperatively in all groups, but was not corrected in the normal range in G3. There were statistically significant differences in preoperative and postoperative LL and mean difference between the pelvic incidence (PI) and LL between G3 and other groups. The most important thing not to cause the instrumentation-related failure is proper correction of the sagittal balance. In the cases with minimal sagittal imbalance with or without coronal imbalance, short fusion by mini-open TLIF or long fusion by corrective TLIF contributes to good clinical results if the lesion is short or easily correctable. However, if the patients have apparent sagittal imbalance with or without coronal imbalance, we should perform proper correction of the sagittal spinal alignment introducing various technologies. PMID:26119895

  9. 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.

  10. 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

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

    PubMed Central

    Nopoulos, Peggy C.

    2016-01-01

    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. PMID:27069383

  12. Senescent cells: SASPected drivers of age-related pathologies.

    PubMed

    Ovadya, Yossi; Krizhanovsky, Valery

    2014-12-01

    The progression of physiological ageing is driven by intracellular aberrations including telomere attrition, genomic instability, epigenetic alterations and loss of proteostasis. These in turn damage cells and compromise their functionality. Cellular senescence, a stable irreversible cell-cycle arrest, is elicited in damaged cells and prevents their propagation in the organism. Under normal conditions, senescent cells recruit the immune system which facilitates their removal from tissues. Nevertheless, during ageing, tissue-residing senescent cells tend to accumulate, and might negatively impact their microenvironment via profound secretory phenotype with pro-inflammatory characteristics, termed senescence-associated secretory phenotype (SASP). Indeed, senescent cells are mostly abundant at sites of age-related pathologies, including degenerative disorders and malignancies. Interestingly, studies on progeroid mice indicate that selective elimination of senescent cells can delay age-related deterioration. This suggests that chronic inflammation induced by senescent cells might be a main driver of these pathologies. Importantly, senescent cells accumulate as a result of deficient immune surveillance, and their removal is increased upon the use of immune stimulatory agents. Insights into mechanisms of senescence surveillance could be combined with current approaches for cancer immunotherapy to propose new preventive and therapeutic strategies for age-related diseases. PMID:25217383

  13. Idiopathic REM sleep behavior disorder in the transition to degenerative disease.

    PubMed

    Postuma, Ronald B; Gagnon, Jean-Francois; Vendette, Melanie; Montplaisir, Jacques Y

    2009-11-15

    Idiopathic REM sleep behavior disorder (RBD) predicts Parkinson's disease (PD) and dementia. However, the nature of the disease that emerges from RBD has not been fully characterized. Since 2004, we have been conducting a prospective study of idiopathic RBD patients, providing an opportunity to directly observe patients as they transitioned to a defined neurodegenerative syndrome. Patients with idiopathic RBD underwent an extensive annual evaluation of motor function, olfaction, color vision, autonomic function, cognition and psychiatric symptoms. Neurodegenerative disease was defined according to standard criteria. We compared these measures in patients who had developed PD to those with dementia, all within the first year of developing disease. Of 67 patients, 6 developed PD and eleven developed dementia. Except for cognitive functioning, all tests of olfaction, color vision, autonomic function, depression, and quantitative measures of motor speed were similar in patients with PD and dementia. Of dementia patients, seven met criteria for probable Lewy body dementia (LBD) and four for Alzheimer's disease (or, possible LBD). In all probable LBD cases, the diagnosis was made because of parkinsonism, with no patient experiencing hallucinations or fluctuations. Patients with "Alzheimer's disease" seemed to have LBD, as they demonstrated typical LBD cognitive profiles on neuropsychological testing and were indistinguishable from LBD patients in ancillary measures. Therefore, among RBD patients with new-onset LBD, hallucinations or fluctuations are absent, suggesting that RBD is a reliable early sign of LBD. The indistinguishability of dementia and PD in all ancillary measures suggests a single unitary "RBD-then-neurodegeneration" process, the clinical presentation of which depends upon selective neuronal vulnerability. PMID:19768814

  14. [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

  15. Implications for degenerative disorders

    PubMed Central

    Ozsoy, Nurten; Candoken, Eda

    2009-01-01

    In order to demonstrate whether the known biological effects of Aloe vera (L.) Burm. fil. could correlate with the antioxidant activity of the plant, the antioxidant activity of the aqueous leaf extract was investigated. The present study demonstrated that the aqueous extract from A. vera leaves contained naturally occuring antioxidant components, including total phenols, flavonoids, ascorbic acid, β-carotene and α-tocopherol. The extract exhibited inhibitory capacity against Fe3+/ascorbic acid induced phosphatidylcholine liposome oxidation, scavenged stable DPPH•, ABTS•+ and superoxide anion radicals, and acted as reductant. In contrast, the leaf inner gel did not show any antioxidant activity. It was concluded that the known beneficial effects of Aloe vera could be attributed to its antioxidant activity and could be related to the presence of phenolic compounds and antioxidant vitamins. PMID:20357932

  16. 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

  17. 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

  18. 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

  19. 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

  20. Cholesterol synthesis is the trigger and isoprenoid dependent interleukin-6 mediated inflammation is the common causative factor and therapeutic target for atherosclerotic vascular disease and age-related disorders including osteoporosis and type 2 diabetes.

    PubMed

    Omoigui, Sota

    2005-01-01

    This is a unifying theory that cholesterol metabolites (isoprenoids) are an integral component of the signaling pathway for interleukin-6 (IL-6) mediated inflammation. IL-6 inflammation is the common causative origin for atherosclerosis, peripheral vascular disease, coronary artery disease, and age-related disorders including osteoporosis, dementia, Alzheimer's disease and type 2 diabetes. Therapeutic effects of bisphosphonates and statins are mediated by isoprenoid depletion. Statins and bisphosphonates act in the cholesterol pathway to deplete isoprenoids. Anti-inflammatory properties of statins and bisphosphonates are due to isoprenoid depletion with subsequent inhibition of IL-6 mediated inflammation. Therapeutic targets for the prevention and control of all the above diseases should focus on cholesterol metabolites and IL-6 mediated inflammation. Prevention of atherosclerotic vascular disease and age-related disorders will be by utilization of cholesterol lowering agents or techniques and/or treatment with statins and/or bisphosphonates to inhibit IL-6 inflammation through regulation of cholesterol metabolism. PMID:15935563

  1. Surgical Management of Minimally Invasive Anterior Lumbar Interbody Fusion with Stand-Alone Interbody Cage for L4-5 Degenerative Disorders: Clinical and Radiographic Findings

    PubMed Central

    Hironaka, Yasuo; Morimoto, Tetsuya; Motoyama, Yasushi; Park, Young-Su; Nakase, Hiroyuki

    2013-01-01

    Surgical treatment for degenerative spinal disorders is controversial, although lumbar fusion is considered an acceptable option for disabling lower back pain. Patients underwent instrumented minimally invasive anterior lumbar interbody fusion (mini-ALIF) using a retroperitoneal approach except for requiring multilevel fusions, severe spinal canal stenosis, high-grade spondylolisthesis, and a adjacent segments disorders. We retrospectively reviewed the clinical records and radiographs of 142 patients who received mini-ALIF for L4-5 degenerative lumbar disorders between 1998 and 2010. We compared preoperative and postoperative clinical data and radiographic measurements, including the modified Japanese Orthopaedic Association (JOA) score, visual analog scale (VAS) score for back and leg pain, disc height (DH), whole lumbar lordosis (WL), and vertebral wedge angle (WA). The mean follow-up period was 76 months. The solid fusion rate was 90.1% (128/142 patients). The average length of hospital stay was 6.9 days (range, 3–21 days). The mean blood loss was 63.7 ml (range, 10–456 ml). The mean operation time was 155.5 min (range, 96–280 min). The postoperative JOA and VAS scores for back and leg pain were improved compared with the preoperative scores. Radiological analysis showed significant postoperative improvements in DH, WL, and WA, and the functional and radiographical outcomes improved significantly after 2 years. The 2.8% complication rate included cases of wound infection, liquorrhea, vertebral body fractures, and a misplaced cage that required revision. Mini-ALIF was found to be associated with improved clinical results and radiographic findings for L4-5 disorders. A retroperitoneal approach might therefore be a valuable treatment option. PMID:24140782

  2. 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

  3. Age-Related Macular Degeneration

    MedlinePlus

    ... this page please turn Javascript on. Age-related Macular Degeneration What is AMD? Click for more information Age-related macular degeneration, ... the macula allows you to see fine detail. AMD Blurs Central Vision AMD blurs the sharp central ...

  4. Degenerative myelopathy.

    PubMed

    Clemmons, R M

    1992-07-01

    DM in the German Shepherd is an immune-related disorder whose clinical signs are explained by a widespread degeneration of the white matter pathways in the thoracolumbar spinal cord. Therapy includes exercise, vitamin supplementation, and EACA medication. Avoiding unnecessary surgical procedures is also important to preclude permanent deterioration that can result following surgery in DM patients. In dogs other than German Shepherds, other identifiable causes should be treated. Additional confirmation of the diagnosis of DM may be assisted by performing cell-mediated immune studies or other serodiagnostic tests as they become available. PMID:1641928

  5. 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.

  6. Degenerative Nerve Diseases

    MedlinePlus

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many ... viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer's disease Amyotrophic lateral sclerosis Friedreich's ...

  7. Macular degeneration - age-related

    MedlinePlus

    Age-related macular degeneration (ARMD); AMD ... distorted and wavy. There may be a small dark spot in the center of your vision that ... leafy vegetables, may also decrease your risk of age-related macular degeneration. If you have wet AMD, ...

  8. 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

  9. 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

  10. 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

  11. [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

  12. [Age-related macular degeneration].

    PubMed

    Budzinskaia, M V

    2014-01-01

    The review provides an update on the pathogenesis and new treatment modalities for neovascular age-related macular degeneration (AMD). The impact of polymorphism in particular genes, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), and serine peptidase (HTRA1), on AMD development is discussed. Clinical presentations of different forms of exudative AMD, that is classic, occult, or more often mixed choroidal neovascularization, retinal angiomatous proliferation, and choroidal polypoidal vasculopathy, are described. Particular attention is paid to the results of recent clinical trials and safety issues around the therapy. PMID:25715554

  13. Age-related hearing loss

    MedlinePlus

    ... is no known single cause of age-related hearing loss. Most commonly, it is caused by changes in the inner ear that occur as you grow older. Your genes and loud noise (from rock concerts or music headphones) may play a large role. The following ...

  14. 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 ...

  15. [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. PMID:10420956

  16. 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

  17. 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

  18. Risk Factors for Age-Related Maculopathy

    PubMed Central

    Connell, Paul P.; Keane, Pearse A.; O'Neill, Evelyn C.; Altaie, Rasha W.; Loane, Edward; Neelam, Kumari; Nolan, John M.; Beatty, Stephen

    2009-01-01

    Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition. PMID:20339564

  19. 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

  20. 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

  1. Degenerative diseases of the vertebral column.

    PubMed

    Resnick, D

    1985-07-01

    Several distinct degenerative processes affect the articulations of the vertebral column; each is associated with characteristic radiographic and pathologic abnormalities, and many are accompanied by significant clinical manifestations. A discussion of these processes is best accomplished according to the type of joint that is involved. With regard to cartilaginous articulations, of which the intervertebral disk is most important, intervertebral (osteo)chondrosis, spondylosis deformans, and, in the cervical spine, uncovertebral arthrosis are the major degenerative disorders. Osteoarthritis (osteoarthrosis) affects any of the synovium-lined joints of the vertebral column, including the apophyseal, costovertebral, transitional lumbosacral, median atlantoaxial, and sacroiliac articulations. Fibrous articulations, ligaments, or entheses (sites of tendon or ligament attachment to bone) are involved in diffuse idiopathic skeletal hyperostosis, ossification of the posterior spinal ligaments, and Baastrup disease. Of the many complications of these degenerative processes, alignment abnormalities (including segmental instability, degenerative spondylolisthesis, senile kyphosis, and degenerative scoliosis), intervertebral disk displacement, calcification or ossification, and spinal stenosis are the most important. PMID:3923556

  2. 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

  3. 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

  4. Degenerative Spinal Deformity.

    PubMed

    Ailon, Tamir; Smith, Justin S; Shaffrey, Christopher I; Lenke, Lawrence G; Brodke, Darrel; Harrop, James S; Fehlings, Michael; Ames, Christopher P

    2015-10-01

    Degenerative spinal deformity afflicts a significant portion of the elderly and is increasing in prevalence. Recent evidence has revealed sagittal plane malalignment to be a key driver of pain and disability in this population and has led to a significant shift toward a more evidence-based management paradigm. In this narrative review, we review the recent literature on the epidemiology, evaluation, management, and outcomes of degenerative adult spinal deformity (ASD). ASD is increasing in prevalence in North America due to an aging population and demographic shifts. It results from cumulative degenerative changes focused in the intervertebral discs and facet joints that occur asymmetrically to produce deformity. Deformity correction focuses on restoration of global alignment, especially in the sagittal plane, and decompression of the neural elements. General realignment goals have been established, including sagittal vertical axis <50 mm, pelvic tilt <22°, and lumbopelvic mismatch <±9°; however, these should be tailored to the patient. Operative management, in carefully selected patients, yields satisfactory outcomes that appear to be superior to nonoperative strategies. ASD is characterized by malalignment in the sagittal and/or coronal plane and, in adults, presents with pain and disability. Nonoperative management is recommended for patients with mild, nonprogressive symptoms; however, evidence of its efficacy is limited. Surgery aims to restore global spinal alignment, decompress neural elements, and achieve fusion with minimal complications. The surgical approach should balance the desired correction with the increased risk of more aggressive maneuvers. In well-selected patients, surgery yields excellent outcomes. PMID:26378361

  5. 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

  6. Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and their roles in development, adulthood, cancer and degenerative disorders.

    PubMed

    Sims, Natalie A

    2015-10-01

    Mutations in cardiotrophin-like cytokine factor (CLCF1) and the related cytokine to which it binds, cytokine receptor-like factor 1 (CRLF1), are associated with Crisponi/cold induced sweating syndromes, and lead to early neonatal death in mice due to a suckling defect. These cytokines are members of the IL-6 superfamily, and form a range of composite cytokines that signal through gp130 bound either to the ciliary neurotrophic factor receptor (CNTFR) or a complex that involves the IL-27 p28 subunit. This review describes current knowledge of the signalling complexes formed by these cytokines, and explores their described and suggested roles in the neural, haematopoietic, skeletal, renal, immune and respiratory systems during development and adulthood, and in degenerative diseases and cancer. PMID:26198769

  7. 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

  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. Immune Mechanisms in Inflammatory and Degenerative Eye Disease

    PubMed Central

    Perez, Victor L.; Caspi, Rachel R.

    2015-01-01

    It has recently been recognized that pathology of age-associated degenerative eye diseases such as adult macular degeneration (AMD), glaucoma and diabetic retinopathy, have strong immunological underpinnings. Attempts have been made to extrapolate to age-related degenerative disease insights from inflammatory processes associated with non-infectious uveitis, but these have not yet been sufficiently informative. Here we review recent findings on the immune processes underlying uveitis and those that have been shown to contribute to AMD, discussing in this context parallels and differences between overt inflammation and para-inflammation in the eye. We propose that mechanisms associated with ocular immune privilege, in combination with paucity of age-related antigen(s) within the target tissue, dampen what could otherwise be overt inflammation and result in the para-inflammation that characterizes age-associated neurodegenerative disease. PMID:25981967

  10. 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...

  11. Age-Related Changes in Creative Thinking

    ERIC Educational Resources Information Center

    Roskos-Ewoldsen, Beverly; Black, Sheila R.; Mccown, Steven M.

    2008-01-01

    Age-related differences in cognitive processes were used to understand age-related declines in creativity. According to the Geneplore model (Finke, Ward, & Smith, 1992), there are two phases of creativity--generating an idea and exploring the implications of the idea--each with different underlying cognitive processes. These two phases are…

  12. Canine degenerative myelopathy.

    PubMed

    Coates, Joan R; Wininger, Fred A

    2010-09-01

    Canine degenerative myelopathy (DM) is an adult-onset fatal neurodegenerative disease that occurs in many breeds. The initial upper motor neuron spastic paraparesis and general proprioceptive ataxia in the pelvic limbs progress to a flaccid lower motor neuron tetraparesis. Recently, a missense mutation in the superoxide dismutase 1 (SOD1) gene was found to be a risk factor for DM, suggesting that DM is similar to some forms of human amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). This article reviews the current knowledge of canine DM with regard to its signalment, clinical spectrum, diagnostic approach, and treatment. The implications of the SOD1 mutation on both diseases are discussed, comparing pathogenic mechanisms while conveying perspectives to translational medicine. PMID:20732599

  13. 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

  14. 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

  15. Age-Related White Matter Changes

    PubMed Central

    Xiong, Yun Yun; Mok, Vincent

    2011-01-01

    Age-related white matter changes (WMC) are considered manifestation of arteriolosclerotic small vessel disease and are related to age and vascular risk factors. Most recent studies have shown that WMC are associated with a host of poor outcomes, including cognitive impairment, dementia, urinary incontinence, gait disturbances, depression, and increased risk of stroke and death. Although the clinical relevance of WMC has been extensively studied, to date, only very few clinical trials have evaluated potential symptomatic or preventive treatments for WMC. In this paper, we reviewed the current understanding in the pathophysiology, epidemiology, clinical importance, chemical biomarkers, and treatments of age-related WMC. PMID:21876810

  16. Pharmacogenetics and age-related macular degeneration.

    PubMed

    Schwartz, Stephen G; Brantley, Milam A

    2011-01-01

    Pharmacogenetics seeks to explain interpatient variability in response to medications by investigating genotype-phenotype correlations. There is a small but growing body of data regarding the pharmacogenetics of both nonexudative and exudative age-related macular degeneration. Most reported data concern polymorphisms in the complement factor H and age-related maculopathy susceptibility 2 genes. At this time, the data are not consistent and no definite conclusions may be drawn. As clinical trials data continue to accumulate, these relationships may become more apparent. PMID:22046503

  17. 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. PMID:26915078

  18. [Ultrasonographic examination of the stifle joint in the dog. Part 2: Impaired wound healing and neoplastic, congenital, developmental, degenerative and traumatic disorders].

    PubMed

    Nayseh, K; Kramer, M; Ondreka, N

    2015-01-01

    Ultrasonography is a cost-effective, non-invasive technique, which can be performed in conscious dogs. It frequently contributes valuable and even crucial diagnostic information in patients with lameness attributed to the stifle joint. Within the first part of this article, technical requirements and limitations as well as the standardized scanning protocol and ultrasonographic anatomy of the stifle joint are described. Additionally, ultrasonographic features of common pathologies of the stifle joint, including cranial cruciate ligament rupture and meniscal pathologies, are discussed. The second part of the article focuses on the ultrasonographic approach to other, less common pathologies of the canine stifle joint, including impaired wound healing and congenital, neoplastic, developmental and traumatic disorders. PMID:25966794

  19. Chronic administration of thiamine pyrophosphate decreases age-related histological atrophic testicular changes and improves sexual behavior in male Wistar rats.

    PubMed

    Hernández-Montiel, H L; Vásquez López, C M; González-Loyola, J G; Vega-Anaya, G C; Villagrán-Herrera, M E; Gallegos-Corona, M A; Saldaña, C; Ramos Gómez, M; García Horshman, P; García Solís, P; Solís-S, J C; Robles-Osorio, M L; Ávila Morales, J; Varela-Echavarría, A; Paredes Guerrero, R

    2014-06-01

    Aging is a multifactorial universal process and constitutes the most important risk factor for chronic-degenerative diseases. Although it is a natural process, pathological aging arises when these changes occur quickly and the body is not able to adapt. This is often associated with the generation of reactive oxygen species (ROS), inflammation, and a decrease in the endogenous antioxidant systems, constituting a physiopathological state commonly found in chronic-degenerative diseases. At the testicular level, aging is associated with tissue atrophy, decreased steroidogenesis and spermatogenesis, and sexual behavior disorders. This situation, in addition to the elevated generation of ROS in the testicular steroidogenesis, provides a critical cellular environment causing oxidative damage at diverse cellular levels. To assess the effects of a reduction in the levels of ROS, thiamine pyrophosphate (TPP) was chronically administered in senile Wistar rats. TPP causes an activation of intermediate metabolism routes, enhancing cellular respiration and decreasing the generation of ROS. Our results show an overall decrease of atrophic histological changes linked to aging, with higher levels of serum testosterone, sexual activity, and an increase in the levels of endogenous antioxidant enzymes in TPP-treated animals. These results suggest that TPP chronic administration decreases the progression of age-related atrophic changes by improving the intermediate metabolism, and by increasing the levels of antioxidant enzymes. PMID:24371036

  20. 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,…

  1. 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…

  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. Driving and Age-Related Macular Degeneration

    PubMed Central

    Owsley, Cynthia; McGwin, Gerald

    2009-01-01

    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, and considers directions for future research. PMID:20046818

  4. Neuromuscular contributions to age-related weakness

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related physiological change of neuromuscular function is not a linear process and is likely influenced by various biological and behavioral factors (e.g., genetics, nutrition, physical activity level, comorbidities, etc.). These factors contribute to heterogeneity among older adults, which chal...

  5. 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

  6. Neuropeptides in experimental and degenerative arthritis.

    PubMed

    Niissalo, S; Hukkanen, M; Imai, S; Törnwall, J; Konttinen, Y T

    2002-06-01

    Classical symptoms of both inflammatory and degenerative arthritides may contribute to neurogenic responses like wheal, flare, edema, and pain. Rheumatoid arthritis (RA) is an autoimmune disease with an immunogenetic background. Neurogenic inflammation has been considered to play an essential role in RA, in part because of the symmetrical involvement (cross-spinal reflexes) and the predominant involvement of the most heavily innervated small joints of the hands and the feet (highly represented in the hominiculus). In contrast, osteoarthritis (OA) is considered to arise as a result of degeneration of the hyaline articular cartilage, which secondarily results in local inflammation and pain. However, it is possible that the age-related and predominant (compared to nociceptive nerves) degeneration of the proprioceptive, kinesthetic and vasoregulatory nerves can represent the primary pathogenic events. This leads to progressive damage of tissue with extremely poor capacity for self-regeneration. Inflammation, be it primary/autoimmune or secondary/degenerative, leads to peripheral sensitization and stimulation, which may further lead to central sensitization, neurogenic amplification of the inflammatory responses and activation of the neuro-endocrine axis. Neuropeptides serve as messengers, which modulate and mediate the actions in these cascades. Accordingly, many neuropeptides have been used successfully as experimental treatments, most recently VIP, which effectively controlled collagen-induced arthritis in mice. Therefore, it can safely be concluded that better treatment/control of disease activity and pain can be achieved by blocking the cascade leading to initiation and/or amplification of inflammatory process combined with effects on central nociceptive and neuroendocrine responses. PMID:12114296

  7. Present and Possible Therapies for Age-Related Macular Degeneration

    PubMed Central

    Kamal, Ahmed

    2014-01-01

    Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly population worldwide and is defined as a chronic, progressive disorder characterized by changes occurring within the macula reflective of the ageing process. At present, the prevalence of AMD is currently rising and is estimated to increase by a third by 2020. Although our understanding of the several components underpinning the pathogenesis of this condition has increased significantly, the treatment options for this condition remain substantially limited. In this review, we outline the existing arsenal of therapies available for AMD and discuss the additional role of further novel therapies currently under investigation for this debilitating disease. PMID:25097787

  8. 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 ...

  9. 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

  10. Age-related eye disease and gender.

    PubMed

    Zetterberg, Madeleine

    2016-01-01

    Worldwide, the prevalence of moderate to severe visual impairment and blindness is 285 millions, with 65% of visually impaired and 82% of all blind people being 50 years and older. Meta-analyses have shown that two out of three blind people are women, a gender discrepancy that holds true for both developed and developing countries. Cataract accounts for more than half of all blindness globally and gender inequity in access to cataract surgery is the major cause of the higher prevalence of blindness in women. In addition to gender differences in cataract surgical coverage, population-based studies on the prevalence of lens opacities indicate that women have a higher risk of developing cataract. Laboratory as well as epidemiologic studies suggest that estrogen may confer antioxidative protection against cataractogenesis, but the withdrawal effect of estrogen in menopause leads to increased risk of cataract in women. For the other major age-related eye diseases; glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy, data are inconclusive. Due to anatomic factors, angle closure glaucoma is more common in women, whereas the dominating glaucoma type; primary open-angle glaucoma (POAG), is more prevalent in men. Diabetic retinopathy also has a male predominance and vascular/circulatory factors have been implied both in diabetic retinopathy and in POAG. For AMD, data on gender differences are conflicting although some studies indicate increased prevalence of drusen and neovascular AMD in women. To conclude, both biologic and socioeconomic factors must be considered when investigating causes of gender differences in the prevalence of age-related eye disease. PMID:26508081

  11. 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

  12. Distraction can reduce age-related forgetting.

    PubMed

    Biss, Renée K; Ngo, K W Joan; Hasher, Lynn; Campbell, Karen L; Rowe, Gillian

    2013-04-01

    In three experiments, we assessed whether older adults' generally greater tendency to process distracting information can be used to minimize widely reported age-related differences in forgetting. Younger and older adults studied and recalled a list of words on an initial test and again on a surprise test after a 15-min delay. In the middle (Experiments 1a and 2) or at the end (Experiment 3) of the delay, participants completed a 1-back task in which half of the studied words appeared as distractors. Across all experiments, older adults reliably forgot unrepeated words; however, older adults rarely or never forgot the words that had appeared as distractors, whereas younger adults forgot words in both categories. Exposure to distraction may serve as a rehearsal episode for older adults, and thus as a method by which general distractibility may be co-opted to boost memory. PMID:23426890

  13. 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

  14. [Age-related changes of sensory system].

    PubMed

    Iwamoto, Toshihiko; Hanyu, Haruo; Umahara, Takahiko

    2013-10-01

    Pathological processes usually superimpose on physiological aging even in the sensory system including visual, hearing, olfactory, taste and somatosensory functions. Representative changes of age-related changes are presbyopia, cataracts, and presbyacusis. Reduced sense of smell is seen in normal aging, but the prominent reduction detected by the odor stick identification test is noticed especially in early stage of Alzheimer or Parkinson disease. Reduced sense of taste is well-known especially in salty sense, while the changes of sweet, bitter, and sour tastes are different among individuals. Finally, deep sensation of vibration and proprioception is decreased with age as well as superficial sensation (touch, temperature, pain). As a result, impaired sensory system could induce deterioration of the activities of daily living and quality of life in the elderly. PMID:24261198

  15. Macular carotenoids and age-related maculopathy.

    PubMed

    O'Connell, Eamonn; Neelam, Kumari; Nolan, John; Au Eong, Kah-Guan; Beatty, Stephan

    2006-11-01

    Lutein (L) and zeaxanthin (Z) are concentrated at the macula, where they are collectively known as macular pigment (MP), and where they are believed to play a major role in protecting retinal tissues against oxidative stress. Whilst the exact pathogenesis of age-related maculopathy (ARM) remains unknown, the disruption of cellular processes by oxidative stress may play an important role. Manipulation of dietary intake of L and Z has been shown to augment MP, thereby raising hopes that dietary supplementation with these carotenoids might prevent, delay, or modify the course of ARM. This article discusses the scientific rationale supporting the hypothesis that L and Z are protective against ARM, and presents the recent evidence germane to this theory. PMID:17160199

  16. 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

  17. [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

  18. 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

  19. Closed-Loop Rehabilitation of Age-Related Cognitive Disorders

    PubMed Central

    Mishra, Jyoti; Gazzaley, Adam

    2015-01-01

    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

  20. 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

  1. 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

  2. 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

  3. 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

  4. Age-related macular degeneration: choroidal ischaemia?

    PubMed Central

    Coleman, D Jackson; Silverman, Ronald H; Rondeau, Mark J; Lloyd, Harriet O; Khanifar, Aziz A; Chan, R V Paul

    2013-01-01

    Aim Our aim is to use ultrasound to non-invasively detect differences in choroidal microarchitecture possibly related to ischaemia among normal eyes and those with wet and dry age-related macular degeneration (AMD). Design Prospective case series of subjects with dry AMD, wet AMD and age-matched controls. Methods Digitised 20 MHz B-scan radiofrequency ultrasound data of the region of the macula were segmented to extract the signal from the retina and choroid. This signal was processed by a wavelet transform, and statistical modelling was applied to the wavelet coefficients to examine differences among dry, wet and non-AMD eyes. Receiver operating characteristic (ROC) analysis was used to evaluate a multivariate classifier. Results In the 69 eyes of 52 patients, 18 did not have AMD, 23 had dry AMD and 28 had wet AMD. Multivariate models showed statistically significant differences between groups. Multiclass ROC analysis of the best model showed an excellent volume-under-curve of 0.892±0.17. The classifier is consistent with ischaemia in dry AMD. Conclusions Wavelet augmented ultrasound is sensitive to the organisational elements of choroidal microarchitecture relating to scatter and fluid tissue boundaries such as seen in ischaemia and inflammation, allowing statistically significant differentiation of dry, wet and non-AMD eyes. This study further supports the association of ischaemia with dry AMD and provides a rationale for treating dry AMD with pharmacological agents to increase choroidal perfusion. ClinicalTrials.gov registration NCT00277784. PMID:23740965

  5. 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.

  6. 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].

  7. Age-related crosslink in skin collagen

    SciTech Connect

    Yamauchi, M.; Mechanic, G.

    1986-05-01

    A stable crosslinking amino acid was isolated from mature bovine skin collagen and its structure was identified as histidinohydroxylysinonorleucine (HHL) using fast atom bombardment mass spectrometry and /sup 1/H, /sup 13/C-NMR. This newly identified crosslink has a linkage between C-2 histidine and C-6 of lysine in the latter's portion of hydroxylysinonorleucine. Quantitative studies using various aged samples of cow and human skin collagen indicated that this acid-heat stable nonreducible compound was the major age-related crosslink. In case of cow skin collagen, for example, during early embryonic development (3 and 5 month old embryos) the content of HHL stayed less than 0.01 residue/mole of collagen, however from the middle of gestation period (7 month old embryo) through the maturation stage it showed rapid increase with age and reached approximately 0.5 residues/mole of collagen in the 3 year old animal. Small increments (up to 0.65 res/mole of collagen) were observed in the 9 year old cow. The amounts of the crosslink unlike pyridinoline do not decrease with aging. Similar patterns were observed in human skin collagen.

  8. 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

  9. 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

  10. 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.…

  11. Bowman lecture on the role of inflammation in degenerative disease of the eye

    PubMed Central

    Forrester, J V

    2013-01-01

    Inflammation, in the pathogenesis of many diseases previously thought to be strictly genetic, degenerative, metabolic, or endocrinologic in aetiology, has gradually entered the framework of a general mechanism of disease. This is exemplified by conditions such as Parkinson's disease, Alzheimer's disease, atherosclerosis, diabetes, and the more recently described Metabolic Syndrome. Chronic inflammatory processes have a significant, if not primary role, in ophthalmic diseases, particularly in retinal degenerative diseases. However, inflammation itself is not easy to define, and some aspects of inflammation may be beneficial, in a process described as ‘para-inflammation' by Medhzitov. In contrast, the damaging effects of inflammation, mediated by pro-inflammatory macrophages through activation of the intracellular protein-signalling complexes, termed inflammasomes, are well recognised and are important therapeutic targets. In this review, the range of inflammatory processes in the eye is evaluated in the context of how these processes impact upon retinal degenerative disease, particularly diabetic retinopathy and age-related macular degeneration. PMID:23288138

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. Fruits, Nuts, and Brain Aging: Nutritional Interventions Targeting Age-Related Neuronal and Behavioral Deficits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    By the year 2050, 30% of the total population of the US will be over 65 years of age. As the aged population expands, the economic burden of care and treatment of those with age-related health disorders also increases, necessitating the immediate implementation of therapeutics to prevent or even rev...

  19. Nutrition and Age-Related Eye Diseases: The ALIENOR (Antioxydants, LIpides Essentiels, Nutrition et Maladies OculaiRes) Study

    PubMed Central

    Delcourt, Cécile; Korobelnik, Jean-François; Barberger-Gateau, Pascale; Delyfer, Marie-Noëlle; Marie-Bénédicte, Rougier; Le Goff, Mélanie; Malet, Florence; Joseph, Colin; Dartigues, Jean-François

    2010-01-01

    Background Worldwide, degenerative eye diseases (age-related maculopathy (ARM), cataract, glaucoma) are the main causes of visual impairment and blindness, which contribute to disability in the elderly. Mainly three types of nutritional factors are investigated for their potential protection against eye ageing: antioxidants; lutein and zeaxanthin (carotenoids which accumulate specifically in the eye); omega 3 polyunsaturated fatty acids. Few epidemiological studies have been conducted in this field, particularly in Europe. Objective The Alienor (Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes) Study aims at assessing the associations of eye diseases with nutritional factors, determined from plasma measurements and estimation of dietary intakes. Design, setting and participants Subjects were recruited in Bordeaux (France) from the ongoing population-based 3C study. In 2006–2008, 963 subjects from the 3C Study, aged 73 years or more, had an eye examination and will have follow-up eye examinations every 2 years. Measurements Vascular, genetic and nutritional factors were assessed at baseline (1999–2001) and follow-up examinations of the 3C Study. Eye diseases were classified according to international classifications. Results Nutritional status and vascular disease and risk factors were similar between participants and non participants, except for a slight difference in plasma triglycerides and HDL-cholesterol. As expected, the prevalence of eye diseases was high: early and late ARM (28.4 % and 5.6 %, respectively), open-angle glaucoma and treated ocular hypertension (4.8 % and 10.0 %, respectively), cataract extraction (45.2 %), retinopathy (8.4 %), retinal vein occlusion (1.1 %), epiretinal membrane (3.9 %), current use of artificial tears (17.3 %). Conclusions This study confirms the high prevalence of eye diseases in the elderly. Its main strength is the combination of nutritional, vascular and genetic information, collected over a 7 year

  20. Alzheimer's disease and age-related memory decline (preclinical).

    PubMed

    Terry, Alvin V; Callahan, Patrick M; Hall, Brandon; Webster, Scott J

    2011-08-01

    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 and 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 and 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

  1. Age-related hypoxia in CNS pathology.

    PubMed

    Bădescu, George Mihai; Fîlfan, Mădălina; Ciobanu, Ovidiu; Dumbravă, DănuŢ Adrian; Popa-Wagner, Aurel

    2016-01-01

    Although neuropathological conditions differ in the etiology of the inflammatory response, cellular and molecular mechanisms of neuroinflammation are probably similar in aging, hypertension, depression and cognitive impairment. Moreover, a number of common risk factors such as obesity, hypertension, diabetes and atherosclerosis are increasingly understood to act as "silent contributors" to neuroinflammation and can underlie the development of disorders such as cerebral small vessel disease (cSVD) and subsequent dementia. On the other hand, acute neuroinflammation, such as in response to traumatic or cerebral ischemia, aggravates the acute damage and can lead to a number of pathological such as depression, post-stroke dementia and potentially neurodegeneration. All of those sequelae impair recovery and most of them provide the ground for further cerebrovascular events and a vicious cycle develops. Therefore, understanding the mechanisms associated with vascular dementia, stroke and related complications is of paramount importance in improving current preventive and therapeutic interventions. Likewise, understanding of molecular factors and pathways associated with neuroinflammation will eventually enable the discovery and implementation of new diagnostic and therapeutic strategies indicated in a wide range of neurological conditions. PMID:27151686

  2. Genetics of Age-Related Macular Degeneration: Current Concepts, Future Directions

    PubMed Central

    DeAngelis, Margaret M.; Silveira, Alexandra C.; Carr, Elizabeth A.; Kim, Ivana K.

    2014-01-01

    Age-related macular degeneration (AMD) is a progressive degenerative disease which leads to blindness, affecting the quality of life of millions of Americans. More than 1.75 million individuals in the United States are affected by the advanced form of AMD. The etiological pathway of AMD is not yet fully understood, but there is a clear genetic influence on disease risk. To date, the 1q32 (CFH) and 10q26 (PLEKHA1/ARMS2/HTRA1) loci are the most strongly associated with disease; however, the variation in these genomic regions alone is unable to predict disease development with high accuracy. Therefore, current genetic studies are aimed at identifying new genes associated with AMD and their modifiers, with the goal of discovering diagnostic or prognostic biomarkers. Moreover, these studies provide the foundation for further investigation into the pathophysiology of AMD by utilizing a systems-biology-based approach to elucidate underlying mechanistic pathways. PMID:21609220

  3. Cellular and molecular mechanisms of age-related macular degeneration: from impaired autophagy to neovascularization.

    PubMed

    Klettner, Alexa; Kauppinen, Anu; Blasiak, Janusz; Roider, Johan; Salminen, Antero; Kaarniranta, Kai

    2013-07-01

    Age-related macular degeneration (AMD) is a complex, degenerative and progressive disease involving multiple genetic and environmental factors. It can result in severe visual loss e.g. AMD is the leading cause of blindness in the elderly in the western countries. Although age, genetics, diet, smoking, and many cardiovascular factors are known to be linked with this disease there is increasing evidence that long-term oxidative stress, impaired autophagy clearance and inflammasome mediated inflammation are involved in the pathogenesis. Under certain conditions these may trigger detrimental processes e.g. release of vascular endothelial growth factor (VEGF), causing choroidal neovascularization e.g. in wet AMD. This review ties together these crucial pathological threads in AMD. PMID:23603148

  4. Age-related changes of mitochondrial transcription factor a expression in rotator cuff degeneration

    PubMed Central

    Ichiseki, Toru; Ueda, Shusuke; Ueda, Yoshimichi; Kaneuji, Ayumi; Kawahara, Norio; Matsumoto, Tadami

    2015-01-01

    One cause of rotator cuff tears is thought to be age-related degenerative changes occurring in the rotator cuff. Using Rat rotator cuff we determined age-related changes in mitochondrial transcription factor A (TFAM) expression in rotator cuff degeneration to clarify the presence/absence of mitochondrial stress. The materials used were rotator cuffs (supraspinatus) of 5-, 24-, 48-, and 100-week-old Wistar Rats (five animals each). Histopathological study revealed a 4-layer structure consisting of a bone layer, calcified cartilage layer, non-calcified cartilage layer, and tendinous component), with age-related narrowing of the non-calcified cartilage layer confirmed to be present. In an immunohistochemical TFAM study positive findings of the non-calcified cartilage layer were less prominent in the 100-week-old group. In an Enzyme-Linked Immunosorbent Assay (ELISA) study, these were more prominent in the 5-week-old to 24-week-old groups, and slightly less so in the 48-week-old group as compared to the 24-week-old one. In the 100-week-old group as compared to the 24-week-old one they were significantly less prominent (p<0.05). The non-calcified cartilage layer is a major site for the dispersion of mechanical energy, and the change in TFAM expression noted at the same site in the present study and the results of ELISA suggest that age-related changes in mitochondrial stress may be one cause of rotator cuff degeneration. PMID:26692954

  5. Age-related macular degeneration—emerging pathogenetic and therapeutic concepts

    PubMed Central

    GEHRS, KAREN M.; ANDERSON, DON H.; JOHNSON, LINCOLN V.; HAGEMAN, GREGORY S.

    2014-01-01

    Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden. Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage ‘wet’ form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common ‘dry’ AMD, except for the use of antioxidants that delay progression in 20%–25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene—which encodes the major inhibitor of the complement alternative pathway—is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development

  6. Cellular models and therapies for age-related macular degeneration

    PubMed Central

    Forest, David L.; Johnson, Lincoln V.; Clegg, Dennis O.

    2015-01-01

    ABSTRACT Age-related macular degeneration (AMD) is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE) cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD). A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease. PMID:26035859

  7. Proinflammatory cytokines, aging, and age-related diseases.

    PubMed

    Michaud, Martin; Balardy, Laurent; Moulis, Guillaume; Gaudin, Clement; Peyrot, Caroline; Vellas, Bruno; Cesari, Matteo; Nourhashemi, Fati

    2013-12-01

    Inflammation is a physiological process that repairs tissues in response to endogenous or exogenous aggressions. Nevertheless, a chronic state of inflammation may have detrimental consequences. Aging is associated with increased levels of circulating cytokines and proinflammatory markers. Aged-related changes in the immune system, known as immunosenescence, and increased secretion of cytokines by adipose tissue, represent the major causes of chronic inflammation. This phenomenon is known as "inflamm-aging." High levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α, and C-reactive protein are associated in the older subject with increased risk of morbidity and mortality. In particular, cohort studies have indicated TNF-α and IL-6 levels as markers of frailty. The low-grade inflammation characterizing the aging process notably concurs at the pathophysiological mechanisms underlying sarcopenia. In addition, proinflammatory cytokines (through a variety of mechanisms, such as platelet activation and endothelial activation) may play a major role in the risk of cardiovascular events. Dysregulation of the inflammatory pathway may also affect the central nervous system and be involved in the pathophysiological mechanisms of neurodegenerative disorders (eg, Alzheimer disease).The aim of the present review was to summarize different targets of the activity of proinflammatory cytokines implicated in the risk of pathological aging. PMID:23792036

  8. 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

  9. [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

  10. Potential mechanisms underlying the role of chronic inflammation in age-related muscle wasting.

    PubMed

    Jo, Edward; Lee, Sang-Rok; Park, Bong-Sup; Kim, Jeong-Su

    2012-10-01

    Sarcopenia, an age-related condition characterized by progressive skeletal muscle degeneration, might exist as one of the primary clinical conditions underlying severe functional impairment as well as increased risk of co-morbidities in the elderly. Although the etiology of sarcopenia remains multifaceted, age-related chronic inflammation has been strongly implicated in muscle wasting and related sequelae during advanced age. Recent evidence suggests that aberrant, unresolved alterations in regular inflammatory processes during advanced age might ultimately operate as the link that drives skeletal muscle to become more degenerative and dysfunctional in nature. Such negative atrophic muscular outcomes might result from inflammation-induced disruption of central mechanisms regulating skeletal muscle morphology and remodeling. In addition, recent findings demonstrate an adverse confluence between sarcopenia and excessive adiposity (i.e. sarcopenic obesity), as the co-existence of such adverse alterations in body composition may exacerbate systemic inflammation and muscle wasting in the elderly. The following evidence-based review serves to examine sarcopenia from a mechanistic perspective with emphasis on chronic inflammation. PMID:22717404

  11. 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

  12. 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

  13. Spinal Deformity in Aged Zebrafish Is Accompanied by Degenerative Changes to Their Vertebrae that Resemble Osteoarthritis

    PubMed Central

    Hayes, Anthony J.; Reynolds, Scott; Nowell, Mari A.; Meakin, Lee B.; Habicher, Judith; Ledin, Johan; Bashford, Andrew; Caterson, Bruce; Hammond, Chrissy L.

    2013-01-01

    Age-related degenerative changes within the vertebral column are a significant cause of morbidity with considerable socio-economic impact worldwide. An improved understanding of these changes through the development of experimental models may lead to improvements in existing clinical treatment options. The zebrafish is a well-established model for the study of skeletogenesis with significant potential in gerontological research. With advancing age, zebrafish frequently develop gross deformities of their vertebral column, previously ascribed to reduced trunk muscle tone. In this study, we assess degenerative changes specifically within the bone and cartilage of the vertebral column of zebrafish at 1, 2 and 3-years of age. We show increased frequency and severity of spinal deformities/curvatures with age. Underlying the most severe phenotypes are partial or complete vertebral dislocations and focal thickening of the vertebral bone at the joint margins. MicroCT examination demonstrates small defects, fractures and morphological evidence suggestive of bone erosion and remodeling (i.e. osteophytes) within the vertebrae during aging, but no significant change in bone density. Light and electron microscopic examination reveal striking age-related changes in cell morphology, suggestive of chondroptosis, and tissue remodelling of the vertebral cartilage, particularly within the pericellular micro-environment. Glycosaminoglycan analysis of the vertebral column by HPLC demonstrates a consistent, age-related increase in the yield of total chondroitin sulfate disaccharide, but no change in sulfation pattern, supported by immunohistochemical analysis. Immunohistochemistry strongly identifies all three chondroitin/dermatan sulphate isoforms (C-0-S, C-4-S/DS and C-6-S) within the vertebral cartilage, particularly within the pericellular micro-environment. In contrast, keratan sulfate immunolocalises specifically with the notochordal tissue of the intervertebral disc, and its

  14. 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

  15. 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

  16. 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

  17. The role of insulin in the vascular contributions to age-related dementia.

    PubMed

    Hughes, Timothy M; Craft, Suzanne

    2016-05-01

    In addition to its well-known role in energy metabolism in the body, insulin is a vasoactive hormone that regulates peripheral and cerebral blood flow and neuronal function. Vascular and metabolic dysfunctions are emerging risk factors for Alzheimer's disease (AD) and age-related dementias, and recent evidence suggests that the two pathways are constitutive and interrelated. As a result, an emphasis on correcting metabolic disorders is emerging as an important strategy in the treatment and prevention of age-related cognitive impairment and AD. We review the evidence regarding the unique and interactive effects of vascular and metabolic disorders in pathological brain aging, with special consideration of the role of insulin dysregulation in promoting AD pathologic processes and vascular brain injury. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26657615

  18. [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

  19. Low Calorie Diet Affects Aging-Related Factors

    MedlinePlus

    ... Research News From NIH Low Calorie Diet Affects Aging-Related Factors Past Issues / Summer 2006 Table of ... project sponsored by the NIH's National Institute on Aging (NIA) to learn more about the effects of ...

  20. 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 ...

  1. Age-related changes in the misinformation effect.

    PubMed

    Sutherland, R; Hayne, H

    2001-08-01

    In these experiments, we examined the relation between age-related changes in retention and age-related changes in the misinformation effect. Children (5- and 6- and 11- and 12-year-olds) and adults viewed a video, and their memory was assessed immediately, 1 day, or 6 weeks later (Experiment 1). There were large age-related differences in retention when participants were interviewed immediately and after 1 day, but after the 6-week delay, age-related differences in retention were minimal. In Experiment 2, 11- and 12-year-olds and adults were exposed to neutral, leading, and misleading postevent information 1 day or 6 weeks after they viewed the video. Exposure to misleading information increased the number of commission errors, particularly when participants were asked about peripheral aspects of the video. At both retention intervals, children were more likely than adults to incorporate the misleading postevent information into their subsequent verbal accounts. These findings indicate that age-related changes in the misinformation effect are not predicted by age-related changes in retention. PMID:11511130

  2. 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

  3. 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

  4. Can DRYAD explain age-related associative memory deficits?

    PubMed

    Smyth, Andrea C; Naveh-Benjamin, Moshe

    2016-02-01

    A recent interesting theoretical account of aging and memory judgments, the DRYAD (density of representations yields age-related deficits; Benjamin, 2010; Benjamin, Diaz, Matzen, & Johnson, 2012), attributes the extensive findings of disproportional age-related deficits in memory for source, context, and associations, to a global decline in memory fidelity. It is suggested that this global deficit, possibly due to a decline in attentional processes, is moderated by weak representation of contextual information to result in disproportional age-related declines. In the current article, we evaluate the DRYAD model, comparing it to specific age-related deficits theories, in particular, the ADH (associative deficit hypothesis, Naveh-Benjamin, 2000). We question some of the main assumptions/hypotheses of DRYAD in light of data reported in the literature, and we directly assess the role of attention in age-related deficits by manipulations of divided attention and of the instructions regarding what to pay attention to in 2 experiments (one from the literature and a new one). The results of these experiments fit the predictions of the ADH and do not support the main assumption/hypotheses of DRYAD. PMID:25961878

  5. 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. PMID:26292978

  6. 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

  7. 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

  8. 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

  9. 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

  10. Polysaccharides from Medicinal Herbs As Potential Therapeutics for Aging and Age-Related Neurodegeneration

    PubMed Central

    Li, Haifeng; Ma, Fangli; Hu, Minghua; Xiao, Lingyun; Zhang, Ju; Xiang, Yanxia

    2014-01-01

    Abstract Recent studies have uncovered important aging clues, including free radicals, inflammation, telomeres, and life span pathways. Strategies to regulate aging-associated signaling pathways are expected to be effective in the delay and prevention of age-related disorders. For example, herbal polysaccharides with considerable anti-oxidant and anti-inflammation capacities have been shown to be beneficial in aging and age-related neurodegenerative diseases. Polysaccharides capable of reducing cellular senescence and modulating life span via telomere and insulin pathways have also been found to have the potential to inhibit protein aggregation and aggregation-associated neurodegeneration. Here we present the current status of polysaccharides in anti-aging and anti-neurodegenerative studies. PMID:24125569

  11. Aging-related nicotinamide adenine dinucleotide oxidase response to dietary supplementation: the French paradox revisited.

    PubMed

    Morré, D James; Morré, Dorothy M; Shelton, Thomas B

    2010-01-01

    Aging-related cell-surface NADH oxidase (arNOX)-specific activities increase with age between age 30 and ages 50-65. The protein is shed and circulates. Activity correlates with a number of aging-related disorders including low-density lipoprotein (LDL) oxidation as a precondition to atherosclerosis as well as oxidation of collagen and elastin as a major contributor to skin aging. arNOX inhibitors formulated for sustained release are capable of maintaining circulating arNOX at low levels with regular use as food supplements formulated with natural compounds. Among the best sources are certain culinary seasonings, all of which are ingredients used extensively in the French kitchen. Their regular use may contribute to an understanding of the nutritional basis for the French Paradox. PMID:19954304

  12. Role of Oxidative RNA Damage in Chronic-Degenerative Diseases

    PubMed Central

    2015-01-01

    Normal cellular metabolism and exposure to ionizing and ultraviolet radiations and exogenous agents produce reactive oxygen species (ROS). Due to their reactivity, they can interact with many critical biomolecules and induce cell damage. The reaction of ROS with free nucleobases, nucleosides, nucleotides, or oligonucleotides can generate numerous distinct modifications in nucleic acids. Oxidative damage to DNA has been widely investigated and is strongly implicated in the development of many chronic-degenerative diseases. In contrast, RNA damage is a poorly examined field in biomedical research. In this review, I discuss the importance of RNA as a target of oxidative damage and the role of oxidative damage to RNA in the pathogenesis of some chronic-degenerative diseases, such as neurological disorders, atherosclerosis, and cancer. Furthermore, I review recent evidence suggesting that RNA may be the target for toxic agents and indicating RNA degradation as a powerful tool to treat any pathology in which there is an aberrant expression of mRNA and/or its gene products. PMID:26078805

  13. 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…

  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. 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…

  16. 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…

  17. Neuroimaging explanations of age-related differences in task performance

    PubMed Central

    Steffener, Jason; Barulli, Daniel; Habeck, Christian; Stern, Yaakov

    2014-01-01

    Advancing age affects both cognitive performance and functional brain activity and interpretation of these effects has led to a variety of conceptual research models without always explicitly linking the two effects. However, to best understand the multifaceted effects of advancing age, age differences in functional brain activity need to be explicitly tied to the cognitive task performance. This work hypothesized that age-related differences in task performance are partially explained by age-related differences in functional brain activity and formally tested these causal relationships. Functional MRI data was from groups of young and old adults engaged in an executive task-switching experiment. Analyses were voxel-wise testing of moderated-mediation and simple mediation statistical path models to determine whether age group, brain activity and their interaction explained task performance in regions demonstrating an effect of age group. Results identified brain regions whose age-related differences in functional brain activity significantly explained age-related differences in task performance. In all identified locations, significant moderated-mediation relationships resulted from increasing brain activity predicting worse (slower) task performance in older but not younger adults. Findings suggest that advancing age links task performance to the level of brain activity. The overall message of this work is that in order to understand the role of functional brain activity on cognitive performance, analysis methods should respect theoretical relationships. Namely, that age affects brain activity and brain activity is related to task performance. PMID:24672481

  18. Glycosaminoglycans in the Human Cornea: Age-Related Changes

    PubMed Central

    Pacella, Elena; Pacella, Fernanda; De Paolis, Giulio; Parisella, Francesca Romana; Turchetti, Paolo; Anello, Giulia; Cavallotti, Carlo

    2015-01-01

    AIM To investigate possible age-related changes in glycosaminoglycans (GAGs) in the human cornea. The substances today called GAGs were previously referred to as mucopolysaccharides. METHODS Samples of human cornea were taken from 12 younger (age 21 ± 1.2) and 12 older (age 72 ± 1.6) male subjects. Samples were weighed, homogenized, and used for biochemical and molecular analyses. All the quantitative results were statistically analyzed. RESULTS The human cornea appears to undergo age-related changes, as evidenced by our biochemical and molecular results. The total GAG and hyaluronic acid counts were significantly higher in the younger subjects than in the older subjects. The sulfated heavy GAGs, such as chondroitin, dermatan, keratan, and heparan sulfate, were lower in the younger subjects than in the older subjects. DISCUSSION GAGs of the human cornea undergo numerous age-related changes. Their quantity is significantly altered in the elderly in comparison with younger subjects. GAGs play an important role in age-related diseases of the human cornea. PMID:25674020

  19. 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

  20. 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…

  1. APOLIPOPROTEIN E GENE AND EARLY AGE-RELATED MACULOPATHY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE: To examine the association between the apolipoprotein E (APOE) gene and early age-related maculopathy (ARM) in middle-aged persons. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Participants from the Atherosclerosis Risk in Communities Study (n = 10139; age range, 49-73 ye...

  2. 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...

  3. 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...

  4. 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…

  5. 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...

  6. Challenges in the Development of Therapy for Dry Age-Related Macular Degeneration.

    PubMed

    Wei, Cynthia X; Sun, Aixu; Yu, Ying; Liu, Qianyong; Tan, Yue-Qing; Tachibana, Isamu; Zeng, Hong; Wei, Ji-Ye

    2016-01-01

    Dry age-related macular degeneration (AMD), a multifactorial progressive degenerative disease of the retinal photoreceptors, pigmented epithelium and Bruch's membrane/choroid in central retina, causes visual impairment in millions of elderly people worldwide. The only available therapy for this disease is the over-the-counter (OTC) multi-vitamins plus macular xanthophyll (lutein/zeaxanthin) which attempts to block the damages of oxidative stress and ionizing blue light. Therefore development of dry AMD prescribed treatment is a pressing unmet medical need. However, this effort is currently hindered by many challenges, including an incomplete understanding of the mechanism of pathogenesis that leads to uncertain targets, confounded by not yet validated preclinical models and the difficulty to deliver the drugs to the posterior segment of the eye. Additionally, with slow disease progression and a less than ideal endpoint measurement method, clinical trials are necessarily large, lengthy and expensive. Increased commitment to research and development is an essential foundation for dealing with these problems. Innovations in clinical trials with novel endpoints, nontraditional study designs and the use of surrogate diseases might shorten the study time, reduce the patient sample size and consequently lower the budget for the development of the new therapies for the dry AMD. PMID:26427400

  7. Treatment of neovascular age-related macular degeneration in patients with diabetes

    PubMed Central

    Cummings, Michael; Cunha-Vaz, José

    2008-01-01

    The number of patients with type 2 diabetes continues to rise; an anticipated 300 million people will be affected by 2025. The immense social and economic burden of the condition is exacerbated by the initial asymptomatic nature of type 2 diabetes, resulting in a high prevalence of micro-and macrovascular complications at presentation. Diabetic retinopathy, one of the potential microvascular complications associated with diabetes, and neovascular age-related macular degeneration (AMD) are the two most frequent retinal degenerative diseases, and are responsible for the majority of blindness due to retinal disease. Both conditions predominantly affect the central macula, and are associated with the presence of retinal edema and an aggressive inflammatory repair process that accelerates disease progression. The associated retinal edema and the inflammatory repair process are directly involved in the breakdown of the blood-retinal barrier (BRB). Yet, the underlying alterations to the BRB caused by the diseases are very different. The coexistence of the two conditions appears to be relatively uncommon, suggesting that diabetes may even protect patients from developing neovascular AMD. However, it is thought that the inflammatory repair responses associated with diabetic retinopathy and neovascular AMD may be cumulative and, in patients affected by both, could result in chronic diffuse cystoid edema. Treatment considerations in such patients should, therefore, include the role of retinal edema and the increased susceptibility of patients with diabetes to potential systemic side effects associated with agents administered repeatedly for neovascular AMD treatment. PMID:19668728

  8. Age-related degeneration of the fornix in the human brain: a diffusion tensor imaging study.

    PubMed

    Jang, Sung Ho; Cho, Sang-Hyun; Chang, Min Cheol

    2011-02-01

    As a part of the Papez circuit, the fornix carries information on episodic memory. Several diffusion tensor imaging (DTI) studies have reported on changes in the fornix that occur with aging; however, these studies have been controversial. Using DTI, we attempted to investigate age-related changes of the fornix in the human brain. Sixty subjects (30 males, 30 females; mean age, 49.2 years; range, 20-78 years) were recruited. We categorized subjects into three groups, including young (20-39 years), middle-aged (40-59 years), and older (60-79 years) adults. DTIs were acquired using a sensitivity-encoding head coil on a 1.5 T. We divided the whole fornix into three parts (column, body, and crus) and constructed tractography for each part. We measured fractional anisotropy (FA), apparent diffusion coefficient (ADC), and tract number for each part of the fornix. In all three parts of the fornix, the FA value and tract number decreased, whereas ADC value increased with aging. In addition, a linear regression model was fitted to all three DTI parameters in each part of the fornix. Degenerative change of the fornix in the human brain appears to have occurred at a near constant rate from the 20s to the30s throughout the lifespan. PMID:21062216

  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. Scotopic Microperimetry in the Early Diagnosis of Age-Related Macular Degeneration: Preliminary Study

    PubMed Central

    Pescosolido, Nicola

    2014-01-01

    Background. Recent clinical studies have shown that, in some degenerative retinal diseases, like age-related macular degeneration (AMD), the sensitivity of the rods decreases more rapidly than the sensitivity of the cones. The aim of this study was to evaluate if there is a correlation between the presence of hard drusen at the macular level and the rod damage responsible for the reduction in scotopic retinal sensitivity in subjects at risk for AMD. Methods. The authors selected 24 subjects (14 men and 10 women) with an average age of 67.25 ± 5.7 years. Macular hard drusen were present in 50% of the subjects at the fundus oculi exam. The researchers evaluated the retinal sensitivity to light in mesopic and scotopic conditions of each subject with an MP-1 scotopic microperimeter (MP-1S). Results. In subjects with hard drusen in the fundus oculi examination, there was a statistically significant reduction in scotopic retinal sensitivity, while the mesopic retinal sensitivity was not compromised. Conclusion. This study revealed how the presence of hard drusen at the macular level is associated with a reduction in scotopic retinal sensitivity compared to a control group of healthy subjects. Retinal functionality in a scotopic setting examined with MP-1S could be useful in early diagnosis of AMD. PMID:25548774

  11. 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

  12. 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

  13. 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

  14. 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…

  15. Dietary compound score and risk of age-related macular degeneration in the Age-Related Eye Disease Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: Because foods provide many nutrients, which may interact with each other to modify risk for multifactorial diseases such as age-related macular degeneration (AMD), we sought to develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on AMD risk. Th...

  16. 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. PMID:26493766

  17. Using Current Data to Define New Approach in Age Related Macular Degeneration: Need to Accelerate Translational Research

    PubMed Central

    Anand, Akshay; Sharma, Kaushal; Chen, Wei; Sharma, Neel Kamal

    2014-01-01

    Age related macular degeneration (AMD) is one of the major retinal degenerative disease of ageing whose complex genetic basis remains undeciphered. The involvement of various other factors like mitochondrial genes, cytoskeletal proteins and the role of epigenetics has been described in this review. Several population based AMD genetic studies have been carried out worldwide. Despite the increased publication of reports, clinical translation still eludes this davastating disease. We suggest models to address roadblocks in clinical translation hoping that these would be beneficial to drive AMD research towards innovative biomarkers and therapeutics Therefore, addressing the need large autopsy studies and combining it with efficient use of bioinformatic tools, statistical modeling and probing SNP-biomarker association are key to time bound resolution of this disease. PMID:25132797

  18. Autophagy and heterophagy dysregulation leads to retinal pigment epithelium dysfunction and development of age-related macular degeneration

    PubMed Central

    Sinha, Debasish; Blasiak, Janusz; Kauppinen, Anu; Veréb, Zoltán; Salminen, Antero; Boulton, Michael E.; Petrovski, Goran

    2013-01-01

    Age-related macular degeneration (AMD) is a complex, degenerative and progressive eye disease that usually does not lead to complete blindness, but can result in severe loss of central vision. Risk factors for AMD include age, genetics, diet, smoking, oxidative stress and many cardiovascular-associated risk factors. Autophagy is a cellular housekeeping process that removes damaged organelles and protein aggregates, whereas heterophagy, in the case of the retinal pigment epithelium (RPE), is the phagocytosis of exogenous photoreceptor outer segments. Numerous studies have demonstrated that both autophagy and heterophagy are highly active in the RPE. To date, there is increasing evidence that constant oxidative stress impairs autophagy and heterophagy, as well as increases protein aggregation and causes inflammasome activation leading to the pathological phenotype of AMD. This review ties together these crucial pathological topics and reflects upon autophagy as a potential therapeutic target in AMD. PMID:23590900

  19. 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.

  20. Degenerative myelopathy in two Boxer dogs.

    PubMed

    Miller, A D; Barber, R; Porter, B F; Peters, R M; Kent, M; Platt, S R; Schatzberg, S J

    2009-07-01

    Degenerative myelopathy (DM) is a common, slowly progressive, debilitating disease reported in several dog breeds, including the German Shepherd Dog and Pembroke Welsh Corgi. Boxer dogs present occasionally for a thoracolumbar myelopathy for which no cause is identified on MRI or cerebrospinal fluid analysis. Despite a lack of a histologic description of DM in the Boxer in the veterinary literature, such dogs are presumed to have DM. Here we report 2 histologically confirmed cases of DM in the Boxer breed in which histologic studies disclosed marked degenerative changes in the spinal cord that were most prominent in the thoracic and cranial lumbar segments. Lesions consisted of myelin vacuolation and degeneration, myelophagocytosis, reactive astrocytosis, and ellipsoid formation most prominent in the lateral and ventral funiculi. We present a detailed histologic description of DM in the Boxer dog and compare it to DM in other purebred dogs. PMID:19276068

  1. Age-related percutaneous penetration part 1: skin factors.

    PubMed

    Konda, S; Meier-Davis, S R; Cayme, B; Shudo, J; Maibach, H I

    2012-05-01

    Changes in the skin that occur in the elderly may put them at increased risk for altered percutaneous penetration from pharmacotherapy along with potential adverse effects. Skin factors that may have a role in age-related percutaneous penetration include blood flow, pH, skin thickness, hair and pore density, and the content and structure of proteins, glycosaminoglycans (GAGs), water, and lipids. Each factor is examined as a function of increasing age along with its potential impact on percutaneous penetration. Additionally, topical drugs that successfully overcome the barrier function of the skin can still fall victim to cutaneous metabolism, thereby producing metabolites that may have increased or decreased activity. This overview discusses the current data and highlights the importance of further studies to evaluate the impact of skin factors in age-related percutaneous penetration. PMID:22622279

  2. 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

  3. Genetic and Environmental Underpinnings to Age-Related Ocular Diseases

    PubMed Central

    Seddon, Johanna M.

    2013-01-01

    Age-related macular degeneration (AMD), cataract, glaucoma and diabetic retinopathy are common causes of visual loss. Both environmental and genetic factors contribute to the development of these diseases. The modifiable factors related to some of these age-related and visually threatening diseases are smoking, obesity, and dietary factors, and a cardiovascular risk profile. Many common and a few rare genetic factors are associated with AMD. The role of genetic variants for the other diseases are less clear. Interactions between environmental, therapeutic, and genetic factors are being explored. Knowledge of genetic risk and environmental factors, especially for AMD, has grown markedly over the past 2.5 decades and has led to some sight-saving approaches in preventive management. PMID:24335064

  4. Idiom understanding in adulthood: examining age-related differences.

    PubMed

    Hung, Pei-Fang; Nippold, Marilyn A

    2014-03-01

    Idioms are figurative expressions such as hold your horses, kick the bucket, and lend me a hand, which commonly occur in everyday spoken and written language. Hence, the understanding of these expressions is essential for daily communication. In this study, we examined idiom understanding in healthy adults in their 20s, 40s, 60s and 80s (n=30 per group) to determine if performance would show an age-related decline. Participants judged their own familiarity with a set of 20 idioms, explained the meaning of each, described a situation in which the idiom could be used, and selected the appropriate interpretation from a set of choices. There was no evidence of an age-related decline on any tasks. Rather, the 60s group reported greater familiarity and offered better explanations than did the 20s group. Moreover, greater familiarity with idioms was associated with better understanding in adults. PMID:24405225

  5. Dietary Approaches that Delay Age-Related Diseases

    PubMed Central

    Everitt, Arthur V; Hilmer, Sarah N; Brand-Miller, Jennie C; Jamieson, Hamish A; Truswell, A Stewart; Sharma, Anita P; Mason, Rebecca S; Morris, Brian J; Le Couteur, David G

    2006-01-01

    Reducing food intake in lower animals such as the rat decreases body weight, retards many aging processes, delays the onset of most diseases of old age, and prolongs life. A number of clinical trials of food restriction in healthy adult human subjects running over 2–15 years show significant reductions in body weight, blood cholesterol, blood glucose, and blood pressure, which are risk factors for the development of cardiovascular disease and diabetes. Lifestyle interventions that lower energy balance by reducing body weight such as physical exercise can also delay the development of diabetes and cardiovascular disease. In general, clinical trials are suggesting that diets high in calories or fat along with overweight are associated with increased risk for cardiovascular disease, type 2 diabetes, some cancers, and dementia. There is a growing literature indicating that specific dietary constituents are able to influence the development of age-related diseases, including certain fats (trans fatty acids, saturated, and polyunsaturated fats) and cholesterol for cardiovascular disease, glycemic index and fiber for diabetes, fruits and vegetables for cardiovascular disease, and calcium and vitamin D for osteoporosis and bone fracture. In addition, there are dietary compounds from different functional foods, herbs, and neutraceuticals such as ginseng, nuts, grains, and polyphenols that may affect the development of age-related diseases. Long-term prospective clinical trials will be needed to confirm these diet—disease relationships. On the basis of current research, the best diet to delay age-related disease onset is one low in calories and saturated fat and high in wholegrain cereals, legumes, fruits and vegetables, and which maintains a lean body weight. Such a diet should become a key component of healthy aging, delaying age-related diseases and perhaps intervening in the aging process itself. Furthermore, there are studies suggesting that nutrition in childhood

  6. 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

  7. Dietary approaches that delay age-related diseases.

    PubMed

    Everitt, Arthur V; Hilmer, Sarah N; Brand-Miller, Jennie C; Jamieson, Hamish A; Truswell, A Stewart; Sharma, Anita P; Mason, Rebecca S; Morris, Brian J; Le Couteur, David G

    2006-01-01

    Reducing food intake in lower animals such as the rat decreases body weight, retards many aging processes, delays the onset of most diseases of old age, and prolongs life. A number of clinical trials of food restriction in healthy adult human subjects running over 2-15 years show significant reductions in body weight, blood cholesterol, blood glucose, and blood pressure, which are risk factors for the development of cardiovascular disease and diabetes. Lifestyle interventions that lower energy balance by reducing body weight such as physical exercise can also delay the development of diabetes and cardiovascular disease. In general, clinical trials are suggesting that diets high in calories or fat along with overweight are associated with increased risk for cardiovascular disease, type 2 diabetes, some cancers, and dementia. There is a growing literature indicating that specific dietary constituents are able to influence the development of age-related diseases, including certain fats (trans fatty acids, saturated, and polyunsaturated fats) and cholesterol for cardiovascular disease, glycemic index and fiber for diabetes, fruits and vegetables for cardiovascular disease, and calcium and vitamin D for osteoporosis and bone fracture. In addition, there are dietary compounds from different functional foods, herbs, and neutraceuticals such as ginseng, nuts, grains, and polyphenols that may affect the development of age-related diseases. Long-term prospective clinical trials will be needed to confirm these diet-disease relationships. On the basis of current research, the best diet to delay age-related disease onset is one low in calories and saturated fat and high in wholegrain cereals, legumes, fruits and vegetables, and which maintains a lean body weight. Such a diet should become a key component of healthy aging, delaying age-related diseases and perhaps intervening in the aging process itself. Furthermore, there are studies suggesting that nutrition in childhood and

  8. 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

  9. Age-related changes in the adaptability of neuromuscular output.

    PubMed

    Morrison, Steven; Sosnoff, Jacob J

    2009-05-01

    The aging process is associated with a general decline in biological function. One characteristic that researchers believe represents this diminished functioning of the aging neuromuscular system is increased physiological tremor. The present study is constructed to assess what age-related differences exist in the dynamics of tremor and forearm muscle activity under postural conditions in which the number of arm segments involved in the task was altered. The authors predicted that any alteration in the tremor or electromyographic (EMG) output of these two groups would provide a clearer understanding of the differential effects of aging or task dynamics on physiological function. Results reveal no age-related differences in finger tremor or forearm extensor muscle EMG activity under conditions in which participants were only required to extend their index finger against gravity. However, when participants had to hold their entire upper limb steady against gravity, the authors observed significant increases in forearm EMG activity, finger-tremor amplitude, power in the 8-12-Hz range, and signal regularity between the 2 age groups. The selective changes in signal regularity, EMG activity, and 8-12-Hz tremor amplitude under more challenging postural demands support the view that the age-related changes in neuromuscular dynamics are not fully elucidated when single task demands are utilized. PMID:19366659

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

    PubMed Central

    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. PMID:26348726

  11. Topography of age-related changes in sleep spindles.

    PubMed

    Martin, Nicolas; Lafortune, Marjolaine; Godbout, Jonathan; Barakat, Marc; Robillard, Rebecca; Poirier, Gaétan; Bastien, Célyne; Carrier, Julie

    2013-02-01

    Aging induces multiple changes to sleep spindles, which may hinder their alleged functional role in memory and sleep protection mechanisms. Brain aging in specific cortical regions could affect the neural networks underlying spindle generation, yet the topography of these age-related changes is currently unknown. In the present study, we analyzed spindle characteristics in 114 healthy volunteers aged between 20 and 73 years over 5 anteroposterior electroencephalography scalp derivations. Spindle density, amplitude, and duration were higher in young subjects than in middle-aged and elderly subjects in all derivations, but the topography of age effects differed drastically. Age-related decline in density and amplitude was more prominent in anterior derivations, whereas duration showed a posterior prominence. Age groups did not differ in all-night spindle frequency for any derivation. These results show that age-related changes in sleep spindles follow distinct topographical patterns that are specific to each spindle characteristic. This topographical specificity may provide a useful biomarker to localize age-sensitive changes in underlying neural systems during normal and pathological aging. PMID:22809452

  12. Hypermnesia: age-related differences between young and older adults.

    PubMed

    Widner, R L; Otani, H; Smith, A D

    2000-06-01

    Hypermnesia is a net improvement in memory performance that occurs across tests in a multitest paradigm with only one study session. Our goal was to identify possible age-related differences in hypermnesic recall. We observed hypermnesia for young adults using verbal (Experiment 1) as well as pictorial (Experiment 2) material, but no hypermnesia for older adults in either experiment. We found no age-related difference in reminiscence (Experiments 1 and 2), though there was a substantial difference in intertest forgetting (Experiments 1 and 2). Older, relative to young, adults produced more forgetting, most of which occurred between Tests 1 and 2 (Experiments 1 and 2). Furthermore, older, relative to young, adults produced more intrusions. We failed to identify a relationship between intrusions and intertest forgetting. We suggest that the age-related difference in intertest forgetting may be due to less efficient reinstatement of cues at test by older adults. The present findings reveal that intertest forgetting plays a critical role in hypermnesic recall, particularly for older adults. PMID:10946539

  13. Age-related differences in working memory updating components.

    PubMed

    Linares, Rocío; Bajo, M Teresa; Pelegrina, Santiago

    2016-07-01

    The aim of this study was to investigate possible age-related changes throughout childhood and adolescence in different component processes of working memory updating (WMU): retrieval, transformation, and substitution. A set of numerical WMU tasks was administered to four age groups (8-, 11-, 14-, and 21-year-olds). To isolate the effect of each of the WMU components, participants performed different versions of a task that included different combinations of the WMU components. The results showed an expected overall decrease in response times and an increase in accuracy performance with age. Most important, specific age-related changes in the retrieval component were found, demonstrating that the effect of retrieval on accuracy was larger in children than in adolescents or young adults. These findings indicate that the availability of representations from outside the focus of attention may change with age. Thus, the retrieval component of updating could contribute to the age-related changes observed in the performance of many updating tasks. PMID:26985577

  14. 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

  15. 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

  16. 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

  17. Age-related changes in mouse bone permeability.

    PubMed

    Rodriguez-Florez, Naiara; Oyen, Michelle L; Shefelbine, Sandra J

    2014-03-21

    The determination of lacunar-canalicular permeability is essential for understanding local fluid flow in bone, which may indicate how bone senses changes in the mechanical environment to regulate mechano-adaptation. The estimates of lacunar-canalicular permeability found in the literature vary by up to eight orders of magnitude, and age-related permeability changes have not been measured in non-osteonal mouse bone. The objective of this study is to use a poroelastic approach based on nanoindentation data to characterize lacunar-canalicular permeability in murine bone as a function of age. Nine wild type C57BL/6 mice of different ages (2, 7 and 12 months) were used. Three tibiae from each age group were embedded in epoxy resin, cut in half and indented in the longitudinal direction in the mid-cortex using two spherical fluid indenter tips (R=238 μm and 500 μm). Results suggest that the lacunar-canalicular intrinsic permeability of mouse bone decreases from 2 to 7 months, with no significant changes from 7 to 12 months. The large indenter tip imposed larger contact sizes and sampled larger ranges of permeabilities, particularly for the old bone. This age-related difference in the distribution was not seen for indents with the smaller radius tip. We conclude that the small tip effectively measured lacunar-canalicular permeability, while larger tip indents were influenced by vascular permeability. Exploring the age-related changes in permeability of bone measured by nanoindentation will lead to a better understanding of the role of fluid flow in mechano-transduction. This understanding may help indicate alterations in bone adaptation and remodeling. PMID:24433671

  18. Pathogenesis of Age-Related Bone Loss in Humans

    PubMed Central

    2013-01-01

    Background. Although data from rodent systems are extremely useful in providing insights into possible mechanisms of age-related bone loss, concepts evolving from animal models need to ultimately be tested in humans. Methods. This review provides an update on mechanisms of age-related bone loss in humans based on the author’s knowledge of the field and focused literature reviews. Results. Novel imaging, experimental models, biomarkers, and analytic techniques applied directly to human studies are providing new insights into the patterns of bone mass acquisition and loss as well as the role of sex steroids, in particular estrogen, on bone metabolism and bone loss with aging in women and men. These studies have identified the onset of trabecular bone loss at multiple sites that begins in young adulthood and remains unexplained, at least based on current paradigms of the mechanisms of bone loss. In addition, estrogen appears to be a major regulator of bone metabolism not only in women but also in men. Studies assessing mechanisms of estrogen action on bone in humans have identified effects of estrogen on RANKL expression by several different cell types in the bone microenvironment, a role for TNF-α and IL-1β in mediating effects of estrogen deficiency on bone, and possible regulation of the Wnt inhibitor, sclerostin, by estrogen. Conclusions. There have been considerable advances in our understanding of age-related bone loss in humans. However, there are also significant gaps in knowledge, particularly in defining cell autonomous changes in bone in human studies to test or validate concepts emerging from studies in rodents. Decision Editor: Luigi Ferrucci, MD, PhD PMID:22923429

  19. Age-Related Changes in Skeletal Muscle of Cattle.

    PubMed

    Costagliola, A; Wojcik, S; Pagano, T B; De Biase, D; Russo, V; Iovane, V; Grieco, E; Papparella, S; Paciello, O

    2016-03-01

    Sarcopenia, the age-related loss of muscle mass and strength, is a multifactorial condition that represents a major healthcare concern for the elderly population. Although its morphologic features have been extensively studied in humans, animal models, and domestic and wild animals, only a few reports about spontaneous sarcopenia exist in other long-lived animals. In this work, muscle samples from 60 healthy Podolica-breed old cows (aged 15-23 years) were examined and compared with muscle samples from 10 young cows (3-6 years old). Frozen sections were studied through standard histologic and histoenzymatic procedures, as well as by immunohistochemistry, immunofluorescence, and Western blot analysis. The most prominent age-related myopathic features seen in the studied material included angular fiber atrophy (90% of cases), mitochondrial alterations (ragged red fibers, 70%; COX-negative fibers, 60%), presence of vacuolated fibers (75%), lymphocytic (predominantly CD8+) inflammation (40%), and type II selective fiber atrophy (40%). Immunohistochemistry revealed increased expression of major histocompatibility complex I in 36 cases (60%) and sarcoplasmic accumulations of β-amyloid precursor protein-positive material in 18 cases (30%). In aged cows, muscle atrophy was associated with accumulation of myostatin. Western blot analysis indicated increased amount of both proteins-myostatin and β-amyloid precursor protein-in muscles of aged animals compared with controls. These findings confirm the presence of age-related morphologic changes in cows similar to human sarcopenia and underline the possible role of amyloid deposition and subsequent inflammation in muscle senescence. PMID:26869152

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

    PubMed

    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

  1. Age-related macular degeneration: Complement in action.

    PubMed

    van Lookeren Campagne, Menno; Strauss, Erich C; Yaspan, Brian L

    2016-06-01

    The complement system plays a key role in host-defense against common pathogens but must be tightly controlled to avoid inflammation and tissue damage. Polymorphisms in genes encoding two important negative regulators of the alternative complement pathway, complement factor H (CFH) and complement factor I (CFI), are associated with the risk for Age-Related Macular Degeneration (AMD), a leading cause of vision impairment in the ageing population. In this review, we will discuss the genetic basis of AMD and the potential impact of complement de-regulation on disease pathogenesis. Finally, we will highlight recent therapeutic approaches aimed at controlling complement activation in patients with AMD. PMID:26742632

  2. 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

  3. The role of mitochondria in age-related hearing loss.

    PubMed

    Chen, Hengchao; Tang, Jianguo

    2014-02-01

    Age-related hearing loss (ARHL), the hearing loss associated with aging, is a vital problem in present society. The severity of hearing loss is possibly associated with the degeneration of cochlear cells. Mitochondria play a key role in the energy supply, cellular redox homeostasis, signaling, and regulation of programmed cell death. In this review, we focus on the central role of mitochondria in ARHL. The mitochondrial redox imbalance and mitochondrial DNA mutation might collaboratively involve in the process of cochlear senescence in response to the aging stress. Subsequent responses, including alteration of mitochondrial biogenesis, mitophagy, apoptosis and paraptosis, participate in the aging process from different respects. PMID:24202185

  4. [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

  5. [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

  6. 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

  7. 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

  8. 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

  9. MR imaging of degenerative disc disease.

    PubMed

    Farshad-Amacker, Nadja A; Farshad, Mazda; Winklehner, Anna; Andreisek, Gustav

    2015-09-01

    Magnet resonance imaging (MRI) is the most commonly used imaging modality for diagnosis of degenerative disc disease (DDD). Lack of precise observations and documentation of aspects within the complex entity of DDD might partially be the cause of poor correlation of radiographic findings to clinical symptoms. This literature review summarizes the current knowledge on MRI in DDD and outlines the diagnostic limitations. The review further sensitizes the reader toward awareness of potentially untended aspects of DDD and the interaction of DDD and endplate changes. A summary of the available classifications for DDD is provided. PMID:26094867

  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. Parainflammation, chronic inflammation and age-related macular degeneration

    PubMed Central

    Chen, Mei; Xu, Heping

    2016-01-01

    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 due to its unique anatomical and physiological 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, undergo low levels of activation (para-inflammation). In many cases, this para-inflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration (AMD), this para-inflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal para-inflammation include genetic predisposition, environmental risk factors and old age. Dysregulated para-inflammation (chronic inflammation) in AMD damages the blood retina barrier (BRB), 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 AMD, and explores the difference between beneficial para-inflammation and the detrimental chronic inflammation in the context of AMD. PMID:26292978

  12. Oxidative stress and age-related neuronal deficits.

    PubMed

    Joseph, J A; Denisova, N; Villalobos-Molina, R; Erat, S; Strain, J

    1996-01-01

    Research from our laboratory has indicated that the loss of sensitivity that occurs in several receptor systems as a function of age may be an index of an increasing inability to respond to oxidative stress (OS). This loss occurs partially as a result of altered signal transduction (ST). Assessments have involved determining the nature of age-related reductions in oxotremorine enhancement of K(+)-evoked dopamine release (K(+)-ERDA) from superfused striatal slices. Using this model, we have found that 1. Reductions can be restored with in vivo administration of the free-radical trapping agent, N-tert-butyl-alpha-phenylnitrone (PBN); 2. Decrements in DA release induced by NO or H2O2 from striatal slices from both young and old animals could be restored with alpha-tocopherol or PBN; 3. ST decrements, such as those seen in aging, could be induced with radiation exposure; and 4. Pre-incubation of the striatal slices with cholesterol decreased subsequent deleterious effects of NO or OH. on DA release. Thus, cholesterol, which increases in neuronal membranes as a function of age, may function as a potent antioxidant and protectant against neuronal damage. These results suggest that therapeutic efforts to restore cognitive deficits in aging and age-related disease might begin with antioxidant reversal of ST decrements. PMID:8871939

  13. Fertility preservation for age-related fertility decline.

    PubMed

    Stoop, Dominic; Cobo, Ana; Silber, Sherman

    2014-10-01

    Cryopreservation of eggs or ovarian tissue to preserve fertility for patients with cancer has been studied since 1994 with R G Gosden's paper describing restoration of fertility in oophorectomised sheep, and for decades previously by others in smaller mammals. Clinically this approach has shown great success. Many healthy children have been born from eggs cryopreserved with the Kuwayama egg vitrification technique for non-medical (social) indications, but until now very few patients with cancer have achieved pregnancy with cryopreserved eggs. Often, oncologists do not wish to delay cancer treatment while the patient goes through multiple ovarian stimulation cycles to retrieve eggs, and the patient can only start using the oocytes after full recovery from cancer. Ovarian stimulation and egg retrieval is not a barrier for patients without cancer who wish to delay childbearing, which makes oocyte cryopreservation increasingly popular to overcome an age-related decline in fertility. Cryopreservation of ovarian tissue is an option if egg cryopreservation is ruled out. More than 35 babies have been born so far with cryopreserved ovarian tissue in patients with cancer who have had a complete return of hormonal function, and fertility to baseline. Both egg and ovarian tissue cryopreservation might be ready for application to the preservation of fertility not only in patients with cancer but also in countering the increasing incidence of age-related decline in female fertility. PMID:25283572

  14. Age-related mutations and chronic myelomonocytic leukemia.

    PubMed

    Mason, C C; Khorashad, J S; Tantravahi, S K; Kelley, T W; Zabriskie, M S; Yan, D; Pomicter, A D; Reynolds, K R; Eiring, A M; Kronenberg, Z; Sherman, R L; Tyner, J W; Dalley, B K; Dao, K-H; Yandell, M; Druker, B J; Gotlib, J; O'Hare, T; Deininger, M W

    2016-04-01

    Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy nearly confined to the elderly. Previous studies to determine incidence and prognostic significance of somatic mutations in CMML have relied on candidate gene sequencing, although an unbiased mutational search has not been conducted. As many of the genes commonly mutated in CMML were recently associated with age-related clonal hematopoiesis (ARCH) and aged hematopoiesis is characterized by a myelomonocytic differentiation bias, we hypothesized that CMML and aged hematopoiesis may be closely related. We initially established the somatic mutation landscape of CMML by whole exome sequencing followed by gene-targeted validation. Genes mutated in ⩾10% of patients were SRSF2, TET2, ASXL1, RUNX1, SETBP1, KRAS, EZH2, CBL and NRAS, as well as the novel CMML genes FAT4, ARIH1, DNAH2 and CSMD1. Most CMML patients (71%) had mutations in ⩾2 ARCH genes and 52% had ⩾7 mutations overall. Higher mutation burden was associated with shorter survival. Age-adjusted population incidence and reported ARCH mutation rates are consistent with a model in which clinical CMML ensues when a sufficient number of stochastically acquired age-related mutations has accumulated, suggesting that CMML represents the leukemic conversion of the myelomonocytic-lineage-biased aged hematopoietic system. PMID:26648538

  15. Age-related Cardiac Disease Model of Drosophila

    PubMed Central

    Ocorr, Karen; Akasaka, Takeshi; Bodmer, Rolf

    2007-01-01

    We have begun to study the genetic basis of deterioration of cardiac function in the fruit fly Drosophila melanogaster as an age-related cardiac disease model. For this purpose we have developed heart function assays in Drosophila and found that the fly's cardiac performance, as that of the human heart, deteriorates with age: aging fruit flies exhibit a progressive increase in electrical pacing-induced heart failure as well as in arrhythmias. The insulin receptor and associated pathways have a dramatic and heart-autonomous influence on age-related cardiac performance in flies, suggestive of potentially similar mechanisms in regulating cardiac aging in vertebrates. Compromised KCNQ and KATP ion channel functions also seem to contribute to the decline in heart performance in aging flies, suggesting that the corresponding vertebrate gene functions may similarly decline with age, in addition to their conserved role in protecting against arrhythmias and hypoxia/ischemia, respectively. The fly heart is thus emerging as a promising genetic model for studying the age-dependent decline in organ function. PMID:17125816

  16. Age-related differences in electroencephalogram connectivity and network topology.

    PubMed

    Knyazev, Gennady G; Volf, Nina V; Belousova, Ludmila V

    2015-05-01

    To better understand age-related differences in brain function and behavior, connectivity between brain regions was estimated from electroencephalogram source time series in eyes closed versus eyes open resting condition. In beta band, decrease of connectivity upon eyes opening was more pronounced in younger than in older participants. The extent of this decrease was associated with reaction time in attention tasks, and this relationship was fully mediated by participants' age, implying that physiological processes, which lead to age-related slowing, include changes in beta reactivity. Graph-theoretical analysis showed a decrease of modularity and clustering in beta and gamma band networks in older adults, implying that age makes brain networks more random. The overall number of nodes identified as hubs in posterior cortical regions decreased in older participants. At the same time, increase of connectedness of anterior nodes, probably reflecting compensatory activation of the anterior attentional system, was observed in beta-band network of older adults. These findings show that normal aging mostly affects interactions in beta band, which are probably involved in attentional processes. PMID:25766772

  17. 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.

  18. 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

  19. Age-related differences in moral identity across adulthood.

    PubMed

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

    2016-06-01

    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 65 years (148 women, M = 33.5 years, SD = 16.9) and a modification of the Good Self-Assessment, it was demonstrated that mean-level of moral identity (averaged across the contexts of family, school/work, and community) significantly increased in the adult years, whereas cross-context differentiation showed a nonlinear trend peaking at the age of 25 years. Value-orientations that define individuals' moral identity shifted so that self-direction and rule-conformity became more important with age. Age-related differences in moral identity were associated with, but not fully attributable to changes in personality traits. Overall, findings suggest that moral identity development is a lifelong process that starts in adolescence but expands well into middle age. (PsycINFO Database Record PMID:27124654

  20. 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

  1. Stem cell treatment of degenerative eye disease☆

    PubMed Central

    Mead, Ben; Berry, Martin; Logan, Ann; Scott, Robert A.H.; Leadbeater, Wendy; Scheven, Ben A.

    2015-01-01

    Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC). Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment. PMID:25752437

  2. Inflammatory networks in ageing, age-related diseases and longevity.

    PubMed

    Vasto, Sonya; Candore, Giuseppina; Balistreri, Carmela Rita; Caruso, Marco; Colonna-Romano, Giuseppina; Grimaldi, Maria Paola; Listi, Florinda; Nuzzo, Domenico; Lio, Domenico; Caruso, Calogero

    2007-01-01

    Inflammation is considered a response set by the tissues in response to injury elicited by trauma or infection. It is a complex network of molecular and cellular interactions that facilitates a return to physiological homeostasis and tissue repair. The individual response against infection and trauma is also determined by gene variability. Ageing is accompanied by chronic low-grade inflammation state clearly showed by 2-4-fold increase in serum levels of inflammatory mediators. A wide range of factors has been claimed to contribute to this state; however, the most important role seems to be played by the chronic antigenic stress, which affects immune system thorough out life with a progressive activation of macrophages and related cells. This pro-inflammatory status, interacting with the genetic background, potentially triggers the onset of age-related inflammatory diseases as atherosclerosis. Thus, the analysis of polymorphisms of the genes that are key nodes of the natural immunity response might clarify the patho-physiology of age-related inflammatory diseases as atherosclerosis. On the other hand, centenarians are characterized by marked delay or escape from age-associated diseases that, on average, cause mortality at earlier ages. In addition, centenarian offspring have increased likelihood of surviving to 100 years and show a reduced prevalence of age-associated diseases, as cardiovascular disease (CVD) and less prevalence of cardiovascular risk factors. So, genes involved in CVD may play an opposite role in human longevity. Thus, the model of centenarians can be used to understand the role of these genes in successful and unsuccessful ageing. Accordingly, we report the results of several studies in which the frequencies of pro-inflammatory alleles were significantly higher in patients affected by infarction and lower in centenarians whereas age-related controls displayed intermediate values. These findings point to a strong relationship between the genetics

  3. Progressive Age-Related Changes Similar to Age-Related Macular Degeneration in a Transgenic Mouse Model

    PubMed Central

    Rakoczy, Piroska Elizabeth; Zhang, Dan; Robertson, Terry; Barnett, Nigel L.; Papadimitriou, John; Constable, Ian Jeffrey; Lai, Chooi-May

    2002-01-01

    Age-related macular degeneration (AMD) is the major cause of blindness in the developed world. Its pathomechanism is unknown and its late onset, complex genetics and strong environmental components have all hampered investigations. Here we demonstrate the development of an animal model for AMD that reproduces features associated with geographic atrophy; a transgenic mouse line (mcd/mcd) expressing a mutated form of cathepsin D that is enzymatically inactive thus impairing processing of phagocytosed photoreceptor outer segments in the retinal pigment epithelial (RPE) cells. Pigmentary changes indicating RPE cell atrophy and a decreased response to flash electroretinograms were observed in 11- to 12-month-old mcd/mcd mice. Histological studies showed RPE cell proliferation, photoreceptor degeneration, shortening of photoreceptor outer segments, and accumulation of immunoreactive photoreceptor breakdown products in the RPE cells. An accelerated photoreceptor cell death was detected in 12-month-old mcd/mcd mice. Transmission electron microscopy demonstrated presence of basal laminar and linear deposits that are considered to be the hallmarks of AMD. Small hard drusen associated with human age-related maculopathy were absent in the mcd/mcd mouse model at the ages analyzed. In summary, this model presents several features of AMD, thus providing a valuable tool for investigating the underlying biological processes and pathomechanism of AMD. PMID:12368224

  4. 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.

  5. 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

  6. Modulation of cell death in age-related diseases.

    PubMed

    Tezil, Tugsan; Basaga, Huveyda

    2014-01-01

    Aging is a stage of life of all living organisms. According to the free-radical theory, aging cells gradually become unable to maintain cellular homeostasis due to the adverse effects of reactive oxygen species (ROS). ROS can cause irreversible DNA mutations, protein and lipid damage which are increasingly accumulated in the course of time if cells could not overcome these effects by the antioxidant defence system. Accrued damaged molecules in cells may either induce cellular death or contribute to develop various pathologies. Hence, programmed cell death mechanisms, apoptosis and autophagy, play a vital role in the aging process. Although they are strictly controlled by various interconnected signalling pathways, alterations in their regulations may contribute to severe pathologies including cancer, Alzheimer's and Parkinson's diseases. In this review, we summarized our current understanding and hypotheses regarding oxidative stress and age-related dysregulation of cell death signalling pathways. PMID:24079770

  7. 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

  8. Complement Factor H Polymorphism in Age-Related Macular Degeneration

    PubMed Central

    Klein, Robert J.; Zeiss, Caroline; Chew, Emily Y.; Tsai, Jen-Yue; Sackler, Richard S.; Haynes, Chad; Henning, Alice K.; SanGiovanni, John Paul; Mane, Shrikant M.; Mayne, Susan T.; Bracken, Michael B.; Ferris, Frederick L.; Ott, Jurg; Barnstable, Colin; Hoh., Josephine

    2006-01-01

    Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene (CFH) is strongly associated with AMD (nominal P value <10−7). In individuals homozygous for the risk allele, the likelihood of AMD is increased by a factor of 7.4 (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyrosine-histidine change at amino acid 402. This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies. PMID:15761122

  9. Retinal phagocytes in age-related macular degeneration

    PubMed Central

    Kim, Soo-Young

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in industrial countries. Vision loss caused by AMD results from geographic atrophy (dry AMD) and/or choroidal neovascularization (wet AMD). Presently, the etiology and pathogenesis of AMD is not fully understood and there is no effective treatment. Oxidative stress in retinal pigment epithelial (RPE) cells is considered to be one of the major factors contributing to the pathogenesis of AMD. Also retinal glia, as scavengers, are deeply related with diseases and could play a role. Therefore, therapeutic approaches for microglia and Müller glia, as well as RPE, may lead to new strategies for AMD treatment. This review summarizes the pathological findings observed in RPE cells, microglia and Müller glia of AMD murine models. PMID:26052551

  10. Treatment of neovascular age-related macular degeneration: Current therapies

    PubMed Central

    Augustin, Albert J; Scholl, Stefan; Kirchhof, Janna

    2009-01-01

    Choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) is now the leading cause of blindness and severe vision loss among people over the age of 40 in the Western world. Its prevalence is certain to increase substantially as the population ages. Treatments currently available for the disease include laser photocoagulation, verteporfin photodynamic therapy, and intravitreal injections of corticosteroids and anti-angiogenic agents. Many studies have reported the benefits of each of these treatments, although none is without its risks. No intervention actually cures AMD, nor the neovascularization associated with it. However, its symptoms are treated with varying degrees of success. Some treatments stabilize or arrest the progress of the disease. Others have been shown to reverse some of the damage that has already been done. These treatments can even lead to visual improvement. This paper will review the major classes of drugs and therapies designed to treat this condition. PMID:19668562

  11. 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

  12. 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

  13. 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. PMID:15761121

  14. Age-Related Macular Degeneration: Insights into Inflammatory Genes

    PubMed Central

    Ragazzo, Michele; Missiroli, Filippo; Borgiani, Paola; Angelucci, Francesco; Marsella, Luigi Tonino; Cusumano, Andrea; Novelli, Giuseppe; Ricci, Federico; Giardina, Emiliano

    2014-01-01

    Age-related macular degeneration (AMD) is a progressive neurodegenerative disease that affects approximately 8.7% of elderly people worldwide (>55 years old). AMD is characterized by a multifactorial aetiology that involves several genetic and environmental risk factors (genes, ageing, smoking, family history, dietary habits, oxidative stress, and hypertension). In particular, ageing and cigarette smoking (including oxidative compounds and reactive oxygen species) have been shown to significantly increase susceptibility to the disease. Furthermore, different genes (CFH, CFI, C2, C3, IL-6, IL-8, and ARMS2) that play a crucial role in the inflammatory pathway have been associated with AMD risk. Several genetic and molecular studies have indicated the participation of inflammatory molecules (cytokines and chemokines), immune cells (macrophages), and complement proteins in the development and progression of the disease. Taking into consideration the genetic and molecular background, this review highlights the genetic role of inflammatory genes involved in AMD pathogenesis and progression. PMID:25478207

  15. 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. (PsycINFO Database Record PMID:26372058

  16. Gene Therapies for Neovascular Age-Related Macular Degeneration.

    PubMed

    Pechan, Peter; Wadsworth, Samuel; Scaria, Abraham

    2015-07-01

    Pathological neovascularization is a key component of the neovascular form (also known as the wet form) of age-related macular degeneration (AMD) and proliferative diabetic retinopathy. Several preclinical studies have shown that antiangiogenesis strategies are effective for treating neovascular AMD in animal models. Vascular endothelial growth factor (VEGF) is one of the main inducers of ocular neovascularization, and several clinical trials have shown the benefits of neutralizing VEGF in patients with neovascular AMD or diabetic macular edema. In this review, we summarize several preclinical and early-stage clinical trials with intraocular gene therapies, which have the potential to reduce or eliminate the repeated intravitreal injections that are currently required for the treatment of neovascular AMD. PMID:25524721

  17. 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

  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. PMID:25215609

  19. Inflammation and its role in age-related macular degeneration.

    PubMed

    Kauppinen, Anu; Paterno, Jussi J; Blasiak, Janusz; Salminen, Antero; Kaarniranta, Kai

    2016-05-01

    Inflammation is a cellular response to factors that challenge the homeostasis of cells and tissues. Cell-associated and soluble pattern-recognition receptors, e.g. Toll-like receptors, inflammasome receptors, and complement components initiate complex cellular cascades by recognizing or sensing different pathogen and damage-associated molecular patterns, respectively. Cytokines and chemokines represent alarm messages for leukocytes and once activated, these cells travel long distances to targeted inflamed tissues. Although it is a crucial survival mechanism, prolonged inflammation is detrimental and participates in numerous chronic age-related diseases. This article will review the onset of inflammation and link its functions to the pathogenesis of age-related macular degeneration (AMD), which is the leading cause of severe vision loss in aged individuals in the developed countries. In this progressive disease, degeneration of the retinal pigment epithelium (RPE) results in the death of photoreceptors, leading to a loss of central vision. The RPE is prone to oxidative stress, a factor that together with deteriorating functionality, e.g. decreased intracellular recycling and degradation due to attenuated heterophagy/autophagy, induces inflammation. In the early phases, accumulation of intracellular lipofuscin in the RPE and extracellular drusen between RPE cells and Bruch's membrane can be clinically detected. Subsequently, in dry (atrophic) AMD there is geographic atrophy with discrete areas of RPE loss whereas in the wet (exudative) form there is neovascularization penetrating from the choroid to retinal layers. Elevations in levels of local and systemic biomarkers indicate that chronic inflammation is involved in the pathogenesis of both disease forms. PMID:26852158

  20. Age-related oxidative modifications of transthyretin modulate its amyloidogenicity

    PubMed Central

    Zhao, Lei; Buxbaum, Joel N; Reixach, Natàlia

    2013-01-01

    The transthyretin amyloidoses are diseases of protein misfolding characterized by the extracellular deposition of fibrils and other aggregates of the homotetrameric protein transthyretin (TTR) in peripheral nerves, heart and other tissues. Age is the major risk factor for the development of these diseases. We hypothesized that an age-associated increase in protein oxidation could be involved in the onset of the senile forms of the TTR amyloidoses. To test this hypothesis we have produced and characterized relevant age-related oxidative modifications of wild type (WT) and the Val122Ile (V122I) TTR variant, both involved in cardiac TTR deposition in the elderly. Our studies show that methionine/cysteine oxidized TTR and carbonylated TTR either from WT or the V122I variant, are thermodynamically less stable than their non-oxidized counterparts. Moreover, carbonylated WT and carbonylated V122I TTR have a greater propensity to form aggregates and fibrils than WT and V122I TTR, respectively, at physiologically attainable pH. It is well known that TTR tetramer dissociation, the limiting step for aggregation and amyloid fibril formation, can be prevented by small molecules that bind the TTR tetramer interface. Here, we report that carbonylated WT TTR is less amenable to resveratrol-mediated tetramer stabilization than WT TTR. All the oxidized forms of TTR tested are cytotoxic to a human cardiomyocyte cell line known to be a target for cardiac-specific TTR variants. Overall these studies demonstrate that age-related oxidative modifications of TTR can contribute to the onset of the senile forms of the TTR amyloidoses. PMID:23414091

  1. Age-related oxidative modifications of transthyretin modulate its amyloidogenicity.

    PubMed

    Zhao, Lei; Buxbaum, Joel N; Reixach, Natàlia

    2013-03-19

    The transthyretin amyloidoses are diseases of protein misfolding characterized by the extracellular deposition of fibrils and other aggregates of the homotetrameric protein transthyretin (TTR) in peripheral nerves, heart, and other tissues. Age is the major risk factor for the development of these diseases. We hypothesized that an age-associated increase in the level of protein oxidation could be involved in the onset of the senile forms of the TTR amyloidoses. To test this hypothesis, we have produced and characterized relevant age-related oxidative modifications of the wild type (WT) and the Val122Ile (V122I) TTR variant, both involved in cardiac TTR deposition in the elderly. Our studies show that methionine/cysteine-oxidized TTR and carbonylated TTR from either the WT or the V122I variant are thermodynamically less stable than their nonoxidized counterparts. Moreover, carbonylated WT and carbonylated V122I TTR have a stronger propensity to form aggregates and fibrils than WT and V122I TTR, respectively, at physiologically attainable pH values. It is well-known that TTR tetramer dissociation, the limiting step for aggregation and amyloid fibril formation, can be prevented by small molecules that bind the TTR tetramer interface. Here, we report that carbonylated WT TTR is less amenable to resveratrol-mediated tetramer stabilization than WT TTR. All the oxidized forms of TTR tested are cytotoxic to a human cardiomyocyte cell line known to be a target for cardiac-specific TTR variants. Overall, these studies demonstrate that age-related oxidative modifications of TTR can contribute to the onset of the senile forms of the TTR amyloidoses. PMID:23414091

  2. 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

  3. Age-related changes in the tiger salamander retina.

    PubMed

    Townes-Anderson, E; Colantonio, A; St Jules, R S

    1998-05-01

    Tiger salamanders have been used in visual science because of the large size of their cells and the ease of preparation and maintenance of in vitro retinal preparations. We have found that salamanders over 27 cm in length show a variety of visual abnormalities. Compared to smaller animals (15-23 cm), large animals exhibited a decrease in visual responses determined by tests of the optomotor reflex. Small animals responded correctly an average of 84.5% of the time in visual testing at three light levels compared to an average of 68.4% for the large animals with the poorest visual performance at the lowest level of illumination. In addition, large animals contained (i) histological degeneration of the outer retina, in particular, loss and disruption of outer segments and abnormalities of the retinal pigmented epithelium, (ii) loss of cells, including photoreceptors, by apoptosis as evaluated with the TUNEL technique, and (iii) an increase in the number of macrophages and lymphocytes within the retina as determined by morphological examination. These histological changes were present in all large animals and all quadrants of their retinas. In contrast, small animals showed virtually no retinal degeneration, no TUNEL-positive cells, and few immune-like cells in the retina. Since large animals are also older animals. the visual changes are age-related. Loss of visual function and histological degeneration in the outer retina also typify aged human eyes. Thus, we propose that large salamanders serve as an animal model for age-related retinal degeneration. In addition to providing a source of aging retina that is readily accessible to experimental manipulation, the salamander provides a pigmented retina with a mixed (2:1, rod:cone) population of photoreceptors, similar to the degeneration-prone parafoveal region of the human eye. PMID:9631666

  4. 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

  5. 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. PMID:25866202

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

    PubMed Central

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

    2015-01-01

    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. PMID:25866202

  7. 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

  8. 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. PMID:26944368

  9. 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. PMID:24243499

  10. [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. PMID:26149505

  11. 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

  12. Anabolic factors in degenerative joint disease.

    PubMed

    Sandell, L J

    2007-02-01

    While a great deal of information is available on the cellular and molecular biology of cartilage degradation, less is known about anabolism in normal cartilage and degenerating cartilage. A consistent amount of evidence is now available on the neo-synthesis of matrix molecules and enzymes in OA: the entire cell metabolism appears to be increased leading to the hypothesis that chondrocytes in OA are actually "activated". This chapter will focus on anabolic events that are now known to occur in articular cartilage. We will begin to view articular cartilage as a complex three-dimensional tissue in which local events may be different. We will also be interested in viewing the development of degenerative arthritis as a continuum from functionally normal tissue to degeneration. PMID:17305513

  13. 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

  14. Role of macrophage migration inhibitory factor in age-related lung disease.

    PubMed

    Sauler, Maor; Bucala, Richard; Lee, Patty J

    2015-07-01

    The prevalence of many common respiratory disorders, including pneumonia, chronic obstructive lung disease, pulmonary fibrosis, and lung cancer, increases with age. Little is known of the host factors that may predispose individuals to such diseases. Macrophage migration inhibitory factor (MIF) is a potent upstream regulator of the immune system. MIF is encoded by variant alleles that occur commonly in the population. In addition to its role as a proinflammatory cytokine, a growing body of literature demonstrates that MIF influences diverse molecular processes important for the maintenance of cellular homeostasis and may influence the incidence or clinical manifestations of a variety of chronic lung diseases. This review highlights the biological properties of MIF and its implication in age-related lung disease. PMID:25957294

  15. Genetic and Functional Dissection of HTRA1 and LOC387715 in Age-Related Macular Degeneration

    PubMed Central

    Zeng, Jiexi; Lu, Fang; Sun, Xufang; Zhao, Chao; Wang, Kevin; Davey, Lisa; Chen, Haoyu; London, Nyall; Muramatsu, Daisuke; Salasar, Francesca; Carmona, Ruben; Kasuga, Daniel; Wang, Xiaolei; Bedell, Matthew; Dixie, Manjuxia; Zhao, Peiquan; Yang, Ruifu; Gibbs, Daniel; Liu, Xiaoqi; Li, Yan; Li, Cai; Li, Yuanfeng; Campochiaro, Betsy; Constantine, Ryan; Zack, Donald J.; Campochiaro, Peter; Fu, Yinbin; Li, Dean Y.; Katsanis, Nicholas; Zhang, Kang

    2010-01-01

    A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD) and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del) that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X) in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits. PMID:20140183

  16. 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

  17. [Impact of age-related cataract on regulation of circadian rhythm in elderly].

    PubMed

    Wang, M S; Liu, M Y; Dong, X R; Wang, W

    2016-04-11

    This review presented an introduction of the visual pathway related circadian rhythm regulation system: the intrinsically photosensitive retinal ganglion cells-suprachiasmatic nucleus-pineal gland-melatonin axis, and discussed the impact of light with different wave length and irradiation received by retina on circadian rhythm and sleep habit. A hypothesis was proposed consequently that the high morbidity of sleep disorder in elderly might be partially attributable to the long-term blue light blocking status induced by age-related cataract. A number of relative literatures were reviewed and a novel research direction was advanced on improving circadian rhythm and sleep condition in elderly based on the current knowledge. (Chin J Ophthalmol, 2016, 52: 309-314). PMID:27094070

  18. Oxidative Stresses and Mitochondrial Dysfunction in Age-Related Hearing Loss

    PubMed Central

    Fujimoto, Chisato

    2014-01-01

    Age-related hearing loss (ARHL), the progressive loss of hearing associated with aging, is the most common sensory disorder in the elderly population. The pathology of ARHL includes the hair cells of the organ of Corti, stria vascularis, and afferent spiral ganglion neurons as well as the central auditory pathways. Many studies have suggested that the accumulation of mitochondrial DNA damage, the production of reactive oxygen species, and decreased antioxidant function are associated with subsequent cochlear senescence in response to aging stress. Mitochondria play a crucial role in the induction of intrinsic apoptosis in cochlear cells. ARHL can be prevented in laboratory animals by certain interventions, such as caloric restriction and supplementation with antioxidants. In this review, we will focus on previous research concerning the role of the oxidative stress and mitochondrial dysfunction in the pathology of ARHL in both animal models and humans and introduce concepts that have recently emerged regarding the mechanisms of the development of ARHL. PMID:25110550

  19. Age-related thermal response: the cellular resilience of juveniles.

    PubMed

    Clark, M S; Thorne, M A S; Burns, G; Peck, L S

    2016-01-01

    Understanding species' responses to environmental challenges is key to predicting future biodiversity. However, there is currently little data on how developmental stages affect responses and also whether universal gene biomarkers to environmental stress can be identified both within and between species. Using the Antarctic clam, Laternula elliptica, as a model species, we examined both the tissue-specific and age-related (juvenile versus mature adult) gene expression response to acute non-lethal warming (12 h at 3 °C). In general, there was a relatively muted response to this sub-lethal thermal challenge when the expression profiles of treated animals, of either age, were compared with those of 0 °C controls, with none of the "classical" stress response genes up-regulated. The expression profiles were very variable between the tissues of all animals, irrespective of age with no single transcript emerging as a universal biomarker of thermal stress. However, when the expression profiles of treated animals of the different age groups were directly compared, a very different pattern emerged. The profiles of the younger animals showed significant up-regulation of chaperone and antioxidant transcripts when compared with those of the older animals. Thus, the younger animals showed evidence of a more robust cellular response to warming. These data substantiate previous physiological analyses showing a more resilient juvenile population. PMID:26364303

  20. Ocular Surface Temperature in Age-Related Macular Degeneration

    PubMed Central

    Sodi, Andrea; Giacomelli, Giovanni; Corvi, Andrea; Menchini, Ugo

    2014-01-01

    Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD) eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The ocular surface temperature (OST) of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA) test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value >0.272). OST in AMD patients was significantly lower than in controls (P > 0.05). Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD. PMID:25436140

  1. 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

  2. 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

  3. Mathematical morphologic analysis of aging-related epidermal changes.

    PubMed

    Moragas, A; Castells, C; Sans, M

    1993-04-01

    Fractographic techniques based on mathematical morphology were used to study aging-related epidermal changes in abdominal skin samples obtained from 96 autopsy cases. Three linear roughness indices were evaluated for the rete peg profile and the shrinkage effect on the basal layer and interface between the granular and horny layers. Elderly subjects had a 36.3% decrease in rete peg-related roughness index when compared with younger subjects. This roughness index has been corrected, with shrinkage due to skin elasticity taken into account. For females, fitting of a logistic decay function yielded a curve with right and left asymptotes and a steeper descent between 40 and 60 years. Half value time--i.e., the time when half rete peg profile flattening occurred--was 46.8 years. In contrast, males showed almost monotonical decay. Epidermal thickness measured between rete pegs showed the same exponential decline for both sexes, with values from 22.6 to 11.4 microns. Skin shrinkage in elderly subjects decreased 22% in superficial layers and only 6% in the lower epidermis. In both cases shrinkage had a linear relation with age, and no sex differences were found. PMID:8318130

  4. 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

  5. Pachychoroid neovasculopathy and age-related macular degeneration

    PubMed Central

    Miyake, Masahiro; Ooto, Sotaro; Yamashiro, Kenji; Takahashi, Ayako; Yoshikawa, Munemitsu; Akagi-Kurashige, Yumiko; Ueda-Arakawa, Naoko; Oishi, Akio; Nakanishi, Hideo; Tamura, Hiroshi; Tsujikawa, Akitaka; Yoshimura, Nagahisa

    2015-01-01

    Pachychoroid neovasculopathy is a recently proposed clinical entity of choroidal neovascularization (CNV). As it often masquerades as neovascular age-related macular degeneration (AMD), it is currently controversial whether pachychoroid neovasculopathy should be distinguished from neovascular AMD. This is because its characteristics have yet to be well described. To estimate the relative prevalence of pachychoroid neovasculopathy in comparison with neovascular AMD and to investigate the phenotypic/genetic differences of the two diseases, we evaluated 200 consecutive Japanese patients who agreed to participate in the genetic study and diagnosed with pachychoroid neovasculopathy or neovascular AMD. Pachychoroid neovasculopathy was observed in 39 individuals (19.5%), which corresponds to one fourth of neovascular AMD. Patients with pachychoroid neovasculopathy were significantly younger (p = 5.1 × 10−5) and showed a greater subfoveal choroidal thickness (p = 3.4 × 10−14). Their genetic susceptibility to AMD was significantly lower than that of neovascular AMD; ARMS2 rs10490924 (p = 0.029), CFH rs800292 (p = 0.013) and genetic risk score calculated from 11 AMD susceptibility genes (p = 3.8 × 10−3). Current results implicate that the etiologies of the two conditions must be different. Thus, it will be necessary to distinguish these two conditions in future studies. PMID:26542071

  6. Angiofluorographic aspects in age-related macular degeneration

    PubMed Central

    Tomi, A; Marin, I

    2014-01-01

    Although AMD (age-related macular degeneration) has been described for over 100 years, there is neither a standard agreement on the definition of specific lesions nor a generally accepted classification system. For example, the age limits for AMD varied widely in different clinical studies; the methods used for examination also vary (visual acuity, perimetry, contrast sensitivity, slit lamp examination of the fundus, retinal photography, fluorescein angiography, indocyanine green angiography). We described the multitude of angiofluorographic aspects in patients with AMD and conceived a classification to be easily used in clinical practice. Although a detailed ophthalmoscopy can often identify the characteristic lesions of AMD, a complete picture is obtained by fluorescein angiography. The angiographic classification of AMD is structured similarly to the clinical one. It has two main patterns, non-exudative and exudative lesions, but it provides more information about the nature of the lesions. In the last three decades, an impressive amount of information regarding the prevalence, progression and risk factors for AMD has been published. The source of this information is mainly represented by the large population studies that are often multicenter studies. Recognizing the clinical signs of AMD and classifying them into different stages is important for the prognosis and the therapeutical decision, but also for conceiving study protocols. PMID:27057244

  7. Age-Related Changes in Demand-Withdraw Communication Behaviors.

    PubMed

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

    2013-08-01

    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

  8. Age-related somatic mutations in the cancer genome

    PubMed Central

    Milholland, Brandon; Auton, Adam; Suh, Yousin; Vijg, Jan

    2015-01-01

    Aging is associated with an increased risk of cancer, possibly in part because of an age-related increase in mutations in normal tissues. Due to their extremely low abundance, somatic mutations in normal tissues frequently escape detection. Tumors, as clonal expansions of single cells, can provide information about the somatic mutations present in these cells prior to tumorigenesis. Here, we used data from The Cancer Genome Atlas (TCGA), to systematically study the frequency and spectrum of somatic mutations in a total of 6,969 patients and 34 different tumor types as a function of the age of the patient. After using linear modeling to control for the age structure of different tumor types, we found that the number of identified somatic mutations increases exponentially with age. Using additional data from the literature, we found that accumulation of somatic mutations is associated with cell division rate, cancer risk and cigarette smoking, with the latter also associated with a distinct spectrum of mutations. Our results confirm that aging is associated with the accumulation of somatic mutations, and strongly suggest that the level of genome instability of normal cells, modified by both endogenous and environmental factors, is the main risk factor for cancer. PMID:26384365

  9. Reversal of age-related neural timing delays with training.

    PubMed

    Anderson, Samira; White-Schwoch, Travis; Parbery-Clark, Alexandra; Kraus, Nina

    2013-03-12

    Neural slowing is commonly noted in older adults, with consequences for sensory, motor, and cognitive domains. One of the deleterious effects of neural slowing is impairment of temporal resolution; older adults, therefore, have reduced ability to process the rapid events that characterize speech, especially in noisy environments. Although hearing aids provide increased audibility, they cannot compensate for deficits in auditory temporal processing. Auditory training may provide a strategy to address these deficits. To that end, we evaluated the effects of auditory-based cognitive training on the temporal precision of subcortical processing of speech in noise. After training, older adults exhibited faster neural timing and experienced gains in memory, speed of processing, and speech-in-noise perception, whereas a matched control group showed no changes. Training was also associated with decreased variability of brainstem response peaks, suggesting a decrease in temporal jitter in response to a speech signal. These results demonstrate that auditory-based cognitive training can partially restore age-related deficits in temporal processing in the brain; this plasticity in turn promotes better cognitive and perceptual skills. PMID:23401541

  10. 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

  11. Functional Visual Acuity in Age-Related Macular Degeneration

    PubMed Central

    Tomita, Yohei; Nagai, Norihiro; Suzuki, Misa; Shinoda, Hajime; Uchida, Atsuro; Mochimaru, Hiroshi; Izumi-Nagai, Kanako; Sasaki, Mariko; Tsubota, Kazuo; Ozawa, Yoko

    2016-01-01

    ABSTRACT Purpose We evaluated whether a functional visual acuity (FVA) system can detect subtle changes in central visual acuity that reflect pathological findings associated with age-related macular degeneration (AMD). Methods Twenty-eight patients with unilateral AMD and logMAR monocular best corrected VA better than 0 in both eyes, as measured by conventional chart examination, were analyzed between November 2012 and April 2013. After measuring conventional VA, FVA, and contrast VA with best correction, routine eye examinations including spectral domain–optical coherence tomography were performed. Standard Schirmer test was performed, and corneal and lens densities were measured. Results The FVA score (p < 0.001) and visual maintenance ratio (p < 0.001) measured by the FVA system, contrast VA (p < 0. 01), and conventional VA (p < 0.01) were significantly worse in the AMD-affected eyes than in the fellow eyes. No significant differences were observed in the anterior segment conditions. Forward stepwise regression analysis demonstrated that the length of interdigitation zone disruption, as visualized by optical coherence tomography imaging, correlated with the FVA score (p < 0.01) but not with any other parameters investigated. Conclusions The FVA system detects subtle changes in best corrected VA in AMD-affected eyes and reflects interdigitation zone disruption, an anatomical change in the retina recorded by optical coherence tomography. Further studies are required to understand the value of the FVA system in detecting subtle changes in AMD. PMID:26583795

  12. Flavonoids and Age Related Disease: Risk, benefits and critical windows

    PubMed Central

    Prasain, JK; Carlson, SH; Wyss, JM

    2010-01-01

    Plant derived products are consumed by a large percentage of the population to prevent, delay and ameliorate disease burden; however, relatively little is known about the efficacy, safety and underlying mechanisms of these traditional health products, especially when taken in concert with pharmaceutical agents. The flavonoids are a group of plant metabolites that are common in the diet and appear to provide some health benefits. While flavonoids are primarily derived from soy, many are found in fruits, nuts and more exotic sources, e.g., kudzu. Perhaps the strongest evidence for the benefits of flavonoids in diseases of aging relates to their effect on components of the metabolic syndrome. Flavonoids from soy, grape seed, kudzu and other sources all lower arterial pressure in hypertensive animal models and in a limited number of tests in humans. They also decrease the plasma concentration of lipids and buffer plasma glucose. The underlying mechanisms appear to include antioxidant actions, central nervous system effects, gut transport alterations, fatty acid sequestration and processing, PPAR activation and increases in insulin sensitivity. In animal models of disease, dietary flavonoids also demonstrate a protective effect against cognitive decline, cancer and metabolic disease. However, research also indicates that the flavonoids can be detrimental in some settings and, therefore, are not universally safe. Thus, as the population ages, it is important to determine the impact of these agents on prevention/attenuation of disease, including optimal exposure (intake, timing/duration) and potential contraindications. PMID:20181448

  13. Reversal of age-related neural timing delays with training

    PubMed Central

    Anderson, Samira; White-Schwoch, Travis; Parbery-Clark, Alexandra; Kraus, Nina

    2013-01-01

    Neural slowing is commonly noted in older adults, with consequences for sensory, motor, and cognitive domains. One of the deleterious effects of neural slowing is impairment of temporal resolution; older adults, therefore, have reduced ability to process the rapid events that characterize speech, especially in noisy environments. Although hearing aids provide increased audibility, they cannot compensate for deficits in auditory temporal processing. Auditory training may provide a strategy to address these deficits. To that end, we evaluated the effects of auditory-based cognitive training on the temporal precision of subcortical processing of speech in noise. After training, older adults exhibited faster neural timing and experienced gains in memory, speed of processing, and speech-in-noise perception, whereas a matched control group showed no changes. Training was also associated with decreased variability of brainstem response peaks, suggesting a decrease in temporal jitter in response to a speech signal. These results demonstrate that auditory-based cognitive training can partially restore age-related deficits in temporal processing in the brain; this plasticity in turn promotes better cognitive and perceptual skills. PMID:23401541

  14. Ocular surface temperature in age-related macular degeneration.

    PubMed

    Sodi, Andrea; Matteoli, Sara; Giacomelli, Giovanni; Finocchio, Lucia; Corvi, Andrea; Menchini, Ugo

    2014-01-01

    Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD) eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The ocular surface temperature (OST) of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA) test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value >0.272). OST in AMD patients was significantly lower than in controls (P > 0.05). Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD. PMID:25436140

  15. Age related susceptibility of pigs to Cryptosporidium scrofarum infection.

    PubMed

    Kváč, Martin; Němejc, Karel; Kestřánová, Michaela; Květoňová, Dana; Wagnerová, Pavla; Kotková, Michaela; Rost, Michael; Samková, Eva; McEvoy, John; Sak, Bohumil

    2014-05-28

    Piglets from 4 to 8 weeks of age originated from a Cryptosporidium-free research breed were orally inoculated with 1 × 10(6) infectious oocysts of Cryptosporidium scrofarum. The number of shed oocysts per gram of faeces served to describe the infection intensity and prepatent period. In addition, faecal samples collected daily and tissue samples of the small and large intestine collected at 30 days post-inoculation were examined for the C. scrofarum small subunit ribosomal RNA gene using PCR. The piglets inoculated at 4-weeks of age remained uninfected, whereas 5-week-old and older animals were fully susceptible with a prepatent period ranging from 4 to 8 days. Susceptible pigs shed oocysts intermittently, and shedding intensity, reaching a mean maximum of 6000 oocysts per gram, did not differ significantly among infected animals. This study demonstrates that pigs become susceptible to C. scrofarum infection as late as 5-weeks of age. The mechanisms of age related susceptibility remain unknown. PMID:24630710

  16. 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

  17. 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

  18. Seven new loci associated with age-related macular degeneration.

    PubMed

    Fritsche, Lars G; Chen, Wei; Schu, Matthew; Yaspan, Brian L; Yu, Yi; Thorleifsson, Gudmar; Zack, Donald J; Arakawa, Satoshi; Cipriani, Valentina; Ripke, Stephan; Igo, Robert P; Buitendijk, Gabriëlle H S; Sim, Xueling; Weeks, Daniel E; Guymer, Robyn H; Merriam, Joanna E; Francis, Peter J; Hannum, Gregory; Agarwal, Anita; Armbrecht, Ana Maria; Audo, Isabelle; Aung, Tin; Barile, Gaetano R; Benchaboune, Mustapha; Bird, Alan C; Bishop, Paul N; Branham, Kari E; Brooks, Matthew; Brucker, Alexander J; Cade, William H; Cain, Melinda S; Campochiaro, Peter A; Chan, Chi-Chao; Cheng, Ching-Yu; Chew, Emily Y; Chin, Kimberly A; Chowers, Itay; Clayton, David G; Cojocaru, Radu; Conley, Yvette P; Cornes, Belinda K; Daly, Mark J; Dhillon, Baljean; Edwards, Albert O; Evangelou, Evangelos; Fagerness, Jesen; Ferreyra, Henry A; Friedman, James S; Geirsdottir, Asbjorg; George, Ronnie J; Gieger, Christian; Gupta, Neel; Hagstrom, Stephanie A; Harding, Simon P; Haritoglou, Christos; Heckenlively, John R; Holz, Frank G; Hughes, Guy; Ioannidis, John P A; Ishibashi, Tatsuro; Joseph, Peronne; Jun, Gyungah; Kamatani, Yoichiro; Katsanis, Nicholas; N Keilhauer, Claudia; Khan, Jane C; Kim, Ivana K; Kiyohara, Yutaka; Klein, Barbara E K; Klein, Ronald; Kovach, Jaclyn L; Kozak, Igor; Lee, Clara J; Lee, Kristine E; Lichtner, Peter; Lotery, Andrew J; Meitinger, Thomas; Mitchell, Paul; Mohand-Saïd, Saddek; Moore, Anthony T; Morgan, Denise J; Morrison, Margaux A; Myers, Chelsea E; Naj, Adam C; Nakamura, Yusuke; Okada, Yukinori; Orlin, Anton; Ortube, M Carolina; Othman, Mohammad I; Pappas, Chris; Park, Kyu Hyung; Pauer, Gayle J T; Peachey, Neal S; Poch, Olivier; Priya, Rinki Ratna; Reynolds, Robyn; Richardson, Andrea J; Ripp, Raymond; Rudolph, Guenther; Ryu, Euijung; Sahel, José-Alain; Schaumberg, Debra A; Scholl, Hendrik P N; Schwartz, Stephen G; Scott, William K; Shahid, Humma; Sigurdsson, Haraldur; Silvestri, Giuliana; Sivakumaran, Theru A; Smith, R Theodore; Sobrin, Lucia; Souied, Eric H; Stambolian, Dwight E; Stefansson, Hreinn; Sturgill-Short, Gwen M; Takahashi, Atsushi; Tosakulwong, Nirubol; Truitt, Barbara J; Tsironi, Evangelia E; Uitterlinden, André G; van Duijn, Cornelia M; Vijaya, Lingam; Vingerling, Johannes R; Vithana, Eranga N; Webster, Andrew R; Wichmann, H-Erich; Winkler, Thomas W; Wong, Tien Y; Wright, Alan F; Zelenika, Diana; Zhang, Ming; Zhao, Ling; Zhang, Kang; Klein, Michael L; Hageman, Gregory S; Lathrop, G Mark; Stefansson, Kari; Allikmets, Rando; Baird, Paul N; Gorin, Michael B; Wang, Jie Jin; Klaver, Caroline C W; Seddon, Johanna M; Pericak-Vance, Margaret A; Iyengar, Sudha K; Yates, John R W; Swaroop, Anand; Weber, Bernhard H F; Kubo, Michiaki; Deangelis, Margaret M; Léveillard, Thierry; Thorsteinsdottir, Unnur; Haines, Jonathan L; Farrer, Lindsay A; Heid, Iris M; Abecasis, Gonçalo R

    2013-04-01

    Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P < 5 × 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P < 5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar 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

  19. 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

  20. 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

  1. 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

  2. Age-related changes in angiogenesis in human dermis.

    PubMed

    Gunin, Andrei G; Petrov, Vadim V; Golubtzova, Natalia N; Vasilieva, Olga V; Kornilova, Natalia K

    2014-07-01

    Present research is aimed to examine the number of dermal blood vessels, vascular endothelial growth factor (VEGF), delta-like ligand 4(Dll4) and Jagged-1 (Jag-1) in dermal blood vessels of human from 20weeks of pregnancy to 85years old. Numbers and proliferative activity of dermal fibroblast-like cells were also examined. Blood vessels were viewed with immunohistochemical staining for von Willebrand factor or CD31. VEGF, Dll4, Jag-1, and proliferating cell nuclear antigen (PCNA) were detected immunohistochemically. Results showed that the numbers of fibroblast-like cells, PCNA positive fibroblast-like cells, von Willebrand factor positive or CD31 positive blood vessels in dermis are dramatically decreased with age. The intensity of immunohistochemical staining for VEGF or Jag-1 in blood vessels of dermis is increased from antenatal to deep old period. The degree of immunohistochemical staining of dermal blood vessels for Dll4 has gone up from 20-40weeks of pregnancy to early life period (0-20years), and further decreased below antenatal values. Age-related decrease in the number of dermal blood vessels is suggested to be due to an impairment of VEGF signaling and to be mediated by Dll4 and Jag-1. It may be supposed that diminishing in blood supply of dermis occurring with age is a cause of a decrease in the number and proliferative pool of dermal fibroblasts. PMID:24768823

  3. 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

  4. 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

  5. Age-related changes in serological susceptibility patterns to measles

    PubMed Central

    Xiong, Yongzhen; Wang, Dong; Lin, Weiyan; Tang, Hao; Chen, Shaoli; Ni, Jindong

    2014-01-01

    The present study was performed to determine the seroprevalence of IgG measles antibodies in Dongguan residents (irrespective of vaccination status), to analyze the changes in age-related serological susceptibility patterns. A total of 1960 residents aged 0–60 years and 315 mother–infant pairs were studied. Serum IgG antibodies against measles virus were measured by ELISA. The overall seroprevalence was 93.4% in the general population in Dongguan, China. In subgroups aged 1–29 years who were likely vaccinated, there was a declining trend of seropositivity with age from 98.6% at 1–4 years to 85.7% at 20–29 years (P < 0.0001). Seroprevalence were near or >95% in the older population (30–39 years and ≥40 years) who had not been immunized against measles. Age and sex were independent factors associated with seropositivity. Seroprevalence in pregnant women and their newborns was 87.0% and 84.1%, respectively. Our results suggest that the waning vaccine-induced immunity may be the main cause of increased serological susceptibility in young adults and young infants. An additional vaccination strategy that targets young adults is important for elimination of measles. PMID:24448194

  6. 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

  7. 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

  8. Melanization and phagocytosis: implications for age related macular degeneration.

    PubMed

    Sarangarajan, Rangaprasad; Apte, Shireesh P

    2005-01-01

    Signaling pathways that upregulate melanization in the retinal pigment epithelium (RPE) may also be implicated in the downregulation of rod outer segment (ROS) phagocytosis by the RPE. Melanization activating pathways may also modulate oxygen consumption by the photoreceptors, apolipoprotein E4 levels, and the rate of photoisomerization events such that the net effect may be a reduction in drusen and/or lipofuscin accumulation. An increase in melanin at the apical microvilli of the RPE may shield ROS from light thereby contributing in part to the decrease in the rate of ROS phagocytosis. This decrease in ROS phagocytosis by the RPE may serve to maintain a balance between ingestion and degradation/recycling thereby avoiding an increase to its already substantial metabolic load. Several experimental drugs for age related macular degeneration (ARMD) coincidentally are also capable of decreasing the rate of ROS phagocytosis. This review attempts to identify the signaling pathways that may link the upregulation of melanization to the downregulation of ROS phagocytosis. Phagocytic pathways that are modulated by melanization need to be studied in isolation to determine what role, if any, they possess in ameliorating the onset and progression of ARMD. Many more empirical studies are needed to unravel specific pathways and mechanisms that seem to link melanization with ARMD. PMID:16030499

  9. Effect of NCAM on aged-related deterioration in vision.

    PubMed

    Luke, Margaret Po-Shan; LeVatte, Terry L; O'Reilly, Amanda M; Smith, Benjamin J; Tremblay, François; Brown, Richard E; Clarke, David B

    2016-05-01

    The neural cell adhesion molecule (NCAM) is involved in developmental processes and age-associated cognitive decline; however, little is known concerning the effects of NCAM in the visual system during aging. Using anatomical, electrophysiological, and behavioral assays, we analyzed age-related changes in visual function of NCAM deficient (-/-) and wild-type mice. Anatomical analyses indicated that aging NCAM -/- mice had fewer retinal ganglion cells, thinner retinas, and fewer photoreceptor cell layers than age-matched controls. Electroretinogram testing of retinal function in young adult NCAM -/- mice showed a 2-fold increase in a- and b-wave amplitude compared with wild-type mice, but the retinal activity dropped dramatically to control levels when the animals reached 10 months. In behavioral tasks, NCAM -/- mice had no visual pattern discrimination ability and showed premature loss of vision as they aged. Together, these findings demonstrate that NCAM plays significant roles in the adult visual system in establishing normal retinal anatomy, physiology and function, and in maintaining vision during aging. PMID:27103522

  10. 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.

  11. 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

  12. 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

  13. Nitroxide pharmaceutical development for age-related degeneration and disease

    PubMed Central

    Zarling, Jacob A.; Brunt, Vienna E.; Vallerga, Anne K.; Li, Weixing; Tao, Albert; Zarling, David A.; Minson, Christopher T.

    2015-01-01

    Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration (AMD) and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress, and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP), Tempol Hydroxylamine (TP-H), and TP-H prodrug (OT-551) are evaluated in (1) non-smokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2) elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3) elderly smoker or non-smoker AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and preserving normal and low light luminance in dry AMD smokers and non-smoker patients. Topical, oral, or injectable drug formulations are discussed. PMID:26594225

  14. 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

  15. 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

  16. 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

  17. Chlamydia infection status, genotype, and age-related macular degeneration

    PubMed Central

    Khandhadia, Sam; Foster, Sebastian; Cree, Angela; Griffiths, Helen; Osmond, Clive; Goverdhan, Srinivas

    2012-01-01

    Purpose To evaluate whether Chlamydia (C.) infections are associated with age-related macular degeneration (AMD) and to assess if this association is influenced by the complement factor H (CFH) Y402H or the high temperature requirement A serine peptidase 1 (HTRA1) rs11200638 risk genotypes. Methods One hundred ninety-nine AMD patients with early and late forms of the disease and 100 unaffected controls, at least 50 years old were included in the study. Patients in the AMD and control groups were selected based on known CFH Y402H variant genotype status (one third homozygous CC, one third heterozygous CT, and one third wild-type TT). Plasma from all patients and controls was tested for C. pneumoniae, C. trachomatis, and C. psittaci IgG seropositivity using a micro-immunofluorescent assay to establish previous infection status. Assays were conducted blind to risk genotypes and the results analyzed using univariate and multivariate (logistic regression) analysis. Results IgG seropositivity to C. pneumoniae was most prevalent (69.2%, n=207), followed by C. trachomatis (7.4%, n=22) and C. psittaci (3.3%, n=10). No association was found between each of the three Chlamydia species IgG seropositivity and AMD status or severity (early/late). There was also no significant association between Chlamydia species IgG seropositivity and AMD status or severity, in patients carrying at least one CFH Y402H risk allele (C) or HTRA1 rs11200638 risk allele (A), with univariate or logistic regression analysis. Conclusions Chlamydia infection status does not appear to be associated with AMD status or severity. The presence of CFH Y402H and HTRA1 rs11200638 risk genotypes does not alter this negative association. PMID:22259222

  18. 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

  19. 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

  20. Wet age related macular degeneration management and follow-up.

    PubMed

    Alexandru, Malciolu Radu; Alexandra, Nica Maria

    2016-01-01

    Age-related macular degeneration (AMD) is referred to as the leading cause of irreversible visual loss in developed countries, with a profound effect on the quality of life. The neovascular form of AMD is characterized by the formation of subretinal choroidal neovascularization, leading to sudden and severe visual loss. Research has identified the vascular endothelial growth factor (VEGF) as an important pathophysiological component in neovascular AMD and its intraocular inhibition as one of the most efficient therapies in medicine. The introduction of anti-VEGF as a standard treatment in wet AMD has led to a great improvement in the prognosis of patients, allowing recovery and maintenance of visual function in the vast majority of cases. However, the therapeutic benefit is accompanied by a difficulty in maintaining the treatment schedule due to the increase in the amount of patients, stress of monthly assessments, as well as the associated economic burden. Therefore, treatment strategies have evolved from fixed monthly dosing, to individualized regimens, aiming for comparable results, with fewer injections. One such protocol is called "pro re nata", or "treat and observe". Patients are given a loading dose of 3 monthly injections, followed by an as-needed decision to treat, based on the worsening of visual acuity, clinical evidence of the disease activity on fundoscopy, or OCT evidence of retinal thickening in the presence of intra or subretinal fluid. A different regimen is called "treat and extend", in which the interval between injections is gradually increased, once the disease stabilization is achieved. This paper aims to review the currently available anti-VEGF agents--bevacizumab, ranibizumab, aflibercept, and the aforementioned treatment strategies. PMID:27220225

  1. 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. PMID:27119585

  2. 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

  3. 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 ...

  4. 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...

  5. Does eating particular diets alter risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Recent information suggests that the Age-Related Eye Disease Study (AREDS) supplement, enhanced intake of omega-3 fatty acids, and diminishing dietary glycemic index (dGI) are protective against advanced age-related macular degeneration (AMD). Methods: Dietary information was collected a...

  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. 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

  8. 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

  9. 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

  10. Influence of Age-Related Versus Non-Age-Related Renal Dysfunctionon Survival in Patients with Left Ventricular Dysfunction

    PubMed Central

    Testani, Jeffrey M.; Brisco, Meredith A.; Han, Gang; Laur, Olga; Kula, Alexander J.; Cheng, Susan J.; Tang, W. H. Wilson; Parikh, Chirag R.

    2013-01-01

    Normal aging results in a predictable decline in glomerular filtration rate (GFR) and low GFR is associated with worsened survival. If this survival disadvantage is directly caused by the low GFR, as opposed to the disease causing the low GFR, the risk should be similar regardless of the underlying mechanism. Our objective was to determine if age related declines in estimated GFR (eGFR) carry the same prognostic importance as disease attributable losses in patients with ventricular dysfunction. We analyzed the Studies Of Left Ventricular Dysfunction (SOLVD) limited data set (n=6337). The primary analysis focused on determining if the eGFR mortality relationship differed by the extent the eGFR was consistent with normal ageing. Mean eGFR was 65.7 ± 19.0ml/min/1.73m2. Across the range of age in the population (27 to 80 years), baseline eGFR decreased by 0.67 ml/min/1.73m2 per year (95% CI 0.63 to 0.71). The risk of death associated with eGFR was strongly modified by the degree to which the low eGFR could be explained by aging (p interaction <0.0001). For example, in a model incorporating the interaction, uncorrected eGFR was no longer significantly related to mortality (adjusted HR=1.0 per 10 ml/min/1.73m2, 95% CI 0.97–1.1, p=0.53) whereas a disease attributable decrease in eGFR above the median carried significant risk (adjusted HR=2.8, 95% CI 1.6–4.7, p<0.001). In conclusion, in the setting of LV dysfunction, renal dysfunction attributable to normal aging had a limited risk for mortality, suggesting that the mechanism underlying renal dysfunction is critical in determining prognosis. PMID:24216124

  11. Lipids, Lipid Genes and Incident Age-Related Macular Degeneration: The Three Continent Age-Related Macular Degeneration Consortium

    PubMed Central

    Klein, Ronald; Myers, Chelsea E.; Buitendijk, Gabriëlle H. S.; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T. V. M.; Sivakumaran, Theru A.; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K.; Lee, Kristine E.; Stricker, Bruno H.; Vingerling, Johannes R.; Mitchell, Paul; Klein, Barbara E. K.; Klaver, Caroline C. W.; Wang, Jie Jin

    2014-01-01

    Purpose To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Design Meta-analysis. Methods Setting Three population-based cohorts. Population 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES) and Rotterdam Study (RS). Observation Procedures Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios (HRs) associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. Main Outcome Measures Incidence of AMD. Results The average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the three studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis. Conclusion In a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD. PMID:24879949

  12. [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

  13. Bevacizumab (AVASTIN) and age-related macular degeneration. Lower cost does not justify taking risks.

    PubMed

    2015-09-01

    Intravitreal injection of ranibizumab, a VEGF inhibitor, is an option for patients with neovascular age-related macular degeneration (AMD). Because of its lower price, bevacizumab, a VEGF inhibitor closely related to ranibizumab and marketed for the treatment of various malignancies, is sometimes used off label for intravitreal injection in AMD. In 2011, the harm-benefit balance of bevacizumab in patients with AMD was uncertain. New data are available in 2015. In six randomised trials including a total of about 3200 patients, funded independently of the pharmaceutical industry, bevacizumab (1.25 mg per dose) was about as effective as ranibizumab (0.5 mg per injection): visual acuity stabilised or improved in 90% to 95% of patients after one to two years of treatment. During these trials, bevacizumab did not reduce the number of injections needed, as compared with ranibizumab. These trials confirmed the known adverse effect profile of bevacizumab, which is similar to that of ranibizumab and includes serious ocular as well as extraocular adverse effects, in particular cardiac disorders. Serious extraocular adverse events, especially gastrointestinal disorders, were more frequent with bevacizumab than with ranibizumab at one year (18% versus 14%). In early 2015, there are no bevacizumab products suitable for intravitreal injection. In 2011, cases of sight-threatening infectious endophthalmitis were reported in the United States, following contamination during syringe preparation for intravitreal administration. In practice, when treatment with a VEGF inhibitor is considered for AMD, it is more prudent to choose ranibizumab, despite its currently unacceptable price. PMID:26417625

  14. MYBL2 haploinsufficiency increases susceptibility to age-related haematopoietic neoplasia

    PubMed Central

    Clarke, M; Dumon, S; Ward, C; Jäger, R; Freeman, S; Dawood, B; Sheriff, L; Lorvellec, M; Kralovics, R; Frampton, J; García, P

    2013-01-01

    The haematopoietic system is prone to age-related disorders ranging from deficits in functional blood cells to the development of neoplastic states. Such neoplasms often involve recurrent cytogenetic abnormalities, among which a deletion in the long arm of chromosome 20 (del20q) is common in myeloid malignancies. The del20q minimum deleted region contains nine genes, including MYBL2, which encodes a key protein involved in the maintenance of genome integrity. Here, we show that mice expressing half the normal levels of Mybl2 (Mybl2+/Δ) develop a variety of myeloid disorders upon ageing. These include myeloproliferative neoplasms, myelodysplasia (MDS) and myeloid leukaemia, mirroring the human conditions associated with del20q. Moreover, analysis of gene expression profiles from patients with MDS demonstrated reduced levels of MYBL2, regardless of del20q status and demonstrated a strong correlation between low levels of MYBL2 RNA and reduced expression of a subset of genes related to DNA replication and checkpoint control pathways. Paralleling the human data, we found that these pathways are also disturbed in our Mybl2+/Δ mice. This novel mouse model, therefore, represents a valuable tool for studying the initiation and progression of haematological malignancies during ageing, and may provide a platform for preclinical testing of therapeutic approaches. PMID:22910183

  15. 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

  16. An immunohistochemical and ultrastructural study on age-related astrocytic gliosis in the central nervous system of dogs.

    PubMed

    Shimada, A; Kuwamura, M; Awakura, T; Umemura, T; Itakura, C

    1992-02-01

    The pattern of astrocytic gliosis (AG) was examined in 2-month-old to 18-year-old dogs using glial fibrillary acidic protein (GFAP) immunohistochemistry and electron microscopy. Coronal sections from various levels of the central nervous system (CNS) were stained with hematoxylin & eosin, Luxol Fast Blue, Nissl, and Bodian in addition to GFAP. A consistent pattern of age-related AG was observed in the dogs. The white matter, cortico-medullary junction, and subcortical nuclei in the cerebrum, central nuclei in the cerebellum, various nuclei in the brain stem, and grey matter of the spinal cord showed even and intense GFAP staining. AG was also prominent in the cerebral and cerebellar cortices and thalamus. Moderate AG was observed in the hippocampus and white matter of the cerebellum and spinal cord. Electron microscopy demonstrated increased number of profiles of degenerative neural components in the vicinity of hypertrophic astrocytes in the cerebral cortex of the aged dogs. Moderate to severe AG was consistently shown in the CNS of the aged dogs. In contrast, young normal dogs showed minimum amounts of GFAP-positive astrocytes in the CNS. These findings suggest that the observed AG in the CNS of the dogs is a morphological expression of aging. PMID:1558887

  17. Age-related differences in internalizing psychopathology amongst the Australian general population.

    PubMed

    Sunderland, Matthew; Slade, Tim; Carragher, Natacha; Batterham, Philip; Buchan, Heather

    2013-11-01

    Two methodological criticisms have limited the reliability and validity of findings from previous studies that seek to examine change across the life span in levels of internalizing psychopathology using general population surveys. The first criticism involves the potential influence of cohort effects that confound true age-related changes whereas the second criticism involves the use of a single form of assessment to measure and compare levels of internalizing psychopathology. This study seeks to address these criticisms by modeling age-related change using multiple measures and multiple surveys. Data from 2 epidemiological surveys conducted 10 years apart in the Australian general population were combined and used for the current study. The latent construct of internalizing psychopathology was modeled using a combination of Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) depression and anxiety diagnoses as well as items from the Kessler Psychological Distress scale (K10; Kessler et al., 2002). Confirmatory factor analysis (CFA) indicated that a single internalizing dimension provided good model fit to the data. Multigroup CFA indicated that strict measurement invariance of the model can be assumed across survey administrations and age bands, justifying comparisons of mean differences in latent trait levels. Significant changes in mean levels of latent internalizing psychopathology were evident between respondents aged 30-39 years old in 1997 and respondents aged 40-49 years old in 2007, suggesting a minor but significant increase in psychopathology across middle age. By contrast, a minor but significant decrease in psychopathology was noted when transitioning from late middle age (50-59 years old) to old age (60-69 years old). The majority of individuals in the general population will experience constant levels of internalizing psychopathology as they age, suggesting that the construct is relatively

  18. Zinc Supplementation Inhibits Complement Activation in Age-Related Macular Degeneration

    PubMed Central

    Blom, Anna M.; Mohlin, Frida C.; den Hollander, Anneke I.; van de Ven, Johannes P. H.; van Huet, Ramon A. C.; Groenewoud, Joannes M. M.; Tian, Yuan; Berendschot, Tos T. J. M.; Lechanteur, Yara T. E.; Fauser, Sascha; de Bruijn, Chris; Daha, Mohamed R.; van der Wilt, Gert Jan; Hoyng, Carel B.; Klevering, B. Jeroen

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. AMD is a multifactorial disorder but complement-mediated inflammation at the level of the retina plays a pivotal role. Oral zinc supplementation can reduce the progression of AMD but the precise mechanism of this protective effect is as yet unclear. We investigated whether zinc supplementation directly affects the degree of complement activation in AMD and whether there is a relation between serum complement catabolism during zinc administration and the complement factor H (CFH) gene or the Age-Related Maculopathy susceptibility 2 (ARMS2) genotype. In this open-label clinical study, 72 randomly selected AMD patients in various stages of AMD received a daily supplement of 50 mg zinc sulphate and 1 mg cupric sulphate for three months. Serum complement catabolism–defined as the C3d/C3 ratio–was measured at baseline, throughout the three months of supplementation and after discontinuation of zinc administration. Additionally, downstream inhibition of complement catabolism was evaluated by measurement of anaphylatoxin C5a. Furthermore, we investigated the effect of zinc on complement activation in vitro. AMD patients with high levels of complement catabolism at baseline exhibited a steeper decline in serum complement activation (p<0.001) during the three month zinc supplementation period compared to patients with low complement levels. There was no significant association of change in complement catabolism and CFH and ARMS2 genotype. In vitro zinc sulphate directly inhibits complement catabolism in hemolytic assays and membrane attack complex (MAC) deposition on RPE cells. This study provides evidence that daily administration of 50 mg zinc sulphate can inhibit complement catabolism in AMD patients with increased complement activation. This could explain part of the mechanism by which zinc slows AMD progression. Trial Registration The Netherlands National Trial Register

  19. Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD)

    ClinicalTrials.gov

    2016-01-05

    Macular Degeneration; Age-Related Maculopathies; Age-Related Maculopathy; Maculopathies, Age-Related; Maculopathy, Age-Related; Retinal Degeneration; Retinal Neovascularization; Gene Therapy; Therapy, Gene; Eye Diseases

  20. 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

  1. Age related changes in gut physiology and nutritional status.

    PubMed

    Lovat, L B

    1996-03-01

    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

  2. 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

  3. Vitamin E-gene interactions in aging and inflammatory age-related diseases: implications for treatment. A systematic review.

    PubMed

    Mocchegiani, Eugenio; Costarelli, Laura; Giacconi, Robertina; Malavolta, Marco; Basso, Andrea; Piacenza, Francesco; Ostan, Rita; Cevenini, Elisa; Gonos, Efstathios S; Franceschi, Claudio; Monti, Daniela

    2014-03-01

    Aging is a complex biological phenomenon in which the deficiency of the nutritional state combined with the presence of chronic inflammation and oxidative stress contribute to the development of many age-related diseases. Under this profile, the free radicals produced by the oxidative stress lead to a damage of DNA, lipids and proteins with subsequent altered cellular homeostasis and integrity. In young-adult age, the cell has a complex efficient system to maintain a proper balance between the levels of free radicals and antioxidants ensuring the integrity of cellular components. In contrast, in old age this balance is poorly efficient compromising cellular homeostasis. Supplementation with Vitamin E can restore the balance and protect against the deteriorating effects of oxidative stress, progression of degenerative diseases, and aging. Experiments in cell cultures and in animals have clearly shown that Vitamin E has a pivotal role as antioxidant agent against the lipid peroxidation on cell membranes preserving the tissue cells from the oxidative damage. Such a role has been well documented in immune, endothelial, and brain cells from old animals describing how the Vitamin E works both at cytoplasmatic and nuclear levels with an influence on many genes related to the inflammatory/immune response. All these findings have supported a lot of clinical trials in old humans and in inflammatory age-related diseases with however contradictory and inconsistent results and even indicating a dangerous role of Vitamin E able to affect mortality. Various factors can contribute to all the discrepancies. Among them, the doses and the various isoforms of Vitamin E family (α,β,γ,δ tocopherols and the corresponding tocotrienols) used in different trials. However, the more plausible gap is the poor consideration of the Vitamin E-gene interactions that may open new roadmaps for a correct and personalized Vitamin E supplementation in aging and age-related diseases with

  4. [Etiology, pathophysiology and conservative therapy of degenerative rheumatic diseases].

    PubMed

    Jandrić, Slavica

    2002-01-01

    ETIOLOGY OF DEGENERATIVE JOINT DISEASES: Etiology of degenerative joint diseases is still not clearly understood and there is no specific management for this group of diseases. Various pathological conditions cause damage of the articular cartilage and lead to clinically and radiographically recognized impairment. Biomechanical, metabolic, genetic factors, inflammation and other risk factors contribute to development of osteoarthrosis. PATHOPHYSIOLOGY OF DEGENERATIVE JOINT DISEASES: Osteoarthrosis is characterized by progressive erosion of articular cartilage and bone overgrowth at the joint margins. Cartilage integrity requires balance between synthesis and degradation of matrix components. Chondrocytes react to various mechanical and chemical stresses in order to stabilize and restore the tissue. Failures in stabilizing and restoring the tissue lead to cartilage degeneration that may be irreversibile. For better understanding of conservative management of degenerative joint diseases it is important to know the impact of pathophysiology mechanisms on development of degenerative joint diseases. There is great variability in the rate of progression of erosive processes in articular cartilage in clinical, radiographic signs and course of the disease. This is in relation with many factors, as well as with management and response to therapy. TREATMENT OF DEGENERATIVE JOINT DISEASES: Treatment should vary depending on the severity of disease and patient's expectations and level of activity. Besides analgesic and anti-inflammatory drugs, conventional and not conventional treatment and techniques can be used for management of osteoarthrosis. Physical therapy and exercises are very important for maintaining muscle strength, joint stability and mobility, but should be closely monitored for optimal efficacy. PMID:12037935

  5. 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. PMID:25664170

  6. 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

  7. A review of creatine supplementation in age-related diseases: more than a supplement for athletes

    PubMed Central

    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. PMID:25664170

  8. [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

  9. 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

  10. 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

  11. 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

  12. Endogenous Retroelements in Cellular Senescence and Related Pathogenic Processes: Promising Drug Targets in Age-Related Diseases.

    PubMed

    Cardelli, Maurizio; Giacconi, Robertina; Malavolta, Marco; Provinciali, Mauro

    2016-01-01

    Endogenous retroelements (ERs) represent nearly half of the human genome. Considered up to recent years as "functionless" DNA sequences, they are now known to be involved in important cellular functions such as stress response and generation of non coding regulatory RNAs. Moreover, an increasing amount of data supports the idea of ERs as key players in cellular senescence and in different senescence-related pathogenic cellular processes, including those leading to inflammation, cancer and major age-related multifactorial diseases. The involvement of ERs in these biological mechanisms can suggest new therapeutic strategies in neoplasms, inflammatory/autoimmune diseases and in different age-related pathologies, such as macular degeneration, diabetes, cardiovascular diseases and major age-related neurodegenerative disorders. The therapeutic approaches which can be suggested range from a set of well-known, common drugs that have been shown to modulate ERs activity, to immune therapy against ER-derived tumor antigens, to more challenging strategies such as those based on anti-ERs RNA interference. PMID:25981608

  13. 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

  14. 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

  15. 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. PMID:26501968

  16. Age-related hearing loss: GABA, nicotinic acetylcholine and NMDA receptor expression changes in spiral ganglion neurons of the mouse.

    PubMed

    Tang, X; Zhu, X; Ding, B; Walton, J P; Frisina, R D; Su, J

    2014-02-14

    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 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 (SGN) of the CBA/CaJ mouse cochlea, that occur in age-related hearing loss, utilizing quantitative immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) techniques. We found that auditory brainstem response (ABR) thresholds shifted over 40dB from 3 to 48kHz in old mice compared to young adults. DPOAE thresholds also shifted over 40dB from 6 to 49kHz in old mice, and their amplitudes were significantly decreased or absent in the same frequency range. 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 1amplitude. 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

  17. Age-related regulation of genes: slow homeostatic changes and age-dimension technology

    NASA Astrophysics Data System (ADS)

    Kurachi, Kotoku; Zhang, Kezhong; Huo, Jeffrey; Ameri, Afshin; Kuwahara, Mitsuhiro; Fontaine, Jean-Marc; Yamamoto, Kei; Kurachi, Sumiko

    2002-11-01

    Through systematic studies of pro- and anti-blood coagulation factors, we have determined molecular mechanisms involving two genetic elements, age-related stability element (ASE), GAGGAAG and age-related increase element (AIE), a unique stretch of dinucleotide repeats (AIE). ASE and AIE are essential for age-related patterns of stable and increased gene expression patterns, respectively. Such age-related gene regulatory mechanisms are also critical for explaining homeostasis in various physiological reactions as well as slow homeostatic changes in them. The age-related increase expression of the human factor IX (hFIX) gene requires the presence of both ASE and AIE, which apparently function additively. The anti-coagulant factor protein C (hPC) gene uses an ASE (CAGGAG) to produce age-related stable expression. Both ASE sequences (G/CAGAAG) share consensus sequence of the transcriptional factor PEA-3 element. No other similar sequences, including another PEA-3 consensus sequence, GAGGATG, function in conferring age-related gene regulation. The age-regulatory mechanisms involving ASE and AIE apparently function universally with different genes and across different animal species. These findings have led us to develop a new field of research and applications, which we named “age-dimension technology (ADT)”. ADT has exciting potential for modifying age-related expression of genes as well as associated physiological processes, and developing novel, more effective prophylaxis or treatments for age-related diseases.

  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. Cardiovascular aspects of experimental meningococcal sepsis in young and older awake piglets: age-related differences.

    PubMed

    Hazelzet, J A; Stubenitsky, R; Petrov, A B; van Wieringen, G W; van der Voort, E; Hess, J; Hop, W C; Thijs, L G; Duncker, D J; Poolman, J T; Verdouw, P D

    1999-08-01

    Severe meningococcal disease is characterized by: a high load of specific endotoxin, capillary leakage and coagulation disorders. We studied the possible age-related differences in global hemodynamic and regional blood flow responses to different dosages (1 and 10 microg/kg body weight) of rough meningococcal endotoxin in young (8 kg) and older piglets (40 kg). Animals were chronically instrumented and studied in the awake state. The response to plasma infusion (30 mL/kg in 30 min) was evaluated after placebo and endotoxin infusion. The clinical picture was similar in all groups. The mortality was 0/8, 3/8,1/8, 4/9 in young-low, young-high, old-low, and old-high dose respectively. Most important findings were that cardiac index (CI) decreased in the young animals after endotoxin infusion, while it was well preserved in the older animals; in the older animals the systemic vascular resistance dropped 20%, while in the younger ones there was no change in resistance. Conductance to the kidneys, intestines, and spleen decreased significantly more in the young animals, while the increase in conductance and flow to the liver was higher in the old animals; subsequent volume loading resulted only partly in a recovery of the hemodynamic parameters, but failed to improve oxygen delivery. PMID:10446896

  20. Search for age-related macular degeneration risk variants in Alzheimer disease genes and pathways.

    PubMed

    Logue, Mark W; Schu, Matthew; Vardarajan, Badri N; Farrell, John; Lunetta, Kathryn L; Jun, Gyungah; Baldwin, Clinton T; Deangelis, Margaret M; Farrer, Lindsay A

    2014-06-01

    Several lines of inquiry point to overlapping molecular mechanisms between late-onset Alzheimer disease (AD) and age-related macular degeneration (AMD). We evaluated summarized results from large genome-wide association studies for AD and AMD to test the hypothesis that AD susceptibility loci are also associated with AMD. We observed association of both disorders with genes in a region of chromosome 7, including PILRA and ZCWPW1 (peak AMD SNP rs7792525, minor allele frequency [MAF] = 19%, odds ratio [OR] = 1.14, p = 2.34 × 10(-6)), and with ABCA7 (peak AMD SNP rs3752228, MAF = 0.054, OR = 1.22, p = 0.00012). Next, we evaluated association of AMD with genes in AD-related pathways identified by canonical pathway analysis of AD-associated genes. Significant associations were observed with multiple previously identified AMD risk loci and 2 novel genes: HGS (peak SNP rs8070488, MAF = 0.23, OR = 0.91, p = 7.52 × 10(-5)), which plays a role in the clathrin-mediated endocytosis signaling pathway, and TNF (peak SNP rs2071590, MAF = 0.34, OR = 0.89, p = 1.17 × 10(-5)), which is a member of the atherosclerosis signaling and the LXR/RXR activation pathways. Our results suggest that AMD and AD share genetic mechanisms. PMID:24439028

  1. Progress and Prospects in Human Genetic Research into Age-Related Hearing Impairment

    PubMed Central

    Sugiura, Saiko; 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. PMID:25140308

  2. 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

  3. 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. PMID:26548366

  4. 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

  5. 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

  6. Causes and consequences of age-related steroid hormone changes: insights gained from nonhuman primates.

    PubMed

    Sorwell, K G; Urbanski, H F

    2013-11-01

    Similar to humans, rhesus macaques (Macaca mulatta) are large, long-lived diurnal primates, and show similar age-related changes in the secretion of many steroid hormones, including oestradiol, testosterone, cortisol and dehydroepiandrosterone (DHEA). Consequently, they represent a pragmatic animal model in which to examine the mechanisms by which these steroidal changes contribute to perturbed sleep-wake cycles and cognitive decline in the elderly. Using remote serial blood sampling, we have found the circulating levels of DHEA sulphate, as well as oestradiol and testosterone, decline markedly in old monkeys. Furthermore, using the real-time polymerase chain reaction, we have shown that the genes for the enzymes associated with the conversion of DHEA to oestradiol and testosterone (3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and aromatase) are highly expressed in brain areas associated with cognition and behaviour, including the hippocampus, prefrontal cortex and amygdala. Taken together, these findings suggest that the administration of supplementary DHEA in the elderly may have therapeutic potential for cognitive and behavioural disorders, although with fewer negative side effects outside of the central nervous system. To test this, we have developed a novel steroid supplementation paradigm for use in old animals; this involves the oral administration of DHEA and testosterone at physiologically relevant times of the day to mimic the circadian hormone patterns observed in young adults. We are currently evaluating the efficacy of this steroid supplementation paradigm with respect to reversing age-associated disorders, including perturbed sleep-wake cycles and cognitive decline, as well as an impaired immune response. PMID:23796387

  7. Age-related cortical thinning in cognitively healthy individuals in their 60s: the PATH Through Life study.

    PubMed

    Shaw, Marnie E; Sachdev, Perminder S; Anstey, Kaarin J; Cherbuin, Nicolas

    2016-03-01

    Although it is recognized that the human cortex thins with age, longitudinal estimates of thinning patterns specific to healthy young-old age (<75 years) individuals are lacking. Importantly, many neurodegenerative disorders first manifest between midlife and old age, and normative estimates may provide a reference for differential change associated with such disorders. Here, we provide longitudinal estimates of cortical thinning observed over 12 years in a large group (n = 396) of healthy individuals, aged 60-66 years at baseline scan, who were scanned with magnetic resonance imaging (1.5T) on 4 occasions. Longitudinal age-related thinning was observed across most of the cortices, with a mean change of -0.3% per year. We measured significant thinning in heteromodal association cortex, with less thinning in regions expected to atrophy later in life (e.g., primary sensory cortex). Men showed more extensive thinning than women. Our comparison of cross-sectional and longitudinal estimates adds to growing evidence that cross-sectional designs may underestimate age-related changes in cortical thickness. PMID:26923417

  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. Age-Related Differences in Muscular Strength and Muscular Endurance among Female Masters Swimmers.

    ERIC Educational Resources Information Center

    Dummer, Gail M.; And Others

    1985-01-01

    This study investigated age-related differences in muscular strength and muscular endurance among 73 female masters swimmers aged 24 to 71 years. While an age-related decline in muscular strength was apparent, the results failed to reveal a similar trend for endurance, suggesting that swimming influences endurance more than strength among women.…

  10. 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 ...

  11. 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,…

  12. The Complement Regulatory Protein CD46 Deficient Mouse Spontaneously Develops Dry-Type Age-Related Macular Degeneration-Like Phenotype.

    PubMed

    Lyzogubov, Valeriy V; Bora, Puran S; Wu, Xiaobo; Horn, Leah E; de Roque, Ryan; Rudolf, Xeniya V; Atkinson, John P; Bora, Nalini S

    2016-08-01

    In the mouse, membrane cofactor protein (CD46), a key regulator of the alternative pathway of the complement system, is only expressed in the eye and on the inner acrosomal membrane of spermatozoa. We noted that although Cd46(-/-) mice have normal systemic alternative pathway activating ability, lack of CD46 leads to dysregulated complement activation in the eye, as evidenced by increased deposition of C5b-9 in the retinal pigment epithelium (RPE) and choroid. A knockout of CD46 induced the following cardinal features of human dry age-related macular degeneration (AMD) in 12-month-old male and female mice: accumulation of autofluorescent material in and hypertrophy of the RPE, dense deposits in and thickening of Bruch's membrane, loss of photoreceptors, cells in subretinal space, and a reduction of choroidal vessels. Collectively, our results demonstrate spontaneous age-related degenerative changes in the retina, RPE, and choroid of Cd46(-/-) mice that are consistent with human dry AMD. These findings provide the exciting possibility of using Cd46(-/-) mice as a convenient and reliable animal model for dry AMD. Having such a relatively straight-forward model for dry AMD should provide valuable insights into pathogenesis and a test model system for novel drug targets. More important, tissue-specific expression of CD46 gives the Cd46(-/-) mouse model of dry AMD a unique advantage over other mouse models using knockout strains. PMID:27295359

  13. 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

  14. [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

  15. DIETARY CARBOHYDRATE AND PROGRESSION OF AGE-RELATED MACULAR DEGENERATION, A PROSPECTIVE STUDY FROM THE AGE-RELATED EYE DISEASE STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background Cross-sectional studies indicate that diets that provide a higher dietary glycemic index (dGI) are associated with increased risk of age-related macular degeneration (AMD). No prospective studies have addressed this issue. Methods dGI was calculated as the weighted average of GIs from foo...

  16. Progressive Agraphia Can Be a Harbinger of Degenerative Dementia

    ERIC Educational Resources Information Center

    Fukui, Toshiya; Lee, Eiyai

    2008-01-01

    By investigating three patients with progressive agraphia, we explored the possibility that this entity is an early sign of degenerative dementia. Initially, these patients complained primarily of difficulties writing Kanji (Japanese morphograms) while other language and cognitive impairments were relatively milder. Impairments in writing Kana…

  17. [Pathobiochemistry of joint destruction in inflammatory and degenerative joint diseases].

    PubMed

    Greiling, H; Kleesiek, K; Reinards, R

    1987-08-01

    While the biochemical mechanism which leads to the destruction of joints in the course of degenerative and inflammatory arthropathies has not been cleared up completely to this day, basic differences have been noted in the way the two types of arthropathy affect the articular cartilage. The differences are described from the viewpoint of pathobiochemistry as they are fundamental to causal therapy. PMID:3314203

  18. 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

  19. Age-related macular degeneration and changes in the extracellular matrix

    PubMed Central

    Nita, Małgorzata; Strzałka-Mrozik, Barbara; Grzybowski, Andrzej; Mazurek, Urszula; Romaniuk, Wanda

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of permanent, irreversible, central blindness (scotoma in the central visual field that makes reading and writing impossible, stereoscopic vision, recognition of colors and details) in patients over the age of 50 years in European and North America countries, and an important role is attributed to disorders in the regulation of the extracellular matrix (ECM). The main aim of this article is to present the crucial processes that occur on the level of Bruch’s membrane, with special consideration of the metalloproteinase substrates, metalloproteinase, and tissue inhibitor of metalloproteinase (TIMP). A comprehensive review of the literature was performed through MEDLINE and PubMed searches, covering the years 2005–2012, using the following keywords: AMD, extracellular matrix, metalloproteinases, tissue inhibitors of metalloproteinases, Bruch’s membrane, collagen, elastin. In the pathogenesis of AMD, a significant role is played by collagen type I and type IV; elastin; fibulin-3, -5, and -6; matrix metalloproteinase (MMP)-2, MMP-9, MMP-14, and MMP-1; and TIMP-3. Other important mechanisms include: ARMS2 and HTR1 proteins, the complement system, the urokinase plasminogen activator system, and pro-renin receptor activation. Continuous rebuilding of the extracellular matrix occurs in both early and advanced AMD, simultaneously with the dysfunction of retinal pigment epithelium (RPE) cells and endothelial cells. The pathological degradation or accumulation of ECM structural components are caused by impairment or hyperactivity of specific MMPs/TIMPs complexes, and is also endangered by the influence of other mechanisms connected with both genetic and environmental factors. PMID:24938626

  20. Role of homocysteine in age-related vascular and non-vascular diseases.

    PubMed

    Parnetti, L; Bottiglieri, T; Lowenthal, D

    1997-08-01

    Homocysteine (Hcy) may represent a metabolic link in the pathogenesis of atherosclerotic vascular diseases and old-age dementias. Hyperhomocysteinemia is an independent risk factor for coronary artery disease and peripheral vascular disease, and is also associated with cerebrovascular disease; specifically, the risk of extracranial carotid atherosclerosis significantly increases in relation to Hcy levels. Hcy is a reliable marker of vitamin B12 deficiency, a common condition in the elderly which is known to induce neurological deficits including cognitive impairment; a high prevalence of folate deficiency has been reported in psychogeriatric patients suffering from depression and dementia. Both these vitamins occupy a key position in the remethylation and synthesis of S-adenosylmethionine (SAMe), a major methyl donor in CNS; therefore, deficiencies in either of these vitamins lead to a decrease in SAMe and increase in Hcy, which can be critical in the aging brain. Another pathogenetic mechanism linking high Hcy levels to reduced cognitive performances in the elderly might be represented by excitotoxicity, since hyperhomocysteinemia may lead to an excessive production of homocysteic acid and cysteine sulphinic acid, which act as endogenous agonists of NMDA receptors. Considering the reasonably high prevalence in the general population of a genetic predisposition to a thermolabile form of the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), hyperhomocysteinemia can be seen as the result of multiple genetic and environmental factors leading to vascular and/or neurodegenerative disorders where age-related involutive phenomena represent a common pathogenetic ground. Systematic studies in different psychogeriatric conditions monitoring Hcy levels and clinical features before and after vitamin supplementation are therefore highly recommended. PMID:9359935

  1. 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.

  2. Evaluation of a proposed therapeutic protocol in 12 dogs with tentative degenerative myelopathy.

    PubMed

    Polizopoulou, Zoe S; Koutinas, Alexander F; Patsikas, Michael N; Soubasis, Nektarios

    2008-09-01

    The objective of this work was to evaluate the long-term efficacy of a proposed therapeutic protocol in 12 dogs with a tentative diagnosis of degenerative myelopathy, followed-up for a 6-month period. Twelve dogs fulfilling the antemortem inclusion criteria (breed, age, adequate vaccination, history of progressive posterior ataxia and/or paraparesis, no radiographic and myelographic abnormalities in the spinal cord and vertebral column) were allocated. All these dogs presented signs of thoracolumbar syndrome (T3-L3), scored as grade I (mild to moderate ataxia and paraparesis) in 10 and grade II (severe ataxia and ambulatory paraparesis) in 2 cases. Treatment included the use of epsilon-aminocaproic acid and N-acetylcysteine, supplemented with vitamins B, C and E. Prednisolone was given for the first two weeks and upon worsening of neurological signs. Daily exercise, performed as walking or swimming, was strongly recommended. Clinicopathological evaluation was normal in all 12 dogs, and survey radiographs and myelograms did not show spinal cord compression. Magnetic resonance imaging (MRI), performed only in 4 dogs, did not disclose compressive disorders or intramedullary lesions. Neurological signs were progressively worsening in all 12 animals, eventually resulting in severe paraparesis (grade III) or paraplegia (grade IV). The applied medications do not appear to be an attractive alternative to conservative management (physiotherapy) or euthanasia in canine degenerative myelopathy, irrespective of its chronicity. PMID:18828481

  3. 78 FR 36305 - Proposed Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-17

    ... AFFAIRS Proposed Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune, Crystalline and Infectious Arthritis) and Dysbaric Osteonecrosis Disability Benefits Questionnaire) Activity... disability benefits related to a claimant's diagnosis of a non-degenerative arthritis or...

  4. 78 FR 65450 - Agency Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-31

    ... AFFAIRS Agency Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune, Crystalline and Infectious Arthritis) and Dysbaric Osteonecrosis Disability Benefits Questionnaire) Activity... oira_submission@omb.eop.gov . Please refer to ``OMB Control No. 2900- NEW (Non-Degenerative...

  5. 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. PMID:26992827

  6. 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...

  7. 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. PMID:26617263

  8. 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...

  9. Three Studies Point to Same Risk Gene for Age-Related Macular Degeneration

    MedlinePlus

    ... macular degeneration Three studies point to same risk gene for age-related macular degeneration NIH-funded research ... in Nature Genetics have converged on the same gene as a rare, but powerful risk factor for ...

  10. 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…

  11. VITAMIN D DEFICIENCY IN NEOVASCULAR VERSUS NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION

    PubMed Central

    Itty, Sujit; Day, Shelley; Lyles, Kenneth W.; Stinnett, Sandra S.; Vajzovic, Lejla M.; Mruthyunjaya, Prithvi

    2014-01-01

    Purpose To compare 25-hydroxyvitamin D (25OHD) levels in patients with neovascular age-related macular degeneration (NVAMD) with patients with nonneovascular age-related macular degeneration and control patients. Methods Medical records of all patients diagnosed with age-related macular degeneration and tested for serum 25OHD level at a single medical center were reviewed. Control patients were selected from patients diagnosed with pseudophakia but without age-related macular degeneration. The lowest 25OHD level available for each patient was recorded. Results Two hundred sixteen patients with nonneovascular age-related macular degeneration, 146 with NVAMD, and 100 non–age-related macular degeneration control patients were included. The levels of 25OHD (mean ± SD) were significantly lower in NVAMD patients (26.1 ± 14.4 ng/mL) versus nonneovascular age-related macular degeneration (31.5 ± 18.2 ng/mL, P = 0.003) and control (29.4 ± 10.1 ng/mL, P = 0.049) patients. The prevalence of vitamin D insufficiency (<30 ng/mL 25OHD), deficiency (<20 ng/mL), and severe deficiency (<10 ng/mL) were highest in the NVAMD group. The highest quintile of 25OHD was associated with a 0.35 (95% confidence interval, 0.18– 0.68) odds ratio for NVAMD. Conclusion This is the largest study to compare 25OHD levels in patients with the different clinical forms of age-related macular degeneration. Mean 25OHD levels were lower and vitamin D deficiency was more prevalent in NVAMD patients. These associations suggest that further research is necessary regarding vitamin D deficiency as a potentially modifiable risk factor for the development of NVAMD. PMID:24946100

  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. 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

  14. A Review of Age-Related Dehydroepiandrosterone Decline and Its Association with Well-Known Geriatric Syndromes: Is Treatment Beneficial?

    PubMed Central

    Samaras, Dimitrios; Frangos, Emilia; Forster, Alexandre; Philippe, Jacques

    2013-01-01

    Abstract Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant steroids in humans. DHEA levels fall with age in men and women, reaching values sometimes as low as 10%–20% of those encountered in young individuals. This age-related decrease suggests an “adrenopause” phenomenon. Studies point toward several potential roles of DHEA, mainly through its hormonal end products, making this decline clinically relevant. Unfortunately, even if positive effects of DHEA on muscle, bone, cardiovascular disease, and sexual function seem rather robust, extremely few studies are large enough and/or long enough for conclusions regarding its effects on aging. Moreover, because it has been publically presented as a “fountain of youth” equivalent, over-the-counter preparations lacking pharmacokinetic and pharmacodynamic data are widely used worldwide. Conceptually, supplementing a pre-hormone is extremely interesting, because it would permit the human organism to adequately use it throughout long periods, increasing or decreasing end products according to his needs. Nevertheless, data on the safety profile of long-term DHEA supplementation are still lacking. In this article, we examine the potential relation between low DHEA levels and well-known age-related diseases, such as sarcopenia, osteoporosis, dementia, sexual disorders, and cardiovascular disease. We also review risks and benefits of existing protocols of DHEA supplementation. PMID:23647054

  15. 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

  16. 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. PMID:26518628

  17. Multiple Brain Markers are Linked to Age-Related Variation in Cognition.

    PubMed

    Hedden, Trey; Schultz, Aaron P; Rieckmann, Anna; Mormino, Elizabeth C; Johnson, Keith A; Sperling, Reisa A; Buckner, Randy L

    2016-04-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. PMID:25316342

  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. 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.

  20. Congenitally corrected transposition and degenerative severe aortic stenosis.

    PubMed

    Faganello, Giorgio; Nelson, Martin; Stuart, Graham

    2008-10-01

    Congenitally corrected transposition is a rare cardiac anomaly characterized by the combination of discordant atrioventricular and ventriculoarterial connections. Young patients with this lesion can present with congestive cardiac failure, usually secondary to a large ventricular septal defect or pulmonary stenosis. We report here our experience with a lady aged 79, admitted to our unit because of deterioration of her congestive cardiac failure as a consequence of uncorrected congenitally corrected transposition associated with degenerative severe aortic stenosis. PMID:18752714

  1. Copeptin constitutes a novel biomarker of degenerative aortic stenosis.

    PubMed

    Mizia-Stec, Katarzyna; Lasota, Bartosz; Mizia, Magdalena; Chmiel, Artur; Adamczyk, Tomasz; Chudek, Jerzy; Gasior, Zbigniew

    2013-09-01

    Copeptin is a new biomarker of cardiovascular diseases. Its diagnostic value in degenerative aortic valve stenosis (AS) with preserved left ventricle systolic function is unknown. We aimed to assess the association of serum copeptin levels with AS severity and coexistence of coronary artery disease (CAD). Sixty-four patients with AS and preserved left ventricle systolic function including 40 with severe degenerative AS (group sAS, effective orifice area EOA = 0.67 cm(2)) and 24 with moderate degenerative AS (group mAS, EOA = 1.40 cm(2)) were enrolled into the study. Twenty-three patients without AS and heart failure, matched for age, sex, and CAD occurrence served as the control group (group C). Serum levels of copeptin and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured using enzyme-linked immunosorbent assay. The mean serum copeptin concentrations were significantly higher in patients with AS: sAS (405 pg/ml) and mAS (351 pg/ml; sAS vs mAS P < 0.05), compared with group C (302 pg/ml, P < 0.05). Serum copeptin levels correlated inversely with EOA (r = -0.55; P < 0.001) in AS patients. There was no correlation between copeptin and NT-proBNP or association with the coexisting CAD. Receiver-operating characteristics analysis showed that copeptin was a good marker of severe/moderate AS (sensitivity 71 %; specificity 87 %), with the optimized cut-off value of 354 pg/ml. Serum copeptin concentration constitutes a novel biomarker of degenerative AS. Coexisting CAD does not interfere with copeptin level. PMID:23142954

  2. Decompression without Fusion for Low-Grade Degenerative Spondylolisthesis

    PubMed Central

    Cheung, Jason Pui Yin; Cheung, Prudence Wing Hang; Cheung, Kenneth Man Chee

    2016-01-01

    Study Design Retrospective series. Purpose Assess results of decompression-only surgery for low-grade degenerative spondylolisthesis with consideration of instability. Overview of Literature There is no consensus on whether fusion or decompression-only surgery leads to better outcomes for patients with low-grade degenerative spondylolisthesis. Current trends support fusion but many studies are flawed due to over-generalization without consideration of radiological instability and their variable presentations and natural history. Methods Patients with surgically treated degenerative spondylolisthesis from 1990–2013 were included. Clinical and radiological instability measures were included. Any residual or recurrence of symptoms, revision surgery performed and functional outcome scores including the numerical global rate of change scale, visual analogue scale, and modified Barthel index were measured. Follow-up periods for patients were divided into short-term (<5 years), mid-term (5–10 years) and long-term (>10 years). Results A total of 64 patients were recruited. Mechanical low back pain was noted in 48 patients and most (85.4%) had relief of back pain postoperatively. Radiological instability was noted in 4 subjects by flexion-extension radiographs and 12 subjects with prone traction radiographs by increased disc height and reduction of olisthesis and slip angle. From the results of the short-term, mid-term and long-term follow-up, reoperation only occurred within the first 5-year follow-up period. All functional scores improved from preoperative to postoperative 1-year follow-up. Conclusions Decompression-only for low-grade degenerative spondylolisthesis has good long-term results despite instability. Further higher-level studies should be performed on this patient group with radiological instability to suggest the superior surgical option. PMID:26949462

  3. Degenerative myelopathy in 18 Pembroke Welsh Corgi dogs.

    PubMed

    March, P A; Coates, J R; Abyad, R J; Williams, D A; O'Brien, D P; Olby, N J; Keating, J H; Oglesbee, M

    2009-03-01

    Postmortem examination was performed on 18 Pembroke Welsh Corgi dogs (mean age 12.7 years) with clinical signs and antemortem diagnostic tests compatible with a diagnosis of degenerative myelopathy. Tissue sections from specific spinal cord and brain regions were systematically evaluated in all dogs. Axonal degeneration and loss were graded according to severity and subsequently compared across different spinal cord segments and funiculi. White matter lesions were identified in defined regions of the dorsal, lateral, and ventral funiculi. The dorsolateral portion of the lateral funiculus was the most severely affected region in all cord segments. Spinal cord segment T12 exhibited the most severe axonal loss. Spinal nerve roots, peripheral nerves, and brain sections were within normal limits, with the exception of areas of mild astrogliosis in gray matter of the caudal medulla. Dogs with more severe lesions showed significant progression of axonal degeneration and loss at T12 and at cord segments cranial and caudal to T12. Severity of axonal loss in individual dogs positively correlated with the duration of clinical signs. The distribution of axonal degeneration resembled that reported in German Shepherd Dog degenerative myelopathy but differed with respect to the transverse and longitudinal extent of the lesions within more clearly defined funicular areas. Although these lesion differences might reflect disease longevity, they could also indicate a form of degenerative myelopathy unique to the Pembroke Welsh Corgi dog. PMID:19261635

  4. 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).

  5. Anatomic Alterations in Aging and Age-Related Diseases of the Eye

    PubMed Central

    Grossniklaus, Hans E.; Nickerson, John M.; Edelhauser, Henry F.; Bergman, Louise A. M. K.; Berglin, Lennart

    2013-01-01

    Purpose. We described anatomic age-related changes in the human eye to determine potential areas of investigation that may lead to identifying eyes at risk for age-related disease. Methods. A descriptive review of anatomic changes in the eye related to aging was performed in the context of current areas of investigation. The review was performed specifically for differing anatomic ocular structures, including cornea, trabecular meshwork, lens, uveal tract, Bruch's membrane, retina, RPE, vitreous, sclera, and optic nerve. Results. Age-related changes occur in all ocular tissues. The cornea flattens and there is an attrition of endothelial cells. The shape of the trabecular meshwork changes and there is a loss of trabecular endothelium. The lens grows and becomes cataractous. The ciliary body becomes collagenized, there are choroidal vascular changes, and Bruch's membrane thickens. Retinal vessels become hyalinized and there is a loss of rods before cones in the macula. RPE morphometric changes occur with aging. The vitreous becomes liquefied and there is a loss of vitreous compartmentalization. The sclera becomes rigid and may become calcified. The optic nerve exhibits structural changes with age. Conclusions. There are numerous anatomic age-related changes in the human eye. Current areas of investigation related to these changes include adaptive optics scanning laser ophthalmoscopy imaging of the RPE mosaic in the context of aging, and drug delivery devices that overcome age-related alterations to retinal and macular perfusion. PMID:24335063

  6. 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

  7. [Age-related macular degeneration – a challenge for public health care].

    PubMed

    Mantel, Irmela

    2016-01-01

    Age-related macular degeneration (AMD) is the predominant cause of legal blindness in the population over 50 years of age. The disorder shows exponentially increasing prevalence with age, and the late forms with their vision threatening evolution are found in approximately one third of cases. The late AMD may be purely atrophic and so far untreatable. Or it may be neovascular and exudative, for which medical treatment is available, consisting of repetitive intravitreous injections of Anti-VEGF molecules. The treatment is highly effective in blocking the growth of the pathological vessels and allowing resolution of the accompanying edema. Visual improvement is variable but often very meaningful for the patients. However, the final visual level depends mostly on early intervention. Thus, screening for the first signs of neovascular AMD is crucial for the endresult. However, the repetitive intraocular injections are an important burden for the patients. Due to the high patient numbers, the chronic care management with steadily adding new patients is a major challenge for treating institutions. Limited resources may put patients at risk of undertreatment with resulting visual loss. Various strategies have been developed to cope with the burden. In addition, the financial cost is high for the health care system. On the other hand, timely and ongoing treatment is the best investment to achieve meaningful visual improvement, which is extremely important for the quality of life and autonomy of the patients. Side effects of the treatment are limited and mostly procedure related. Systemic side effects are possible but despite the large studies not conclusive. However, care must be taken in cases of high cardiovascular risk, as thromboembolic risk increase may rarely happen. So far unsolved problems include the long term visual results, the degree of reversibility of neovascularization, and the missing treatment options of atrophic AMD. Basic and clinical research on various

  8. 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

  9. When feeling different pays off: how older adults can counteract negative age-related information.

    PubMed

    Weiss, David; Sassenberg, Kai; Freund, Alexandra M

    2013-12-01

    Negative age stereotypes are pervasive and threaten older adults' self-esteem. Two experiments tested the hypothesis that differentiation from one's age group reduces the impact of negative age-related information on older adults' self-evaluation. In Experiment 1, older adults (N = 83, M = 71.9 years) were confronted with neutral or negative age-related information followed by a manipulation of self-differentiation. Experiment 2 (N = 44, M = 73.55 years) tested the moderating role of self-differentiation in the relationship of implicit attitudes toward older adults and implicit self-esteem. Results suggest that self-differentiation prevents the impact of negative age-related information on older adults' self-esteem. PMID:23957227

  10. Perspective: A Critical Look at the Ancillary Age-Related Eye Disease Study 2: Nutrition and Cognitive Function Results in Older Individuals with Age-Related Macular Degeneration.

    PubMed

    Hammond, Billy R; Renzi-Hammond, Lisa M

    2016-05-01

    A large body of literature suggests that the dietary carotenoids lutein and zeaxanthin and long-chain polyunsaturated fatty acids such as docosahexaenoic acid are related to improved cognitive function across the life span. A recent report by the Age-Related Eye Disease Study (AREDS) group appears to contradict the general findings of others in the field. In this review, we look critically at the methods, study designs, and analysis techniques used in the larger body of literature and compare them with the recent AREDS reports. PMID:27184270

  11. 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

  12. Relation of smoking to the incidence of age-related maculopathy. The Beaver Dam Eye Study.

    PubMed

    Klein, R; Klein, B E; Moss, S E

    1998-01-15

    To date, a number of reports have been published on the relation of cigarette smoking to age-related maculopathy, an important cause of blindness in the United States. However, few studies have examined the relation between smoking and the incidence of age-related maculopathy. In this report, the authors examine this association in persons aged 43-86 years (n = 3,583) at baseline who were participants in the baseline examination and 5-year follow-up of the Beaver Dam Eye Study, Beaver Dam, Wisconsin (1988-1990 and 1993-1995). Exposure data on cigarette smoking were obtained from questions about present and past smoking, duration of smoking, and the number of cigarettes smoked per day. Age-related maculopathy status was determined by grading stereoscopic color fundus photographs using the Wisconsin Age-related Maculopathy Grading System. After controlling for age, sex, vitamin supplement use, and beer consumption, men who smoked greater amounts of cigarettes were more likely to develop early age-related maculopathy (odds ratio (OR) per 10 pack-years smoked = 1.06, 95% confidence interval (CI) 1.00-1.13, p = 0.06) than men who had smoked less. This association was not observed in women. Men (OR = 3.21, 95% CI 1.09-9.45) and women (OR = 2.20, 95% CI 1.04-4.66) who were current smokers at the time of the baseline examination had significantly higher odds of developing large drusen (> or = 250 microns in diameter) after 5 years than those who had never smoked or who quit before the baseline study. Current or past history of cigarette smoking was not related to the incidence of retinal pigment epithelial depigmentation. The authors conclude that smoking appears to be related to the incidence of some lesions associated with early age-related maculopathy. PMID:9456998

  13. 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

  14. 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

  15. 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

  16. Smoking and age-related macular degeneration: biochemical mechanisms and patient support.

    PubMed

    Willeford, Kevin T; Rapp, Jerry

    2012-11-01

    A small percentage of the population associates smoking with ocular disease. Most optometrists do not stress the importance of smoking cessation to their patients, and the centrality of smoking regarding the risk for ocular disease is not emphasized in optometric education. Age-related macular degeneration has strong epidemiological associations with smoking, and so serves as an appropriate model for the adverse effects of cigarette smoke on the eye. This article aims to provide basic scientific information to optometrists and optometry students so that they can better understand the pathogenesis of age-related macular degeneration and provide education and support to their patients wishing to stop smoking. PMID:23034338

  17. 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

  18. 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.

  19. Fatty old hearts: role of cardiac lipotoxicity in age-related cardiomyopathy.

    PubMed

    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

  20. 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.

  1. European survey on the opinion and use of micronutrition in age-related macular degeneration: 10 years on from the Age-Related Eye Disease Study

    PubMed Central

    Aslam, Tariq; Delcourt, Cécile; Holz, Frank; García-Layana, Alfredo; Leys, Anita; Silva, Rufino M; Souied, Eric

    2014-01-01

    Purpose To evaluate ophthalmologists’ opinion of, and use of, micronutritional dietary supplements 10 years after publication of the first Age-Related Eye Disease Study (AREDS) study. Methods Participation was solicited from 4,000 European ophthalmologists. Responding physicians were screened, and those treating at least 40 patients with age-related macular degeneration (AMD) per month and prescribing nutrition supplements at least 4 times per month were admitted and completed a 40-item questionnaire. Results The surveyed sample included 112 general ophthalmologists and 104 retinal specialists. Most nutritional supplements (46%) were initiated when early/intermediate AMD was confirmed, although 18% were initiated on confirmation of neovascular AMD. Clinical studies were well known: 90% were aware of AREDS, with 88% aware of AREDS1 and 36% aware of the, as-yet-unpublished, AREDS2 studies. Respondents considered lutein, zeaxanthin, zinc, omega-3, and vitamins to be the most important components of nutritional supplements, with the results of AREDS2 already having been taken into consideration by many. Ophthalmologists anticipate more scientific studies as well as improved product quality but identify cost as a barrier to wider uptake. Conclusion Micronutrition is now part of the routine management of AMD for many ophthalmologists. Ophthalmologists choosing to use nutritional supplements are well-informed regarding current scientific studies. PMID:25336904

  2. 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. PMID:27142156

  3. Age-related axonal swellings precede other neuropathological hallmarks in a knock-in mouse model of Huntington's disease.

    PubMed

    Marangoni, Martina; Adalbert, Robert; Janeckova, Lucie; Patrick, Jane; Kohli, Jaskaren; Coleman, Michael P; Conforti, Laura

    2014-10-01

    Axon degeneration precedes cell body death in many age-related neurodegenerative disorders, often determining symptom onset and progression. A sensitive method for revealing axon pathology could indicate whether this is the case also in Huntington's disease (HD), a fatal, devastating neurodegenerative disorder causing progressive deterioration of both physical and mental abilities, and which brain region is affected first. We studied the spatio-temporal relationship between axon pathology, neuronal loss, and mutant Huntingtin aggregate formation in HD mouse models by crossing R6/2 transgenic and HdhQ140 knock-in mice with YFP-H mice expressing the yellow fluorescent protein in a subset of neurons. We found large axonal swellings developing age-dependently first in stria terminalis and then in corticostriatal axons of HdhQ140 mice, whereas alterations of other neuronal compartments could not be detected. Although mutant Huntingtin accumulated with age in several brain areas, inclusions in the soma did not correlate with swelling of the corresponding axons. Axon abnormalities were not a prominent feature of the rapid progressive pathology of R6/2 mice. Our findings in mice genetically similar to HD patients suggest that axon pathology is an early event in HD and indicate the importance of further studies of stria terminalis axons in man. PMID:24906892

  4. 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…

  5. 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.…

  6. 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…

  7. 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…

  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. 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…

  10. 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…

  11. Myelin Breakdown Mediates Age-Related Slowing in Cognitive Processing Speed in Healthy Elderly Men

    ERIC Educational Resources Information Center

    Lu, Po H.; Lee, Grace J.; Tishler, Todd A.; Meghpara, Michael; Thompson, Paul M.; Bartzokis, George

    2013-01-01

    Background: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer's disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). Materials and methods: The prefrontal lobe white matter and the genu of…

  12. Age-related difference in relationships between cognitive processing speed and general cognitive status.

    PubMed

    Tam, Helena M K; Lam, Charlene L M; Huang, Haixia; Wang, Baolan; Lee, Tatia M C

    2015-01-01

    General cognitive status (GCS) is a composite of cognitive abilities reflecting full function. The literature suggests a relationship between cognitive processing speed and GCS, as well as age-related changes of processing speed on cognitive performance. Therefore, this study recruited 34 younger and 39 older adults to verify age-related differences in relationships between cognitive processing speed and GCS. We measured cognitive processing speed with the Processing Speed Index of the Wechsler Adult Intelligence Scale. Findings indicated that cognitive processing speed predicted GCS in older but not younger adults. Future research may be needed to verify the training effect of processing speed on GCS. This study also further examined cognitive factors related to processing speed in aging and the relationships between cognitive processing speed and verbal fluency, cognitive inhibition, and divided attention. A stepwise regression analysis indicated that only verbal fluency contributed significantly to cognitive processing speed in older adults, accounting for 21% of the variance. These observations suggest that age-related changes of prefrontal regions may not fully explain age-related decline in cognitive processing speed. PMID:24927241

  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 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,…

  15. 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

  16. Assessing age-related etiologic heterogeneity in the onset of islet autoimmunity.

    PubMed

    Frederiksen, Brittni N; Kroehl, Miranda; Barón, Anna; Lamb, Molly M; Crume, Tessa L; Sontag, Marci K; Rewers, Marian; Norris, Jill M

    2015-01-01

    Type 1 diabetes (T1D), a chronic autoimmune disease, is often preceded by a preclinical phase of islet autoimmunity (IA) where the insulin-producing beta cells of the pancreas are destroyed and circulating autoantibodies can be detected. The goal of this study was to demonstrate methods for identifying exposures that differentially influence the disease process at certain ages by assessing age-related heterogeneity. The Diabetes Autoimmunity Study in the Young (DAISY) has followed 2,547 children at increased genetic risk for T1D from birth since 1993 in Denver, Colorado, 188 of whom developed IA. Using the DAISY population, we evaluated putative determinants of IA, including non-Hispanic white (NHW) ethnicity, maternal age at birth, and erythrocyte membrane n-3 fatty acid (FA) levels, for age-related heterogeneity. A supremum test, weighted Schoenfeld residuals, and restricted cubic splines were used to assess nonproportional hazards, that is, an age-related association of the exposure with IA risk. NHW ethnicity, maternal age, and erythrocyte membrane n-3 FA levels demonstrated a significant age-related association with IA risk. Assessing heterogeneity in disease etiology enables researchers to identify associations that may lead to better understanding of complex chronic diseases. PMID:25883970

  17. Modulative effects of COMT haplotype on age-related associations with brain morphology.

    PubMed

    Lee, Annie; Qiu, Anqi

    2016-06-01

    Catechol-O-methyltransferase (COMT), located on chromosome 22q11.2, encodes an enzyme critical for dopamine flux in the prefrontal cortex. Genetic variants of COMT have been suggested to functionally manipulate prefrontal morphology and function in healthy adults. This study aims to investigate modulative roles of individuals COMT SNPs (rs737865, val158met, rs165599) and its haplotypes in age-related brain morphology using an Asian sample with 174 adults aged from 21 to 80 years. We showed an age-related decline in cortical thickness of the dorsal visual pathway, including the left dorsolateral prefrontal cortex, bilateral angular gyrus, right superior frontal cortex, and age-related shape compression in the basal ganglia as a function of the genotypes of the individual COMT SNPs, especially COMT val158met. Using haplotype trend regression analysis, COMT haplotype probabilities were estimated and further revealed an age-related decline in cortical thickness in the default mode network (DMN), including the posterior cingulate, precuneus, supramarginal and paracentral cortex, and the ventral visual system, including the occipital cortex and left inferior temporal cortex, as a function of the COMT haplotype. Our results provided new evidence on an antagonistic pleiotropic effect in COMT, suggesting that genetically programmed neural benefits in early life may have a potential bearing towards neural susceptibility in later life. Hum Brain Mapp 37:2068-2082, 2016. © 2016 Wiley Periodicals, Inc. PMID:26920810

  18. 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...

  19. Age-Related Changes to the Neural Correlates of Social Evaluation

    PubMed Central

    Cassidy, Brittany S.; Shih, Joanne Y.; Gutchess, Angela H.

    2012-01-01

    Recent work suggests the existence of a specialized neural system underlying social processing that may be relatively spared with age, unlike pervasive aging-related decline occurring in many cognitive domains. We investigated how neural mechanisms underlying social evaluation are engaged with age, and how age-related changes to socioemotional goals affect recruitment of regions within this network. In a functional MRI study, fifteen young and fifteen older adults formed behavior-based impressions of individuals. They also responded to a prompt that was interpersonally meaningful, social but interpersonally irrelevant, or non-social. Both age groups engaged regions implicated in mentalizing and impression formation when making social relative to non-social evaluations, including dorsal and ventral medial prefrontal cortices, precuneus, and temporoparietal junction. Older adults had increased activation over young in right temporal pole when making social relative to non-social evaluations, suggesting reliance on past experiences when evaluating others. Young had greater activation than old in posterior cingulate gyrus when making interpersonally irrelevant, compared to interpersonally meaningful, evaluations, potentially reflecting enhanced valuation of this information. The findings demonstrate the age-related preservation of the neural correlates underlying social evaluation, and suggest that functioning in these regions might be mediated by age-related changes in socioemotional goals. PMID:22439896

  20. 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...

  1. Recent Advances in Berry Supplementation and Age-Related Cognitive Decline

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To summarize recent findings and current concepts in the beneficial effects of berry consumption on brain function during aging. Berryfruit supplementation has continued to demonstrate efficacy in reversing age-related cognitive decline in animal studies. In terms of the mechanisms behind the effe...

  2. Age-Related Macular Degeneration: New Eye Treatment Saves Former Math Teacher's Sight

    MedlinePlus

    ... turn JavaScript on. Feature: Age-related Macular Degeneration New Eye Treatment Saves Former Math Teacher's Sight Summer ... and sends images to your brain. (“Neovascular” means “new vessels.”) These vessels can leak fluid and blood, ...

  3. Motor Control and Aging: Links to Age-Related Brain Structural, Functional, and Biochemical Effects

    PubMed Central

    Seidler, Rachael D.; Bernard, Jessica A.; Burutolu, Taritonye B.; Fling, Brett W.; Gordon, Mark T.; Gwin, Joseph T.; Kwak, Youngbin; Lipps, David B.

    2009-01-01

    Although connections between cognitive deficits and age-associated brain differences have been elucidated, relationships with motor performance are less well understood. Here, we broadly review age-related brain differences and motor deficits in older adults in addition to cognition-action theories. Age-related atrophy of the motor cortical regions and corpus callosum may precipitate or coincide with motor declines such as balance and gait deficits, coordination deficits, and movement slowing. Correspondingly, degeneration of neurotransmitter systems—primarily the dopaminergic system—may contribute to age-related gross and fine motor declines, as well as to higher cognitive deficits. In general, older adults exhibit involvement of more widespread brain regions for motor control than young adults, particularly the prefrontal cortex and basal ganglia networks. Unfortunately these same regions are the most vulnerable to age-related effects, resulting in an imbalance of “supply and demand”. Existing exercise, pharmaceutical, and motor training interventions may ameliorate motor deficits in older adults. PMID:19850077

  4. Who, When, and Where? Age-Related Differences on a New Memory Test

    ERIC Educational Resources Information Center

    Sumida, Catherine A.; Holden, Heather M.; Van Etten, Emily J.; Wagner, Gabrielle M.; Hileman, Jacob D.; Gilbert, Paul E.

    2016-01-01

    Our study examined age-related differences on a new memory test assessing memory for "who," "when," and "where," and associations among these elements. Participants were required to remember a sequence of pictures of different faces paired with different places. Older adults remembered significantly fewer correct…

  5. 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).…

  6. PHARMACOKINETIC DIFFERENCES MAY EXPLAIN THE AGE-RELATED SENSITIVITY OF DELTAMETHRIN, A PYRETHROID INSECTICIDE, IN RATS.

    EPA Science Inventory

    This study was designed to examine the age-related sensitivity to the pyrethroid insecticide, deltamethrin [(S)- -cyano-3-phenoxybenzyl (1R,3R)-3-(2,2-dibromomovinyl)2,2-dimethylcyclopropanecarboxylate], in Long Evans, hooded, male rats. Deltamethrin has been shown to be more ...

  7. 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…

  8. The Prevalence of Age-Related Eye Diseases and Visual Impairment in Aging: Current Estimates

    PubMed Central

    Klein, Ronald; Klein, Barbara E. K.

    2013-01-01

    Purpose. To examine prevalence of five age-related eye conditions (age-related cataract, AMD, open-angle glaucoma, diabetic retinopathy [DR], and visual impairment) in the United States. Methods. Review of published scientific articles and unpublished research findings. Results. Cataract, AMD, open-angle glaucoma, DR, and visual impairment prevalences are high in four different studies of these conditions, especially in people over 75 years of age. There are disparities among racial/ethnic groups with higher age-specific prevalence of DR, open-angle glaucoma, and visual impairment in Hispanics and blacks compared with whites, higher prevalence of age-related cataract in whites compared with blacks, and higher prevalence of late AMD in whites compared with Hispanics and blacks. The estimates are based on old data and do not reflect recent changes in the distribution of age and race/ethnicity in the United States population. There are no epidemiologic estimates of prevalence for many visually-impairing conditions. Conclusions. Ongoing prevalence surveys designed to provide reliable estimates of visual impairment, AMD, age-related cataract, open-angle glaucoma, and DR are needed. It is important to collect objective data on these and other conditions that affect vision and quality of life in order to plan for health care needs and identify areas for further research. PMID:24335069

  9. Muscle-specificity of age-related changes in markers of autophagy and sphingolipid metabolism.

    PubMed

    Russ, David W; Boyd, Iva M; McCoy, Katherine M; McCorkle, Katherine W

    2015-12-01

    Our previous findings indicate that the gastrocnemius muscle of aging rats exhibits impairments of muscle quality (force/unit muscle tissue) and autophagy and increased sarcoplasmic reticulum stress. The purpose of this study was to examine age-related changes in soleus muscle contractility and in markers of autophagy in the soleus and gastrocnemius muscles. We assessed in situ muscle force and size in the soleus muscle of adult (7-8 months) and aged (24-26 months) male, F344/BN rats. We used immunoblotting to compare abundance of markers of autophagy, sarcoplasmic reticulum (SR) stress and sphingolipid metabolism in the soleus and medial gastrocnemius (MG) muscles of these animals. Relative to adults, aged rats maintained soleus muscle quality and increased muscle size, resulting in increased tetanic force production. Immunoblotting revealed a general pattern of an age-related reduction of basal autophagy, despite increases in indicators of SR stress and upstream autophagic pathway activation in the MG. The MG also exhibited changes in markers of sphingolipid metabolism suggestive of increased muscle ceramide. Minimal age-related changes were observed in the soleus. The soleus maintains muscle mass and quality with age, and exhibits fewer age-related changes in markers of stress and autophagy than the MG. Based on these data, we suggest that maintenance of autophagy may preserve muscle quality by preventing excessive SR stress. PMID:26296420

  10. Repetition Priming in Adults with Williams Syndrome: Age-Related Dissociation between Implicit and Explicit Memory

    ERIC Educational Resources Information Center

    Krinsky-McHale, Sharon J.; Kittler, Phyllis; Brown, W. Ted; Jenkins, Edmund C.; Devenny, Darlynne A.

    2005-01-01

    We examined implicit and explicit memory in adults with Williams syndrome. An age-related dissociation was found; repetition priming (reflecting implicit memory) did not show change with age, but free recall (reflecting explicit memory) was markedly reduced. We also compared the performance of adults with Williams syndrome to adults with Down…

  11. Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma.

    PubMed

    Sandhu, Rupninder; Chollet-Hinton, Lynn; Kirk, Erin L; Midkiff, Bentley; Troester, Melissa A

    2016-02-01

    Complete age-related regression of mammary epithelium, often termed postmenopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study. High-resolution digital images of normal breast hematoxylin and eosin-stained slides were partitioned into epithelium, adipose tissue, and nonfatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models. Stromal area decreased (P = 0.0002), and adipose tissue area increased (P < 0.0001), with an approximate 0.7% change in area for each component, until age 55 years when these area measures reached a steady state. Although epithelial area did not show linear changes with age, epithelial nuclear density decreased linearly beginning in the third decade of life. No significant age-related trends were observed for stromal or adipose nuclear density. Digital image analysis offers a high-throughput method for quantitatively measuring tissue morphometry and for objectively assessing age-related changes in adipose tissue, stroma, and epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period. PMID:26772400

  12. 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...

  13. 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...

  14. 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...

  15. Assessing Age-Related Etiologic Heterogeneity in the Onset of Islet Autoimmunity

    PubMed Central

    Frederiksen, Brittni N.; Barón, Anna; Lamb, Molly M.; Crume, Tessa L.; Sontag, Marci K.; Norris, Jill M.

    2015-01-01

    Type 1 diabetes (T1D), a chronic autoimmune disease, is often preceded by a preclinical phase of islet autoimmunity (IA) where the insulin-producing beta cells of the pancreas are destroyed and circulating autoantibodies can be detected. The goal of this study was to demonstrate methods for identifying exposures that differentially influence the disease process at certain ages by assessing age-related heterogeneity. The Diabetes Autoimmunity Study in the Young (DAISY) has followed 2,547 children at increased genetic risk for T1D from birth since 1993 in Denver, Colorado, 188 of whom developed IA. Using the DAISY population, we evaluated putative determinants of IA, including non-Hispanic white (NHW) ethnicity, maternal age at birth, and erythrocyte membrane n-3 fatty acid (FA) levels, for age-related heterogeneity. A supremum test, weighted Schoenfeld residuals, and restricted cubic splines were used to assess nonproportional hazards, that is, an age-related association of the exposure with IA risk. NHW ethnicity, maternal age, and erythrocyte membrane n-3 FA levels demonstrated a significant age-related association with IA risk. Assessing heterogeneity in disease etiology enables researchers to identify associations that may lead to better understanding of complex chronic diseases. PMID:25883970

  16. The potential effects of meditation on age-related cognitive decline: a systematic review

    PubMed Central

    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. PMID:24571182

  17. 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...

  18. 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

  19. 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…

  20. Age-Related Effects on the Acquisition of Second Language Phonology and Grammar

    ERIC Educational Resources Information Center

    Huang, Hsuan-hua Becky

    2009-01-01

    The current study set out to examine the age-related effects on ultimate attainment of second language (L2) phonology and grammar. The goals of the study are threefold: (1) to unravel the complexity of ultimate L2 attainment by surveying multiple contributing factors, (2) to explore the relative strength of the Age of Arrival (AOA) variable and…

  1. 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

  2. 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…

  3. 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...

  4. 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…

  5. 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

  6. Age-related increase in prostacyclin production in the rat aorta.

    PubMed

    Panganamala, R V; Hanumaiah, B; Merola, A J

    1981-02-01

    Normal Sprague-Dawley rats convert a substantial percentage of exogenous arachidonic acid to prostacyclin. This conversion can be quantitated by an aqueous sampling technique utilizing thin layer chromatography and liquid scintillation counting. There is a clear age-related increase in this conversion that can be demonstrated in aortas from rats of 3 weeks to 20 weeks of age. PMID:7017783

  7. 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…

  8. 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…

  9. 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…

  10. Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases.

    PubMed

    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

  11. P2X7-pannexin-1 and amyloid β-induced oxysterol input in human retinal cell: Role in age-related macular degeneration?

    PubMed

    Olivier, Elodie; Dutot, Mélody; Regazzetti, Anne; Leguillier, Teddy; Dargère, Delphine; Auzeil, Nicolas; Laprévote, Olivier; Rat, Patrice

    2016-08-01

    Age-related macular degeneration (AMD) is the most common cause of severe vision loss worldwide. Amyloid β involvement in degenerative diseases such as AMD is well known and its toxicity has been related to P2X7 receptor-pannexin-1. Recently, oxysterols (oxidized derivatives of cholesterol) have been implicated in AMD pathogenesis. The aim of our study was to highlight amyloid β/oxysterols relationship and to describe P2X7 receptor-pannexin-1 role in oxysterols toxicity. Using retinal epithelial cells, we first quantified sterols levels after amyloid β incubation and second we investigated the cytotoxic effects induced by oxysterols. For the first time, our results showed that amyloid β induced oxysterols formation in human retinal pigmented epithelial cells. We showed that oxysterol toxicity is mediated by P2X7 receptor activation. This activation was dependent on pannexin-1 with 25-hydroxycholesterol whereas P2X7 receptor signaling pathway was pannexin-1-independent for 7-ketocholesterol. Taken together our data suggest a pivotal role of P2X7 receptor-pannexin-1 in oxysterols toxicity in retinal cells which could be an important target to develop new treatments for AMD. PMID:27109381

  12. Low levels of aluminum can lead to behavioral and morphological changes associated with Alzheimer's disease and age-related neurodegeneration.

    PubMed

    Bondy, Stephen C

    2016-01-01

    Aluminum (Al) is a very common component of the earth's mineral composition. It is not essential element for life and is a constituent of rather inert minerals. Therefore, it has often been regarded as not presenting a significant health hazard. As a result, aluminum-containing agents been used in the preparation of many foodstuffs processing steps and also in elimination of particulate organic matter from water. More recently, the reduced pH of bodies of water resulting from acid rain has led to mobilization of aluminum-containing minerals into a more soluble form, and these have thus entered residential drinking water resources. By this means, the body burden of aluminum in humans has increased. Epidemiological and experimental findings indicate that aluminum is not as harmless as was previously thought, and that aluminum may contribute to the inception and advancement of Alzheimer's disease. Epidemiological data is reinforced by indications that aluminum exposure can result in excess inflammatory activity within the brain. Activation of the immune system not initiated by an infectious agent, typifies the aging brain and is even more augmented in several neurodegenerative diseases. The origin of most age-related neurological disorders is generally not known but as they are largely not of genetic derivation, their development is likely triggered by unknown environmental factors. There is a growing and consistent body of evidence that points to aluminum as being one such significant influence. Evidence is presented that reinforces the likelihood that aluminum is a factor speeding the rate of brain aging. Such acceleration would inevitably enlarge the incidence of age-related neurological diseases. PMID:26687397

  13. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    PubMed Central

    Bennis, Anna; Gorgels, Theo G. M. F.; ten Brink, Jacoline B.; van der Spek, Peter J.; Bossers, Koen; Heine, Vivi M.; Bergen, Arthur A.

    2015-01-01

    Background The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new therapeutics. This requires further in-depth knowledge of the similarities and differences between mouse and human RPE. Methods We performed a microarray study to identify and functionally annotate RPE specific gene expression in mouse and human RPE. We used a meticulous method to determine C57BL/6J mouse RPE signature genes, correcting for possible RNA contamination from its adjacent layers: the choroid and the photoreceptors. We compared the signature genes, gene expression profiles and functional annotations of the mouse and human RPE. Results We defined sets of mouse (64), human (171) and mouse–human interspecies (22) RPE signature genes. Not unexpectedly, our gene expression analysis and comparative functional annotation suggested that, in general, the mouse and human RPE are very similar. For example, we found similarities for general features, like “organ development” and “disorders related to neurological tissue”. However, detailed analysis of the molecular pathways and networks associated with RPE functions, suggested also multiple species-specific differences, some of which may be relevant for the development of AMD. For example, CFHR1, most likely the main complement regulator in AMD pathogenesis was highly expressed in human RPE, but almost absent in mouse RPE. Furthermore, functions assigned to mouse and human RPE expression profiles indicate (patho-) biological differences related to AMD, such as oxidative stress, Bruch’s membrane, immune-regulation and outer blood retina barrier. Conclusion These differences may be important for the development of new therapeutic strategies and translational studies in age-related macular

  14. Age related-changes in the neural basis of self-generation in verbal paired associate learning.

    PubMed

    Vannest, Jennifer; Maloney, Thomas; Kay, Benjamin; Siegel, Miriam; Allendorfer, Jane B; Banks, Christi; Altaye, Mekibib; Szaflarski, Jerzy P

    2015-01-01

    Verbal information is better retained when it is self-generated rather than when it is received passively. The application of self-generation procedures has been found to improve memory in healthy elderly and in individuals with impaired cognition. Overall, the available studies support the notion that active participation in verbal encoding engages memory mechanisms that supplement those used during passive observation. Thus, the objective of this study was to investigate the age-related changes in the neural mechanisms involved in the encoding of paired-associates using a self-generation method that has been shown to improve memory performance across the lifespan. Subjects were 113 healthy right-handed adults (Edinburgh Handedness Inventory >50; 67 females) ages 18-76, native speakers of English with no history of neurological or psychiatric disorders. Subjects underwent fMRI at 3 T while performing didactic learning ("read") or self-generation learning ("generate") of 30 word pairs per condition. After fMRI, recognition memory for the second word in each pair was evaluated outside of the scanner. On the post-fMRI testing more "generate" words were correctly recognized than "read" words (p < 0.001) with older adults recognizing the "generated" words less accurately (p < 0.05). Independent component analysis of fMRI data identified task-related brain networks. Several components were positively correlated with the task reflecting multiple cognitive processes involved in self-generated encoding; other components correlated negatively with the task, including components of the default-mode network. Overall, memory performance on generated words decreased with age, but the benefit from self-generation remained consistently significant across ages. Independent component analysis of the neuroimaging data revealed an extensive set of components engaged in self-generation learning compared with didactic learning, and identified areas that were associated with age-related

  15. Mineralization of the connective tissue: a complex molecular process leading to age-related loss of function.

    PubMed

    Shindyapina, Anastasia V; Mkrtchyan, Garik V; Gneteeva, Tatiana; Buiucli, Sveatoslav; Tancowny, B; Kulka, M; Aliper, Alexander; Zhavoronkov, Alexander

    2014-04-01

    Age-related metastatic mineralization of soft tissues has been considered a passive and spontaneous process. Recent data have demonstrated that calcium salt deposition in soft tissues could be a highly regulated process. Although calcification occurs in any tissue type, vascular calcification has been of particular interest due to association with atherosclerosis, chronic kidney disease (CKD), and osteoporosis. Different mechanisms underlying calcium apatite accumulation are explored with these age-related disorders. In the case of atherosclerotic plaques, oxy-lipids trigger release of the pro-inflammatory cytokines and inflammation that activate calcification processes in aorta intimae. In CKD patients, renal failure alters the balance between calcium and phosphate levels usually regulated by fibroblast growth factor-23 (FGF23), Klotho, and vitamin D, and vascular smooth muscle cells (VSMCs) begin to explore an osteoblastosteoblast-like phenotype. Calcification could affect extracellular matrix along with VSMCs. Collagen is a major component of extracellular matrix and its modifications accumulate with age. The formation of cross-links between collagen fibers is regulated by the action of lysine hydroxylases and lysyl oxidase and could occur spontaneously. Oxidation-induced advanced glycation end products (AGEs) are a major type of spontaneous cross-links that accelerate with age and may result in tissue stiffness, problems with recycling, and potential accumulation of calcium apatite. Applying strategies for clearing the AGEs proposed by de Grey may be more difficult in the highly mineralized extracellular matrix. We performed bioinformatic analysis of the molecular pathways underlying calcification in atherosclerotic and CKD patients, signaling pathways of collagen cross-links formation, and bone mineralization, and we propose new potential targets and review drugs for calcification treatment. PMID:23902273

  16. Chemical pathology of homocysteine. V. Thioretinamide, thioretinaco, and cystathionine synthase function in degenerative diseases.

    PubMed

    McCully, Kilmer S

    2011-01-01

    Hyperhomocysteinemia was first associated with degenerative disease by observation of accelerated arteriosclerosis in children with inherited disorders of cystathionine synthase, methionine synthase, and methylene tetrohydrofolate reductase. The metabolic blockade of sulfate synthesis from homocysteine thiolactone in malignant cells is ascribed to a deficiency of a chemopreventive derivative of homocysteine thiolactone that occurs in normal cells. Its chemical structure was elucidated by the organic synthesis of thioretinamide from retinoic acid and homocysteine thiolactone. Oxidation of the sulfur atom of homocysteine is inhibited in scorbutic guinea pigs, demonstrating ascorbate function in sulfate synthesis from homocysteine. Studies of homocysteine metabolism in protein energy malnutrition led to the conclusion that the biosynthesis of thioretinamide from the retinol of transthyretin is catalyzed by dehydroascorbate and superoxide generated from the heme oxygenase group of cystathionine synthase. Newly synthesized thioretinamide is complexed with cobalamin to form thioretinaco, which is activated by ozone and oxygen to function as the active site of oxidative phosphorylation. In accordance with the trophoblastic theory of cancer, pancreatic enzymes are believed to be oncolytic because they hydrolyze the homocysteinylated proteins, nucleic acids and glycosaminoglycans of malignant tissues. The clonal selection of malignant cells that are deficient in the heme oxygenase function of cystathionine synthase produces cells dependent upon glycolysis for ATP synthesis, since they are deficient in synthesis of thioretinamide, thioretinaco and thioretinaco ozonide. The vulnerable plaque of arteriosclerosis originates from complexes of microbes with homocysteinylated lipoproteins, obstructing vasa vasorum narrowed by endothelial dysfunction, causing arterial ischemia, and intimal micro-abscesses. Degenerative diseases may be ameliorated by a proposed therapeutic protocol

  17. Early onset degenerative dementias: demographic characteristics and etiologic classification in a tertiary referral center.

    PubMed

    Maiovis, Pantelis; Ioannidis, Panagiotis; Konstantinopoulou, Elina; Karacostas, Dimitris

    2015-03-01

    Early onset dementia (EOD) is a major diagnostic challenge as it often presents with atypical features and may be attributed to treatable diseases. Primary degenerative dementias (Alzheimer's disease-AD, frontotemporal lobar degeneration-FTLD, Lewy body dementia-LBD), although traditionally considered to affect older people, are still a main cause of EOD. 491 demented patients were assessed from January 1, 2003 to December 31, 2010 in the Neurology Department of a tertiary referral center. Patients were classified as AD, behavioral variant frontotemporal dementia (bvFTD), non-fluent agrammatic variant primary progressive aphasia (naPPA), semantic variant PPA (svPPA), corticobasal degeneration (CBD), or progressive supranuclear palsy (PSP) who also met criteria for naPPA and LBD. Finally, their demographic characteristics were analysed, according to age at onset (EOD <65 years, late onset dementia-LOD ≥65 years). From the 491 patients, 137 (27.9 %) were EOD. In the EOD group, 52 (38 %) were diagnosed with bvFTD, 34 (24.8 %) with AD, 27 (19.7 %) with naPPA, 10 (7.2 %) with svPPA, 12 (8.8 %) with CBD or PSP, and 2 (1.5 %) with LBD. Demographic characteristics did not differ significantly among diagnostic categories in the EOD group, while in the LOD group FTLD patients were younger and more frequently men compared to both AD and LBD patients. EOD patients had more years of education than LOD patients. Degenerative disorders as causes of EOD are not rare. High clinical alertness is warranted to achieve correct and timely diagnosis. PMID:24878660

  18. MicroRNA Expression Signature in Degenerative Aortic Stenosis

    PubMed Central

    2016-01-01

    Degenerative aortic stenosis, characterized by narrowing of the exit of the left ventricle of the heart, has become the most common valvular heart disease in the elderly. The aim of this study was to investigate the microRNA (miRNA) signature in degenerative AS. Through microarray analysis, we identified the miRNA expression signature in the tissue samples from healthy individuals (n = 4) and patients with degenerative AS (n = 4). Six miRNAs (hsa-miR-193a-3p, hsa-miR-29b-1-5p, hsa-miR-505-5p, hsa-miR-194-5p, hsa-miR-99b-3p, and hsa-miR-200b-3p) were overexpressed and 14 (hsa-miR-3663-3p, hsa-miR-513a-5p, hsa-miR-146b-5p, hsa-miR-1972, hsa-miR-718, hsa-miR-3138, hsa-miR-21-5p, hsa-miR-630, hsa-miR-575, hsa-miR-301a-3p, hsa-miR-636, hsa-miR-34a-3p, hsa-miR-21-3p, and hsa-miR-516a-5p) were downregulated in aortic tissue from AS patients. GeneSpring 13.1 was used to identify potential human miRNA target genes by comparing a 3-way comparison of predictions from TargetScan, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify potential pathways and functional annotations associated with AS. Twenty miRNAs were significantly differentially expressed between patients with AS samples and normal controls and identified potential miRNA targets and molecular pathways associated with this morbidity. This study describes the miRNA expression signature in degenerative AS and provides an improved understanding of the molecular pathobiology of this disease. PMID:27579316

  19. Health assessment of environmental pollutants; Proliferative and degenerative diseases

    SciTech Connect

    Stuart, B.O. )

    1987-01-01

    The health assessments of environmental air contaminants are at present frequently based upon probability of cancer, if this has been identified as a potential result of prolonged exposure to the particular inhalation hazard. However, for many airborne hazards chronic inhalation exposure may result in morbidity or mortality risks due to chronic degenerative diseases such as emphysema, fibrosis, or chronic obstructive pulmonary disease that may be nearly as great or greater than those of more widely recognized neoplastic or proliferative disease. The relative hazards of environmentally released radioactive and chemical air contaminants, i.e., radon daughters and diesel engine exhaust, are discussed as examples.

  20. Revisiting the Term Neuroprotection in Chronic and Degenerative Diseases.

    PubMed

    Orsini, Marco; Nascimento, Osvaldo J M; Matta, Andre P C; Reis, Carlos Henrique Melo; de Souza, Olivia Gameiro; Bastos, Victor Hugo; Moreira, Rayele; Ribeiro, Pedro; Fiorelli, Stenio; Novellino, Pietro; Pessoa, Bruno; Cunha, Mariana; Pupe, Camila; Morales, Pedro S; Filho, Pedro F Moreira; Trajano, Eduardo Lima; Oliveira, Acary Bulle

    2016-04-01

    Thanks to the development of several new researches, the lifetime presented a significant increase, even so, we still have many obstacles to overcome - among them, manage and get responses regarding neurodegenerative diseases. Where we are in the understanding of neuroprotection? Do we really have protective therapies for diseases considered degeneratives such as amyotrophic lateral sclerosis and its variants, Parkinson's disease, Alzheimer's disease and many others? Neuroprotection is defined by many researches as interactions and interventions that can slow down or even inhibit the progression of neuronal degeneration process. We make some considerations on this neuroprotective effect. PMID:27127599

  1. Revisiting the Term Neuroprotection in Chronic and Degenerative Diseases

    PubMed Central

    Orsini, Marco; Nascimento, Osvaldo J.M.; Matta, Andre P.C.; Reis, Carlos Henrique Melo; de Souza, Olivia Gameiro; Bastos, Victor Hugo; Moreira, Rayele; Ribeiro, Pedro; Fiorelli, Stenio; Novellino, Pietro; Pessoa, Bruno; Cunha, Mariana; Pupe, Camila; Morales, Pedro S.; Filho, Pedro F. Moreira; Trajano, Eduardo Lima; Oliveira, Acary Bulle

    2016-01-01

    Thanks to the development of several new researches, the lifetime presented a significant increase, even so, we still have many obstacles to overcome – among them, manage and get responses regarding neurodegenerative diseases. Where we are in the understanding of neuroprotection? Do we really have protective therapies for diseases considered degeneratives such as amyotrophic lateral sclerosis and its variants, Parkinson’s disease, Alzheimer’s disease and many others? Neuroprotection is defined by many researches as interactions and interventions that can slow down or even inhibit the progression of neuronal degeneration process. We make some considerations on this neuroprotective effect. PMID:27127599

  2. MicroRNA Expression Signature in Degenerative Aortic Stenosis.

    PubMed

    Shi, Jing; Liu, Hui; Wang, Hui; Kong, Xiangqing

    2016-01-01

    Degenerative aortic stenosis, characterized by narrowing of the exit of the left ventricle of the heart, has become the most common valvular heart disease in the elderly. The aim of this study was to investigate the microRNA (miRNA) signature in degenerative AS. Through microarray analysis, we identified the miRNA expression signature in the tissue samples from healthy individuals (n = 4) and patients with degenerative AS (n = 4). Six miRNAs (hsa-miR-193a-3p, hsa-miR-29b-1-5p, hsa-miR-505-5p, hsa-miR-194-5p, hsa-miR-99b-3p, and hsa-miR-200b-3p) were overexpressed and 14 (hsa-miR-3663-3p, hsa-miR-513a-5p, hsa-miR-146b-5p, hsa-miR-1972, hsa-miR-718, hsa-miR-3138, hsa-miR-21-5p, hsa-miR-630, hsa-miR-575, hsa-miR-301a-3p, hsa-miR-636, hsa-miR-34a-3p, hsa-miR-21-3p, and hsa-miR-516a-5p) were downregulated in aortic tissue from AS patients. GeneSpring 13.1 was used to identify potential human miRNA target genes by comparing a 3-way comparison of predictions from TargetScan, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify potential pathways and functional annotations associated with AS. Twenty miRNAs were significantly differentially expressed between patients with AS samples and normal controls and identified potential miRNA targets and molecular pathways associated with this morbidity. This study describes the miRNA expression signature in degenerative AS and provides an improved understanding of the molecular pathobiology of this disease. PMID:27579316

  3. Differential proteomics analysis of proteins from human diabetic and age-related cataractous lenses

    PubMed Central

    Zhu, Jing; Shao, Jun; Yao, Yong; Chu, Zhao Dong; Yu, Qian Qian; Zhao, Wei; Lin, Qing; Zhang, Zi Yin

    2013-01-01

    Backgound: To investigate the differential lens proteomics between diabetic cataract, age-related cataract, and natural subjects. Materials and Methods: Two-dimensional electrophoresis (2-DE), mass spectrometry (MS), and enzyme-linked immunosorbent assay (ELISA) were employed. Total soluble proteins in lenses of type I diabetic cataract, age-related cataract (nondiabetic) patients, and normal control were extracted and subjected to 2-DE. The differential protein spots were recovered, digested with trypsin, and further applied to MALDI-TOF-MS. ELISA analysis was used to determine the levels of differential proteins in lenses of three groups. Results: 2-DE analysis reflected that lens proteins of normal control, diabetic, and age-related cataract subjects were in the section of pH 5-9 and the relative molecular weights were 14-97 kDa, while relative molecular weight of more abundant crystallines was localized at 20-31 kDa. five differential protein spots were detected and identified using MALDI-TOF-MS, including beta-crystallin A3, alpha-crystallin B chain, chain A of crystal structure of truncated human beta-B1-crystallin, beta-crystallin B1, and an interesting unnamed protein product highly similar to alpha-crystallin B chain, respectively. ELISA analysis revealed that lenses of diabetic cataract patients should contain significantly more concentrations of beta-crystallin A3, alpha-crystallin B chain, and beta-crystallin B1 than those of age-related cataract patients and normal control. Conclusion: This study clearly reflected the differential proteins of diabetic cataract, age-related cataract lenses compared with natural subjects, and it is helpful for the further research on the principles and mechanisms of different types of cataract. PMID:24520233

  4. Age-related change of technetium-99m-HMDP distribution in the skeleton

    SciTech Connect

    Kigami, Yusuke; Yamamoto, Itsuo; Ohnishi, Hideo

    1996-05-01

    To understand age-related changes of whole-body and regional skeletal metabolism, it is important to investigate the mechanisms of age-related bone loss and to develop suitable treatments for it. Bone biopsies show metabolism of the particular site examined while biochemical markers for bone metabolism reflect total skeletal metabolis. Bone scintigraphy is a convenient and simple way to analyze whole-body and regional skeletal metabolism. We attempted to study and understand age-related changes in bone metabolism by quantifying the bone scan and correlating it with biochemical bone metabolic markers. The whole-body skeletal uptake (WBSU) and whole-body skeletal tracer distribution pattern were studied in men and women by bone scintigraphy using {sup 99m}Tc-hydroxy-methane-diphosphonate (HMDP). Bone scans were performed using a standard protocol and quantified by setting regions of interest (ROIs) on selected regions. WBSU and the skeletal distribution pattern were compared with simultaneously obtained serum biochemical markers. WBSU showed an increase with age in both sexes, but in women, uptake in the head and legs increased more relatively than in the thoracic region, while in men no such tendency was observed. Increase of WBSU and relative increase of uptakes in the head demonstrated a weak correlation with the serum levels of alkaline phosphatase and type 1 collagen metabolites. These results show an age-related increase of skeletal turnover and sex-dependent regional skeletal metabolism. The age-related changes seen in bone scintigrams might be a sign of progressive bone loss, reflecting changes in local bone matabolism. 23 refs., 3 figs., 1 tab.

  5. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering

    PubMed Central

    Pereira, Ana C.; Lambert, Hilary K.; Grossman, Yael S.; Dumitriu, Dani; Waldman, Rachel; Jannetty, Sophia K.; Calakos, Katina; Janssen, William G.; McEwen, Bruce S.; Morrison, John H.

    2014-01-01

    The dementia of Alzheimer’s disease (AD) results primarily from degeneration of neurons that furnish glutamatergic corticocortical connections that subserve cognition. Although neuron death is minimal in the absence of AD, age-related cognitive decline does occur in animals as well as humans, and it decreases quality of life for elderly people. Age-related cognitive decline has been linked to synapse loss and/or alterations of synaptic proteins that impair function in regions such as the hippocampus and prefrontal cortex. These synaptic alterations are likely reversible, such that maintenance of synaptic health in the face of aging is a critically important therapeutic goal. Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats. Riluzole increases glutamate uptake through glial transporters and is thought to decrease glutamate spillover to extrasynaptic NMDA receptors while increasing synaptic glutamatergic activity. Treated aged rats were protected against age-related cognitive decline displayed in nontreated aged animals. Memory performance correlated with density of thin spines on apical dendrites in CA1, although not with mushroom spines. Furthermore, riluzole-treated rats had an increase in clustering of thin spines that correlated with memory performance and was specific to the apical, but not the basilar, dendrites of CA1. Clustering of synaptic inputs is thought to allow nonlinear summation of synaptic strength. These findings further elucidate neuroplastic changes in glutamatergic circuits with aging and advance therapeutic development to prevent and treat age-related cognitive decline. PMID:25512503

  6. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering.

    PubMed

    Pereira, Ana C; Lambert, Hilary K; Grossman, Yael S; Dumitriu, Dani; Waldman, Rachel; Jannetty, Sophia K; Calakos, Katina; Janssen, William G; McEwen, Bruce S; Morrison, John H

    2014-12-30

    The dementia of Alzheimer's disease (AD) results primarily from degeneration of neurons that furnish glutamatergic corticocortical connections that subserve cognition. Although neuron death is minimal in the absence of AD, age-related cognitive decline does occur in animals as well as humans, and it decreases quality of life for elderly people. Age-related cognitive decline has been linked to synapse loss and/or alterations of synaptic proteins that impair function in regions such as the hippocampus and prefrontal cortex. These synaptic alterations are likely reversible, such that maintenance of synaptic health in the face of aging is a critically important therapeutic goal. Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats. Riluzole increases glutamate uptake through glial transporters and is thought to decrease glutamate spillover to extrasynaptic NMDA receptors while increasing synaptic glutamatergic activity. Treated aged rats were protected against age-related cognitive decline displayed in nontreated aged animals. Memory performance correlated with density of thin spines on apical dendrites in CA1, although not with mushroom spines. Furthermore, riluzole-treated rats had an increase in clustering of thin spines that correlated with memory performance and was specific to the apical, but not the basilar, dendrites of CA1. Clustering of synaptic inputs is thought to allow nonlinear summation of synaptic strength. These findings further elucidate neuroplastic changes in glutamatergic circuits with aging and advance therapeutic development to prevent and treat age-related cognitive decline. PMID:25512503

  7. Severity of Age-Related Macular Degeneration in 1 Eye and the Incidence and Progression of Age-Related Macular Degeneration in the Fellow Eye

    PubMed Central

    Gangnon, Ronald E.; Lee, Kristine E.; Klein, Barbara E. K.; Iyengar, Sudha K.; Sivakumaran, Theru A.; Klein, Ronald

    2014-01-01

    Importance Previous studies of the implications of age-related macular degeneration (AMD) severity in one eye on prognosis for the fellow eye have focused on incidence of neovascular AMD in the fellow eye of subjects with neovascular AMD in the other eye. It is unclear to what extent AMD severity in one eye impacts incidence, progression, and regression of AMD in its fellow eye across the entire range of AMD severity. Objective To investigate the impact of severity of AMD in one eye on incidence, progression, and regression of AMD in the fellow eye. Design, Setting and Participants The Beaver Dam Eye Study, a longitudinal population-based study of age-related eye diseases conducted in the city and township of Beaver Dam, Wisconsin. Examinations were performed every 5 years over a 20-year period (1988-1990 through 2008-2010). Study participants (N=4379) were aged 43 to 86 years at the baseline examination. At baseline and up to 4 subsequent examinations, retinal photographs were taken. Exposures Age, sex, and the Y402H polymorphism in the Complement Factor H gene on chromosome 1q; AMD severity in the fellow eye. Main Outcome Measures Incidence, progression, and regression of AMD assessed in retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System; mortality. Results More severe AMD in one eye was associated with increased incidence and progression of AMD in its fellow eye (Level 1 to 2: hazard ratio [HR] 4.90, 95% confidence interval [CI] 4.26-5.63; Level 2 to 3: HR 2.09, CI 1.42-3.06; Level 3 to 4: HR 2.38, CI 1.74-3.25; Level 4 to Level 5: HR 2.46, CI 1.65-3.66). Less severe AMD in one eye was associated with less progression of AMD in its fellow eye (Level 2 to 3: HR 0.42, CI 0.33-0.55; Level 3 to 4: HR 0.50, CI 0.34-0.83). We estimate that 51% of subjects who develop any AMD always maintain AMD severity states within 1 step of each other between eyes; 90% stay within 2 steps. Conclusions and Relevance Using multi-state models, we

  8. Genetic Evidence for Role of Carotenoids in Age-Related Macular Degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS)

    PubMed Central

    Meyers, Kristin J.; Mares, Julie A.; Igo, Robert P.; Truitt, Barbara; Liu, Zhe; Millen, Amy E.; Klein, Michael; Johnson, Elizabeth J.; Engelman, Corinne D.; Karki, Chitra K.; Blodi, Barbara; Gehrs, Karen; Tinker, Lesley; Wallace, Robert; Robinson, Jennifer; LeBlanc, Erin S.; Sarto, Gloria; Bernstein, Paul S.; SanGiovanni, John Paul; Iyengar, Sudha K.

    2014-01-01

    Purpose. We tested variants in genes related to lutein and zeaxanthin status for association with age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study (CAREDS). Methods. Of 2005 CAREDS participants, 1663 were graded for AMD from fundus photography and genotyped for 424 single nucleotide polymorphisms (SNPs) from 24 candidate genes for carotenoid status. Of 337 AMD cases 91% had early or intermediate AMD. The SNPs were tested individually for association with AMD using logistic regression. A carotenoid-related genetic risk model was built using backward selection and compared to existing AMD risk factors using the area under the receiver operating characteristic curve (AUC). Results. A total of 24 variants from five genes (BCMO1, BCO2, NPCL1L1, ABCG8, and FADS2) not previously related to AMD and four genes related to AMD in previous studies (SCARB1, ABCA1, APOE, and ALDH3A2) were associated independently with AMD, after adjusting for age and ancestry. Variants in all genes (not always the identical SNPs) were associated with lutein and zeaxanthin in serum and/or macula, in this or other samples, except for BCO2 and FADS2. A genetic risk score including nine variants significantly (P = 0.002) discriminated between AMD cases and controls beyond age, smoking, CFH Y402H, and ARMS2 A69S. The odds ratio (95% confidence interval) for AMD among women in the highest versus lowest quintile for the risk score was 3.1 (2.0–4.9). Conclusions. Variants in genes related to lutein and zeaxanthin status were associated with AMD in CAREDS, adding to the body of evidence supporting a protective role of lutein and zeaxanthin in risk of AMD. PMID:24346170

  9. Fellowship and Practice Composition Affect Surgical Decision Making in Patients with Adult Degenerative Scoliosis: Spinal Deformity versus Degenerative Spinal Surgeons

    PubMed Central

    Protopsaltis, Themistocles; Patel, Ashish; Yoo, Andrew; Lonner, Baron

    2015-01-01

    Background For the Adult Degenerative Scoliosis (ADS) patient with radiculopathy, there is no clear data in the literature to guide the spine surgeon's decision making in choosing between limited decompression alone, short segment fusion, or longer arthrodesis of the deformity. This study investigates the differences in operative planning, for patients with ADS and radiculopathy, between two groups of spine surgeons based on fellowship experience and practice composition. Methods Six Degenerative Spine surgeons (Group 1) and 6 Spinal Deformity surgeons (Group 2) were shown 7 cases of patients with ADS and radiculopathy. Surgeons completed a questionnaire detailing their planned operative intervention including the number of fusion levels, if any, approach, choice of bone graft, and interbody device. Pearson Correlation was used to investigate the association between fellowship training, practice composition, number of levels fused, and other variables. Intraclass correlation (ICC) analysis was used to investigate the internal consistency among the groups. Results There was a direct correlation between fellowship deformity experience and practice composition (r=0.75, p<0.01), and between deformity practice composition and the number of planned fusion levels (r=0.90, p<0.001). Group 1 surgeons fused a mean 3.7 vertebral levels (range 0-6.7), while Group 2 surgeons fused a mean 10.8 levels (range 4-16.5). Group 2 surgeons fused a significantly greater number of levels for each case than degenerative surgeons on paired student t-test (p=0.002). Group 1 surgeons chose decompression alone more commonly than deformity surgeons (p<0.05). Group 2 surgeons had significantly higher group consistency by ICC analysis (p=0.004). Conclusions Fellowship and practice composition influence the physician's surgical planning in ADS. There is a lack of standardized treatment paradigms for the management of radiculopathy in patients with ADS. PMID:26114090

  10. Characterization of Intercostal Muscle Pathology in Canine Degenerative Myelopathy: A Disease Model for Amyotrophic Lateral Sclerosis

    PubMed Central

    Morgan, Brandie R.; Coates, Joan R.; Johnson, Gayle C.; Bujnak, Alyssa C.; Katz, Martin L.

    2014-01-01

    Dogs homozygous for missense mutations in the SOD1 gene develop a late-onset neuromuscular disorder called degenerative myelopathy (DM) that has many similarities to amyotrophic lateral sclerosis (ALS). Both disorders are characterized by widespread progressive declines in motor functions accompanied by atrophic changes in the descending spinal cord tracts , and some forms of ALS are also associated with SOD1 mutations. In end-stage ALS, death usually occurs as a result of respiratory failure due to severe functional impairment of respiratory muscles. The mechanisms that lead to this loss of function are not known. Dogs with DM are euthanized at all stages of disease progression providing an opportunity to characterize the onset and progression of any pathological changes in the respiratory muscles that may precede respiratory failure. To characterize such potential disease-related pathology we evaluated intercostal muscles from Boxer and Pembroke Welsh Corgi dogs that were euthanized at various stages of DM disease progression. DM was found to result in intercostal muscle atrophy, fibrosis, increased variability in muscle fiber size and shape, and an alteration in muscle fiber type composition. This pathology was not accompanied by retraction of the motor neuron terminals from the muscle acetylcholine receptor complexes, suggesting that the muscle atrophy did not result from physical denervation. These findings provide a better understanding of the mechanisms that likely lead to respiratory failure in at least some forms of ALS and will be useful in the development and evaluation of potential therapeutic interventions using the DM model. PMID:24043596

  11. Motion-preserving technologies for degenerative lumbar spine: The past, present, and future horizons

    PubMed Central

    Serhan, Hassan; Mhatre, Devdatt; Defossez, Henri; Bono, Christopher M.

    2011-01-01

    Over the past few decades, remarkable advancements in the understanding of the origin of low-back pain and lumbar spinal disorders have been achieved. Spinal fusion is generally considered the “gold standard” in the treatment of low-back pain; however, fusion is also associated with accelerated degeneration of adjacent levels. Spinal arthroplasty and dynamic stabilization technologies, as well as the continuous improvement in diagnosis and surgical interventions, have opened a new era of treatment options. Recent advancements in nonfusion technologies such as motion-preservation devices and posterior dynamic stabilization may change the gold standard. These devices are designed with the intent to provide stabilization and eliminate pain while preserving motion of the functional spinal unit. The adaption of nonfusion technologies by the surgical community and payers for the treatment of degenerative spinal conditions will depend on the long-term clinical outcome of controlled randomized clinical studies. Although the development of nonfusion technology has just started and the adoption is very slow, it may be considered a viable option for motion preservation in coming years. This review article provides technical and surgical views from the past and from the present, as well as a glance at the future endeavors and challenges in instrumentation development for lumbar spinal disorders. © 2011 SAS - The International Society for the Advancement of Spine Surgery. Published by Elsevier Inc. All rights reserved. PMID:25802672

  12. Characterization of intercostal muscle pathology in canine degenerative myelopathy: a disease model for amyotrophic lateral sclerosis.

    PubMed

    Morgan, Brandie R; Coates, Joan R; Johnson, Gayle C; Bujnak, Alyssa C; Katz, Martin L

    2013-12-01

    Dogs homozygous for missense mutations in the SOD1 gene develop a late-onset neuromuscular disorder called degenerative myelopathy (DM) that has many similarities to amyotrophic lateral sclerosis (ALS). Both disorders are characterized by widespread progressive declines in motor functions, accompanied by atrophic changes in the descending spinal cord tracts. Some forms of ALS are also associated with SOD1 mutations. In end-stage ALS, death usually occurs as a result of respiratory failure from severe functional impairment of respiratory muscles. The mechanisms that lead to this loss of function are not known. Dogs with DM are euthanized at all stages of disease progression, providing an opportunity to characterize the onset and progression of any pathological changes in the respiratory muscles that may precede respiratory failure. To characterize such potential disease-related pathology, we evaluated intercostal muscles from Boxer and Pembroke Welsh Corgi dogs that were euthanized at various stages of DM disease progression. DM was found to result in intercostal muscle atrophy, fibrosis, increased variability in muscle fiber size and shape, and alteration in muscle fiber type composition. This pathology was not accompanied by retraction of the motor neuron terminals from the muscle acetylcholine receptor complexes, suggesting that the muscle atrophy did not result from physical denervation. These findings provide a better understanding of the mechanisms that likely lead to respiratory failure in at least some forms of ALS and will be useful in the development and evaluation of potential therapeutic interventions using the DM model. PMID:24043596

  13. Spontaneous degenerative polioencephalomyelopathy in feeder pigs--a new motor neuron disease?

    PubMed

    Wohlsein, Peter; Brügmann, Michael; Pfeiffer, Ina; Ammer, Hermann; Wolf, Petra; Baumgartner, Wolfgang; Peters, Martin

    2012-01-01

    A central nervous disorder occurred spontaneously in a herd of feeder pigs characterized by muscle fasciculations, convulsions, squealing, and acute death in numerous animals. Histopathology revealed a degenerative poliomyeloencephalopathy of brain stem and spinal cord consisting of neuronal hypertrophy, chromatolysis, neuronophagia, and satellitosis associated with Wallerian degeneration of ventral rootlets and neurogenic muscle atrophy of limb musculature. The sudden onset of clinical signs and the pattern of morphological findings were suggestive of intoxication. Though parathion was found in two animals, serum acetylcholine esterase activity and morphological findings were not compatible with an organophosphate poisoning. A hereditary disorder was excluded by genetic analysis. Summarized findings in the present cases are reminiscent of changes observed in ruminants suffering from patulin poisoning, a neuromycotoxicosis caused by Aspergillus clavatus. However, toxicological and microbiological investigations failed to identify the cause of this unusual and so far not described disease in pigs. Morphologically, lesion distribution and alterations of motor neurons resemble changes observed in equine motor neuron disease, spinal muscular atrophy of certain canine breeds, and amyotrophic lateral sclerosis (Lou Gehrig's disease) in man. Therefore, the term spontaneous porcine motor neuron disease (SPMND) is proposed for this new and unique entitiy. PMID:23227771

  14. Analysis of surgeries for Degenerative lumbarstenosis in elderly patients

    PubMed Central

    Bai, Bin; Li, Yuxin

    2016-01-01

    Objective: To analyze the effect of decompression alone and combined decompression, fusion and internal fixation procedure for degenerative lumbar stenosis in elderly patients. Methods: We reviewed 168 lumbar stenosis patients treated using decompression alone or with combined procedures in the department of orthopaedics of Tianjin 4th Centre Hospital from October 2010 to January 2014. The clinical data including age, gender, procedure type, operation time, follow-up period, blood loss, preoperative and postoperative JOA and ODI scores were recorded. The patients were divided into decompression alone group and combined surgeries group according to the procedure type. Results: The combined surgeries group presented with larger blood loss (p<0.05) and more operation time (p<0.05), compared with the group of decompression alone. The preoperative and postoperative JOA scores were significantly higher (p<0.05), and the ODI scores significantly lower in the decompression alone group (P<0.05), but at the final follow-up, there were no significant difference between the two groups (p>0.05). The complication rate was lower in the group of decompression alone, but there was no significant difference between the two groups (p>0.05). Conclusion: Both the decompression alone and combined surgeries can result in a satisfactory effects in elderly patients with degenerative lumbar spinal stenosis, but the combined surgeries presented with a relatively higher complication rate. PMID:27022361

  15. Retrolisthesis as a Compensatory Mechanism in Degenerative Lumbar Spine

    PubMed Central

    Jeon, Ikchan

    2015-01-01

    Objective Posterior vertebral translation as a type of spondylolisthesis, retrolisthesis is observed commonly in patients with degenerative spinal problems. Nevertheless, there is insufficient literature on retrolisthesis compared to anterolisthesis. The purpose of this study is to clarify the clinical features of retrolisthesis, and its developmental mechanism associated with a compensatory role in sagittal imbalance of the lumbar spine. Methods From 2003 to 2012, 230 Korean patients who underwent spinal surgery in our department under the impression of degenerative lumbar spinal disease were enrolled. All participants were divided into four groups : 35 patients with retrolisthesis (group R), 32 patients with simultaneous retrolisthesis and anterolisthesis (group R+A), 76 patients with anterolisthesis (group A), and 87 patients with non-translation (group N). The clinical features and the sagittal parameters related to retrolisthesis were retrospectively analyzed based on the patients' medical records. Results There were different clinical features and developmental mechanisms between retrolisthesis and anterolisthesis. The location of retrolisthesis was affected by the presence of simultaneous anterolisthesis, even though it predominantly manifest in L3. The relative lower pelvic incidence, pelvic tilt, and lumbar lordosis compared to anterolisthesis were related to the generation of retrolisthesis, with the opposite observations of patients with anterolisthesis. Conclusion Retrolisthesis acts as a compensatory mechanism for moving the gravity axis posteriorly for sagittal imbalance in the lumbar spine under low pelvic incidence and insufficient intra-spinal compensation. PMID:25810857

  16. Total Disc Arthroplasty for Treating Lumbar Degenerative Disc Disease

    PubMed Central

    2015-01-01

    Study Design Lumber disc arthroplasty is a technological advancement that has occurred in the last decade to treat lumbar degenerative disk diseases. Purpose The aim of this retrospective study was to establish the impact and outcomes of managing patients with lumbar degenerative disk disease who have been treated with lumbar total disc arthroplasty (TDA). Overview of Literature Several studies have shown promising results following this surgery. Methods We reviewed the files of 104 patients at the Department of Neurosurgery in Colmar (France) who had been operated on by lumbar spine arthroplasty (Prodisc) between April 2002 and October 2008. Results Among the 104 patients, 67 were female and 37 were male with an average age of 33.1 years. We followed the cases for a mean of 20 months. The most frequent level of discopathy was L4-L5 with 62 patients (59.6%) followed by L5-S1 level with 52 patients (50%). Eighty-three patients suffered from low back pain, 21 of which were associated with radiculopathy. The status of 82 patients improved after surgery according to the Oswestry Disability Index score, and 92 patients returned to work. Conclusions The results indicate that TDA is a good alternative treatment for lumbar spine disk disease, particularly for patients with disabling and chronic low back pain. This technique contributes to improve living conditions with correct patient selection for surgery. PMID:25705336

  17. Total Disc Replacement in Lumbar Degenerative Disc Diseases

    PubMed Central

    2015-01-01

    More than 10 years have passed since lumbar total disc replacement (LTDR) was introduced for the first time to the world market for the surgical management of lumbar degenerative disc disease (DDD). It seems like the right time to sum up the relevant results in order to understand where LTDR stands on now, and is heading forward to. The pathogenesis of DDD has been currently settled, but diagnosis and managements are still controversial. Fusion is recognized as golden standard of surgical managements but has various kinds of shortcomings. Lately, LTDR has been expected to replace fusion surgery. A great deal of LTDR reports has come out. Among them, more than 5-year follow-up prospective randomized controlled studies including USA IDE trials were expected to elucidate whether for LTDR to have therapeutic benefit compared to fusion. The results of these studies revealed that LTDR was not inferior to fusion. Most of clinical studies dealing with LTDR revealed that there was no strong evidence for preventive effect of LTDR against symptomatic degenerative changes of adjacent segment disease. LTDR does not have shortcomings associated with fusion. However, it has a potentiality of the new complications to occur, which surgeons have never experienced in fusion surgeries. Consequently, longer follow-up should be necessary as yet to confirm the maintenance of improved surgical outcome and to observe any very late complications. LTDR still may get a chance to establish itself as a substitute of fusion both nominally and virtually if it eases the concerns listed above. PMID:26713139

  18. Flexible Stabilisation of the Degenerative Lumbar Spine Using PEEK Rods

    PubMed Central

    Benezech, Jacques; Garlenq, Bruno; Larroque, Gilles

    2016-01-01

    Posterior lumbar interbody fusion using cages, titanium rods, and pedicle screws is considered today as the gold standard of surgical treatment of lumbar degenerative disease and has produced satisfying long-term fusion rates. However this rigid material could change the physiological distribution of load at the instrumental and adjacent segments, a main cause of implant failure and adjacent segment disease, responsible for a high rate of further surgery in the following years. More recently, semirigid instrumentation systems using rods made of polyetheretherketone (PEEK) have been introduced. This clinical study of 21 patients focuses on the clinical and radiological outcomes of patients with lumbar degenerative disease treated with Initial VEOS PEEK®-Optima system (Innov'Spine, France) composed of rods made from PEEK-OPTIMA® polymer (Invibio Biomaterial Solutions, UK) without arthrodesis. With an average follow-up of 2 years and half, the chances of reoperation were significantly reduced (4.8%), quality of life was improved (ODI = 16%), and the adjacent disc was preserved in more than 70% of cases. Based on these results, combined with the biomechanical and clinical data already published, PEEK rods systems can be considered as a safe and effective alternative solution to rigid ones. PMID:26981285

  19. Age-related differences in gap detection: Effects of task difficulty and cognitive ability

    PubMed Central

    Harris, Kelly C.; Eckert, Mark A.; Ahlstrom, Jayne B.; Dubno, Judy R.

    2009-01-01

    Differences in gap detection for younger and older adults have been shown to vary with the complexity of the task or stimuli, but the factors that contribute to these differences remain unknown. To address this question, we examined the extent to which age-related differences in processing speed and workload predicted age-related differences in gap detection. Gap detection thresholds were measured for 10 younger and 11 older adults in two conditions that varied in task complexity but used identical stimuli: (1) gap location fixed at the beginning, middle, or end of a noise burst and (2) gap location varied randomly from trial to trial from the beginning, middle, or end of the noise. We hypothesized that gap location uncertainty would place increased demands on cognitive and attentional resources and result in significantly higher gap detection thresholds for older but not younger adults. Overall, gap detection thresholds were lower for the middle location as compared to beginning and end locations and were lower for the fixed than the random condition. In general, larger age-related differences in gap detection were observed for more challenging conditions. That is, gap detection thresholds for older adults were significantly larger for the random condition than for the fixed condition when the gap was at the beginning and end locations but not the middle. In contrast, gap detection thresholds for younger adults were not significantly different for the random and fixed condition at any location. Subjective ratings of workload indicated that older adults found the gap-detection task more mentally demanding than younger adults. Consistent with these findings, results of the Purdue Pegboard and Connections tests revealed age-related slowing of processing speed. Moreover, age group differences in workload and processing speed predicted gap detection in younger and older adults when gap location varied from trial to trial; these associations were not observed when gap

  20. Primary and secondary control over age-related changes in physical appearance.

    PubMed

    Thompson, S C; Thomas, C; Rickabaugh, C A; Tantamjarik, P; Otsuki, T; Pan, D; Garcia, B F; Sinar, E

    1998-08-01

    Beliefs about appearance-related changes due to aging were used to test the effects of perceived control and secondary control (acceptance) in a sample of 412 young, early-middle-age, and late-middle-age college-educated adults. Mean difference in aging-related appearance control and hypotheses regarding the adaptiveness of primary and secondary control were examined. Primary control over aging-related appearance was lower in older adults and secondary control was higher. In addition, the results indicated support for the Primacy/Back-Up Model that primary perceived control is important at all levels of actual control. Those with stronger beliefs in their primary control were less distressed. Secondary control served a back-up function in that it was related to less distress only for those who had medium or lower beliefs in primary control. The implications of these findings, that primary control may be advantageous even in low-control circumstances, are discussed. PMID:9728417