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Sample records for age disease duration

  1. Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson's Disease.

    PubMed

    Claassen, Daniel O; Dobolyi, David G; Isaacs, David A; Roman, Olivia C; Herb, Joshua; Wylie, Scott A; Neimat, Joseph S; Donahue, Manus J; Hedera, Peter; Zald, David H; Landman, Bennett A; Bowman, Aaron B; Dawant, Benoit M; Rane, Swati

    2016-05-01

    Advancing age and disease duration both contribute to cortical thinning in Parkinson's disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson's Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2(nd), or 3(rd) order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning. PMID:27330836

  2. Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson’s Disease

    PubMed Central

    Claassen, Daniel O.; Dobolyi, David G.; Isaacs, David A.; Roman, Olivia C.; Herb, Joshua; Wylie, Scott A.; Neimat, Joseph S.; Donahue, Manus J.; Hedera, Peter; Zald, David H.; Landman, Bennett A.; Bowman, Aaron B.; Dawant, Benoit M.; Rane, Swati

    2016-01-01

    Advancing age and disease duration both contribute to cortical thinning in Parkinson’s disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson’s Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2nd, or 3rd order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning. PMID:27330836

  3. The HTT CAG-Expansion Mutation Determines Age at Death but Not Disease Duration in Huntington Disease.

    PubMed

    Keum, Jae Whan; Shin, Aram; Gillis, Tammy; Mysore, Jayalakshmi Srinidhi; Abu Elneel, Kawther; Lucente, Diane; Hadzi, Tiffany; Holmans, Peter; Jones, Lesley; Orth, Michael; Kwak, Seung; MacDonald, Marcy E; Gusella, James F; Lee, Jong-Min

    2016-02-01

    Huntington disease (HD) is caused by an expanded HTT CAG repeat that leads in a length-dependent, completely dominant manner to onset of a characteristic movement disorder. HD also displays early mortality, so we tested whether the expanded CAG repeat exerts a dominant influence on age at death and on the duration of clinical disease. We found that, as with clinical onset, HD age at death is determined by expanded CAG-repeat length and has no contribution from the normal CAG allele. Surprisingly, disease duration is independent of the mutation's length. It is also unaffected by a strong genetic modifier of HD motor onset. These findings suggest two parsimonious alternatives. (1) HD pathogenesis is driven by mutant huntingtin, but before or near motor onset, sufficient CAG-driven damage occurs to permit CAG-independent processes and then lead to eventual death. In this scenario, some pathological changes and their clinical correlates could still worsen in a CAG-driven manner after disease onset, but these CAG-related progressive changes do not themselves determine duration. Alternatively, (2) HD pathogenesis is driven by mutant huntingtin acting in a CAG-dependent manner with different time courses in multiple cell types, and the cellular targets that lead to motor onset and death are different and independent. In this scenario, processes driven by HTT CAG length lead directly to death but not via the striatal pathology associated with motor manifestations. Each scenario has important ramifications for the design and testing of potential therapeutics, especially those aimed at preventing or delaying characteristic motor manifestations. PMID:26849111

  4. [Epidemiology of occupational disease among bricklayers in Nigeria. Effects of age and duration of contact].

    PubMed

    Soyinka, F

    1977-10-01

    Clinical and epidemiological investigations on 240 bricklayers in Nigeria show an incidence of 2,3% of cement-eczema, 2,0% of wear and tear dermatosis, and 2,8% of sensitivity against chrome. None of the examined showed a concomitant reaction to cobalt chloride. The workers with longest professional contact with cement showed the highest incidence of cement-eczema, and sensitivity against chrome. Workers of the lower age group had a higher alkali neutralization power of the skin than the older workers. The same tendency was noticed in the control tests. Generally, the African skin showed a higher alkali neutralization power than the white skin. The discussion tried to expand on the possible factors which could have influenced the observed rate of sensitization in Nigeria. PMID:145220

  5. Prolonged contraction duration in aged myocardium.

    PubMed

    Lakatta, E G; Gerstenblith, G; Angell, C S; Shock, N W; Weisfeldt, M L

    1975-01-01

    Isometric performance at 29degreesC was measured in left ventricular trabeculae carneae from young adult (6-mo) and aged (25-mo) rats (n equals 18 in each group). Active tension and maximal rate of tension development did not differ with age, but contraction duration was 255plus or minus6 ms in the young adult and 283plus or minus6 ms in the aged group (P less than0.001). Although catecholamine content per gram heart weight was less in the aged myocardium, additional experiments showed that neither 1 times 10-6 M propranolol nor pretreatment with 6-hydroxydopamine eliminated the age difference in contraction duration. To determine if this age difference resulted from a prolonged active state, electromechanical dissociation and the overshoot of contraction duration during recovery from hypoxia were measured. During paired stimulation greater mechanical refractoriness was found in aged muscles (P less than0.01), but intracellular action potential recordings showed no age difference in the electrical refractory period. On recovery from hypoxia, contraction duration overshoot was 117plus or minus 4percent of control in the young and 138plus or minus 4percent of control in the aged muscles (P less than0.01). The greater electromechanical dissociation and greater overshoot in contraction duration following hypoxia in aged myocardium suggests that prolonged contraction duration in aged myocardium results from a prolonged active state rather than changes in passive properties or myocardial catecholamine content. PMID:1109181

  6. Reliability of reported breastfeeding duration among reproductive-aged women from Mexico.

    PubMed

    Cupul-Uicab, Lea A; Gladen, Beth C; Hernández-Avila, Mauricio; Longnecker, Matthew P

    2009-04-01

    Breastfed children have lower risk of infectious diseases, post-neonatal mortality and chronic diseases later in life. Because epidemiologic studies usually rely on reported history of previous breastfeeding, data on the accuracy and precision of recalled histories allow improved interpretation of the epidemiologic findings. We evaluated the reliability of two reported breastfeeding durations in 567 reproductive-aged women from Mexico using information obtained from nearly identical sets of questions applied at different times after weaning. We compared differences between reports, and examined the intraclass correlation coefficient (ICC) for any and for exclusive breastfeeding (EBF). Logistic regression was used to evaluate the determinants of poor recall (difference between reports of >20%). The reliability of duration of any breastfeeding was high (ICC 0.94). Overall, differences between reports of duration were usually <1 month, and for 385/567, the difference was < or =0.5 months. Predictors of poorer recall were having > or =4 children, and time between reports of >2 months. The only predictor of better recall was greater age of the baby at weaning. The reliability of EBF duration was lower (ICC 0.49). In this population with a relatively long duration of breastfeeding, reliability of any breastfeeding duration was high. Age, education and previous breastfeeding were not important predictors of recall, in contrast to findings in earlier studies. Consistent with previous reports, however, parity and length of recall were associated with poorer recall of duration of any breastfeeding. Future studies that use reported breastfeeding duration may want to consider the effect of these variables on recall. PMID:19292747

  7. Reliability of reported breastfeeding duration among reproductive-aged women from Mexico

    PubMed Central

    Cupul-Uicab, Lea A.; Gladen, Beth C.; Hernández-Ávila, Mauricio; Longnecker, Matthew P.

    2010-01-01

    Breastfed children have lower risk of infectious diseases, post-neonatal mortality and chronic diseases later in life. Because epidemiologic studies usually rely on reported history of previous breastfeeding, data on the accuracy and precision of recalled histories allow improved interpretation of the epidemiologic findings. We evaluated the reliability of two reported breastfeeding durations in 567 reproductive-aged women from Mexico using information obtained from nearly identical sets of questions applied at different times after weaning. We compared differences between reports, and examined the intra-class correlation coefficient (ICC) for any and for exclusive breastfeeding (EBF). Logistic regression was used to evaluate the determinants of poor recall (difference between reports of >20%). The reliability of duration of any breastfeeding was high (ICC 0.94). Overall, differences between reports of duration were usually <1 month, and for 385/567, the difference was ≤0.5 months. Predictors of poorer recall were having ≥4 children, and time between reports of >2 months. The only predictor of better recall was greater age of the baby at weaning. The reliability of EBF duration was lower (ICC 0.49). In this population with a relatively long duration of breastfeeding, reliability of any breast-feeding duration was high. Age, education and previous breastfeeding were not important predictors of recall, in contrast to findings in earlier studies. Consistent with previous reports, however, parity and length of recall were associated with poorer recall of duration of any breastfeeding. Future studies that use reported breastfeeding duration may want to consider the effect of these variables on recall. PMID:19292747

  8. Relationship Between Age, Tenure, and Disability Duration in Persons With Compensated Work-Related Conditions

    PubMed Central

    Besen, Elyssa; Young, Amanda E.; Gaines, Brittany; Pransky, Glenn

    2016-01-01

    Objective: The aim of the study was to examine the relationships among age, tenure, and the length of disability following a work-related injury/illness. Methods: This study utilized 361,754 administrative workers’ compensation claims. The relationships between age, tenure, and disability duration was estimated with random-effects models. Results: The age-disability duration relationship was stronger than the tenure-disability duration relationship. An interaction was observed between age and tenure. At younger ages, disability duration varied little based on tenure. In midlife, disability duration was greater for workers with lower tenure than for workers with higher tenure. At the oldest ages, disability duration increased as tenure increased. Conclusions: Findings indicate that age is a more important factor in disability duration than tenure; however, the relationship between age and disability duration varies based on tenure, suggesting that both age and tenure are important influences in the work-disability process. PMID:26645384

  9. Sleep Duration and Cardiovascular Disease Risk: Epidemiologic and Experimental Evidence.

    PubMed

    Covassin, Naima; Singh, Prachi

    2016-03-01

    Inadequate sleep is increasingly pervasive, and the impact on health remains to be fully understood. The cardiovascular consequences alone appear to be substantial. This review summarizes epidemiologic evidence regarding the association between extremes of sleep duration and the prevalence and incidence of cardiovascular diseases. The adverse effects of experimental sleep loss on physiological functions are discussed, along with cardiovascular risk factors that may underlie the association with increased morbidity and mortality. Current data support the concept that inadequate sleep duration confers heightened cardiovascular risk. Thus implementation of preventative strategies may reduce the potential disease burden associated with this high-risk behavior. PMID:26972035

  10. Stop Aging Disease! ICAD 2014

    PubMed Central

    Ilia, Stambler

    2015-01-01

    On November 1–2, 2014, there took place in Beijing, China, the first International Conference on Aging and Disease (ICAD 2014) of the International Society on Aging and Disease (ISOAD). The conference participants presented a wide and exciting front of work dedicated to amelioration of aging-related conditions, ranging from regenerative medicine through developing geroprotective substances, elucidating a wide range of mechanisms of aging and aging-related diseases, from energy metabolism through genetics and immunomodulation to systems biology. The conference further emphasized the need to intensify and support research on aging and aging-related diseases to provide solutions for the urgent health challenges of the aging society. PMID:25821637

  11. The Iceland Basin excursion: Age, duration, and excursion field geometry

    NASA Astrophysics Data System (ADS)

    Channell, J. E. T.

    2014-12-01

    Iceland Basin geomagnetic excursion coincided with the marine isotope stage (MIS) 6/7 boundary. The age and duration of the excursion, at seven North Atlantic sites with sufficient isotope data, are estimated by matching marine isotope stage (MIS) 7a-7c to a calibrated template. Two criteria for defining the excursion, virtual geomagnetic pole (VGP) latitudes <0° and <40°N, yield excursion durations of 1-4 and 2-5 kyr, respectively. The midpoints of the excursion are in the 189-192 ka range, with a mean of ˜190.2 ka. Although component magnetization directions are generally well defined, rapid changes in field direction during a time of low field intensity are not adequately recorded. During the excursion, VGPs transit southward over Africa and the South Atlantic, reach high southern latitudes at the culmination of the excursion, with partial recovery in relative paleointensity (RPI), and then track northward through the western Pacific. The high southern latitude VGPs, and the recovery in RPI, imply that the Earth's main axial dipole reversed polarity during the excursion, if only for ˜1 kyr; implying that excursions can be manifested globally and are important in millennial-scale stratigraphy. VGP clustering in the South Atlantic and NW Pacific roughly coincide with maxima in the vertical-downward component of the modern nondipole (ND) field determined at the Earth's surface, which implies that the ND field became dominant as the geocentric dipole field weakened during the excursion, and also that the ND field configuration is long-lived on multimillennial timescales.

  12. [Duration of antivitamin K therapy in venous thromboembolic disease].

    PubMed

    Ferrari, E; Baudouy, M; Morand, P

    1995-12-01

    The necessity for anticoagulant treatment after pulmonary embolism or deep vein thrombosis has been demonstrated. The modalities of this treatment have been established, especially the value of initial heparin relayed by oral antivitamin K therapy with a target INR value between 2 and 3. The last question remaining in this protocol is that of the duration of anticoagulant treatment. The choice of duration of anticoagulation should take into consideration two potential complications: haemorrhage due to over-anticoagulation and excessive duration of therapy, and recurrent thromboembolism which could result from an inadequate duration of therapy. Several trials have addressed this question and have led to a consensus of opinion: therefore, secondary venous thrombo-embolic disease, occurring under known, special circumstances, the cause of which has been treated, should be given 4 to 6 weeks anticoagulant therapy. In the other cases, so-called idiopathic venous thromboembolism (the proportion of which is on the increase), recent studies are inadequate to reach a consensus. These "idiopathic" forms are characterised by a higher incidence of recurrent thromboembolism of "secondary" cancer and coagulation abnormalities. The search for the optimal duration of anticoagulant therapy in these forms requires prospective trials taking their features into account and should lead to further therapeutic options. The evaluation of longer treatment protocols with less intensive degrees of anticoagulation and of alternatives to oral vitamin K antagonists is justified. PMID:8729371

  13. 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…

  14. Correlates of Self-Reported Sleep Duration in Middle-Aged and Elderly Koreans: from the Health Examinees Study

    PubMed Central

    Yoon, Hyung-Suk; Yang, Jae Jeong; Song, Minkyo; Lee, Hwi-Won; Han, Sohee; Lee, Sang-Ah; Choi, Ji-Yeob; Lee, Jong-koo; Kang, Daehee

    2015-01-01

    Though various factors related to fluctuations in sleep duration have been identified, information remains limited regarding the correlates of short and long sleep duration among the Korean population. Thus, we investigated characteristics that could be associated with short and/or long sleep duration among middle-aged and elderly Koreans. A total of 84,094 subjects (27,717 men and 56,377 women) who participated in the Health Examinees Study were analyzed by using multinomial logistic regression models. To evaluate whether sociodemographic factors, lifestyle factors, psychological conditions, anthropometry results, and health conditions were associated with short and/or long sleep duration, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with sleep duration of 6–7 hours as the reference group, accounting for putative covariates. Regardless of sexual differences, we found that adverse behaviors and lifestyle factors including low educational attainment, unemployment, being unmarried, current smoking status, lack of exercise, having irregular meals, poor psychosocial well-being, frequent stress events, and poor self-rated health were significantly associated with abnormal sleep duration. Similarly, diabetes mellitus and depression showed positive associations with abnormal sleep duration in both men and women. Our findings suggest that low sociodemographic characteristics, adverse lifestyle factors, poor psychological conditions, and certain disease morbidities could be associated with abnormal sleep duration in middle-aged and elderly Koreans. PMID:25933418

  15. Duration of chronic kidney disease reduces attention and executive function in pediatric patients.

    PubMed

    Mendley, Susan R; Matheson, Matthew B; Shinnar, Shlomo; Lande, Marc B; Gerson, Arlene C; Butler, Robert W; Warady, Bradley A; Furth, Susan L; Hooper, Stephen R

    2015-04-01

    Chronic kidney disease (CKD) in childhood is associated with neurocognitive deficits. Affected children show worse performance on tests of intelligence than their unaffected siblings and skew toward the lower end of the normal range. Here we further assessed this association in 340 pediatric patients (ages 6-21) with mild-moderate CKD in the Chronic Kidney Disease in Childhood cohort from 48 pediatric centers in North America. Participants underwent a battery of age-appropriate tests including Conners' Continuous Performance Test-II (CPT-II), Delis-Kaplan Executive Function System Tower task, and the Digit Span Backward task from the age-appropriate Wechsler Intelligence Scale. Test performance was compared across the range of estimated glomerular filtration rate and duration of CKD with relevant covariates including maternal education, household income, IQ, blood pressure, and preterm birth. Among the 340 patients, 35% had poor performance (below the mean by 1.5 or more standard deviations) on at least one test of executive function. By univariate nonparametric comparison and multiple logistic regression, longer duration of CKD was associated with increased odds ratio for poor performance on the CPT-II Errors of Commission, a test of attention regulation and inhibitory control. Thus, in a population with mild-to-moderate CKD, the duration of disease rather than estimated glomerular filtration rate was associated with impaired attention regulation and inhibitory control. PMID:25252026

  16. Activity enhances dopaminergic long-duration response in Parkinson disease

    PubMed Central

    Auinger, Peggy; Fahn, Stanley; Oakes, David; Shoulson, Ira; Kieburtz, Karl; Rudolph, Alice; Marek, Kenneth; Seibyl, John; Lang, Anthony; Olanow, C. Warren; Tanner, Caroline; Schifitto, Giovanni; Zhao, Hongwei; Reyes, Lydia; Shinaman, Aileen; Comella, Cynthia L.; Goetz, Christopher; Blasucci, Lucia M.; Samanta, Johan; Stacy, Mark; Williamson, Kelli; Harrigan, Mary; Greene, Paul; Ford, Blair; Moskowitz, Carol; Truong, Daniel D.; Pathak, Mayank; Jankovic, Joseph; Ondo, William; Atassi, Farah; Hunter, Christine; Jacques, Carol; Friedman, Joseph H.; Lannon, Margaret; Russell, David S.; Jennings, Danna; Fussell, Barbara; Standaert, David; Schwarzschild, Michael A.; Growdon, John H.; Tennis, Marsha; Gauthier, Serge; Panisset, Michel; Hall, Jean; Gancher, Stephen; Hammerstad, John P.; Stone, Claudia; Alexander-Brown, Barbara; Factor, Stewart A.; Molho, Eric; Brown, Diane; Evans, Sharon; Clark, Jeffrey; Manyam, Bala; Simpson, Patricia; Wulbrecht, Brian; Whetteckey, Jacqueline; Martin, Wayne; Roberts, Ted; King, Pamela; Hauser, Robert; Zesiewicz, Theresa; Gauger, Lisa; Trugman, Joel; Wooten, G. Frederick; Rost-Ruffner, Elke; Perlmutter, Joel; Racette, Brad A.; Suchowersky, Oksana; Ranawaya, Ranjit; Wood, Susan; Pantella, Carol; Kurlan, Roger; Richard, Irene; Pearson, Nancy; Caviness, John N.; Adler, Charles; Lind, Marlene; Simuni, Tanya; Siderowf, Andrew; Colcher, Amy; Lloyd, Mary; Weiner, William; Shulman, Lisa; Koller, William; Lyons, Kelly; Feldman, Robert G.; Saint-Hilaire, Marie H.; Ellias, Samuel; Thomas, Cathi-Ann; Juncos, Jorge; Watts, Ray; Partlow, Anna; Tetrud, James; Togasaki, Daniel M.; Stewart, Tracy; Mark, Margery H.; Sage, Jacob I.; Caputo, Debbie; Gould, Harry; Rao, Jayaraman; McKendrick, Ann; Brin, Mitchell; Danisi, Fabio; Benabou, Reina; Hubble, Jean; Paulson, George W.; Reider, Carson; Birnbaum, Alex; Miyasaki, Janis; Johnston, Lisa; So, Julie; Pahwa, Rajesh; Dubinsky, Richard M.; Wszolek, Zbigniew; Uitti, Ryan; Turk, Margaret; Tuite, Paul; Rottenberg, David; Hansen, Joy; Ramos, Serrano; Waters, Cheryl; Lew, Mark; Welsh, Mickie; Kawai, Connie; O'Brien, Christopher; Kumar, Rajeev; Seeberger, Lauren; Judd, Deborah; Barclay, C. Lynn; Grimes, David A.; Sutherland, Laura; Dawson, Ted; Reich, Stephen; Dunlop, Rebecca; Albin, Roger; Frey, Kirk; Wernette, Kristine; Fahn, Stanley; Oakes, David; Shoulson, Ira; Kieburtz, Karl; Rudolph, Alice; Marek, Kenneth; Seibyl, John; Lang, Anthony; Olanow, C. Warren; Tanner, Caroline; Schifitto, Giovanni; Zhao, Hongwei; Reyes, Lydia; Shinaman, Aileen; Comella, Cynthia L.; Goetz, Christopher; Blasucci, Lucia M.; Samanta, Johan; Stacy, Mark; Williamson, Kelli; Harrigan, Mary; Greene, Paul; Ford, Blair; Moskowitz, Carol; Truong, Daniel D.; Pathak, Mayank; Jankovic, Joseph; Ondo, William; Atassi, Farah; Hunter, Christine; Jacques, Carol; Friedman, Joseph H.; Lannon, Margaret; Russell, David S.; Jennings, Danna; Fussell, Barbara; Standaert, David; Schwarzschild, Michael A.; Growdon, John H.; Tennis, Marsha; Gauthier, Serge; Panisset, Michel; Hall, Jean; Gancher, Stephen; Hammerstad, John P.; Stone, Claudia; Alexander-Brown, Barbara; Factor, Stewart A.; Molho, Eric; Brown, Diane; Evans, Sharon; Clark, Jeffrey; Manyam, Bala; Simpson, Patricia; Wulbrecht, Brian; Whetteckey, Jacqueline; Martin, Wayne; Roberts, Ted; King, Pamela; Hauser, Robert; Zesiewicz, Theresa; Gauger, Lisa; Trugman, Joel; Wooten, G. Frederick; Rost-Ruffner, Elke; Perlmutter, Joel; Racette, Brad A.; Suchowersky, Oksana; Ranawaya, Ranjit; Wood, Susan; Pantella, Carol; Kurlan, Roger; Richard, Irene; Pearson, Nancy; Caviness, John N.; Adler, Charles; Lind, Marlene; Simuni, Tanya; Siderowf, Andrew; Colcher, Amy; Lloyd, Mary; Weiner, William; Shulman, Lisa; Koller, William; Lyons, Kelly; Feldman, Robert G.; Saint-Hilaire, Marie H.; Ellias, Samuel; Thomas, Cathi-Ann; Juncos, Jorge; Watts, Ray; Partlow, Anna; Tetrud, James; Togasaki, Daniel M.; Stewart, Tracy; Mark, Margery H.; Sage, Jacob I.; Caputo, Debbie; Gould, Harry; Rao, Jayaraman; McKendrick, Ann; Brin, Mitchell; Danisi, Fabio; Benabou, Reina; Hubble, Jean; Paulson, George W.; Reider, Carson; Birnbaum, Alex; Miyasaki, Janis; Johnston, Lisa; So, Julie; Pahwa, Rajesh; Dubinsky, Richard M.; Wszolek, Zbigniew; Uitti, Ryan; Turk, Margaret; Tuite, Paul; Rottenberg, David; Hansen, Joy; Ramos, Serrano; Waters, Cheryl; Lew, Mark; Welsh, Mickie; Kawai, Connie; O'Brien, Christopher; Kumar, Rajeev; Seeberger, Lauren; Judd, Deborah; Barclay, C. Lynn; Grimes, David A.; Sutherland, Laura; Dawson, Ted; Reich, Stephen; Dunlop, Rebecca; Albin, Roger; Frey, Kirk; Wernette, Kristine; Mendis, Tilak

    2012-01-01

    Objective: We tested the hypothesis that dopamine-dependent motor learning mechanism underlies the long-duration response to levodopa in Parkinson disease (PD) based on our studies in a mouse model. By data-mining the motor task performance in dominant and nondominant hands of the subjects in a double-blind randomized trial of levodopa therapy, the effects of activity and dopamine therapy were examined. Methods: We data-mined the Earlier versus Later Levodopa Therapy in Parkinson's Disease (ELLDOPA) study published in 2005 and performed statistical analysis comparing the effects of levodopa and dominance of handedness over 42 weeks. Results: The mean change in finger-tapping counts from baseline before the initiation of therapy to predose at 9 weeks and 40 weeks increased more in the dominant compared to nondominant hand in levodopa-treated subjects in a dose-dependent fashion. There was no significant difference in dominant vs nondominant hands in the placebo group. The short-duration response assessed by the difference of postdose performance compared to predose performance at the same visit did not show any significant difference between dominant vs nondominant hands. Conclusions: Active use of the dominant hand and dopamine replacement therapy produces synergistic effect on long-lasting motor task performance during “off” medication state. Such effect was confined to dopamine-responsive symptoms and not seen in dopamine-resistant symptoms such as gait and balance. We propose that long-lasting motor learning facilitated by activity and dopamine is a form of disease modification that is often seen in trials of medications that have symptomatic effects. PMID:22459675

  17. Duration of disease does not equally influence all aspects of quality of life in Parkinson's disease.

    PubMed

    Benge, Jared F; Kekecs, Zoltán; Encarnacion, Elmyra; Ainslie, Melissa; Herff, Christina; Elkins, Gary; Herath, Priyantha

    2016-06-01

    Health related quality of life (HRQoL) is negatively impacted in patients suffering from Parkinson's disease (PD). For the specific components that comprise HRQoL, the relationship between clinical variables, such as disease duration, is not fully characterized. In this cross-sectional study (n=302), self-reported HRQoL on the Parkinson's Disease Questionnaire (PDQ-39) was evaluated as a global construct as well as individual subscale scores. HRQoL was compared in three groups: those within 5years of diagnosis, those within 6-10years of diagnosis, and those greater than 11years since diagnosis. Non-parametric analyses revealed lower HRQoL with increasing disease duration when assessed as a global construct. However, when subscales were evaluated, difficulties with bodily discomfort and cognitive complaints were comparable in individuals in the 1-5years and 6-10year duration groups. Exploratory regression analyses suggested disease duration does explain unique variance in some subscales, even after controlling for Hoehn and Yahr stage and neuropsychiatric features. Our findings show that HRQoL domains in PD patients are affected differentially across the duration of the disease. Clinicians and researchers may need to tailor interventions intended to improve HRQoL at different domains as the disease progresses. PMID:26778512

  18. Endocrine Disease in Aged Horses.

    PubMed

    Durham, Andy E

    2016-08-01

    Aging horses may be at particular risk of endocrine disease. Two major equine endocrinopathies, pituitary pars intermedia dysfunction and equine metabolic syndrome, are commonly encountered in an aging population and may present with several recognizable signs, including laminitis. Investigation, treatment, and management of these diseases are discussed. Additionally, aging may be associated with development of rarer endocrinopathic problems, often associated with neoplasia, including diabetes mellitus and other confounders of glucose homeostasis, as well as thyroid, parathyroid, and adrenal diseases. Brief details of the recognition and management of these conditions are presented. PMID:27449391

  19. The Relationship between Age and Illness Duration in Chronic Fatigue Syndrome.

    PubMed

    Kidd, Elizabeth; Brown, Abigail; McManimen, Stephanie; Jason, Leonard A; Newton, Julia L; Strand, Elin Bolle

    2016-01-01

    Chronic fatigue syndrome (CFS) is a debilitating illness, but it is unclear if patient age and illness duration might affect symptoms and functioning of patients. In the current study, participants were categorized into four groups based upon age (under or over age 55) and illness duration (more or less than 10 years). The groups were compared on functioning and symptoms. Findings indicated that those who were older with a longer illness duration had significantly higher levels of mental health functioning than those who were younger with a shorter or longer illness duration and the older group with a shorter illness duration. The results suggest that older patients with an illness duration of over 10 years have significantly higher levels of mental health functioning than the three other groups. For symptoms, the younger/longer illness duration group had significantly worse immune and autonomic domains than the older/longer illness group. In addition, the younger patients with a longer illness duration displayed greater autonomic and immune symptoms in comparison to the older group with a longer illness duration. These findings suggest that both age and illness duration need to be considered when trying to understand the influence of these factors on patients. PMID:27110826

  20. The Relationship between Age and Illness Duration in Chronic Fatigue Syndrome

    PubMed Central

    Kidd, Elizabeth; Brown, Abigail; McManimen, Stephanie; Jason, Leonard A.; Newton, Julia L.; Strand, Elin Bolle

    2016-01-01

    Chronic fatigue syndrome (CFS) is a debilitating illness, but it is unclear if patient age and illness duration might affect symptoms and functioning of patients. In the current study, participants were categorized into four groups based upon age (under or over age 55) and illness duration (more or less than 10 years). The groups were compared on functioning and symptoms. Findings indicated that those who were older with a longer illness duration had significantly higher levels of mental health functioning than those who were younger with a shorter or longer illness duration and the older group with a shorter illness duration. The results suggest that older patients with an illness duration of over 10 years have significantly higher levels of mental health functioning than the three other groups. For symptoms, the younger/longer illness duration group had significantly worse immune and autonomic domains than the older/longer illness group. In addition, the younger patients with a longer illness duration displayed greater autonomic and immune symptoms in comparison to the older group with a longer illness duration. These findings suggest that both age and illness duration need to be considered when trying to understand the influence of these factors on patients. PMID:27110826

  1. Aging and dry eye disease

    PubMed Central

    Ding, Juan; Sullivan, David A.

    2012-01-01

    Dry eye disease is a prevalent eye disorder that in particular affects the elderly population. One of the major causes of dry eye, meibomian gland dysfunction (MGD), shows increased prevalence with aging. MGD is caused by hyperkeratinization of the ductal epithelium of meibomian gland and reduced quantity and/or quality of meibum, the holocrine product that stabilizes and prevents the evaporation of the tear film. Of note, retinoids which are used in current anti-aging cosmetics may promote the development of MGD and dry eye disease. In this review, we will discuss the possible mechanisms of age-related MGD. PMID:22569356

  2. 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…

  3. Sleep Duration and Age-Related Changes in Brain Structure and Cognitive Performance

    PubMed Central

    Lo, June C.; Loh, Kep Kee; Zheng, Hui; Sim, Sam K.Y.; Chee, Michael W.L.

    2014-01-01

    Study Objectives: To investigate the contribution of sleep duration and quality to age-related changes in brain structure and cognitive performance in relatively healthy older adults. Design: Community-based longitudinal brain and cognitive aging study using a convenience sample. Setting: Participants were studied in a research laboratory. Participants: Relatively healthy adults aged 55 y and older at study commencement. Interventions: N/A. Measurements and Results: Participants underwent magnetic resonance imaging and neuropsychological assessment every 2 y. Subjective assessments of sleep duration and quality and blood samples were obtained. Each hour of reduced sleep duration at baseline augmented the annual expansion rate of the ventricles by 0.59% (P = 0.007) and the annual decline rate in global cognitive performance by 0.67% (P = 0.050) in the subsequent 2 y after controlling for the effects of age, sex, education, and body mass index. In contrast, global sleep quality at baseline did not modulate either brain or cognitive aging. High-sensitivity C-reactive protein, a marker of systemic inflammation, showed no correlation with baseline sleep duration, brain structure, or cognitive performance. Conclusions: In healthy older adults, short sleep duration is associated with greater age-related brain atrophy and cognitive decline. These associations are not associated with elevated inflammatory responses among short sleepers. Citation: Lo JC, Loh KK, Zheng H, Sim SK, Chee MW. Sleep duration and age-related changes in brain structure and cognitive performance. SLEEP 2014;37(7):1171-1178. PMID:25061245

  4. Effects of Internal Clock and Memory Disorders on Duration Reproductions and Duration Productions in Patients with Parkinson's Disease

    ERIC Educational Resources Information Center

    Perbal, S.; Deweer, B.; Pillon, B.; Vidailhet, M.; Dubois, B.; Pouthas, V.

    2005-01-01

    Patients with Parkinson's disease (PD) exhibit deficits in perceptual and motor timing as well as impairments in memory and attentional processes that are related to dysfunction of dopaminergic systems in the basal ganglia. The aim of the present study was to assess the relationships existing between impaired duration judgments and defective…

  5. Reductions in disease activity in the AMPLE trial: clinical response by baseline disease duration

    PubMed Central

    Schiff, Michael; Weinblatt, Michael E; Valente, Robert; Citera, Gustavo; Maldonado, Michael; Massarotti, Elena; Yazici, Yusuf; Fleischmann, Roy

    2016-01-01

    Objectives To evaluate clinical response by baseline disease duration using 2-year data from the AMPLE trial. Methods Patients were randomised to subcutaneous abatacept 125 mg weekly or adalimumab 40 mg bi-weekly, with background methotrexate. As part of a post hoc analysis, the achievement of validated definitions of remission (Clinical Disease Activity Index (CDAI) ≤2.8, Simplified Disease Activity Index (SDAI) ≤3.3, Routine Assessment of Patient Index Data 3 (RAPID3) ≤3.0, Boolean score ≤1), low disease activity (CDAI <10, SDAI <11, RAPID3 ≤6.0), Health Assessment Questionnaire-Disability Index response and American College of Rheumatology responses were evaluated by baseline disease duration (≤6 vs >6 months). Disease Activity Score 28 (C-reactive protein) <2.6 or ≤3.2 and radiographic non-progression in patients achieving remission were also evaluated. Results A total of 646 patients were randomised and treated (abatacept, n=318; adalimumab, n=328). In both treatment groups, comparable responses were achieved in patients with early rheumatoid arthritis (≤6 months) and in those with later disease (>6 months) across multiple clinical measures. Conclusions Abatacept or adalimumab with background methotrexate were associated with similar onset and sustainability of response over 2 years. Patients treated early or later in the disease course achieved comparable clinical responses. Trial registration number NCT00929864, Post-results. PMID:27110385

  6. Cerebrovascular disease in ageing and Alzheimer's disease.

    PubMed

    Love, Seth; Miners, J Scott

    2016-05-01

    Cerebrovascular disease (CVD) and Alzheimer's disease (AD) have more in common than their association with ageing. They share risk factors and overlap neuropathologically. Most patients with AD have Aβ amyloid angiopathy and degenerative changes affecting capillaries, and many have ischaemic parenchymal abnormalities. Structural vascular disease contributes to the ischaemic abnormalities in some patients with AD. However, the stereotyped progression of hypoperfusion in this disease, affecting first the precuneus and cingulate gyrus, then the frontal and temporal cortex and lastly the occipital cortex, suggests that other factors are more important, particularly in early disease. Whilst demand for oxygen and glucose falls in late disease, functional MRI, near infrared spectroscopy to measure the saturation of haemoglobin by oxygen, and biochemical analysis of myelin proteins with differential susceptibility to reduced oxygenation have all shown that the reduction in blood flow in AD is primarily a problem of inadequate blood supply, not reduced metabolic demand. Increasing evidence points to non-structural vascular dysfunction rather than structural abnormalities of vessel walls as the main cause of cerebral hypoperfusion in AD. Several mediators are probably responsible. One that is emerging as a major contributor is the vasoconstrictor endothelin-1 (EDN1). Whilst there is clearly an additive component to the clinical and pathological effects of hypoperfusion and AD, experimental and clinical observations suggest that the disease processes also interact mechanistically at a cellular level in a manner that exacerbates both. The elucidation of some of the mechanisms responsible for hypoperfusion in AD and for the interactions between CVD and AD has led to the identification of several novel therapeutic approaches that have the potential to ameliorate ischaemic damage and slow the progression of neurodegenerative disease. PMID:26711459

  7. The relation among sleep duration, homework burden, and sleep hygiene in chinese school-aged children.

    PubMed

    Sun, Wan-Qi; Spruyt, Karen; Chen, Wen-Juan; Jiang, Yan-Rui; Schonfeld, David; Adams, Ryan; Tseng, Chia-Huei; Shen, Xiao-Ming; Jiang, Fan

    2014-09-01

    Insufficient sleep in school-aged children is common in modern society, with homework burden being a potential risk factor. The aim of this article is to explore the effect of sleep hygiene on the association between homework and sleep duration. Children filled out the Chinese version of the Adolescent Sleep Hygiene Scale, and parents filled out a sociodemographic questionnaire. The final sample included 363 boys and 371 girls with a mean age of 10.82 ± 0.38 years. Children with more homework went to bed later and slept less. Better sleep hygiene was associated with earlier bedtimes and longer sleep duration. Findings suggest that homework burden had a larger effect on sleep duration than sleep hygiene. Fifth-grade children in Shanghai have an excessive homework burden, which overwrites the benefit of sleep hygiene on sleep duration. PMID:24188543

  8. Homework schedule: an important factor associated with shorter sleep duration among Chinese school-aged children.

    PubMed

    Li, Shenghui; Yang, Qian; Chen, Zhe; Jin, Xingming; Jiang, Fan; Shen, Xiaoming

    2014-09-01

    This study was designed to examine the hypothesis that homework schedule has adverse impacts on Chinese children's sleep-wake habits and sleep duration. A random sample of 19,299 children aged 5.08 to 11.99 years old participated in a large, cross-sectional survey. A parent-administered questionnaire was completed to quantify children's homework schedule and sleep behaviors. Generally, it was demonstrated that more homework schedule was significantly associated with later bedtime, later wake time, and shorter sleep duration. Among all sleep variables, bedtime and sleep duration during weekdays appeared to be most affected by homework schedule, especially homework schedule during weekdays. PMID:24256420

  9. Sonographic Findings in Gouty Arthritis: Diagnostic Value and Association with Disease Duration.

    PubMed

    Elsaman, Ahmed M; Muhammad, Eman M S; Pessler, Frank

    2016-06-01

    The objective of this work was to evaluate the sonographic features of gouty arthritis and correlate findings with disease duration. The study was conducted on 100 patients in ambulatory care aged ≥40 y. Inclusion criteria included mono- or oligo-arthritis with effusion of the knee or the first metatarsophalangeal (MTP) joint and no known history of gout. A complete medical history was obtained with emphasis on the known risk factors or causes of gouty arthritis. A 12-MHz Medison linear probe was used for ultrasonography (US). Synovial fluid analysis with polarizing light microscopy was performed on all patients. Ninety-eight knee joints and 33 first MTP joints were examined. Gouty arthritis was found by US in four forms: (i) floating echogenic foci in effusion fluid or Baker cysts, (ii) deposits on the cartilage surface (double contour sign), (iii) erosions and (iv) mature tophus/tophi. These were found in 78.9%, 42.3%, 39.4% and 28.2% of patients, respectively. The overall sensitivity and specificity of US in detecting gout (as defined by the clinical gold standard, i.e., detection of urate crystals by polarizing light microscopy) were 85.9% and 86.7%, respectively. Detection of echogenic foci in effusion fluid was associated with the shortest duration of symptoms (median duration 2 y) followed by double contour sign (3.5 y), erosions (4 y) and tophus (12.5 y). Sonographic findings in gout can be assigned a temporal pattern, with echogenic foci being associated with the shortest and full tophus formation with the longest disease duration. PMID:26995154

  10. [Old age and joint disease].

    PubMed

    d'Harcourt, G; Meignan-Debray, S; Mémin, Y

    1987-01-01

    The seriousness of articular diseases in old persons is related to the loss of function and the rapid way this can lead to them being bed ridden. Rheumatoid polyarthritis is often difficult to distinguish from rhizomelic pseudopolyarthritis, these two diseases resemble each other at this age with the asthenia and loss of general health, the inflammatory pains which are peripheral and of nerve root origin. Among the metabolic arthropathies, articular chondrocalcinosis is frequent, and often latent, but sometimes it is destructive in particular in the hips and knees; septic arthritis today mainly occurs in the elderly, and the algoneurodystrophies are more frequent in old persons than in young subjects, following trauma or a hemiplegia. Arthrosis is obviously the main articular disease of senescence especially involving the joints of the lower limb, hip disease being less incapacitating than knee disease where surgical treatment is less often considered. The arthroses of the upper limbs especially of the shoulder are well tolerated. Osteochondromatosis, osteonecrosis of the internal condyle of the knee, the rapidly destructive arthropathies and hemarthrosis can develop as a complication of a simple arthrosis. In the spine vertebral hyperostosis is especially a disease of the elderly, it can occur alone or with an arthrosis of the posterior vertebral joints, a narrow spinal canal straight or narrowed. Medical treatment, physiotherapy, and finally surgery can give very satisfactory results in an old patient, avoiding loss of function, a miserable existence and becoming bed ridden. PMID:3496925

  11. Heart Disease Affects Women of All Ages

    MedlinePlus

    ... percent of smokers begin before age 18. Middle-Aged Women: At menopause, a woman's heart disease risk ... risk of developing high blood pressure for women aged 55 is about 90 percent. Beginning at age ...

  12. Gastric emptying scintigraphy results in children are affected by age, anthropometric factors, and study duration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A standardized 4-hour adult-based gastric emptying scintigraphy (GES) protocol is increasingly being used in children to evaluate for gastroparesis. We sought to determine the effect of age, anthropometrics, and study duration on GES results using this protocol in children. Retrospective review of c...

  13. Effect of Duration of Disease on Ventilatory Function in an Ethnic Saudi Group of Diabetic Patients

    PubMed Central

    Meo, Sultan A.; Al Drees, Abdul Majeed; Ahmed, Jehangeer; Ahmed Shah, Sayed Fayaz; Al-Regaiey, Khalid; Husain, Ashraf; Al-Rubean, Khalid

    2007-01-01

    Background Diabetes mellitus is a leading cause of illness and death across the world and is responsible for a growing proportion of global health care expenditures. The present study was designed to observe the effect of diabetes mellitus on lung function in patients with diabetes belonging to a specific ethnic group, namely Saudis. Method In this study, a group of 47 apparently healthy volunteer male Saudi patients with diabetes was randomly selected. Their ages ranged from 20 to 70 years. The patients were matched with another group of 50 healthy male control subjects in terms of age, height, weight, ethnicity, and socioeconomic status. Both groups met exclusion criteria as per standard. Spirometry was performed with an electronic spirometer (Schiller AT-2 Plus, Switzerland), and results were compared by a Student's t test. Results Subjects with diabetes showed a significant reduction in forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) relative to their matched controls. However, there were no significant differences in the forced expiratory ratio (FEV1/FVC%) and the middle half of the FVC (FEF25–75%) between the groups. We observed a significantly negative correlation between duration of disease and pulmonary function, as measured by FEV1 (r = 0.258, p = 0.04), FVC (r = 0.282, p = 0.28), and the middle half of the FVC (FEF25–75%) (r = 0.321, p = 0.014). Conclusions Pulmonary function in a specific ethnic group of patients with diabetes was impaired as evidenced by a decrease in FVC and FEV1 compared to pulmonary function in matched controls. Stratification of results by years of disease revealed a significant correlation between duration of disease and a decline in pulmonary function. PMID:19885139

  14. Interactive vs passive screen time and nighttime sleep duration among school-aged children

    PubMed Central

    Yland, Jennifer; Guan, Stanford; Emanuele, Erin; Hale, Lauren

    2016-01-01

    Background Insufficient sleep among school-aged children is a growing concern, as numerous studies have shown that chronic short sleep duration increases the risk of poor academic performance and specific adverse health outcomes. We examined the association between weekday nighttime sleep duration and 3 types of screen exposure: television, computer use, and video gaming. Methods We used age 9 data from an ethnically diverse national birth cohort study, the Fragile Families and Child Wellbeing Study, to assess the association between screen time and sleep duration among 9-year-olds, using screen time data reported by both the child (n = 3269) and by the child's primary caregiver (n= 2770). Results Within the child-reported models, children who watched more than 2 hours of television per day had shorter sleep duration by approximately 11 minutes per night compared to those who watched less than 2 hours of television (β = −0.18; P < .001). Using the caregiver-reported models, both television and computer use were associated with reduced sleep duration. For both child- and parent-reported screen time measures, we did not find statistically significant differences in effect size across various types of screen time. Conclusions Screen time from televisions and computers is associated with reduced sleep duration among 9-year-olds, using 2 sources of estimates of screen time exposure (child and parent reports). No specific type or use of screen time resulted in significantly shorter sleep duration than another, suggesting that caution should be advised against excessive use of all screens. PMID:27540566

  15. Duration reproduction: lossy integration and effects of sensory modalities, cognitive functioning, age, and sex.

    PubMed

    Pütz, Peter; Wittmann, Marc; Wackermann, Jirí

    2012-10-01

    The "dual klepsydra model" (DKM) of internal time representation successfully models duration reproduction data, but relations between the DKM-based parameter kappa ("loss rate") and procedural variables (presentation modality) or individual characteristics (cognitive indices, age, sex) remained as yet unexplored. For that purpose, were-analyzed data from an earlier time reproduction study (N = 100), using visually or acoustically presented intervals of 1-5 sec. duration. Typical values of parameter kappa were approximately 0.03-0.04 sec.(-1), corresponding to relaxation times of internal "lossy integrators" of approximately 30 sec. Significant effects of presentation modality (smaller kappa values for the visual reproduction task) and of age (greater kappa in acoustic reproduction with increasing age) were observed. Cognitive variables (working memory, general fluid reasoning, attention) and sex of participants were not associated with kappa. Cognitive functions seem to play only a minor, if any, role at the level of time representation addressed by the DKM. PMID:23265003

  16. Gender-specific factors associated with shorter sleep duration at age 3 years.

    PubMed

    Plancoulaine, Sabine; Lioret, Sandrine; Regnault, Nolwenn; Heude, Barbara; Charles, Marie-Aline

    2015-12-01

    Total sleep duration has been decreasing among children in the last decades. Short sleep duration (SSD) has been associated with deleterious health consequences, such as excess weight/obesity. Risk factors for SSD have already been studied among school-aged children and adolescents, but inconsistent results have been reported regarding possible gender differences. Studies reporting such relationships are scarce in preschoolers, despite the importance of this period for adopting healthy behaviour. We aimed to investigate factors associated with SSD in 3-year-old boys (n = 546) and girls (n = 482) in a French Mother-Child Cohort (EDEN Study). Children were born between 2003 and 2006 in two French university hospitals. Clinical examinations and parent self-reported questionnaires allowed us to collect sociodemographic (e.g. income, education, family situation, child-minding system), maternal [e.g. body mass index (BMI), parity, depression, breastfeeding duration] and child's characteristics (e.g. gender, birth weight, term, physical activity and TV viewing duration, food consumption, usual sleep time). Sleep duration/24-h period was calculated and SSD was defined as <12 h. Analyses were performed using logistic regression. The mean sleep duration was 12 h 35 ± 56 min, with 91% of the children napping. Patterns of risk factors associated with SSD differed according to gender. In addition to parental presence when falling asleep, short sleep duration was associated strongly positively with high BMI Z-score and TV viewing duration among boys and with familial home child-minding and lower scores on the 'fruits and vegetables' dietary pattern among girls. These results suggest either a patterning of parental behaviours that differs according to gender, or a gender-specific sleep physiology, or both. PMID:26041449

  17. Effect of disease duration on personality type in multiple sclerosis patients and healthy individual

    PubMed Central

    Vesal, Sahar; Dehghani, Leila; Etemadifar, Masoud; Poorazizi, Elahe; Akhavan, Sima; Mazrouei, Samaneh; Mehdizadeh, Nasim; Saraf, Zahra

    2016-01-01

    Background: Multiple sclerosis may have profound emotional consequences. The relation between psychological and physical factors could lead patients toward unforeseen disease. This study focuses on multiple sclerosis (MS) disease duration on personality type A and B in relation to individuals’ behaviors. Materials and Methods: This descriptive-analytical study was conducted in Isfahan Alzahra hospital in 2013. Three hundred MS patients and 100 healthy individuals were determined. The distributed questionnaires related to MS patients and considering the descriptive statistics such as demographic variables. Data were analyzed by SPSS software (version 18) based on Chi-square test and independent T-test. Results: Disease duration varied between 1 to 38 years: 30% (1-4 years), 38% (5-10 years), 20% (10-20 years), and 12% (more than 20 years). Significant relationship was observed between disease duration and tendency to type A (higher stress). This relation was positive and significant in Relapsing Remitting MS patients; but negative correlation was seen in Secondary Progressive MS patients. These patients tended to type B (lower stress) when disease duration increased. Conclusions: Individuals with disease duration of one year and less than one year tend to type A personality, while patients with increment of disease duration have tendency to type B. PMID:27099848

  18. Electrophysiological Indicators of the Age-Related Deterioration in the Sensitivity to Auditory Duration Deviance

    PubMed Central

    Nowak, Kamila; Oron, Anna; Szymaszek, Aneta; Leminen, Miika; Näätänen, Risto; Szelag, Elzbieta

    2016-01-01

    The present study investigates age-related changes in duration discrimination in millisecond time domain. We tested young (N = 20, mean age = 24.5, SD = 2.97) and elderly (N = 20, mean age = 65.2, SD = 2.94) subjects using the mismatch negativity (MMN) paradigm. White-noise bursts of two different durations (50 and 10 ms) were presented in two oddball blocks. In one block (Increment Condition), the repetitive sequence of 10 ms standards was interspersed by occasional 50 ms deviants. In the Decrement Condition, the roles of the two stimuli were reversed. We analyzed the P1-N1 complex, MMN and P3a and found the effect of age for all these components. Moreover, the impact of stimulus presentation condition (increment/decrement) was observed for MMN and P3a. Our results confirmed the previous evidence for deteriorated duration discrimination in elderly people. Additionally, we found that this effect may be influenced by procedural factors. PMID:26834628

  19. Duration of gluten exposure in adult coeliac disease does not correlate with the risk for autoimmune disorders

    PubMed Central

    Sategna, G; Solerio, E; Scaglione, N; Aimo, G; Mengozzi, G

    2001-01-01

    BACKGROUND AND AIMS—Duration of gluten exposure seems to predispose adolescents with coeliac disease to autoimmune diseases. In a retrospective cohort study, we assessed the relationship between autoimmune disorders and actual gluten exposure in patients in whom coeliac disease was diagnosed in adult life (⩾16 years).
METHODS—We screened for the presence of autoimmunity in 605 controls (16-84 years) and 422 patients (16-84 years), all of whom had been on gluten withdrawal for at least one year (median follow up 9.5 years). A logistic regression analysis, setting the prevalence of autoimmunity as the dependent variable, was employed to control for independent covariates as predictors of the risk of autoimmunity.
RESULTS—The prevalence of autoimmunity was threefold higher (p<0.00001) in patients than in controls. Mean duration of gluten exposure was 31.2 and 32.6 years for patients with or without autoimmunity. Logistic regression showed that increased age at diagnosis of coeliac disease was related to the prevalence of autoimmune disease while "actual gluten exposure" which takes into account diet compliance, follow up, and age at diagnosis of autoimmune disorders were not predictive for the risk of developing autoimmune diseases (odds ratio 0.82 per year).
CONCLUSION—The prevalence of autoimmune diseases in patients with a late coeliac disease diagnosis does not correlate with duration of gluten intake. Early exposure to gluten may modify the immunological response. Gluten withdrawal does not protect patients with a late diagnosis from autoimmune diseases.


Keywords: coeliac disease; autoimmune disorders; prevalence PMID:11559646

  20. Treatment of Calves with Bovine Respiratory Disease: Duration of Therapy and Posttreatment Intervals.

    PubMed

    Apley, Michael D

    2015-11-01

    When treating bovine respiratory disease, it is important to consider the decision to initiate treatment, the treatment regimen used, and whether to continue treatment. It is necessary to define the duration of drug exposure and when a success/failure decision will be made. No data are available to define the optimal duration of antimicrobial exposure. A pattern seen in human pneumonia studies is that shorter durations of therapy were equivalent with longer durations. Some studies suggest defining success or failure based on pharmacokinetics and pharmacodynamics may lead to earlier than optimal intervention. Optimal intervals are best defined by randomized clinical trials. PMID:26253265

  1. Duration of depressive symptoms and mortality risk: the English Longitudinal Study of Ageing (ELSA)

    PubMed Central

    White, James; Zaninotto, Paola; Walters, Kate; Kivimäki, Mika; Demakakos, Panayotes; Biddulph, Jane; Kumari, Meena; De Oliveira, Cesar; Gallacher, John; Batty, G. David

    2016-01-01

    Background The relationship between the duration of depressive symptoms and mortality remains poorly understood. Aims To examine whether the duration of depressive symptoms is associated with mortality risk. Method Data (n = 9560) came from the English Longitudinal Study of Ageing (ELSA). We assessed depressive symptom duration as the sum of examinations with an eight-item Center for Epidemiologic Studies Depression Scale score of ⩾3; we ascertained mortality from linking our data to a national register. Results Relative to those participants who never reported symptoms, the age- and gender-adjusted hazard ratios for elevated depressive symptoms over 1, 2, 3 and 4 examinations were 1.41 (95% CI 1.15–1.74), 1.80 (95% CI 1.44–2.26), 1.97 (95% CI 1.57–2.47) and 2.48 (95% CI 1.90–3.23), respectively (P for trend <0.001). This graded association can be explained largely by differences in physical activity, cognitive function, functional impairments and physical illness. Conclusions In this cohort of older adults, the duration of depressive symptoms was associated with mortality in a dose–response manner. PMID:26795425

  2. Duration of extracorporeal therapy in acute maple syrup urine disease: a kinetic model.

    PubMed

    Phan, Véronique; Clermont, Marie-José; Merouani, Aicha; Litalien, Catherine; Tucci, Marisa; Lambert, Marie; Mitchell, Grant; Jouvet, Philippe

    2006-05-01

    Maple syrup urine disease (MSUD, MIM 248600) can be complicated by metabolic crises necessitating extracorporeal removal therapy (ECRT). Since leucine levels are usually not immediately available during therapy, an accurate kinetic model of leucine plasma levels during removal would be useful to establish the duration of ECRT. Such a kinetic model is available for neonates undergoing continuous ECRT (CECRT) with a leucine clearance>or=35 ml min-1 1.73 m-2. The current study tests the validity of this model in older children. Plasma leucine levels were obtained from eleven ECRT sessions [seven CECRT and four intermittent hemodialysis (HDi) sessions] in seven children aged 1-14 years. No hemodynamic instability or neurological complications were observed during treatment. HDi provided a higher leucine clearance and required shorter sessions than CECRT (5.4+/-0.6 vs. 17.1+/-6.0 h). All patients regained precrisis neurological status except for one patient who had severe neurological damage (severe cerebral edema) at the time of dialysis and subsequently died despite efficient leucine removal. A leucine clearance>or=50 ml min-1 1.73 m-2 is required to obtain a kinetic model similar to that reported in neonates, both with CECRT and HDi. This model should be helpful in predicting the duration of therapy needed to attain desired leucine levels. PMID:16518628

  3. The ratio of N-acetyl aspartate to glutamate correlates with disease duration of amyotrophic lateral sclerosis.

    PubMed

    Sako, Wataru; Abe, Takashi; Izumi, Yuishin; Harada, Masafumi; Kaji, Ryuji

    2016-05-01

    Glutamate (Glu)-induced excitotoxicity has been implicated in the neuronal loss of amyotrophic lateral sclerosis. To test the hypothesis that Glu in the primary motor cortex contributes to disease severity and/or duration, the Glu level was investigated using MR spectroscopy. Seventeen patients with amyotrophic lateral sclerosis were diagnosed according to the El Escorial criteria for suspected, possible, probable or definite amyotrophic lateral sclerosis, and enrolled in this cross-sectional study. We measured metabolite concentrations, including N-acetyl aspartate (NAA), creatine, choline, inositol, Glu and glutamine, and performed partial correlation between each metabolite concentration or NAA/Glu ratio and disease severity or duration using age as a covariate. Considering our hypothesis that Glu is associated with neuronal cell death in amyotrophic lateral sclerosis, we investigated the ratio of NAA to Glu, and found a significant correlation between NAA/Glu and disease duration (r=-0.574, p=0.02). The "suspected" amyotrophic lateral sclerosis patients showed the same tendency as possible, probable and definite amyotrophic lateral sclerosis patients in regard to correlation of NAA/Glu ratio with disease duration. The other metabolites showed no significant correlation. Our findings suggested that glutamatergic neurons are less vulnerable compared to other neurons and this may be because inhibitory receptors are mainly located presynaptically, which supports the notion of Glu-induced excitotoxicity. PMID:26765768

  4. Breastfeeding duration, age of starting solids and high BMI risk and adiposity in Indian children.

    PubMed

    Caleyachetty, Amrit; Krishnaveni, Ghattu V; Veena, Sargoor R; Hill, Jacqui; Karat, Samuel C; Fall, Caroline H D; Wills, Andrew K

    2013-04-01

    This study utilized data from a prospective birth cohort study on 568 Indian children, to determine whether a longer duration of breastfeeding and later introduction of solid feeding were associated with a reduced higher body mass index (BMI) and less adiposity. Main outcomes were high BMI (>90th within-cohort sex-specific BMI percentile) and sum of skinfold thickness (triceps and subscapular) at age 5. Main exposures were breastfeeding (six categories from 1-4 to ≥21 months) and age of starting regular solid feeding (four categories from ≤3 to ≥6 months). Data on infant-feeding practices, socio-economic and maternal factors were collected by questionnaire. Birthweight, maternal and child anthropometry were measured. Multiple regression analysis that accounted for potential confounders demonstrated a small magnitude of effect for breastfeeding duration or introduction of solid feeds on the risk of high BMI but not for lower skinfold thickness. Breastfeeding duration was strongly negatively associated with weight gain (0-2 years) [adjusted β = -0.12 standard deviation, 95% confidence interval (CI): -0.19 to -0.05 per category change in breastfeeding duration, P = 0.001], and weight gain (0-2 years) was strongly associated with high BMI at 5 years (adjusted odds ratio = 3.8, 95% CI: 2.53-5.56, P < 0.001). In our sample, findings suggest that longer breastfeeding duration and later introduction of solids has a small reduction on later high BMI risk and a negligible effect on skinfold thickness. However, accounting for sampling variability, these findings cannot exclude the possibility of no effect at the population level. PMID:21978208

  5. 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...

  6. Glycoconjugate changes in aging and age-related diseases.

    PubMed

    Ando, Susumu

    2014-01-01

    The significance of glycosphingolipids and glycoproteins is discussed in their relation to normal aging and pathological aging, aging with diseases. Healthy myelin that looks stable is found to be gradually degraded and reconstructed throughout life for remodeling. An exciting finding is that myelin P0 protein is located in neurons and glycosylated in aging brains. In pathological aging, the roles of glycosphingolipids and glycoproteins as risk factors or protective agents for Alzheimer's and Parkinson's diseases are discussed. Intensive studies have been performed aiming to remove the risks from and to restore the functional deficits of the brain. Some of them are expected to be translated to therapeutic means. PMID:25151390

  7. 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

  8. Better stay together: pair bond duration increases individual fitness independent of age-related variation.

    PubMed

    Sánchez-Macouzet, Oscar; Rodríguez, Cristina; Drummond, Hugh

    2014-07-01

    Prolonged pair bonds have the potential to improve reproductive performance of socially monogamous animals by increasing pair familiarity and enhancing coordination and cooperation between pair members. However, this has proved very difficult to test robustly because of important confounds such as age and reproductive experience. Here, we address limitations of previous studies and provide a rigorous test of the mate familiarity effect in the socially monogamous blue-footed booby, Sula nebouxii, a long-lived marine bird with a high divorce rate. Taking advantage of a natural disassociation between age and pair bond duration in this species, and applying a novel analytical approach to a 24 year database, we found that those pairs which have been together for longer establish their clutches five weeks earlier in the season, hatch more of their eggs and produce 35% more fledglings, regardless of age and reproductive experience. Our results demonstrate that pair bond duration increases individual fitness and further suggest that synergistic effects between a male and female's behaviour are likely to be involved in generating a mate familiarity effect. These findings help to explain the age- and experience-independent benefits of remating and their role in life-history evolution. PMID:24827435

  9. Better stay together: pair bond duration increases individual fitness independent of age-related variation

    PubMed Central

    Sánchez-Macouzet, Oscar; Rodríguez, Cristina; Drummond, Hugh

    2014-01-01

    Prolonged pair bonds have the potential to improve reproductive performance of socially monogamous animals by increasing pair familiarity and enhancing coordination and cooperation between pair members. However, this has proved very difficult to test robustly because of important confounds such as age and reproductive experience. Here, we address limitations of previous studies and provide a rigorous test of the mate familiarity effect in the socially monogamous blue-footed booby, Sula nebouxii, a long-lived marine bird with a high divorce rate. Taking advantage of a natural disassociation between age and pair bond duration in this species, and applying a novel analytical approach to a 24 year database, we found that those pairs which have been together for longer establish their clutches five weeks earlier in the season, hatch more of their eggs and produce 35% more fledglings, regardless of age and reproductive experience. Our results demonstrate that pair bond duration increases individual fitness and further suggest that synergistic effects between a male and female's behaviour are likely to be involved in generating a mate familiarity effect. These findings help to explain the age- and experience-independent benefits of remating and their role in life-history evolution. PMID:24827435

  10. Modulating Human Aging and Age-Associated Diseases

    PubMed Central

    Fontana, Luigi

    2009-01-01

    Population aging is progressing rapidly in many industrialized countries. The United States population aged 65 and over is expected to double in size within the next 25 years. In sedentary people eating Western diets aging is associated with the development of serious chronic diseases, including type 2 diabetes mellitus, cancer and cardiovascular diseases. About 80 percent of adults over 65 years of age have at least one chronic disease, and 50 percent have at least two chronic diseases. These chronic diseases are the most important cause of illness and mortality burden, and they have become the leading driver of healthcare costs, constituting an important burden for our society. Data from epidemiological studies and clinical trials indicate that many age-associated chronic diseases can be prevented, and even reversed, with the implementation of healthy lifestyle interventions. Several recent studies suggest that more drastic interventions (i.e. calorie restriction without malnutrition and moderate protein restriction with adequate nutrition) may have additional beneficial effects on several metabolic and hormonal factors that are implicated in the biology of aging itself. Additional studies are needed to understand the complex interactions of factors that regulate aging and age-associated chronic disease. PMID:19364477

  11. Association of Sleep Duration with Chronic Diseases in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study

    PubMed Central

    von Ruesten, Anne; Weikert, Cornelia; Fietze, Ingo; Boeing, Heiner

    2012-01-01

    Background In view of the reduced number of hours devoted to sleep in modern western societies the question arises what effects might result from sleep duration on occurrence of chronic diseases. Methods Data from 23 620 middle-aged participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, that were recruited between 1994–1998, were analyzed by using Cox proportional hazard regression to examine the association between self-reported sleep duration at baseline and incidence of chronic diseases, such as diabetes, myocardial infarction, stroke, and cancer. Results During a mean follow-up period of 7.8 years 841 incident cases of type 2 diabetes, 197 cases of myocardial infarction, 169 incident strokes, and 846 tumor cases were observed. Compared to persons sleeping 7-<8 h/day, participants with sleep duration of <6 h had a significantly increased risk of stroke (Hazard Ratio (HR) = 2.06, 95% confidence interval (CI): 1.18–3.59), cancer (HR = 1.43, 95% CI: 1.09–1.87), and overall chronic diseases (HR = 1.31, 95% CI: 1.10–1.55) in multivariable adjusted models. Self-reported daytime sleep at baseline was not associated with incident chronic diseases in the overall study sample. However, there had been an effect modification of daytime sleep by hypertension showing that daytime sleep was inversely related to chronic disease risk among non-hypertensive participants but directly related to chronic diseases among hypertensives. Conclusion Sleep duration of less than 6 h is a risky behavior for the development of chronic diseases, particularly stroke and cancer, and should be therefore addressed in public health campaigns. PMID:22295122

  12. Age and residency duration of loggerhead turtles at a North Pacific bycatch hotspot using skeletochronology

    PubMed Central

    Tomaszewicz, Calandra N. Turner; Seminoff, Jeffrey A.; Avens, Larisa; Goshe, Lisa R.; Peckham, S. Hoyt; Rguez-Baron, Juan M.; Bickerman, Kalyn; Kurle, Carolyn M.

    2015-01-01

    For migratory marine animals, like sea turtles, effective conservation can be challenging because key demographic information such as duration of life stages and exposure to spatially explicit threats in different habitats are often unknown. In the eastern Pacific near the Baja California Peninsula (BCP), Mexico, tens of thousands of endangered North Pacific loggerhead sea turtles (Caretta caretta) concentrate at a foraging area known to have high rates of fishery bycatch. Because stage survivorship of loggerheads in the BCP will vary significantly depending on the number of years spent in this region, we applied skeletochronology to empirically estimate residency duration in this loggerhead hotspot. The observed age distribution obtained from skeletochronology analysis of 146 dead-stranded loggerheads ranged from three to 24 years old, suggesting a BCP residency of >20 years. Given the maximum estimated age and a one-year migration to western Pacific nesting beaches, we infer age-at-maturation for BCP loggerheads at ~25 years old. We also examine survivorship at varying BCP residency durations by applying our findings to current annual mortality estimates. Predicted survivorship of loggerheads spending over 20 years in this BCP foraging habitat is less than 10%, and given that ~43,000 loggerhead turtles forage here, a significant number of turtles are at extreme risk in this region. This is the first empirical evidence supporting estimated age-at-maturation for BCP North Pacific loggerheads, and the first estimates of BCP stage survivorship. Our findings emphasize the urgent need for continued and effective international conservation efforts to minimize bycatch of this endangered species. PMID:25848136

  13. Long sleep duration: a nonconventional indicator of arterial stiffness in Japanese at high risk of cardiovascular disease: the J-HOP study.

    PubMed

    Niijima, Satoshi; Nagai, Michiaki; Hoshide, Satoshi; Takahashi, Mami; Shimpo, Masahisa; Kario, Kazuomi

    2016-05-01

    Long and short sleep durations were reported as independently associated with hypertension, aortic stiffness, and cardiovascular disease. High-sensitivity C-reactive protein (hs-CRP) was shown to be associated with increased aortic stiffness. Here, we investigated the relationship between self-reported sleep duration and pulse wave velocity (PWV) in the elderly at high risk of cardiovascular disease. We also investigated whether hs-CRP moderates this relationship. Among 4310 patients with ≥1 cardiovascular risks recruited for the Japan Morning Surge-Home Blood Pressure Study, a questionnaire including items on daily sleep duration was completed. We measured the brachial-ankle PWV (baPWV) and hs-CRP levels in 2304 of these patients (mean age 64.7 years, 49.6% males). In accord with the patients' sleep duration (<6 hours, ≥6 to <8 hours, and ≥8 hours per night), significant associations between sleep duration and the PWV were observed (1594 vs. 1644 vs. 1763 cm/s, P < .0001). In the multiple regression analysis adjusted for age, body mass index, total cholesterol, HbA1c and clinic systolic blood pressure, long sleep duration (≥8 hours per night) (P < .05), and log hs-CRP (P < .05) were significantly positively associated with PWV when the patients with 6- to 8-hour sleep duration were defined as a reference group. Significant interactions of long sleep duration by age and that by antihypertensive medication for baPWV were observed. The effect of long sleep on PWV was greatest in the oldest age group. Long sleep duration and hs-CRP were significant indicators of increased baPWV in this elderly high-risk Japanese population. Age and antihypertensive medication use were significant modulators of the relationship between long sleep duration and arterial stiffness. PMID:27151211

  14. Timing Issues with Early Childhood Education Programs: How Effect Sizes Vary by Starting Age, Program Duration and Persistence of Effects

    ERIC Educational Resources Information Center

    Duncan, Greg J.; Leak, James A.; Li, Weilin; Magnuson, Katherine; Schindler, Holly; Yoshikawa, Hiro

    2011-01-01

    The focus of this paper centers around timing associated with early childhood education programs and interventions using meta-analytic methods. At any given assessment age, a child's current age equals starting age, plus duration of program, plus years since program ended. Variability in assessment ages across the studies should enable everyone to…

  15. 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

  16. New U-Pb zircon ages and the duration and division of Devonian time

    USGS Publications Warehouse

    Tucker, R.D.; Bradley, D.C.; Ver Straeten, C.A.; Harris, A.G.; Ebert, J.R.; McCutcheon, S.R.

    1998-01-01

    Newly determined U-Pb zircon ages of volcanic ashes closely tied to biostratigraphic zones are used to revise the Devonian time-scale. They are: 1) 417.6 ?? 1.0 Ma for an ash within the conodont zone of Icriodus woschmidti/I. w. hesperius Lochkovian); 2) 408.3 ?? 1.9 Ma for an ash of early Emsian age correlated with the conodont zones of Po. dehiscens--Lower Po. inversus; 3) 391.4 ?? 1.8 Ma for an ash within the Po. c. costatus Zone and probably within the upper half of the zone (Eifelian); and 4) 381.1 ?? 1.3 Ma for an ash within the range of the Frasnian conodont Palmatolepis punctata (Pa. punctata Zone to Upper Pa. hassi Zone). U-Pb zircon ages for two rhyolites bracketing a palyniferous bed of the pusillites-lepidophyta spore zone, are dated at 363.8 ?? 2.2 Ma and 363 ?? 2.2 Ma and 363.4 ?? 1.8 Ma, respectively, suggesting an age of ~363 Ma for a level within the late Famennian Pa. g. expansa Zone. These data, together with other published zircon ages, suggest that the base and top of the Devonian lie close to 418 Ma and 362 Ma, respectively, thus lengthening the period of ~20% over current estimates. We suggest that the duration of the Middle Devonian (Eifelian and Givitian) is rather brief, perhaps no longer than 11.5 Myr (394 Ma-382.5 Ma), and that the Emsian and Famennian are the longest stages in the period with estimated durations of ~15.5 Myr and 14.5 Myr, respectively.

  17. Duration of periventricular densities in preterm infants and neurological outcome at 6 years of age.

    PubMed Central

    Jongmans, M; Henderson, S; de Vries, L; Dubowitz, L

    1993-01-01

    Parenchymal echogenicities that break down into extensive cystic lesions are generally followed by severe motor deficit. However, the effect of echodensities in the periventricular white matter, so called 'flares', on later development is less well documented. The aim of the present study was to investigate the impact of neonatal flares in preterm infants on neurological status and motor competence at 6 years of age and to see to what extent outcome was related to duration of flares. Forty four children with flares, subdivided into three groups according to the duration of flares, and 62 children with normal scans were assessed on Touwen's neurological examination, the Movement ABC, and the British Ability Scales. No differences in cognitive abilities were found between the groups. The results of the motor assessments showed that performance decreased significantly with increasing duration of flares. In addition, there was a suggestion that this trend was stronger in measures assessing lower limb function than those of upper limb. Teachers were also able to identify differences between the groups of children on the basis of their motor performance in school. PMID:8346967

  18. 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

  19. Nutritional Interventions in Aging and Age-Associated Diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary interventions have proven to be the most robust and consistent means of ameliorating the diseases and dysfunctions of aging. A large literature includes both quantitative (caloric restriction [CR]) and qualitative (micronutrients, antioxidants, etc.) alterations of nutrient and caloric inta...

  20. Effects of Age, Exercise Duration, and Test Conditions on Heart Rate Variability in Young Endurance Horses.

    PubMed

    Younes, Mohamed; Robert, Céline; Barrey, Eric; Cottin, François

    2016-01-01

    Although cardiac recovery is an important criterion for ranking horses in endurance competitions, heart rate variability (HRV) has hardly ever been studied in the context of this equestrian discipline. In the present study, we sought to determine whether HRV is affected by parameters such as age, exercise duration and test site. Accordingly, HRV might be used to select endurance horses with the fastest cardiac recovery. The main objective of the present study was to determine the effects of age, exercise duration, and test site on HRV variables at rest and during exercise and recovery in young Arabian endurance horses. Over a 3-year period, 77 young Arabian horses aged 4-6 years performed one or more exercise tests (consisting of a warm-up, cantering at 22 km.h(-1)and a final 500 m gallop at full speed) at four different sites. Beat-to-beat RR intervals were continuously recorded and then analyzed (using a time-frequency approach) to determine the instantaneous HRV components before, during and after the test. At rest, the root-mean-square of successive differences in RR intervals (RMSSD) was higher in the 4-year-olds (54.4 ± 14.5 ms) than in the 5-or 6-year-olds (44.9 ± 15.5 and 49.1 ± 11.7 ms, respectively). During the first 15 min of exercise (period T), the heart rate (HR) and RMSSD decreased with age. In 6-year-olds, RMSSD decreased as the exercise duration increased (T: 3.0 ± 1.4 vs. 2T: 3.6 ± 2.2 vs. 3T: 2.8 ± 1.0). During recovery, RMSSD was negatively correlated with the cardiac recovery time (CRT) and the recovery heart rate (RHR; R = -0.56 and -0.53, respectively; p < 0.05). At rest and during exercise and recovery, RMSSD and several HRV variables differed significantly as a function of the test conditions. HRV in endurance horses appears to be strongly influenced by age and environmental factors (such as ambient temperature, ambient humidity, and track quality). Nevertheless, RMSSD can be used to select endurance horses with the fastest cardiac

  1. Effects of Age, Exercise Duration, and Test Conditions on Heart Rate Variability in Young Endurance Horses

    PubMed Central

    Younes, Mohamed; Robert, Céline; Barrey, Eric; Cottin, François

    2016-01-01

    Although cardiac recovery is an important criterion for ranking horses in endurance competitions, heart rate variability (HRV) has hardly ever been studied in the context of this equestrian discipline. In the present study, we sought to determine whether HRV is affected by parameters such as age, exercise duration and test site. Accordingly, HRV might be used to select endurance horses with the fastest cardiac recovery. The main objective of the present study was to determine the effects of age, exercise duration, and test site on HRV variables at rest and during exercise and recovery in young Arabian endurance horses. Over a 3-year period, 77 young Arabian horses aged 4–6 years performed one or more exercise tests (consisting of a warm-up, cantering at 22 km.h−1and a final 500 m gallop at full speed) at four different sites. Beat-to-beat RR intervals were continuously recorded and then analyzed (using a time-frequency approach) to determine the instantaneous HRV components before, during and after the test. At rest, the root-mean-square of successive differences in RR intervals (RMSSD) was higher in the 4-year-olds (54.4 ± 14.5 ms) than in the 5-or 6-year-olds (44.9 ± 15.5 and 49.1 ± 11.7 ms, respectively). During the first 15 min of exercise (period T), the heart rate (HR) and RMSSD decreased with age. In 6-year-olds, RMSSD decreased as the exercise duration increased (T: 3.0 ± 1.4 vs. 2T: 3.6 ± 2.2 vs. 3T: 2.8 ± 1.0). During recovery, RMSSD was negatively correlated with the cardiac recovery time (CRT) and the recovery heart rate (RHR; R = −0.56 and −0.53, respectively; p < 0.05). At rest and during exercise and recovery, RMSSD and several HRV variables differed significantly as a function of the test conditions. HRV in endurance horses appears to be strongly influenced by age and environmental factors (such as ambient temperature, ambient humidity, and track quality). Nevertheless, RMSSD can be used to select endurance horses with the fastest

  2. Will the age of peak ultra-marathon performance increase with increasing race duration?

    PubMed Central

    2014-01-01

    Background Recent studies found that the athlete’s age of the best ultra-marathon performance was higher than the athlete’s age of the best marathon performance and it seemed that the athlete’s age of peak ultra-marathon performance increased in distance-limited races with rising distance. Methods We investigated the athlete’s age of peak ultra-marathon performance in the fastest finishers in time-limited ultra-marathons from 6 hrs to 10 d. Running performance and athlete’s age of the fastest women and men competing in 6 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 144 hrs (6 d) and 240 hrs (10 d) were analysed for races held between 1975 and 2012 using analysis of variance and multi-level regression analysis. Results The athlete’s ages of the ten fastest women ever in 6 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 6 d and 10 d were 41 ± 9, 41 ± 6, 42 ± 5, 46 ± 5, 44 ± 6, 42 ± 4, and 37 ± 4 yrs, respectively. The athlete’s age of the ten fastest women was different between 48 hrs and 10 d. For men, the athlete’s ages were 35 ± 6, 37 ± 9, 39 ± 8, 44 ± 7, 48 ± 3, 48 ± 8 and 48 ± 6 yrs, respectively. The athlete’s age of the ten fastest men in 6 hrs and 12 hrs was lower than the athlete’s age of the ten fastest men in 72 hrs, 6 d and 10 d, respectively. Conclusion The athlete’s age of peak ultra-marathon performance did not increase with rising race duration in the best ultra-marathoners. For the fastest women ever in time-limited races, the athlete’s age was lowest in 10 d (~37 yrs) and highest in 48 hrs (~46 yrs). For men, the athlete’s age of the fastest ever in 6 hrs (~35 yrs) and 12 hrs (~37 yrs) was lower than the athlete’s age of the ten fastest in 72 hrs (~48 yrs), 6 d (~48 yrs) and 10 d (~48 yrs). The differences in the athlete’s age of peak performance between female and male ultra-marathoners for the different race durations need further

  3. Comparison of Frequency and Duration of Periodontal Disease With Progression of Coronary Artery Calcium in Patients With and Without Type 1 Diabetes Mellitus.

    PubMed

    Groves, Daniel W; Krantz, Mori J; Hokanson, John E; Johnson, Lonnie R; Eckel, Robert H; Kinney, Gregory L; Rewers, Marian; Snell-Bergeon, Janet K; Alman, Amy C

    2015-09-15

    People with type 1 diabetes mellitus manifest a greater burden of both periodontal disease and coronary artery disease (CAD); however, little is known about their interrelation. Coronary artery calcium (CAC) measures subclinical atherosclerosis and predicts major adverse coronary events. The relation between periodontal disease and CAC progression in individuals with type 1 diabetes has not been previously described. We determined the prevalence and progression of CAC in relation to self-reported periodontal disease. Multivariate logistic and tobit regression models were used to examine the relation between periodontal disease duration and CAC progression and whether this relation differs by diabetes status after controlling for age, gender, total and high-density lipoprotein cholesterol, hypertension, smoking, body mass index (BMI), duration of diabetes, and baseline CAC. A total of 473 patients with type 1 diabetes and 548 without diabetes were followed for a mean of 6.1 years. At baseline, the prevalence and duration of periodontal disease did not differ between subjects with and without diabetes (14.5% vs 13.4%, p = 0.60; 6 vs 9 years, p = 0.18). Duration of periodontal disease was not significantly associated with baseline CAC prevalence. In patients with type 1 diabetes, periodontal disease duration was significantly related to CAC progression (p = 0.004) but not in subjects without diabetes (p = 0.63). In conclusion, this study suggests that periodontal disease is an independent predictor of long-term progression of CAC in patients with type 1 diabetes. PMID:26189036

  4. Food Variety at 2 Years of Age is Related to Duration of Breastfeeding

    PubMed Central

    Scott, Jane A.; Chih, Tsz Ying; Oddy, Wendy H.

    2012-01-01

    The aim of this study was to investigate the association of breastfeeding duration and food variety at 2 years of age. A secondary data analysis was undertaken of the Western Australian Pregnancy Cohort (Raine) Study, an ongoing longitudinal study. Data collected from a single 24 h dietary recall of 1905, 2 year-old children were used to calculate two food variety scores; a core food variety score (CFVS) and a fruit and vegetable variety score (FVVS). Multivariate linear regression analysis was used to identify those factors independently associated with the CFVS and FVVS. The mean CFVS was 7.52 (range 1–18) of a possible 34 food items or groups and the mean FVVS was 2.84 (range 0–10) of a possible 16 food items or groups. Breastfeeding duration was independently directly associated with the CFVS (p < 0.001) and FVVS (p < 0.001). In addition, maternal age was independently directly associated with the CFVS (p < 0.001) and FVVS (p = 0.001) as was maternal education (CFVS p < 0.001 and FVVS p = 0.043). The presence of older siblings was independently inversely associated with the CFVS (p = 0.003) and FVVS (p = 0.001). This study demonstrated a direct modest association between breastfeeding duration and food variety in 2 year-old children, independent of maternal demographic characteristics known to predict food variety in children. This finding supports the hypothesis that flavours transferred in breast milk provide repeated early exposure to different tastes and positively shape children’s food preferences and food variety. PMID:23201765

  5. Magnetic Resonance Phase Alterations in Multiple Sclerosis Patients with Short and Long Disease Duration

    PubMed Central

    Bozin, Ivan; Ge, Yulin; Kuchling, Joseph; Dusek, Petr; Chawla, Sanjeev; Harms, Lutz; Ruprecht, Klemens; Niendorf, Thoralf; Paul, Friedemann; Kister, Ilya

    2015-01-01

    Objective The analysis of the MR phase provides additional information on the tissue microstructure. In multiple sclerosis (MS) lesions phase alterations may reflect different stages of inflammatory activity. Here we investigated lesion morphology in MS patients with short and long disease duration on T2* weighted, phase, magnitude and susceptibility weighted imaging (SWI) at 7 Tesla (T). Methods 17 MS or clinically isolated syndrome patients with short (<60 months) and 11 with long (>60 months) disease duration underwent 7T MRI. Lesions were subsequently analyzed side-by-side with regard to morphology and visibility on T2* weighted, SWI, magnitude and SWI-filtered phase images. Results 126 of 192 T2* weighted lesions (65.6%) were characterized by a phase alteration pattern, and hence could be differentiated on phase images. In detail, a significantly reduced proportion of lesions showing phase alterations was detectable in patients with longer disease duration (mean±SD 51±37%, range 0–100%) compared to patients with short disease duration (mean±SD 90±19.5%, range 50–100%, p = 0.003). Conclusion This cross-sectional study identified different patterns of phase changes in lesions of MS patients with short and long standing disease. Longitudinal studies are warranted to prove that MR phase imaging is useful in determining the activity and the developmental stage of individual MS plaques. PMID:26186349

  6. Age and duration of eclogite-facies metamorphism, North Qaidam HP/UHP terrane, Western China

    USGS Publications Warehouse

    Mattinson, C.G.; Wooden, J.L.; Liou, J.G.; Bird, D.K.; Wu, C.L.

    2006-01-01

    Amphibolite-facies para-and orthogneisses near Dulan, at the southeast end of the North Qaidam terrane, enclose minor eclogite and peridotite which record ultra-high pressure (UHP) metamorphism associated with the Early Paleozoic continental collision of the Qilian and Qaidam microplates. Field relations and coesite inclusions in zircons from paragneiss suggest that felsic, mafic, and ultramafic rocks all experienced UHP metamorphism and a common amphibolite-facies retrogression. SHRIMP-RG U-Pb and REE analyses of zircons from four eclogites yield weighted mean ages of 449 to 422 Ma, and REE patterns (flat HREE, no Eu anomaly) and inclusions of garnet, omphacite, and rutile indicate these ages record eclogite-facies metamorphism. The coherent field relations of these samples, and the similar range of individual ages in each sample suggests that the ???25 m.y. age range reflects the duration of eclogite-facies conditions in the studied samples. Analyses from zircon cores in one sample yield scattered 433 to 474 Ma ages, reflecting partial overlap on rims, and constrain the minimum age of eclogite protolith crystallization. Inclusions of Th + REE-rich epidote, and zircon REE patterns are consistent with prograde metamorphic growth. In the Lu??liang Shan, approximately 350 km northwest in the North Qaidam terrane, ages interpreted to record eclogite-facies metamorphism of eclogite and garnet peridotite are as old as 495 Ma and as young as 414 Ma, which suggests that processes responsible for extended high-pressure residence are not restricted to the Dulan region. Evidence of prolonged eclogite-facies metamorphism in HP/UHP localities in the Northeast Greenland eclogite province, the Western Gneiss Region of Norway, and the western Alps suggests that long eclogite-facies residence may be globally significant in continental subduction/collision zones.

  7. Increased Levels of Eotaxin and MCP-1 in Juvenile Dermatomyositis Median 16.8 Years after Disease Onset; Associations with Disease Activity, Duration and Organ Damage

    PubMed Central

    Flatø, Berit; Vistnes, Maria; Christensen, Geir; Sjaastad, Ivar

    2014-01-01

    Objective To compare cytokine profiles in patients with juvenile dermatomyositis (JDM) after medium to long-term follow-up with matched controls, and to examine associations between cytokine levels and disease activity, disease duration and organ damage. Methods Fifty-four JDM patients were examined median 16.8 years (2–38) after disease onset (follow-up) and compared with 54 sex- and age-matched controls. Cytokine concentrations in serum were quantified by Luminex technology. In patients, disease activity score (DAS), myositis damage index (MDI) and other disease parameters were collected by chart review (early parameters) and clinical examination (follow-up). Results Serum levels of eotaxin, monocyte chemoattractant protein-1 (MCP-1) and interferon-inducible protein 10 (IP-10) were elevated in JDM patients compared to controls (31.5%, 37.2% and 43.2% respectively, all p<0.05). Patients with active (n = 28), but not inactive disease (n = 26) had a higher level of MCP-1 than their respective controls. Levels of eotaxin and MCP-1 correlated with disease duration (r = 0.47 and r = 0.64, both p<0.001) and age in patients, but not with age in controls. At follow-up, MDI was associated with MCP-1(standardized β = 0.43, p = 0.002) after adjusting for disease duration and gender. High MDI 1 year post-diagnosis predicted high levels of eotaxin and MCP-1 at follow-up (standardized β = 0.24 and 0.29, both p<0.05) after adjusting for disease duration and gender. Conclusion Patients with JDM had higher eotaxin, MCP-1 and IP-10 than controls. High eotaxin and MCP-1 at follow-up was predicted by early disease parameters, and MCP-1 was associated with organ damage at follow-up, highlighting a role of these chemokines in JDM. PMID:24647150

  8. Liver diseases and aging: friends or foes?

    PubMed

    Sheedfar, Fareeba; Di Biase, Stefano; Koonen, Debby; Vinciguerra, Manlio

    2013-12-01

    The liver is the only internal human organ capable of natural regeneration of lost tissue, as little as 25% of a liver can regenerate into a whole liver. The process of aging predisposes to hepatic functional and structural impairment and metabolic risk. Therefore, understanding how aging could affect the molecular pathology of liver diseases is particularly important, and few studies to date have tackled this complex process. The most common liver disease, affecting one-third of the overall population, is nonalcoholic fatty liver disease (NAFLD), characterized by an intrahepatic accumulation of lipids. NAFLD can evolve into nonalcoholic steatohepatitis (NASH) in the presence of oxidative stress and inflammation. NASH is a serious risk factor for disabling and deadly liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Old age seems to favor NAFLD, NASH, and ultimately HCC, in agreement with the inflamm-aging theory, according to which aging accrues inflammation. However, the incidence of HCC drops significantly in the very elderly (individuals aged more than 70) and the relationship between the progression of NAFLD/NASH/HCC and very old age is obscure. In this review, we discuss the literature and we argue that there might be an age window in which the liver becomes resistant to the development of injury; this needs to be studied to understand fully the interaction between age and liver diseases from a therapeutic perspective. PMID:23815295

  9. Self-Management in Early Adolescence and Differences by Age at Diagnosis and Duration of Type 1 Diabetes

    PubMed Central

    Chao, Ariana; Whittemore, Robin; Minges, Karl E.; Murphy, Kathryn M.; Grey, Margaret

    2014-01-01

    Purpose The purpose of the study was to describe the frequency of diabetes self-management activities, processes, and goals among early adolescents. In addition, differences in self-management by age at diagnosis and duration of diabetes were explored. Methods A cross-sectional design was used to analyze baseline data from 320 adolescents with T1DM enrolled in a multisite clinical trial. Participants completed questionnaires on demographic/clinical characteristics and self-management. Results There was a transitional pattern of self-management with a high frequency of diabetes care activities, problem solving, and goals and variable amounts of collaboration with parents. After controlling for therapy type and age, youth with short diabetes duration reported performing significantly more diabetes care activities than individuals with a longer duration. Individuals with short diabetes duration had more frequent communication than individuals with a longer duration, which was associated with diagnosis in adolescence. Among those diagnosed as school age children, those with short diabetes duration reported significantly more diabetes goals than those with a longer duration. Conclusions A more specific understanding of self-management may help clinicians provide more targeted education and support. Adolescents with a long duration of diabetes need additional self-management support, particularly for diabetes care activities and communication. PMID:24470042

  10. Sleep Duration and the Risk of Fatty Liver Disease: A Systematic Review and Meta-analysis.

    PubMed

    Shen, Na; Wang, Peng; Yan, Weiming

    2016-01-01

    Recent studies have reported inconsistent results on the association between sleep duration and the risk of fatty liver disease (FLD). Thus, we quantitatively evaluated this association by performing a systematic review and meta-analysis, based on a comprehensive electronic search in databases of PubMed, Web of Science, EMBASE, ClinicalTrials.gov, Wanfangdata and Chinese National Knowledge Infrastructure (CNKI) (updated to April 2016). Multivariate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were extracted and pooled by using a random-effects model. Eight eligible studies involving 97,371 participants were included. We found that neither short nor long sleep duration was significantly related with FLD risk. For short sleep duration, the pooled OR was 1.17 (95% CI = 0.98-1.38), and for long sleep duration, the pooled OR was 1.01 (95% CI = 0.72-1.41). Subgroup analyses by sex, outcome, and exposure reference also did not identify any effect of sleep duration on FLD onset. In summary, our findings suggested that short or long sleep duration was not significantly associated with FLD risk. Further cohort studies with refined designs are still warranted to validate our results. PMID:27549512

  11. Sleep Duration and the Risk of Fatty Liver Disease: A Systematic Review and Meta-analysis

    PubMed Central

    Shen, Na; Wang, Peng; Yan, Weiming

    2016-01-01

    Recent studies have reported inconsistent results on the association between sleep duration and the risk of fatty liver disease (FLD). Thus, we quantitatively evaluated this association by performing a systematic review and meta-analysis, based on a comprehensive electronic search in databases of PubMed, Web of Science, EMBASE, ClinicalTrials.gov, Wanfangdata and Chinese National Knowledge Infrastructure (CNKI) (updated to April 2016). Multivariate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were extracted and pooled by using a random-effects model. Eight eligible studies involving 97,371 participants were included. We found that neither short nor long sleep duration was significantly related with FLD risk. For short sleep duration, the pooled OR was 1.17 (95% CI = 0.98–1.38), and for long sleep duration, the pooled OR was 1.01 (95% CI = 0.72–1.41). Subgroup analyses by sex, outcome, and exposure reference also did not identify any effect of sleep duration on FLD onset. In summary, our findings suggested that short or long sleep duration was not significantly associated with FLD risk. Further cohort studies with refined designs are still warranted to validate our results. PMID:27549512

  12. The age factor in Alzheimer's disease.

    PubMed

    Guerreiro, Rita; Bras, Jose

    2015-01-01

    Alzheimer's disease is the most common type of dementia, and it is characterized by a decline in memory or other thinking skills. The greatest risk factor for Alzheimer's disease is advanced age. A recent genome-wide study identified a locus on chromosome 17 associated with the age at onset, and a specific variant in CCL11 is probably responsible for the association. The association of a protective haplotype with a 10-year delay in the onset of Alzheimer's disease and the identification of a CCL11 variant with possible functional roles in this association might allow the future development of immunomodulators with the potential to halve disease incidence. PMID:26482651

  13. Parkinson's disease as a result of aging

    PubMed Central

    Rodriguez, Manuel; Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Sabate, Magdalena

    2015-01-01

    It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinson's disease seems to be restricted to certain brain centers and cell populations. However, reviewed data suggest that Parkinson's disease may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. The development of new knowledge about Parkinson's disease could be accelerated if the research on aging and Parkinson's disease were planned together, and the perspective provided by gerontology gains relevance in this field. PMID:25677794

  14. Gastric Emptying Scintigraphy Results in Children are Affected by Age, Anthropometric Factors, and Study Duration

    PubMed Central

    Wong, Gregory K.; Shulman, Robert J.; Chumpitazi, Bruno P.

    2014-01-01

    Background A standardized 4-hour adult-based gastric emptying scintigraphy (GES) protocol is increasingly being used in children to evaluate for gastroparesis. We sought to determine the effect of age, anthropometrics, and study duration on GES results using this protocol in children. Methods Retrospective review of children who underwent a 4-hour solid-meal GES study at a tertiary care center. GES results and anthropometric data (e.g., weight, stature, body surface area) were systematically captured. Key Results Of 216 children, 188 (87%) were able to complete the study meal. Children unable to complete the meal were younger and smaller. In multivariate analysis, only increasing body surface area (BSA) was identified as being positively associated with ability to complete the meal (odds ratio: 19.7; P<0.001). Of those completing the meal, 48 (26%) had delayed emptying (4-hour retention value >10%). These children were significantly younger and smaller than those with normal emptying. In multivariate analysis of those completing the meal, only increasing BSA (odds ratio: 0.26; P=0.006) was identified as being negatively associated with delayed emptying. There was a progressive increase in the positive predictive value for identification of delayed gastric emptying as the duration of the study increased (0.25, 0.60, and 0.71 at 1, 2, and 3 hr, respectively) using the 4-hr value as a comparator. Conclusions and Inferences Young children have more difficulty completing the GES meal. Childhood gastric retention is affected by age and anthropometric factors, primarily BSA. The standardized 4-hr GES protocol may need to take these factors into account in children. PMID:25557417

  15. Age and Duration of the Paraná-Etendeka Flood Basalts and Related Plumbing System

    NASA Astrophysics Data System (ADS)

    Renne, P. R.

    2015-12-01

    The Paraná-Etendeka Igneous Province (PEIP) comprises a large volume sequence of continental flood basalts presently distributed assymetrically between South America (mainly southern Brazil but also parts of Uruguay, Paraguay and Argentina) and southwestern Africa (Namibia, Angola), following opening of the South Atlantic ocean. The PEIP is dominated by tholeiitic basalts to basaltic andesites, with subordinate silicic rocks spanning the dacite-trachyte-rhyolite fields, which occur as lava flows, sills and dike swarms as well as intrusive complexes closely related to the eruptive rocks. The PEIP has long been subject of 40Ar/39Ar geochronologic and paleomagnetic studies which led to conclude its rapid formation near the Hauterivian stage (~133 Ma) with onward progression to Barremian from the intrusive equivalents exposed northwards. Two decades after publication of the first 40Ar/39Ar ages for the Paraná flood basalts (Renne et al., 1992) we report here an updated study of the age and duration of this magmatic event. We calibrated a set of sixty published and new results to the calibration of Renne et al. (2011), which indicates an inception age of the volcanism now estimated at 135 ± 1 Ma, before the initiation of sea floor spreading. Lava extrusion progressed over ~2 Ma from south to north. A protracted duration of ~10 Ma inferred by Stewart et al. (1996) for PEIP volcanism is clearly incorrect, as also concluded by Thiede and Vasconcelos (2010). Low-Ti mafic magmas prevailed during the earlier stages followed over time by enhanced dominance of their silicic equivalents. Eruption of the high-Ti (mafic and silicic) magmas initiated simultaneously ~0.5 m.y. later, continuing up to ~133 Ma with injection of the Ponta Grossa dyke swarm. Despite several paleomagnetic polarity intervals recorded by the lava piles in the southern (> 27°S) and central (latitudes of ~24-27°S) domains of the Brazilian PEIP, the paleomagnetic data show small dispersion in agreement

  16. The impact of disease duration on quality of life in children with nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study

    PubMed Central

    Troost, Jonathan P.; Massengill, Susan F.; Gbadegesin, Rasheed A.; Greenbaum, Larry A.; Shatat, Ibrahim F.; Cai, Yi; Kapur, Gaurav; Hebert, Diane; Somers, Michael J.; Trachtman, Howard; Pais, Priya; Seifert, Michael E.; Goebel, Jens; Sethna, Christine B.; Mahan, John D.; Gross, Heather E.; Herreshoff, Emily; Liu, Yang; Song, Peter X.; Reeve, Bryce B.; DeWalt, Darren A.; Gipson, Debbie S.

    2015-01-01

    Background The Patient Reported Outcomes Measurement Information System (PROMIS) II is a prospective study that evaluates patient reported outcomes in pediatric chronic diseases as a measure of health-related quality of life (HRQOL). We have evaluated the influence of disease duration on HRQOL and, for the first time, compared the findings of the PROMIS measures to those of the PedsQL™ 4.0 Generic Scales (PedsQL) from the PROMIS II nephrotic syndrome (NS) longitudinal cohort. Methods This was a prospective study in which 127 children (age range 8–17 years) with active NS from 14 centers were enrolled. Children with active NS defined as the presence of nephrotic range proteinuria (>2+ urinalysis and edema or urine protein/creatinine ratio >2 g/g) were eligible. Comparisons were made between children with prevalent (N=67) and incident (N=60) disease at the study enrollment visit. Results The PROMIS scores were worse in prevalent patients in the domains of peer relationship (p=0.01) and pain interference (p < 0.01). The PedsQL showed worse scores in prevalent patients for social functioning (p < 0.01) and school functioning (p = 0.03). Multivariable analyses showed that prevalent patients had worse scores in PROMIS pain interference (p=0.02) and PedsQL social functioning (p<0.01). Conclusion The PROMIS measures detected a significant impact of disease duration on HRQOL in children, such that peer relationships were worse and pain interfered with daily life to a greater degree among those with longer disease duration. These findings were in agreement with those for similar domains in the PedsQL legacy instrument. PMID:25784017

  17. Sleep Apnea, Sleep Duration and Brain MRI Markers of Cerebral Vascular Disease and Alzheimer’s Disease: The Atherosclerosis Risk in Communities Study (ARIC)

    PubMed Central

    Lutsey, Pamela L.; Norby, Faye L.; Gottesman, Rebecca F.; Mosley, Thomas; MacLehose, Richard F.; Punjabi, Naresh M.; Shahar, Eyal; Jack, Clifford R.; Alonso, Alvaro

    2016-01-01

    Background A growing body of literature has suggested that obstructive sleep apnea (OSA) and habitual short sleep duration are linked to poor cognitive function. Neuroimaging studies may provide insight into this relation. Objective We tested the hypotheses that OSA and habitual short sleep duration, measured at ages 54–73 years, would be associated with adverse brain morphology at ages 67–89 years. Methods Included in this analysis are 312 ARIC study participants who underwent in-home overnight polysomnography in 1996–1998 and brain MRI scans about 15 years later (2012–2013). Sleep apnea was quantified by the apnea-hypopnea index and categorized as moderate/severe (≥15.0 events/hour), mild (5.0–14.9 events/hour), or normal (<5.0 events/hour). Habitual sleep duration was categorized, in hours, as <7, 7 to <8, ≥8. MRI outcomes included number of infarcts (total, subcortical, and cortical) and white matter hyperintensity (WMH) and Alzheimer’s disease signature region volumes. Multivariable adjusted logistic and linear regression models were used. All models incorporated inverse probability weighting, to adjust for potential selection bias. Results At the time of the sleep study participants were 61.7 (SD: 5.0) years old and 54% female; 19% had moderate/severe sleep apnea. MRI imaging took place 14.8 (SD: 1.0) years later, when participants were 76.5 (SD: 5.2) years old. In multivariable models which accounted for body mass index, neither OSA nor abnormal sleep duration were statistically significantly associated with odds of cerebral infarcts, WMH brain volumes or regional brain volumes. Conclusions In this community-based sample, mid-life OSA and habitually short sleep duration were not associated with later-life cerebral markers of vascular dementia and Alzheimer’s disease. However, selection bias may have influenced our results and the modest sample size led to relatively imprecise associations. PMID:27415826

  18. Type I collagen degradation does not diminish with RA disease duration

    PubMed Central

    Hakala, M; Aho, K; Aman, S; Luukkainen, R; Kauppi, M; Risteli, J

    2001-01-01

    OBJECTIVE—To assess the relation between type I collagen degradation and the duration of rheumatoid arthritis (RA).
METHODS—The serum concentrations of cross linked carboxyterminal telopeptide of type I collagen (ICTP) measured earlier in a community based series (90 patients) and a hospital based series (59 patients) were re-evaluated with reference to the duration of RA.
RESULTS—The serum ICTP showed a positive correlation with the duration of the disease in the hospital based series (rs=0.40, p<0.01) but not in the community based one (rs=0.18, p=0.10).
CONCLUSIONS—Type I collagen degradation predominantly reflecting pathological bone destruction does not seem to diminish in longlasting RA.

 PMID:11247878

  19. Age-at-onset in Huntington disease

    PubMed Central

    Orth, Michael; Schwenke, Carsten

    2011-01-01

    Background: In Huntington disease, the accurate determination of age-at-onset is critical to identify modifiers and therapies that aim to delay it. Methods: Retrospective data from the European Huntington’s Disease Network’s REGISTRY and PREDICT-HD, a longitudinal study in prodromal huntingtin gene expansion mutation carriers. Data (age, gender, CAG repeat length, parent affected, and Unified Huntington’s Disease Rating Scale motor score, total functional capacity) from at least three visits in 423 REGISTRY and 124 PREDICT-HD participants were included. Data based extrapolations of individual age-at-onset using generalized linear mixed models based on individual slopes of motor score or total functional capacity, and predictions using the Langbehn, or Ranen formula, were compared with clinicians’ estimates. Results: Concordance was best for the observed age-at-onset in PREDICT-HD and the calculated onset using the PREDICT-HD UHDRS longitudinal motor scores. This was superior to the REGISTRY data. For total functional capacity, the investigator’s estimate was 4 years before the data derived age-at-onset. The concordance of predictions of probability of age-at-onset is better with the observed age-at-onset in the PREDICT-HD data (difference in 25%tile -5 to 10 years) than the REGISTRY data (±20 years). Conclusions: Estimating or predicting age-at-onset in Huntington disease may be inaccurate. It can be useful to 1) add in the manifest population motor score regression derived age-at-onset as additional motor onset and 2) add total functional capacity regression derived age-at-onset for the onset of functional impact of Huntington disease when patients are in mid- to late-stage. PMID:22453877

  20. 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

  1. Mitochondrial DNA damage is associated with damage accrual and disease duration in patients with Systemic Lupus Erythematosus

    PubMed Central

    López-López, Linnette; Nieves-Plaza, Mariely; Castro, María del R.; Font, Yvonne M.; Torres-Ramos, Carlos; Vilá, Luis M.; Ayala-Peña, Sylvette

    2014-01-01

    Objective To determine the extent of mitochondrial DNA (mtDNA) damage in systemic lupus erythematosus (SLE) patients compared to healthy subjects and to determine the factors associated with mtDNA damage among SLE patients. Methods A cross-sectional study was performed in 86 SLE patients (per American College of Rheumatology classification criteria) and 86 healthy individuals matched for age and gender. Peripheral blood mononuclear cells (PBMCs) were collected from subjects to assess the relative amounts of mtDNA damage. Quantitative polymerase chain reaction assay was used to measure the frequency of mtDNA lesions and mtDNA abundance. Socioeconomic-demographic features, clinical manifestations, pharmacologic treatment, disease activity, and damage accrual were determined. Statistical analyses were performed using t test, pairwise correlation, and Pearson’s chi-square test (or Fisher’s exact test) as appropriate. Results Among SLE patients, 93.0% were women. The mean (SD) age was 38.0 (10.4) years and the mean (SD) disease duration was 8.7 (7.5) years. SLE patients exhibited increased levels of mtDNA damage as shown by higher levels of mtDNA lesions and decreased mtDNA abundance as compared to healthy individuals. There was a negative correlation between disease damage and mtDNA abundance and a positive correlation between mtDNA lesions and disease duration. No association was found between disease activity and mtDNA damage. Conclusion PBMCs from SLE patients exhibited more mtDNA damage compared to healthy subjects. Higher levels of mtDNA damage were observed among SLE patients with major organ involvement and damage accrual. These results suggest that mtDNA damage have a potential role in the pathogenesis of SLE. PMID:24899636

  2. The aging mouth: differentiating normal aging from disease.

    PubMed

    Lamster, Ira B; Asadourian, Lynda; Del Carmen, Tessa; Friedman, Paula K

    2016-10-01

    Aging is the physiologic change that occurs over time. In humans, this change occurs at different rates and are related to lifestyle, environment and genetics. It can be challenging to differentiate normal aging from disease. In the oral cavity, with increasing age the teeth demonstrate wearing of the enamel, chipping and fracture lines, and a darker color. The pulp chamber and canals are reduced in size as a result of the deposition of secondary dentin. Coronal or root caries, however, represent disease. A limited amount of periodontal attachment loss occurs in association with aging, usually manifesting as recession on the buccal surface of teeth. Severe periodontitis occurs in 10.5-12% of the population, with the peak incidence being observed at 35-40 years of age. Changes to the mucosal tissue that occur with age include reduced wound-healing capacity. However, environmental factors, such as smoking, dramatically increase the risk of mucosal pathology. Reduced salivary gland function is often seen in association with medication usage, as well as with disorders such as diabetes mellitus. Both medication use and chronic disorders are more common in older adults. Masticatory function is of particular importance for older adults. Maintenance of a nutritionally complete diet is important for avoiding sarcopenia and the frailty syndrome. Successful oral aging is associated with adequate function and comfort. A reduced, but functional, dentition of 20 teeth in occlusion has been proposed as a measure of successful oral aging. Healthy oral aging is important to healthy aging from both biological and social perspectives. PMID:27501493

  3. Stochastic undersampling steepens auditory threshold/duration functions: implications for understanding auditory deafferentation and aging

    PubMed Central

    Marmel, Frédéric; Rodríguez-Mendoza, Medardo A.; Lopez-Poveda, Enrique A.

    2015-01-01

    It has long been known that some listeners experience hearing difficulties out of proportion with their audiometric losses. Notably, some older adults as well as auditory neuropathy patients have temporal-processing and speech-in-noise intelligibility deficits not accountable for by elevated audiometric thresholds. The study of these hearing deficits has been revitalized by recent studies that show that auditory deafferentation comes with aging and can occur even in the absence of an audiometric loss. The present study builds on the stochastic undersampling principle proposed by Lopez-Poveda and Barrios (2013) to account for the perceptual effects of auditory deafferentation. Auditory threshold/duration functions were measured for broadband noises that were stochastically undersampled to various different degrees. Stimuli with and without undersampling were equated for overall energy in order to focus on the changes that undersampling elicited on the stimulus waveforms, and not on its effects on the overall stimulus energy. Stochastic undersampling impaired the detection of short sounds (<20 ms). The detection of long sounds (>50 ms) did not change or improved, depending on the degree of undersampling. The results for short sounds show that stochastic undersampling, and hence presumably deafferentation, can account for the steeper threshold/duration functions observed in auditory neuropathy patients and older adults with (near) normal audiometry. This suggests that deafferentation might be diagnosed using pure-tone audiometry with short tones. It further suggests that the auditory system of audiometrically normal older listeners might not be “slower than normal”, as is commonly thought, but simply less well afferented. Finally, the results for both short and long sounds support the probabilistic theories of detectability that challenge the idea that auditory threshold occurs by integration of sound energy over time. PMID:26029098

  4. Duration of recurrent ileitis after ileocolonic resection correlates with presurgical extent of Crohn's disease.

    PubMed Central

    D'Haens, G R; Gasparaitis, A E; Hanauer, S B

    1995-01-01

    Crohn's disease of the terminal ileum recurs in a predictable sequence proximal to the ileocolonic anastomosis after surgical resection. To confirm the suspicion that the duration of recurrent ileitis correlates with the extent of presurgical disease, this study investigated 23 consecutive patients with recurrent Crohn's disease symptoms who had undergone ileocaecal resections between 1982 and 1992 at our institution and had both preoperative and postoperative small bowel follow through studies available for comparison. All films were reviewed by a blinded gastrointestinal radiologist using uniform criteria. Symptomatic recurrence was reported at a mean (SEM) of 29 (25) months after resection. Presurgical length of inflammation averaged 26 (15) (8-57) cm and at recurrence 24 (14) (7-55) cm. The correlation coefficient (r) between pre and postsurgical extent of ileal disease was 0.70 (p < 0.0001). Seven patients had sequential small bowel series after 20 (10) (7-36) months without intervening surgery. The extent of measured inflammation between examinations correlated with r = 0.995 (p < 0.0001), showing the consistency of the measurement process. The close correlation between the duration of postoperative recurrence with the extent of presurgical disease is another example of individual patterns of recurrent Crohn's disease and is an additional factor to be considered when contemplating surgical resections. Images Figure 2 PMID:7797122

  5. NAD+ and sirtuins in aging and disease.

    PubMed

    Imai, Shin-ichiro; Guarente, Leonard

    2014-08-01

    Nicotinamide adenine dinucleotide (NAD(+)) is a classical coenzyme mediating many redox reactions. NAD(+) also plays an important role in the regulation of NAD(+)-consuming enzymes, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38/157 ectoenzymes. NAD(+) biosynthesis, particularly mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1 function together to regulate metabolism and circadian rhythm. NAD(+) levels decline during the aging process and may be an Achilles' heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies. Restoring NAD(+) by supplementing NAD(+) intermediates can dramatically ameliorate these age-associated functional defects, counteracting many diseases of aging, including neurodegenerative diseases. Thus, the combination of sirtuin activation and NAD(+) intermediate supplementation may be an effective antiaging intervention, providing hope to aging societies worldwide. PMID:24786309

  6. Assessment of Telomere Length in Archived Formalin-Fixed, Paraffinized Human Tissue Is Confounded by Chronological Age and Storage Duration.

    PubMed

    Kong, Po-Lian; Looi, Lai-Meng; Lau, Tze-Pheng; Cheah, Phaik-Leng

    2016-01-01

    Telomeres shorten with physiological aging but undergo substantial restoration during cancer immortalization. Increasingly, cancer studies utilize the archive of formalin-fixed, paraffin-embedded (FFPE) tissues in diagnostic pathology departments. Conceptually, such studies would be confounded by physiological telomere attrition and loss of DNA integrity from prolonged tissue storage. Our study aimed to investigate these two confounding factors. 145 FFPE tissues of surgically-resected, non-diseased appendixes were retrieved from our pathology archive, from years 2008 to 2014. Cases from 2013 to 2014 were categorized by patient chronological age (0-20 years, 21-40 years, 41-60 years, > 60 years). Telomere lengths of age categories were depicted by telomere/chromosome 2 centromere intensity ratio (TCR) revealed by quantitative fluorescence in situ hybridization. Material from individuals aged 0-20 years from years 2013/2014, 2011/2012, 2009/2010, and 2008 were compared for storage effect. Telomere integrity was assessed by telomere fluorescence intensity (TFI). Epithelial TCRs (mean ± SD) for the respective age groups were 4.84 ± 2.08, 3.64 ± 1.21, 2.03 ± 0.37, and 1.93 ± 0.45, whereas corresponding stromal TCRs were 5.16 ± 2.55, 3.84 ± 1.36, 2.49 ± 1.20, and 2.93 ± 1.24. A trend of inverse correlation with age in both epithelial and stromal tissues is supported by r = -0.69, p < 0.001 and r = -0.42, p < 0.001 respectively. Epithelial TFIs (mean ± SD) of years 2013/2014, 2011/2012, 2009/2010 and 2008 were 852.60 ± 432.46, 353.04 ± 127.12, 209.24 ± 55.57 and 429.22 ± 188.75 respectively. Generally, TFIs reduced with storage duration (r = -0.42, p < 0.001). Our findings agree that age-related telomere attrition occurs in normal somatic tissues, and suggest that an age-based reference can be established for telomere studies on FFPE tissues. We also showed that FFPE tissues archived beyond 2 years are suboptimal for telomere analysis. PMID:27598341

  7. Incidence and Duration of Cumulative Bisphosphonate Use among Community-Dwelling Persons with or without Alzheimer's Disease.

    PubMed

    Tiihonen, Miia; Taipale, Heidi; Tanskanen, Antti; Tiihonen, Jari; Hartikainen, Sirpa

    2016-01-01

    We studied the incidence and duration of cumulative bisphosphonate use among older Finnish women and men with or without Alzheimer's disease (AD). The MEDALZ-2005 cohort is a nationwide sample of all persons with clinically diagnosed AD on 31 December 2005 and their age-, gender-, and region of residence-matched control persons without AD. Information on bisphosphonate use by persons with an AD diagnosis and their controls without AD during 2002-2009 was obtained from the prescription register database containing reimbursed medications. A total of 6,041 (11.8%) persons used bisphosphonates during the 8-year follow-up. Bisphosphonates were more commonly used among persons without AD (n = 3121, 12.3%) than among persons with AD (n = 2,920, 11.2%) (p = 0.001). The median duration of bisphosphonate use was 743 days (IQR). Among persons with AD, the median duration of use was 777 days (IQR) and among persons without AD, 701 days (IQR) (p = 0.011). People without AD more often used bisphosphonate combination preparations including vitamin D than did people with AD (p <  0.0001). Bisphosphonate use was more common among people without AD who had comorbidities, asthma/COPD, or rheumatoid arthritis compared with users with AD. Short-term users were more likely to be male, at least 80 years old, and not having AD. Although the incidence of bisphosphonate use was slightly higher among persons without AD, the cumulative duration of bisphosphonate use was longer in persons with AD. Short-term use was associated with male gender, older age, and not having AD. PMID:26967224

  8. Incidence and Duration of Cumulative Bisphosphonate Use among Community-Dwelling Persons with or without Alzheimer’s Disease

    PubMed Central

    Tiihonen, Miia; Taipale, Heidi; Tanskanen, Antti; Tiihonen, Jari; Hartikainen, Sirpa

    2016-01-01

    We studied the incidence and duration of cumulative bisphosphonate use among older Finnish women and men with or without Alzheimer’s disease (AD). The MEDALZ-2005 cohort is a nationwide sample of all persons with clinically diagnosed AD on 31 December 2005 and their age-, gender-, and region of residence-matched control persons without AD. Information on bisphosphonate use by persons with an AD diagnosis and their controls without AD during 2002–2009 was obtained from the prescription register database containing reimbursed medications. A total of 6,041 (11.8%) persons used bisphosphonates during the 8-year follow-up. Bisphosphonates were more commonly used among persons without AD (n = 3121, 12.3%) than among persons with AD (n = 2,920, 11.2%) (p = 0.001). The median duration of bisphosphonate use was 743 days (IQR). Among persons with AD, the median duration of use was 777 days (IQR) and among persons without AD, 701 days (IQR) (p = 0.011). People without AD more often used bisphosphonate combination preparations including vitamin D than did people with AD (p <  0.0001). Bisphosphonate use was more common among people without AD who had comorbidities, asthma/COPD, or rheumatoid arthritis compared with users with AD. Short-term users were more likely to be male, at least 80 years old, and not having AD. Although the incidence of bisphosphonate use was slightly higher among persons without AD, the cumulative duration of bisphosphonate use was longer in persons with AD. Short-term use was associated with male gender, older age, and not having AD. PMID:26967224

  9. Th1/Th2 cytokines in Type 1 diabetes: Relation to duration of disease and gender

    PubMed Central

    Vaseghi, Hajar; Jadali, Zohreh

    2016-01-01

    Background: T-cells are important in the pathogenesis of Type 1 diabetes (T1D). However, the exact role of T-cell subpopulations in this pathway remains unknown. The purpose of this study was to assess the expression pattern of T helper 1 (Th1) interferon-gamma (IFN-γ) and Th2 interleukin-4 (IL-4) cytokines and their relationship with sex and disease duration in T1D patients. Materials and Methods: This study was conducted on 21 T1D patients and 22 healthy subjects. Gene expression analysis of peripheral blood mononuclear cells (PBMCs) was performed using real-time reverse transcriptase polymerase chain reaction. Results: IFN-γ gene expression was significantly lower in T1D patients compared with controls (P < 0.05). Conversely, IL-4 mRNAs were significantly increased in the PBMCs from patients as compared to controls (P < 0.05). There was no significant difference in the expression of IL-4 and IFN-γ between men and women with T1D (P > 0.05) while IL-4 mRNA expression in male patients was about 1.9 folds higher than female patients. Moreover, IFN-γ mRNA expression in female patients was about 1.8 folds lower than male patients. Patients were divided into two groups regarding their disease duration: <10 years and >10 years. A significant increase in the IL-4 expression was observed between two groups of patients compared to controls (P < 0.0001). Conversely, there was a significant difference in the expression of IFN-γ only between patients with more than 10 years of disease duration (P = 0.02). Conclusion: These data propose supplementary implications for the role of Th1/Th2 imbalance in T1D immunopathogenesis. Moreover, factors such as sex and disease duration may have some influence on cytokine mRNA expression. PMID:27186546

  10. Molecular mechanisms of ageing and related diseases.

    PubMed

    Liu, Jun-Ping

    2014-07-01

    Human and other multicellular life species age, and ageing processes become dominant during the late phase of life. Recent studies challenge this dogma, suggesting that ageing does not occur in some animal species. In mammals, cell replicative senescence occurs as early as before birth (i.e. in embryos) under physiological conditions. How the molecular machinery operates and why ageing cells dominate under some circumstances are intriguing questions. Recent studies show that cell ageing involves extensive cellular remodelling, including telomere attrition, heterochromatin formation, endoplasmic reticulum stress, mitochondrial disorders and lysosome processing organelles and chromatins. This article provides an update on the molecular mechanisms underlying the ageing of various cell types, the newly described developmental and programmed replicative senescence and the critical roles of cellular organelles and effectors in Parkinson's disease, diabetes, hypertension and dyskeratosis congenita. PMID:24798238

  11. Aging, inflammation, immunity and periodontal disease.

    PubMed

    Ebersole, Jeffrey L; Graves, Christina L; Gonzalez, Octavio A; Dawson, Dolph; Morford, Lorri A; Huja, Pinar Emecen; Hartsfield, James K; Huja, Sarandeep S; Pandruvada, Subramanya; Wallet, Shannon M

    2016-10-01

    The increased prevalence and severity of periodontal disease have long been associated with aging, such that this oral condition affects the majority of the adult population over 50 years of age. Although the immune system is a critical component for maintaining health, aging can be characterized by quantitative and qualitative modifications of the immune system. This process, termed 'immunosenescence', is a progressive modification of the immune system that leads to greater susceptibility to infections, neoplasia and autoimmunity, presumably reflecting the prolonged antigenic stimulation and/or stress responses that occur across the lifespan. Interestingly, the global reduction in the host capability to respond effectively to these challenges is coupled with a progressive increase in the general proinflammatory status, termed 'inflammaging'. Consistent with the definition of immunosenescence, it has been suggested that the cumulative effect of prolonged exposure of the periodontium to microbial challenge is, at least in part, a contributor to the effects of aging on these tissues. Thus, it has also been hypothesized that alterations in the function of resident immune and nonimmune cells of the periodontium contribute to the expression of inflammaging in periodontal disease. Although the majority of aging research has focused on the adaptive immune response, it is becoming increasingly clear that the innate immune compartment is also highly affected by aging. Thus, the phenomenon of immunosenescence and inflammaging, expressed as age-associated changes within the periodontium, needs to be more fully understood in this era of precision and personalized medicine and dentistry. PMID:27501491

  12. Cardiac and Respiratory Disease in Aged Horses.

    PubMed

    Marr, Celia M

    2016-08-01

    Respiratory and cardiac diseases are common in older horses. Advancing age is a specific risk factor for cardiac murmurs and these are more likely in males and small horses. Airway inflammation is the most common respiratory diagnosis. Recurrent airway obstruction can lead to irreversible structural change and bronchiectasis; with chronic hypoxia, right heart dysfunction and failure can develop. Valvular heart disease most often affects the aortic and/or the mitral valve. Management of comorbidity is an essential element of the therapeutic approach to cardiac and respiratory disease in older equids. PMID:27329492

  13. Exercise training in aging and diseases.

    PubMed

    Conti, Valeria; Russomanno, Giusy; Corbi, Graziamaria; Filippelli, Amelia

    2012-05-01

    Sedentary lifestyle along with high blood pressure, abnormal values for blood lipids, smoking, and obesity are recognized risk factors for cardiovascular diseases and for many other chronic diseases, such as diabetes, osteoporosis, breast and colon cancer. Several studies conducted on large cohort of individuals have documented the protective effects of physical activity for both vascular and nonvascular syndromes. Exercise training is an integral part of cardiac rehabilitation, a complex therapeutic approach, effective both in young and elderly patients. Despite the number of evidences underling the benefits associated with physical fitness, the cardiac rehabilitation is still an underused medical resource. The molecular mechanism behind physical activity protective effect is presently unresolved, and further studies are also needed to establish the best protocol in terms of specificity, volume and duration of the training. PMID:23905056

  14. Age- and gender-specific associations between sleep duration and incident hypertension in a Chinese population: the Kailuan study.

    PubMed

    Song, Q; Liu, X; Wang, X; Wu, S

    2016-08-01

    The objective of this study was to explore the age- and sex-dependent association between sleep duration and incident hypertension in a Chinese population. The Kailuan prospective cohort study recruited 101 510 participants. Those participants were followed for an average of 3.98 years and the data obtained from 32 137 participants out of 101 510 were analyzed in this study. Sleep duration was categorized as five groups of⩽5, 6, 7, 8 and ⩾9 h. Cox proportional-hazards models were used to analyze the association of sleep duration with incident hypertension. The 3.98 years' follow-up data showed that 12 732 out of 32 137 participants developed hypertension. Short duration of sleep (⩽5 h per night) was associated with an increased risk of hypertension in woman (hazard ratio (HR) 1.27; 95% confidence interval (CI) 1.02 to 1.58) and participants aged <60 years (HR 1.11; 95% CI 1.02-1.21), when compared with the group reported with 7 h of sleep per day. This study suggested that short sleep duration could cause an increased risk of hypertension in Chinese females and population aged <60 years. PMID:26763887

  15. 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

  16. So! What's aging? Is cardiovascular aging a disease?

    PubMed

    Lakatta, Edward G

    2015-06-01

    "Inside every old person is a young person wondering what happened." So, what is aging? Aging is a manifestation of progressive, time-dependent failure of molecular mechanisms that create disorder within a system of DNA and its environment (nuclear, cytosolic, tissue, organ, organism, other organisms, society, terra firma, atmosphere, universe). Continuous signaling, transmitted with different kinetics across each of these environments, confers a "mutual enslavement" that creates ordered functions among the components within the system. Accrual of this molecular disorder over time, i.e. during aging, causes progressive changes in the structure and function of the heart and arteries that are quite similar in humans, non-human primates, rabbits and rats that compromise cardiovascular reserve function, and confer a marked risk for incident cardiovascular disease. Nearly all aspects of signaling within the DNA environment system within the heart and arteries become disordered with advancing age: Signals change, as does sensing of the signals, transmission of signals and responses to signals, impaired cell renewal, changes in the proteome due to alterations in genomic transcription, mRNA translation, and proteostasis. The density of some molecules becomes reduced, and post-translational modifications, e.g. oxidation and nitration phosphorylation, lead to altered misfolding and disordered molecular interactions. The stoichiometry and kinetics of enzymatic and those reactions which underlie crucial cardiac and vascular cell functions and robust reserve mechanisms that remove damaged organelles and proteins deteriorate. The CV cells generate an inflammatory defense in an attempt to limit the molecular disorder. The resultant proinflammatory milieu is not executed by "professional" inflammatory cells (i.e. white blood cells), however, but by activation of renin-angiotensin-aldosterone endothelin signaling cascades that leads to endothelial and vascular smooth muscle and

  17. 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

  18. Point Vowel Duration in Children with Hearing Aids and Cochlear Implants at 4 and 5 Years of Age

    ERIC Educational Resources Information Center

    Vandam, Mark; Ide-Helvie, Dana; Moeller, Mary Pat

    2011-01-01

    This work investigates the developmental aspects of the duration of point vowels in children with normal hearing compared with those with hearing aids and cochlear implants at 4 and 5 years of age. Younger children produced longer vowels than older children, and children with hearing loss (HL) produced longer and more variable vowels than their…

  19. Role of physical activity and sleep duration in growth and body composition of preschool-aged children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The impact of physical activity patterns and sleep duration on growth and body composition of preschool-aged children remains unresolved. Aims were (1) to delineate cross-sectional associations among physical activity components, sleep, total energy expenditure (TEE), and body size and composition; ...

  20. Association Between Duration of Overall and Abdominal Obesity Beginning in Young Adulthood and Coronary Artery Calcification in Middle Age

    PubMed Central

    Reis, Jared P.; Loria, Catherine M.; Lewis, Cora E.; Powell-Wiley, Tiffany M.; Wei, Gina S.; Carr, J. Jeffrey; Terry, James G.; Liu, Kiang

    2014-01-01

    IMPORTANCE Younger individuals are experiencing a greater cumulative exposure to excess adiposity over their lifetime. However, few studies have determined the consequences of long-term obesity. OBJECTIVE To examine whether the duration of overall and abdominal obesity was associated with the presence and 10-year progression of coronary artery calcification (CAC), a subclinical predictor of coronary heart disease. DESIGN, SETTING, AND PARTICIPANTS Prospective study of 3275 white and black adults aged 18 to 30 years at baseline in 1985–1986 who did not initially have overall obesity (body mass index [BMI] ≥30) or abdominal obesity (men: waist circumference [WC] >102 cm; women: >88 cm) in the multicenter, community-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants completed computed tomography scanning for the presence of CAC during the 15-, 20-, or 25-year follow-up examinations. Duration of overall and abdominal obesity was calculated using repeat measurements of BMI and WC, respectively, performed 2, 5, 7, 10, 15, 20, and 25 years after baseline. MAIN OUTCOMES AND MEASURES Presence of CAC was measured by computed tomography at the year 15 (2000–2001), year 20 (2005–2006), or year 25 (2010–2011) follow-up examinations. Ten-year progression of CAC (2000–2001 to 2010–2011) was defined as incident CAC in 2010–2011 or an increase in CAC score of 20 Agatston units or greater. RESULTS During follow-up, 40.4% and 41.0% developed overall and abdominal obesity, respectively. Rates of CAC per 1000 person-years were higher for those who experienced more than 20 years vs 0 years of overall obesity (16.0 vs 11.0, respectively) and abdominal obesity (16.7 vs 11.0). Approximately 25.2% and 27.7% of those with more than 20 years of overall and abdominal obesity, respectively, experienced progression of CAC vs 20.2% and 19.5% of those with 0 years. After adjustment for BMI or WC and potential confounders, the hazard ratios for CAC

  1. [ANALYSIS OF ULTRASONIC, CYTOLOGICAL AND MORPHOLOGIC RESEARCHES RESULTS OF PATIENTS WITH GRAVES' DISEASE (TOXIC GOITER) DEPENDING ON DISEASE DURATION].

    PubMed

    Tronco, N D; Shlyahtych, S L; Buldygina, Yu V; Berezhna, I Y; Antoniv, V R

    2015-01-01

    The aim of research is to arrange the results of ultrasonic and cytological researches during long-term drug treatment (more than 1 year) of patients with Graves' disease. From 2008 to 2013 the detailed examination of 220 patients was carried out in Kyiv City Centre for Endocrine Surgery which operates on the basis of the 3d Clinical Hospital. There were established three kinds of echographic patterns which pointed out the ultrasonic changes of the thyroid gland tissue, occurred during the drug treatment. Among 63 (28.6%) patients with long-term drug treatment the development of space-occupying lesions, occurred due to long duration of disease with long-term usage of tyreostatics, was recorded. After the surgical treatment the extracted thyroid gland tissue was subjected to histological study. The papillary carcinoma of thyroid gland was verified in 4 (6,3 %) of 63 patients with space-occupying lesions. The ultrasonic research of thyroid gland in combination with aspiration puncture biopsy and cytological research are the highly informative methods of examination of patients with Graves' disease which allow to objectify the organ structural condition while the disease duration. PMID:26827451

  2. Growth factors, aging and age-related diseases.

    PubMed

    Balasubramanian, Priya; Longo, Valter D

    2016-06-01

    Simple organisms including yeast and flies with mutations in the IGF-1 and Tor-S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes. These findings are in agreement with the effect of defects in the Tor-S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6000 US subjects in the NHANES CDC database. Respondents aged 50-65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3-4 fold increased risk of cancer mortality in agreement with findings in mouse experiments. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases. PMID:26883276

  3. An Event Related Potentials Study of the Effects of Age, Load and Maintenance Duration on Working Memory Recognition

    PubMed Central

    Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

    2015-01-01

    Age-related decline in cognitive capacities has been attributed to a generalized slowing of processing speed and a reduction in working memory (WM) capacity. Nevertheless, it is unclear how age affects visuospatial WM recognition and its underlying brain electrical activity. Whether age modulates the effects of memory load or information maintenance duration, which determine the limits of WM, remains also elusive. In this exploratory study, performance in a delayed match to sample task declined with age, particularly in conditions with high memory load. Event related potentials analysis revealed longer N2 and P300 latencies in old than in young adults during WM recognition, which may reflect slowing of stimulus evaluation and classification processes, respectively. Although there were no differences between groups in N2 or P300 amplitudes, the latter was more homogeneously distributed in old than in young adults, which may indicate an age-related increased reliance in frontal vs parietal resources during WM recognition. This was further supported by an age-related reduced posterior cingulate activation and increased superior frontal gyrus activation revealed through standardized low resolution electromagnetic tomography. Memory load and maintenance duration effects on brain activity were similar in both age groups. These behavioral and electrophysiological results add evidence in support of age-related decline in WM recognition theories, with a slowing of processing speed that may be limited to stimulus evaluation and categorization processes -with no effects on perceptual processes- and a posterior to anterior shift in the recruitment of neural resources. PMID:26569113

  4. Sleep Duration as a Risk Factor for Cardiovascular Disease- a Review of the Recent Literature

    PubMed Central

    Nagai, Michiaki; Hoshide, Satoshi; Kario, Kazuomi

    2010-01-01

    Sleep loss is a common condition in developed countries, with evidence showing that people in Western countries are sleeping on average only 6.8 hour (hr) per night, 1.5 hr less than a century ago. Although the effects of sleep deprivation on our organs have been obscure, recent epidemiological studies have revealed relationships between sleep deprivation and hypertension (HT), coronary heart disease (CHD), and diabetes mellitus (DM). This review article summarizes the literature on these relationships. Because sleep deprivation increases sympathetic nervous system activity, this increased activity serves as a common pathophysiology for HT and DM. Adequate sleep duration may be important for preventing cardiovascular diseases in modern society. PMID:21286279

  5. Short Duration, Intensive Tango Dancing for Parkinson Disease: An Uncontrolled Pilot Study

    PubMed Central

    Hackney, Madeleine E.; Earhart, Gammon M.

    2009-01-01

    Objective The goal of this pilot study was to determine the effects of short duration, intensive tango lessons on functional mobility in people with Parkinson disease. Design This study employed a within-subject, prospective, repeated measures design. Subjects/Patients Fourteen people with idiopathic Parkinson disease participated. Setting All balance and gait assessments were performed in a laboratory, but dance classes took place in a large, open classroom. Interventions Participants completed ten 1.5 hour long Argentine tango dance lessons within two weeks. Their balance, gait and mobility were assessed before and after the training sessions. Main Outcome Measures Measures included the Berg Balance Scale, the Unified Parkinson Disease Rating Scale, gait velocity, functional ambulation profile, step length, stance and single support percent of gait, Timed Up and Go, and the six minute walk. Results Participants significantly improved on the Berg Balance Scale (effect size (ES) = 0.83, p = 0.021), Unified Parkinson Disease Rating Scale Motor Subscale III (ES = −0.64, p = 0.029), and percent of time spent in stance during forward walking (ES = 0.97, p = 0.015). Non-significant improvements were noted on the Timed Up and Go (ES = −0.38, p = 0.220) and 6-minute walk (ES = 0.35, p = 0.170). Conclusions Frequent social dance lessons completed within a short time period appear to be appropriate and effective for these individuals with mild-moderately severe Parkinson disease. PMID:19632547

  6. Thorium-230 ages of corals and duration of the last interglacial sea-level high stand on Oahu, Hawaii

    SciTech Connect

    Szabo, B.J.; Ludwig, K.R.; Muhs, D.R.; Simmons, K.R.

    1994-10-07

    Thorium-230 ages of emergent marine deposits on Oahu, Hawaii, have a uniform distribution of ages from {approximately}114,000 to {approximately}131,000 years, indicating a duration for the last interglacial sea-level high stand of {approximately}17,000 years, in contrast to a duration of {approximately}8000 years inferred from the orbitally tuned marine oxygen isotope record. Sea level on Oahu rose to {>=}1 to 2 meters higher than present by 131,000 years ago or {approximately}6000 years earlier than inferred from the marine record. Although the latter record suggests a shift back to glacial conditions beginning at {approximately}119,000 years ago, the Oahu coral ages indicate a near present sea level until {approximately}114,000 years ago.

  7. Altered cortical thickness related to clinical severity but not the untreated disease duration in schizophrenia.

    PubMed

    Xiao, Yuan; Lui, Su; Deng, Wei; Yao, Li; Zhang, Wenjing; Li, Shiguang; Wu, Min; Xie, Teng; He, Yong; Huang, Xiaoqi; Hu, Junmei; Bi, Feng; Li, Tao; Gong, Qiyong

    2015-01-01

    Although previous studies have reported deficits in the gray matter volume of schizophrenic patients, it remains unclear whether these deficits occur at the onset of the disease, before treatment, and whether they are progressive over the duration of untreated disease. Furthermore, the gray matter volume represents the combinations of cortical thickness and surface area; these features are believed to be influenced by different genetic factors. However, cortical thickness and surface area in antipsychotic-naive first-episode schizophrenic patients have seldom been investigated. Here, the cortical thicknesses and surface areas of 128 antipsychotic-naive first-episode schizophrenic patients were compared with 128 healthy controls. The patients exhibited significantly lower cortical thickness, primarily in the bilateral prefrontal and parietal cortex, and increased thickness in the bilateral anterior temporal lobes, left medial orbitofrontal cortex, and left cuneus. Furthermore, decreased cortical thickness was related to positive schizophrenia symptoms but not to the severity of negative symptoms and the untreated disease duration. No significant difference of surface area was observed between the 2 groups. Thus, without the confounding factors of medication and illness progression, this study provides further evidence to support anatomical deficits in the prefrontal and parietal cortex early in course of the illness. The increased thicknesses of the bilateral anterior temporal lobes may represent a compensatory factor or may be an early-course neuronal pathology caused by preapoptotic osmotic changes or hypertrophy. Furthermore, these anatomical deficits are crucial to the pathogenesis of positive symptoms and relatively stable instead of progressing during the early stages of the disease. PMID:24353097

  8. Molecular genetics of Alzheimer's disease and aging.

    PubMed

    Cacabelos, Ramon; Fernandez-Novoa, Lucia; Lombardi, Valter; Kubota, Yasuhiko; Takeda, Masatoshi

    2005-07-01

    Alzheimer's disease is a genetically complex disorder associated with multiple genetic defects, either mutational or of susceptibility. Although potentially associated with an accelerated stochastically driven aging process, Alzheimer's disease is an independent clinical entity in which the aging process exerts a deleterious effect on brain activity in conjunction with polymodal genetic factors and other pathological conditions (i.e., age-related cerebrovascular deterioration) and environmental factors (i.e., nutrition). Alzheimer's disease genetics does not explain in full the etiopathogenesis of this disease. Therefore, it is likely that environmental factors and/or epigenetic phenomena also contribute to Alzheimer's disease pathology and phenotypic expression of dementia. The genomics of Alzheimer's disease is still in its infancy, but this field is aiding the understanding of novel aspects of this disease, including genetic epidemiology, multifactorial risk factors, pathogenic mechanisms associated with genetic networks and genetically regulated metabolic cascades. Alzheimer's disease genomics is also helping to develop new strategies in pharmacogenomic research and prevention. Functional genomics, proteomics, pharmacogenomics, high-throughput methods, combinatorial chemistry and modern bioinformatics will greatly contribute to accelerate drug development for Alzheimer's disease and other complex disorders. The multifactorial genetic dysfunction in dementia includes mutational loci (APP, PS1, PS2, TAU) and diverse susceptibility loci (APOE, alpha2M, alphaACT, LRP1, IL1 alpha, TNF, ACE, BACE, BCHE, CST3, MTHFR, GSK3 beta, NOS3 and many other genes) distributed across the human genome, probably converging in a common pathogenic mechanism that leads to premature neuronal death, in which mitochondrial DNA mutations may contribute to increased genetic variability and heterogeneity. In Alzheimer's disease, multiple pathogenic events, including genetic factors

  9. Infant Attention to Dynamic Audiovisual Stimuli: Look Duration from 3 to 9 Months of Age

    ERIC Educational Resources Information Center

    Reynolds, Greg D.; Zhang, Dantong; Guy, Maggie W.

    2013-01-01

    The goal of this study was to examine developmental change in visual attention to dynamic visual and audiovisual stimuli in 3-, 6-, and 9-month-old infants. Infant look duration was measured during exposure to dynamic geometric patterns and Sesame Street video clips under three different stimulus modality conditions: unimodal visual, synchronous…

  10. Health-related quality of life in adults with epilepsy: the effect of age, age at onset and duration of epilepsy in a multicentre Italian study

    PubMed Central

    2011-01-01

    Background The potential effect of age-related factors on health-related quality of life (HRQOL) of patients with epilepsy has rarely been analyzed in the literature. Methods We examined this association in a selected population of 815 adults with epilepsy recruited in the context of a multicentre study for the evaluation of Epi-QoL, one of the first Italian epilepsy-specific measures of HRQOL for adults with epilepsy. The Epi-QoL is a 46-item self-administered questionnaire focusing on six domains, which was successfully tested for reproducibility and validity. Ordinary least-squares regression models were used to assess the relationships between age-related factors (patient's age, age at seizure onset, and duration of epilepsy) and overall Epi-QoL score, controlling for the effect of potential confounders. We fitted simple regression models including each age-related factor alone to assess the independent role of each factor on the overall Epi-QoL score. We also fitted multiple regression models including pairs of age-related factors solely, as well as one or two age-related factors together with the same set of confounders. Results Simple regression models showed that age and duration of epilepsy were significant negative predictors of the overall Epi-QoL score: the higher was each age-related factor, the lower was the overall Epi-QoL score; age at onset alone was a nonsignificant predictor of the overall Epi-QoL score. Multiple regression models including two age-related factors solely showed that duration of epilepsy was still a significant negative predictor of the overall Epi-QoL score in both pairwise models, whereas age was a significant negative predictor only in the model including age at onset. Age at onset emerged as a significant positive predictor of the overall Epi-QoL score only in the model including age: the higher was age at onset, the higher was the overall Epi-QoL score. Adjusted regression models including either one or two age

  11. Astrocytes in physiological aging and Alzheimer's disease.

    PubMed

    Rodríguez-Arellano, J J; Parpura, V; Zorec, R; Verkhratsky, A

    2016-05-26

    Astrocytes are fundamental for homoeostasis, defence and regeneration of the central nervous system. Loss of astroglial function and astroglial reactivity contributes to the aging of the brain and to neurodegenerative diseases. Changes in astroglia in aging and neurodegeneration are highly heterogeneous and region-specific. In animal models of Alzheimer's disease (AD) astrocytes undergo degeneration and atrophy at the early stages of pathological progression, which possibly may alter the homeostatic reserve of the brain and contribute to early cognitive deficits. At later stages of AD reactive astrocytes are associated with neurite plaques, the feature commonly found in animal models and in human diseased tissue. In animal models of the AD reactive astrogliosis develops in some (e.g. in the hippocampus) but not in all regions of the brain. For instance, in entorhinal and prefrontal cortices astrocytes do not mount gliotic response to emerging β-amyloid deposits. These deficits in reactivity coincide with higher vulnerability of these regions to AD-type pathology. Astroglial morphology and function can be regulated through environmental stimulation and/or medication suggesting that astrocytes can be regarded as a target for therapies aimed at the prevention and cure of neurodegenerative disorders. PMID:25595973

  12. Effect of post-hatch transportation duration and parental age on broiler chicken quality, welfare, and productivity

    PubMed Central

    Jacobs, Leonie; Delezie, Evelyne; Duchateau, Luc; Goethals, Klara; Ampe, Bart; Lambrecht, Evelien; Gellynck, Xavier; Tuyttens, Frank A. M.

    2016-01-01

    Broiler chicks are transported to production sites within one to 2 d post-hatch. Possible effects of this transportation are poorly understood and could vary among chicks from breeder flocks of different ages. The aim of the present study was to investigate the effects of transportation duration and parental flock age on chick welfare, productivity, and quality. After hatch in a commercial hatchery, 1,620 mixed-sex chicks from 29-wk old (young) and 1,620 chicks from 60-wk old (old) breeders were subjected to transportation of 1.5 h or 11 h duration. After transportation, 2,800 chicks were divided among 100 pens, with each pen containing 28 chicks from one transportation crate (2 or 3 pens per crate). From the remaining chicks, on average 6 chicks (min 4, max 8) per crate (n = 228) were randomly selected and assessed for chick quality, weighed, and culled for yolk sac weighing (one d). Chicks that had not been assigned to pens or were not used for post-transportation measurements, were removed from the experiment (n = 212). Mortality, ADG, BW, and feed conversion (FC) of the experimental chicks were recorded until 41 d. Meat quality was measured for breast fillets (n = 47). No interaction effect of parental age and transportation duration was found for any variables. BW and yolk sac weight at one d were lower for chicks transported 11 h than 1.5 h and for chicks from young versus old breeders. The effect of parental flock age on BW persisted until slaughter. Additionally, parental age positively affected ADG until slaughter. Chick quality was lower in chicks from old versus young breeders. Chick quality and productivity were not affected by transportation duration. Mortality and meat quality were not affected by either parental age or transportation duration. To conclude, no long-term detrimental effects were found from long post-hatch transportation in chicks from young or old parent flocks. Based on these results, we suggest that 11 h post

  13. Effect of post-hatch transportation duration and parental age on broiler chicken quality, welfare, and productivity.

    PubMed

    Jacobs, Leonie; Delezie, Evelyne; Duchateau, Luc; Goethals, Klara; Ampe, Bart; Lambrecht, Evelien; Gellynck, Xavier; Tuyttens, Frank A M

    2016-09-01

    Broiler chicks are transported to production sites within one to 2 d post-hatch. Possible effects of this transportation are poorly understood and could vary among chicks from breeder flocks of different ages. The aim of the present study was to investigate the effects of transportation duration and parental flock age on chick welfare, productivity, and quality. After hatch in a commercial hatchery, 1,620 mixed-sex chicks from 29-wk old (young) and 1,620 chicks from 60-wk old (old) breeders were subjected to transportation of 1.5 h or 11 h duration. After transportation, 2,800 chicks were divided among 100 pens, with each pen containing 28 chicks from one transportation crate (2 or 3 pens per crate). From the remaining chicks, on average 6 chicks (min 4, max 8) per crate (n = 228) were randomly selected and assessed for chick quality, weighed, and culled for yolk sac weighing (one d). Chicks that had not been assigned to pens or were not used for post-transportation measurements, were removed from the experiment (n = 212). Mortality, ADG, BW, and feed conversion ( FC: ) of the experimental chicks were recorded until 41 d. Meat quality was measured for breast fillets (n = 47). No interaction effect of parental age and transportation duration was found for any variables. BW and yolk sac weight at one d were lower for chicks transported 11 h than 1.5 h and for chicks from young versus old breeders. The effect of parental flock age on BW persisted until slaughter. Additionally, parental age positively affected ADG until slaughter. Chick quality was lower in chicks from old versus young breeders. Chick quality and productivity were not affected by transportation duration. Mortality and meat quality were not affected by either parental age or transportation duration. To conclude, no long-term detrimental effects were found from long post-hatch transportation in chicks from young or old parent flocks. Based on these results, we suggest that 11 h post

  14. Systematic review of the relationships between sleep duration and health indicators in school-aged children and youth.

    PubMed

    Chaput, Jean-Philippe; Gray, Casey E; Poitras, Veronica J; Carson, Valerie; Gruber, Reut; Olds, Timothy; Weiss, Shelly K; Connor Gorber, Sarah; Kho, Michelle E; Sampson, Margaret; Belanger, Kevin; Eryuzlu, Sheniz; Callender, Laura; Tremblay, Mark S

    2016-06-01

    The objective of this systematic review was to examine the relationships between objectively and subjectively measured sleep duration and various health indicators in children and youth aged 5-17 years. Online databases were searched in January 2015 with no date or study design limits. Included studies were peer-reviewed and met the a priori-determined population (apparently healthy children and youth aged 5-17 years), intervention/exposure/comparator (various sleep durations), and outcome (adiposity, emotional regulation, cognition/academic achievement, quality of life/well-being, harms/injuries, and cardiometabolic biomarkers) criteria. Because of high levels of heterogeneity across studies, narrative syntheses were employed. A total of 141 articles (110 unique samples), including 592 215 unique participants from 40 different countries, met inclusion criteria. Overall, longer sleep duration was associated with lower adiposity indicators, better emotional regulation, better academic achievement, and better quality of life/well-being. The evidence was mixed and/or limited for the association between sleep duration and cognition, harms/injuries, and cardiometabolic biomarkers. The quality of evidence ranged from very low to high across study designs and health indicators. In conclusion, we confirmed previous investigations showing that shorter sleep duration is associated with adverse physical and mental health outcomes. However, the available evidence relies heavily on cross-sectional studies using self-reported sleep. To better inform contemporary sleep recommendations, there is a need for sleep restriction/extension interventions that examine the changes in different outcome measures against various amounts of objectively measured sleep to have a better sense of dose-response relationships. PMID:27306433

  15. Breast-feeding Duration, Age of Starting Solids, and High BMI Risk and Adiposity in Indian Children

    PubMed Central

    2011-01-01

    This study utilized data from a prospective birth cohort study on 568 Indian children, to determine whether a longer duration of breast-feeding and later introduction of solid feeding was associated with a reduced higher body mass index (BMI) and less adiposity. Main outcomes were high BMI (>90th within-cohort sex-specific BMI percentile) and sum of skinfold thickness (triceps and subscapular) at age 5. Main exposures were breast-feeding (6 categories from 1-4 to ≥21 months) and age of starting regular solid feeding (4 categories from ≤3 to ≥6 months). Data on infant feeding practices, socioeconomic and maternal factors were collected by questionnaire. Birthweight, maternal and child anthropometry were measured. Multiple regression analysis which accounted for potential confounders, demonstrated a small magnitude of effect for breast-feeding duration or introduction of solid feeds on the risk of high BMI but not for lower skinfold thickness. Breast-feeding duration was strongly negatively associated with weight gain (0-2 years) (adjusted β= −0.12 SD 95% CI: −0.19 to −0.05 per category change in breast-feeding duration, p=0.001) and weight gain (0-2 years) was strongly associated with high BMI at 5 years (adjusted OR = 3.8, 95 % CI: 2.53 to 5.56, p<0.001). In our sample, findings suggest that longer breast-feeding duration and later introduction of solids has a small reduction on later high BMI risk and a negligible effect on skinfold thickness. However, accounting for sampling variability, these findings cannot exclude the possibility of no effect at the population-level. PMID:21978208

  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. Brain atrophy in Alzheimer's Disease and aging.

    PubMed

    Pini, Lorenzo; Pievani, Michela; Bocchetta, Martina; Altomare, Daniele; Bosco, Paolo; Cavedo, Enrica; Galluzzi, Samantha; Marizzoni, Moira; Frisoni, Giovanni B

    2016-09-01

    Thanks to its safety and accessibility, magnetic resonance imaging (MRI) is extensively used in clinical routine and research field, largely contributing to our understanding of the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the main findings in AD and normal aging over the past twenty years, focusing on the patterns of gray and white matter changes assessed in vivo using MRI. Major progresses in the field concern the segmentation of the hippocampus with novel manual and automatic segmentation approaches, which might soon enable to assess also hippocampal subfields. Advancements in quantification of hippocampal volumetry might pave the way to its broader use as outcome marker in AD clinical trials. Patterns of cortical atrophy have been shown to accurately track disease progression and seem promising in distinguishing among AD subtypes. Disease progression has also been associated with changes in white matter tracts. Recent studies have investigated two areas often overlooked in AD, such as the striatum and basal forebrain, reporting significant atrophy, although the impact of these changes on cognition is still unclear. Future integration of different MRI modalities may further advance the field by providing more powerful biomarkers of disease onset and progression. PMID:26827786

  18. Fiber: The Rx for Disease-Free Aging

    MedlinePlus

    ... 159530.html Fiber: The Rx for Disease-Free Aging Lots of this dietary nutrient can keep you ... a host of chronic diseases," she said. "Successful aging" was defined in the study as the continued ...

  19. Vector species richness increases haemorrhagic disease prevalence through functional diversity modulating the duration of seasonal transmission.

    PubMed

    Park, Andrew W; Cleveland, Christopher A; Dallas, Tad A; Corn, Joseph L

    2016-06-01

    Although many parasites are transmitted between hosts by a suite of arthropod vectors, the impact of vector biodiversity on parasite transmission is poorly understood. Positive relationships between host infection prevalence and vector species richness (SR) may operate through multiple mechanisms, including (i) increased vector abundance, (ii) a sampling effect in which species of high vectorial capacity are more likely to occur in species-rich communities, and (iii) functional diversity whereby communities comprised species with distinct phenologies may extend the duration of seasonal transmission. Teasing such mechanisms apart is impeded by a lack of appropriate data, yet could highlight a neglected role for functional diversity in parasite transmission. We used statistical modelling of extensive host, vector and microparasite data to test the hypothesis that functional diversity leading to longer seasonal transmission explained variable levels of disease in a wildlife population. We additionally developed a simple transmission model to guide our expectation of how an increased transmission season translates to infection prevalence. Our study demonstrates that vector SR is associated with increased levels of disease reporting, but not via increases in vector abundance or via a sampling effect. Rather, the relationship operates by extending the length of seasonal transmission, in line with theoretical predictions. PMID:26206418

  20. 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

  1. 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

  2. Fracture, aging and disease in bone

    SciTech Connect

    Ager, J.W.; Balooch, G.; Ritchie, R.O.

    2006-02-01

    fracture resistance, whereas regulating the level of the cytokine TGF-beta can offer significant improvements in the stiffness, strength and toughness of bone, and as such may be considered as a therapeutic target to treat increased bone fragility induced by aging, drugs, and disease.

  3. Prevalence of Metabolic Syndrome in Psoriasis Patients and its Relation to Disease Duration: A Hospital Based Case-Control Study

    PubMed Central

    Praveenkumar, Udayakumar; Ganguly, Satyaki; Nanda, Sunil Kumar; Kuruvila, Sheela

    2016-01-01

    Introduction Previous studies indicate a higher prevalence of metabolic syndrome in psoriatic patients. This study aimed to investigate the association of metabolic syndrome and its components with psoriasis. It also studied the relation between presence of metabolic syndrome and disease duration in psoriasis patients. Materials and Methods This was a hospital-based, case-control study conducted with 30 clinically diagnosed patients of chronic plaque psoriasis and 30 age- and sex-matched control subjects. Height, weight, BMI, blood pressure and waist circumference were assessed in all the subjects. Fasting levels of serum glucose, serum triglycerides and serum HDL were estimated by automated clinical chemistry analyser. Metabolic syndrome was diagnosed by the presence of at least 3 criteria of NCEP ATP III with Asian modification for waist circumference. Results Metabolic syndrome was more common in psoriatic patients than in controls but the difference was statistically insignificant (60% vs. 40%, p-value=0.12). The psoriasis group had a higher prevalence of elevated blood glucose levels and higher waist circumference compared to controls. Psoriasis patients had a higher prevalence of high triglyceride levels than controls, the difference being statistically insignificant (40% vs. 30%, p-value = 0.41). The prevalence of low HDL levels was significantly higher in cases compared to controls (86.7% vs. 60%, p-value = 0.02). There was no relation between presence of metabolic syndrome and duration of psoriasis. Conclusion Our findings suggest that metabolic syndrome as well as dyslipidaemia is commoner in psoriasis patients. This underlines the need for screening of all psoriasis patients for early diagnosis and treatment of associated metabolic syndrome to reduce the high burden of morbidity and mortality. PMID:27042565

  4. Younger age at onset of sporadic Parkinson's disease among subjects occupationally exposed to metals and pesticides

    PubMed Central

    Farb, David H.; Ozer, Josef; Feldman, Robert G.; Durso, Raymon

    2014-01-01

    An earlier age at onset of Parkinson's disease (PD) has been reported to be associated with occupational exposures to manganese and hydrocarbon solvents suggesting that exposure to neurotoxic chemicals may hasten the progression of idiopathic PD. In this study the role of occupational exposure to metals and pesticides in the progression of idiopathic PD was assessed by looking at age at disease onset. The effects of heritable genetic risk factors, which may also influence age at onset, was minimized by including only sporadic cases of PD with no family history of the disease (n=58). Independent samples Student t-test revealed that subjects with occupational exposure to metals and/or pesticides (n=36) were significantly (p=0.013) younger than unexposed controls (n=22). These subjects were then divided into three groups [high (n=18), low (n=18), and unexposed (n=22)] to ascertain if duration of exposure further influenced age at onset of PD. One-way ANOVA revealed that subjects in the high exposure group were significantly (p=0.0121) younger (mean age: 50.33 years) than unexposed subjects (mean age: 60.45 years). Subjects were also stratified by exposure type (metals vs. pesticides). These results suggest that chronic exposure to metals and pesticides is associated with a younger age at onset of PD among patients with no family history of the disease and that duration of exposure is a factor in the magnitude of this effect. PMID:26109889

  5. [Sodium and diseases in the aged].

    PubMed

    Pentimone, F; del Corso Daniela Moruzzo, L; Romanelli, A M

    The authors describe serum sodium levels in elderly patients at hospitalization and evaluate the role attributable to drugs, diseases, nutrition and fluid balance. Among 167 patients (average age 75.29 +/- 7.14), 132 (79.04%) had normal sodium balance, 34 (20.36%) were hyponatremic and only 1 (0.60%) was hypernatremic. Patients who had serum sodium levels above 129 mEq/l were asymptomatic. In five cases hyponatremia was acute and severe (less than or equal to 127 mEq/l). Seven patients who had serum sodium levels less than 127 mEq/l presented psychiatric and neurological manifestations, which subsided completely after prompt correction of the electrolyte disorder. The authors suggest that the pathogenesis of hyponatremia in pathological states in the elderly is complex, although iatrogenic causes play a fundamental role. PMID:1836167

  6. Evaluating the Effects of Chronological Age and Sentence Duration on Degree of Perceived Foreign Accent

    ERIC Educational Resources Information Center

    Mackay, Ian R. A.; Flege, James E.; Imai, Satomi

    2006-01-01

    Immigrants' age of arrival (AOA) in a country where a second language (L2) must be learned has consistently been shown to affect the degree of perceived L2 foreign accent. Although the effect of AOA appears strong, AOA is typically correlated with other variables that might influence degree of foreign accent. This study examined the pronunciation…

  7. Lycopene Deficiency in Ageing and Cardiovascular Disease.

    PubMed

    Petyaev, Ivan M

    2016-01-01

    Lycopene is a hydrocarbon phytochemical belonging to the tetraterpene carotenoid family and is found in red fruit and vegetables. Eleven conjugated double bonds predetermine the antioxidant properties of lycopene and its ability to scavenge lipid peroxyl radicals, reactive oxygen species, and nitric oxide. Lycopene has a low bioavailability rate and appears in the blood circulation incorporated into chylomicrons and other apo-B containing lipoproteins. The recent body of evidence suggests that plasma concentration of lycopene is not only a function of intestinal absorption rate but also lycopene breakdown via enzymatic and oxidative pathways in blood and tissues. Oxidative stress and the accumulation of reactive oxygen species and nitric oxide may represent a major cause of lycopene depletion in ageing, cardiovascular disease, and type 2 diabetes mellitus. It has been shown recently that low carotenoid levels, and especially decreased serum lycopene levels, are strongly predictive of all-cause mortality and poor outcomes of cardiovascular disease. However, there is a poor statistical association between dietary and serum lycopene levels which occurs due to limited bioavailability of lycopene from dietary sources. Hence, it is very unlikely that nutritional intervention alone could be instrumental in the correction of lycopene and carotenoid deficiency. Therefore, new nutraceutical formulations of carotenoids with enhanced bioavailability are urgently needed. PMID:26881023

  8. Lycopene Deficiency in Ageing and Cardiovascular Disease

    PubMed Central

    Petyaev, Ivan M.

    2016-01-01

    Lycopene is a hydrocarbon phytochemical belonging to the tetraterpene carotenoid family and is found in red fruit and vegetables. Eleven conjugated double bonds predetermine the antioxidant properties of lycopene and its ability to scavenge lipid peroxyl radicals, reactive oxygen species, and nitric oxide. Lycopene has a low bioavailability rate and appears in the blood circulation incorporated into chylomicrons and other apo-B containing lipoproteins. The recent body of evidence suggests that plasma concentration of lycopene is not only a function of intestinal absorption rate but also lycopene breakdown via enzymatic and oxidative pathways in blood and tissues. Oxidative stress and the accumulation of reactive oxygen species and nitric oxide may represent a major cause of lycopene depletion in ageing, cardiovascular disease, and type 2 diabetes mellitus. It has been shown recently that low carotenoid levels, and especially decreased serum lycopene levels, are strongly predictive of all-cause mortality and poor outcomes of cardiovascular disease. However, there is a poor statistical association between dietary and serum lycopene levels which occurs due to limited bioavailability of lycopene from dietary sources. Hence, it is very unlikely that nutritional intervention alone could be instrumental in the correction of lycopene and carotenoid deficiency. Therefore, new nutraceutical formulations of carotenoids with enhanced bioavailability are urgently needed. PMID:26881023

  9. Duration of the immune response to MMR vaccine in children of two age-different groups.

    PubMed

    Li Volti, S; Giammanco-Bilancia, G; Grassi, M; Garozzo, R; Gluck, R; Giammanco, G

    1993-05-01

    A combined vaccine against measles, mumps and rubella (MMR) was administered to both a group of children aged 10-12 months simultaneously with booster doses of compulsory diphtheria-tetanus toxoids and oral poliovirus vaccine and a group of children aged 15-24 months who had previously received booster doses of the compulsory vaccines. Apart from one subject belonging to the second group who was non responder and one from the same group who did not seroconvert against the mumps virus alone, 5 to 6 weeks after MMR vaccine administration we found protective levels of antibodies against measles, mumps and rubella viruses in all children. The follow up of both groups at 3 years did not reveal difference between the two groups. Protective levels of serum antibodies against measles and mumps were found in the two groups, although a significant decline of rubella antibodies was shown (p < 0.05). Since the immunogenicity of the vaccines in the two groups did not differ, we recommend that the scientific community reconsider the vaccination schedule until now recommended. In our opinion the MMR vaccine should be administered simultaneously with booster doses of diphtheria-tetanus toxoids and oral poliovirus vaccine at 10-12 months of age because this policy improves parents' compliance, markedly reduces community costs and simplifies routine immunization schedule. PMID:8405317

  10. Developmental determinants in non-communicable chronic diseases and ageing.

    PubMed

    Bousquet, J; Anto, J M; Berkouk, K; Gergen, P; Antunes, J Pinto; Augé, P; Camuzat, T; Bringer, J; Mercier, J; Best, N; Bourret, R; Akdis, M; Arshad, S H; Bedbrook, A; Berr, C; Bush, A; Cavalli, G; Charles, M A; Clavel-Chapelon, F; Gillman, M; Gold, D R; Goldberg, M; Holloway, J W; Iozzo, P; Jacquemin, S; Jeandel, C; Kauffmann, F; Keil, T; Koppelman, G H; Krauss-Etschmann, S; Kuh, D; Lehmann, S; Carlsen, K C Lodrup; Maier, D; Méchali, M; Melén, E; Moatti, J P; Momas, I; Nérin, P; Postma, D S; Ritchie, K; Robine, J M; Samolinski, B; Siroux, V; Slagboom, P E; Smit, H A; Sunyer, J; Valenta, R; Van de Perre, P; Verdier, J M; Vrijheid, M; Wickman, M; Yiallouros, P; Zins, M

    2015-06-01

    Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases. PMID:25616486

  11. Histopathological lesions in the pancreas of the BB Wistar rat as a function of age and duration of diabetes.

    PubMed

    Wright, J; Yates, A; Sharma, H; Thibert, P

    1985-01-01

    Pancreatic histopathology was studied in 121 BBWd, 43 BBWnd, and 33 Wistar rats. Insulitis was the most common inflammatory lesion in both BBW and BBWnd rats. The incidence was inversely associated with age and with duration of diabetes in BBWd rats, but there was no age-related pattern in BBWnd rats. Small end-stage islets were typical of BBWd rats but were not seen in BBWnd rats. Several BBWd rats showed hyperplastic islets months after the onset of diabetes, a pattern that is also seen in a small percentage of human JOD patients. Several non-specific exocrine inflammatory lesions occurred in both BBWd and BBWnd rats: acute and/or chronic pancreatitis, eosinophilic infiltrates, granulomatous lesions and acute and/or chronic interstitial inflammation. Only chronic interstitial inflammation was seen in outbred Wistar rats. PMID:3882779

  12. [Car driving, cognitive aging and Alzheimer disease].

    PubMed

    Fabrigoule, Colette; Lafont, Sylviane

    2015-10-01

    Older drivers are more numerous on the roads. They are expert drivers, but with increasing age certain physiological changes can interfere with driving, which is a complex activity of daily living. Older drivers are involved in fewer accidents than younger drivers, but they have a higher accident rate per kilometer driven. The elderly are heavily represented in the balance sheet of road deaths, being motorists or pedestrians. This high mortality is largely explained by their physical frailty. In the presence of deficits, self-regulation of driving habits, changes/reductions or stopping in driving activity occur in the elderly. But cognitive deficits are associated with an increased risk of accidents. Among drivers with Alzheimer's disease, there is a heterogeneity of driving ability, making difficult the advisory role of a physician for driving. A protocol for physicians was developed to assess cognitive impairments that may affect driving in an elderly patient. The car plays an important role in the autonomy of the elderly and patient advice on stopping driving should take into account the risk/benefit ratio. PMID:26009241

  13. AID in aging and autoimmune diseases

    PubMed Central

    FRASCA, DANIELA; ANDRISANI, GIANLUCA; DIAZ, ALAIN; FELICE, CARLA; GUIDI, LUISA; BLOMBERG, BONNIE B.

    2016-01-01

    The aim of this study was to evaluate the quality of B cell responses in patients with Inflammatory Bowel Disease (IBD) and healthy individuals of different ages, vaccinated with the pandemic (p)2009 influenza vaccine. The in vivo response was measured by the hemagglutination inhibition (HAI) assay, which represents the most established correlate with vaccine protectiveness. The in vitro response was measured by activation-induced cytidine deaminase (AID) in cultures of vaccine-stimulated PBMC. Both responses are somewhat impaired in IBD patients undergoing anti-TNF-α treatment but these are much more decreased in IBD patients undergoing treatment with anti-TNF-α and immunosuppressive (IS) drugs. These latter patients had in vivo and in vitro B cell responses similar to those of elderly individuals. Moreover, as we have previously demonstrated in healthy subjects, the in vitro response to the polyclonal stimulus CpG may be used as a biomarker for subsequent vaccine response and AID activation is correlated with the serum response in IBD patients, as it is in healthy individuals. These results altogether indicate that IBD patients on anti-TNF-α and IS have significantly impaired in vivo and in vitro B cell responses, as compared to those on monotherapy. This is the first report to demonstrate that B cell defects, as measured by the autonomous AID reporter, in IBD patients contribute to reduced humoral responses to the influenza vaccine, as we have previously shown for elderly individuals. PMID:23190037

  14. Association of smoking status, cumulative smoking, duration of smoking cessation, age of starting smoking, and depression in Korean adults

    PubMed Central

    2012-01-01

    Background Many previous studies did not sufficiently control for several confounding factors that may affect the association between smoking and depression, such as socioeconomic status. We investigated the association between depression and smoking status, smoking exposure, duration of smoking cessation, and age of starting smoking while controlling for socioeconomic factors. Methods This study was based on a community health survey performed in Jeollanam-do, South Korea, between September and November 2009. In total, 20,084 subjects (9,118 males and 10,966 females) were included in the analysis. Information on smoking characteristics, such as smoking status, pack-years of smoking, and age of starting smoking, was collected using a standardized questionnaire. Depression was defined using the Korean CES-D score. Results The odds ratios (ORs) of depression were 1.35 (0.92–1.98) for former smokers and 1.77 (1.27–2.48) for current-smokers among males, and 2.67 (1.38–5.16) for former smokers and 3.72 (2.11–6.54) for current-smokers among females, after adjusting for other confounding factors. Compared to light smoking, heavy smoking was significantly associated with depression in males [OR = 3.97, 95% confidence interval (CI) = 1.42–11.14], but not in females (OR = 1.24, 95% CI = 0.73–2.09). No significant associations between depression and age of starting smoking and duration of smoking cessation were observed among former smokers. Conclusions Our data demonstrate that smoking is strongly associated with depression, particularly among females. These findings suggest that depression prevention may need to be combined with smoking prevention and that different strategies may be needed for males and females. PMID:22938088

  15. Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children.

    PubMed

    Yi, Dae Yong; Chang, Eun Jae; Kim, Ji Young; Lee, Eun Hye; Yang, Hye Ran

    2016-10-01

    We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491

  16. Geomagnetic polarity epochs: age and duration of the olduvai normal polarity event

    USGS Publications Warehouse

    Gromme, C.S.; Hay, R.L.

    1971-01-01

    New data show that the Olduvai normal geomagnetic polarity event is represented in Olduvai Gorge, Tanzania, by rocks covering a time span of roughly from 0.1 to 0.2 my and is no older than 2.0 my. Hence the long normal polarity event of this age that is seen in deep-sea sediment cores and in magnetic profiles over oceanic ridges should be called the Olduvai event. The lava from which the Gilsa?? event was defined may have been erupted during the Olduvai event and, if so, the term Gilsa?? should now be abandoned. Many dated lavas that were originally assigned to the Olduvai event represent one or two much shorter normal polarity events that preceded the Olduvai event; these are herein named the Re??union normal polarity events. This revision brings the geomagnetic reversal time scale into conformity with the one implied by assumptions of uniform sedimentation rates on the ocean floor and uniform rates of sea-floor spreading. ?? 1971.

  17. The aging-disease false dichotomy: understanding senescence as pathology.

    PubMed

    Gems, David

    2015-01-01

    From a biological perspective aging (senescence) appears to be a form of complex disease syndrome, though this is not the traditional view. This essay aims to foster a realistic understanding of aging by scrutinizing ideas old and new. The conceptual division between aging-related diseases and an underlying, non-pathological aging process underpins various erroneous traditional ideas about aging. Among biogerontologists, another likely error involves the aspiration to treat the entire aging process, which recent advances suggest is somewhat utopian. It also risks neglecting a more modest but realizable goal: to develop preventative treatments that partially protect against aging. PMID:26136770

  18. The aging-disease false dichotomy: understanding senescence as pathology

    PubMed Central

    Gems, David

    2015-01-01

    From a biological perspective aging (senescence) appears to be a form of complex disease syndrome, though this is not the traditional view. This essay aims to foster a realistic understanding of aging by scrutinizing ideas old and new. The conceptual division between aging-related diseases and an underlying, non-pathological aging process underpins various erroneous traditional ideas about aging. Among biogerontologists, another likely error involves the aspiration to treat the entire aging process, which recent advances suggest is somewhat utopian. It also risks neglecting a more modest but realizable goal: to develop preventative treatments that partially protect against aging. PMID:26136770

  19. Age-Associated Chronic Diseases Require Age-Old Medicine: Role of Chronic Inflammation

    PubMed Central

    Prasad, Sahdeo; Sung, Bokyung; Aggarwal, Bharat B.

    2012-01-01

    Most chronic diseases - such as cancer, cardiovascular disease (CVD), Alzheimer disease, Parkinson disease, arthritis, diabetes and obesity - are becoming leading causes of disability and death all over the world. Some of the most common causes of these age-associated chronic diseases are lack of physical activity, poor nutrition, tobacco use, and excessive alcohol consumption. All the risk factors linked to these chronic diseases have been shown to up-regulate inflammation. Therefore, downregulation of inflammation-associated risk factors could prevent or delay these age-associated diseases. Although modern science has developed several drugs for treating chronic diseases, most of these drugs are enormously expensive and are associated with serious side effects and morbidity. In this review, we present evidence on how chronic inflammation leads to age-associated chronic disease. Furthermore, we discuss diet and lifestyle as solutions for age-associated chronic disease. PMID:22178471

  20. Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

    PubMed Central

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-01-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

  1. Chronic Respiratory Diseases of School-Age Children

    ERIC Educational Resources Information Center

    McGovern, John P.

    1976-01-01

    The author examines the problems of chronic respiratory disease in school-age children from a medical viewpoint, including recognition and diagnosis, commonly encountered diseases, their effect on participation in physical exercise, emotional factors, medication, and emergency care. (MB)

  2. Ageing and Parkinson's disease: substantia nigra regional selectivity.

    PubMed

    Fearnley, J M; Lees, A J

    1991-10-01

    The micro-architecture of the substantia nigra was studied in control cases of varying age and patients with parkinsonism. A single 7 mu section stained with haematoxylin and eosin was examined at a specific level within the caudal nigra using strict criteria. The pars compacta was divided into a ventral and a dorsal tier, and each tier was further subdivided into 3 regions. In 36 control cases there was a linear fallout of pigmented neurons with advancing age in the pars compacta of the caudal substantia nigra at a rate of 4.7% per decade. Regionally, the lateral ventral tier was relatively spared (2.1% loss per decade) compared with the medial ventral tier (5.4%) and the dorsal tier (6.9%). In 20 Parkinson's disease (PD) cases of varying disease duration there was an exponential loss of pigmented neurons with a 45% loss in the first decade. Regionally, the pattern was opposite to ageing. Loss was greatest in the lateral ventral tier (average loss 91%) followed by the medial ventral tier (71%) and the dorsal tier (56%). The presymptomatic phase of PD from the onset of neuronal loss was estimated to be about 5 yrs. This phase is represented by incidental Lewy body cases: individuals who die without clinical signs of PD or dementia, but who are found to have Lewy bodies at post-mortem. In 7 cases cell loss was confined to the lateral ventral tier (average loss 52%) congruent with the lateral ventral selectivity of symptomatic PD. It was calculated that at the onset of symptoms there was a 68% cell loss in the lateral ventral tier and a 48% loss in the caudal nigra as a whole. The regional selectivity of PD is relatively specific. In 15 cases of striatonigral degeneration the distribution of cell loss was similar, but the loss in the dorsal tier was greater than PD by 21%. In 14 cases of Steele-Richardson-Olszewski syndrome (SRO) there was no predilection for the lateral ventral tier, but a tendency to involve the medial nigra and spare the lateral. These findings

  3. Age and duration of inflammatory environment differentially affect the neuroimmune response and catecholaminergic neurons in the midbrain and brainstem.

    PubMed

    Bardou, Isabelle; Kaercher, Roxanne M; Brothers, Holly M; Hopp, Sarah C; Royer, Sarah; Wenk, Gary L

    2014-05-01

    Neuroinflammation and degeneration of ascending catecholaminergic systems occur early in the neurodegenerative process. Age and the duration of a pro-inflammatory environment induced by continuous intraventricular lipopolysaccharide (LPS) differentially affect the expression profile of pro- and anti-inflammatory genes and proteins as well as the number of activated microglia (express major histocompatibility complex II; MHC II) and the integrity and density of ascending catecholaminergic neural systems originating from the locus coeruleus (LC) and substantia nigra pars compacta (SNpc) in rats. LPS infusion increased gene expression and/or protein levels for both pro- and anti-inflammatory biomarkers. Although LPS infusion stimulated a robust increase in IL-1ß gene and protein expression, this increase was blunted with age. LPS infusion also increased the density of activated microglia cells throughout the midbrain and brainstem. Corresponding to the development of a pro-inflammatory environment, LC and SNpc neurons immunopositive for tyrosine-hydroxylase (the rate-limiting synthetic enzyme for dopamine and norepinephrine) decreased in number, along with a decrease in tyrosine-hydroxylase gene expression in the midbrain and/or brainstem region. Our data support the concept that continuous exposure to a pro-inflammatory environment drives exaggerated changes in the production and release of inflammatory mediators that interact with age to impair functional capacity of the SNpc and LC. PMID:24315728

  4. Parkinson's disease duration determines effect of dopaminergic therapy on ventral striatum function.

    PubMed

    MacDonald, Alex A; Monchi, Oury; Seergobin, Ken N; Ganjavi, Hooman; Tamjeedi, Ruzbeh; MacDonald, Penny A

    2013-02-01

    We investigated the hypothesis that variation in endogenous dopamine (DA) across brain regions explains dissimilar effects of dopaminergic therapy on aspects of cognition in early Parkinson's disease (PD). Extensive degeneration of DA-producing cells in the substantia nigra cause dorsal striatum (DS) DA deficiency and movement abnormalities. Particularly in early PD, this contrasts with relative sparing of the dopaminergic cells of the ventral tegmental area (VTA). The hypothesis predicts that DS-mediated cognitive functions are deficient at baseline and improved by DA replacement, whereas functions depending upon VTA-innervated brain regions are normal off medication and worsen with treatment. The latter pattern presumably owes to overdose of relatively DA-replete VTA-supplied brain regions with medication levels titrated to DS-mediated motor symptoms. As PD progresses, however, VTA degeneration increases. Impairment in cognitive operations performed by VTA-innervated brain regions, such as the ventral striatum (VS), is expected. We compared the performance of early and late PD patients, on and off dopaminergic medication, relative to age-matched controls, on reward learning, previously shown to implicate the VS. As expected, in early PD, stimulus-reward learning was normal off medication, but worsened with DA replacement. At more advanced disease stages, PD patients learned stimulus-reward contingencies more poorly than controls and early PD patients off medication. Furthermore, dopaminergic medication did not worsen reward learning in late PD patients, in line with the dopamine overdose hypothesis. Unlike its effect on DS-mediated functions, however, DA-replacement therapy did not improve reward learning in late PD patients. PMID:23165957

  5. Hypoglycemia-Related Electroencephalogram Changes Are Independent of Gender, Age, Duration of Diabetes, and Awareness Status in Type 1 Diabetes

    PubMed Central

    Remvig, Line Sofie; Elsborg, Rasmus; Sejling, Anne-Sophie; Sørensen, Jens Ahm; Sønder Snogdal, Lena; Folkestad, Lars; Juhl, Claus B.

    2012-01-01

    Introduction Neuroglycopenia in type 1 diabetes mellitus (T1DM) results in reduced cognition, unconsciousness, seizures, and possible death. Characteristic changes in the electroencephalogram (EEG) can be detected even in the initial stages. This may constitute a basis for a hypoglycemia alarm device. The aim of the present study was to explore the characteristics of the EEG differentiating normoglycemia and hypoglycemia and to elucidate potential group differences. Methods We pooled data from experiments in T1DM where EEG was available during both normoglycemia and hypo-glycemia for each subject. Temporal EEG was analyzed by quantitative electroencephalogram (qEEG) analysis with respect to absolute amplitude and centroid frequency of the delta, theta, alpha, and beta bands, and the peak frequency of the unified theta–alpha band. To elucidate possible group differences, data were subsequently stratified by age group (± 50 years), gender, duration of diabetes (± 20 years), and hypoglycemia awareness status (normal/impaired awareness of hypoglycemia). Results An increase in the log amplitude of the delta, theta, and alpha band and a decrease in the alpha band centroid frequency and the peak frequency of the unified theta–alpha band constituted the most significant hypoglycemia indicators (all p < .0001). The size of these qEEG changes remained stable across all strata. Conclusions Hypoglycemia-associated EEG changes remain stable across age group, gender, duration of diabetes, and hypoglycemia awareness status. This indicates that it may be possible to establish a general algorithm for hypoglycemia detection based on EEG measures. PMID:23294778

  6. The influence of worm age, duration of exposure and endpoint selection on bioassay sensitivity for Neanthes arenaceodentata (Annelida: Polychaeta)

    SciTech Connect

    Bridges, T.S.; Farrar, J.D.

    1997-08-01

    The influence of worm age, duration of exposure, and endpoint selection on bioassay sensitivity were evaluated for Neanthes arenaceodentata. Worms were exposed to contaminated sediment collected from Black Rock Harbor (BRH) near Bridgeport, Connecticut, USA. This sediment was diluted with clean control sediment to result in five experimental treatments: 0, 25, 50, 75, and 100% BRH. Three exposure scenarios were employed: (1) a 4-week exposure beginning with newly emerged juveniles (EJ-4w), (2) a 7-week exposure beginning with newly emerged juveniles (EJ-7w), and (3) a 4-week exposure beginning with 3-week-old juveniles (3WO-4w). Six measures of worm size were recorded at the conclusion of each exposure to evaluate differences among measurement endpoints. Survival was significantly reduced at the 25% BRH level for the EJ-7w scenario and at the 100% BRH level for the EJ-4w and 3WO-4w scenarios. Growth was significantly reduced at the 25% BRH level in each exposure scenario. Estimates based on the calculated minimum detectable difference indicated that considerably lower concentrations of BRH (6--10%) should be distinguishable by measuring effects on Neanthes growth. Worm size measured in terms of projected area, dry weight, and ash-free dry weight provided the most sensitive measures of effects. Increasing the length of exposure from 4 to 7 weeks and initiating exposures with emergent juveniles rather than 3-week-old worms increased the sensitivity of the bioassay. The results of this study demonstrate that N. arenacedentata is sensitive to the presence of sediment-associated contaminants and that test animal age, duration of exposure, and choice of endpoint can have a large effect on the magnitude of the toxic response observed.

  7. Oxysterols and Parkinson's disease: evidence that levels of 24S-hydroxycholesterol in cerebrospinal fluid correlates with the duration of the disease.

    PubMed

    Björkhem, Ingemar; Lövgren-Sandblom, Anita; Leoni, Valerio; Meaney, Steve; Brodin, Lovisa; Salveson, Lisette; Winge, Kristian; Pålhagen, Sven; Svenningsson, Per

    2013-10-25

    Oxysterols are important for cholesterol homeostasis in the brain and may be affected in neurodegenerative diseases. The levels of the brain-derived oxysterol 24S-hydroxycholesterol (24S-OH) have been reported to be markedly reduced in the circulation of patients with Parkinson's disease (PD) (Lee et al., Antioxid. Redox Signal. 11 (2009) 407-420). The finding is surprising in view of the fact that other neurodegenerative diseases are associated with relatively modest effects on the circulating levels of 24S-OH. We determined the plasma and cerebrospinal fluid (CSF) levels of 24S-OH and 27-hydroxycholesterol (27-OH) in patients with PD with different disease duration using a highly accurate method based on isotope dilution-mass spectrometry. All the patients had plasma levels of the different oxysterols within the normal range. When analyzing CSF, 10% of the PD patients were found to have levels of 24S-OH above the cut-off level and interestingly there was a significant correlation between levels of 24S-OH in CSF and duration of the disease (r=0.40, P<0.05). The CSF level of 27-OH was found to be above the cut-off level in 10% of the patients, indicating a defect blood-brain barrier function. There was no correlation between levels of 27-OH in CSF and duration of the disease. These data indicates that oxysterol levels in CSF may be of value to follow disease progression. PMID:24035896

  8. TAGE (toxic AGEs) hypothesis in various chronic diseases.

    PubMed

    Takeuchi, M; Yamagishi, S

    2004-01-01

    The advanced stage of the glycation process (one of the post-translational modifications of proteins) leads to the formation of advanced glycation end-products (AGEs) and plays an important role in the pathogenesis of angiopathy in diabetic patients, in aging, and in neurodegenerative diseases. However, it is still not clear which AGEs subtypes play a pathogenetic role and which of several AGEs receptor mediate AGEs effects on cells. We have provided direct immunochemical evidence for the existence of six distinct AGEs structures (AGEs-1 to -6) within the AGEs-modified proteins and peptides that circulate in the serum of diabetic patients. Recently we demonstrated for the first time that glyceraldehyde-derived AGEs (AGEs-2) and glycolaldehyde-derived AGEs (AGE-3) have diverse biological activities on vascular wall cells, mesangial cells, Schwann cells, malignant melanoma cells and cortical neurons. We also demonstrated for the first time that acetaldehyde (AA)-derived AGEs (AA-AGE) have cytotoxic activity on cortical neurons and the AA-AGE epitope was detected in human brain of alcoholics. These results indicate that of the various types of AGEs structures that can form in vivo, the toxic AGEs (TAGE) structures (AGEs 2, 3, and AA-AGE), but not non-toxic AGEs (N-carboxymethyllysine, pentosidine, pyrraline etc.) are likely to play an important role in the pathophysiological processes associated with AGEs formation. PMID:15288366

  9. Blue Journal Conference. Aging and Susceptibility to Lung Disease

    PubMed Central

    Thannickal, Victor J.; Murthy, Mahadev; Balch, William E.; Chandel, Navdeep S.; Meiners, Silke; Eickelberg, Oliver; Selman, Moisés; Pardo, Annie; White, Eric S.; Levy, Bruce D.; Busse, Paula J.; Tuder, Rubin M.; Antony, Veena B.; Sznajder, Jacob I.

    2015-01-01

    The aging of the population in the United States and throughout the developed world has increased morbidity and mortality attributable to lung disease, while the morbidity and mortality from other prevalent diseases has declined or remained stable. Recognizing the importance of aging in the development of lung disease, the American Thoracic Society (ATS) highlighted this topic as a core theme for the 2014 annual meeting. The relationship between aging and lung disease was discussed in several oral symposiums and poster sessions at the annual ATS meeting. In this article, we used the input gathered at the conference to develop a broad framework and perspective to stimulate basic, clinical, and translational research to understand how the aging process contributes to the onset and/or progression of lung diseases. A consistent theme that emerged from the conference was the need to apply novel, systems-based approaches to integrate a growing body of genomic, epigenomic, transcriptomic, and proteomic data and elucidate the relationship between biologic hallmarks of aging, altered lung function, and increased susceptibility to lung diseases in the older population. The challenge remains to causally link the molecular and cellular changes of aging with age-related changes in lung physiology and disease susceptibility. The purpose of this review is to stimulate further research to identify new strategies to prevent or treat age-related lung disease. PMID:25590812

  10. Distinct Mechanisms of Impairment in Cognitive Ageing and Alzheimer's Disease

    ERIC Educational Resources Information Center

    Mapstone, Mark; Dickerson, Kathryn; Duffy, Charles J.

    2008-01-01

    Similar manifestations of functional decline in ageing and Alzheimer's disease obscure differences in the underlying cognitive mechanisms of impairment. We sought to examine the contributions of top-down attentional and bottom-up perceptual factors to visual self-movement processing in ageing and Alzheimer's disease. We administered a novel…

  11. Aging and Alzheimer's Disease: Lessons from the Nun Study.

    ERIC Educational Resources Information Center

    Snowdon, David A.

    1997-01-01

    Describes a woman who maintained high cognitive test scores until her death at 101 years of age despite anatomical evidence of Alzheimer's disease. The woman was part of a larger "Nun Study" in which 678 sisters donated their brains to teach others about the etiology of aging and Alzheimer's disease. Findings are discussed. (RJM)

  12. 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

  13. 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

  14. [Decline in renal function in old age : Part of physiological aging versus age-related disease].

    PubMed

    Braun, F; Brinkkötter, P T

    2016-08-01

    The incidence and prevalence of chronic renal disease (CKD) in elderly patients are continuously increasing worldwide. Loss of renal function is not only considered to be part of the aging process itself but also reflects the multimorbidity of many geriatric patients. Calculating the glomerular filtration rate using specific algorithms validated for the elderly population and measuring the amount of proteinuria allow an estimation of renal function in elderly patients with high accuracy. Chronic renal failure has many clinical consequences and not only results in a delayed excretion of toxins cleared by the kidneys but also affects hematogenesis, water and electrolyte balance as well as mineral bone metabolism. Furthermore, CKD directly leads to and aggravates geriatric syndromes and in particular the onset of frailty. Therapeutic strategies to halt progression of CKD not only comprise treatment of the underlying disease but also efficient blood pressure and diabetic control and the avoidance of nephrotoxic medications. PMID:27457360

  15. Sorption Characteristic of Phenanthrene on Biochar-Amended Soils: Effect of feedstock, pyrolysis temperature, and aging duration

    NASA Astrophysics Data System (ADS)

    Hyun, S.; Kim, C.; Kim, Y. S.; Kim, J.

    2015-12-01

    The high sorption capacity of biochar is widely known in environmental studies. Especially, biochar is effective for removal of hydrophobic organic compounds (HOCs) due to high surface area and porosity. In this study, the sorption characteristic of biochar-amended soil was evaluated by sorption kinetic experiment of phenanthrene (PHE). For PHE sorption test, the effect of biochar feedstock (sludge waste char (SWC), municipal waste char (MWC) and wood char (WC), Giant Miscanthus (GM)), pyrolysis temperature (400°C, 500°C and 700°C,), and duration of amending period (0, 3, 6, and 12 months) was assessed. Field Emission-Scanning Electron Microscopy (FE-SEM) and Fourier Transform-Infrared Spectroscopy (FT-IR) techniques were used to detect pore structure and the surface functional group of biochar amended soils. For all kinetic tests, apparent sorption equilibrium was attained in 24 hr. The result showed that sorption capacity of biochar amended soils was greatly influenced by biochar feedstock and pyrolysis temperature. For all samples, the sorption capacity of PHE by biochar amended soils decreased with aging period. This observation is due to the fact that the aromatic characters of biochar are different by feedstock and pyrolysis temperature and the amount of O-containing hydrophilic functional groups increased surfaces of biochar by natural oxidation (e.g. carboxyl groups) as confirmed by the result of FT-IR and FE-SEM. In addition, biochar pore blockage by inorganic minerals, which tended to increase with aging period, might attenuate the sorption capacity of samples. In conclusion, biochar derived from various feed stocks are all effective for PHE sorption. But the sorption capacity of biochar amended soils decreased with increasing aging duration most likely due to increasing hydrophilic functional groups of biochar surfaces and pore blockage by inorganic minerals in the weathering processes. Therefore, for the design of biochar amendment to attenuate

  16. Insights into neurogenesis and aging: potential therapy for degenerative disease?

    PubMed Central

    Marr, Robert A; Thomas, Rosanne M; Peterson, Daniel A

    2010-01-01

    Neurogenesis is the process by which new neural cells are generated from a small population of multipotent stem cells in the adult CNS. This natural generation of new cells is limited in its regenerative capabilities and also declines with age. The use of stem cells in the treatment of neurodegenerative disease may hold great potential; however, the age-related incidence of many CNS diseases coincides with reduced neurogenesis. This review concisely summarizes current knowledge related to adult neurogenesis and its alteration with aging and examines the feasibility of using stem cell and gene therapies to combat diseases of the CNS with advancing age. PMID:20806052

  17. Aromatase, adiposity, aging and disease. The hypogonadal-metabolic-atherogenic-disease and aging connection.

    PubMed

    Cohen, P G

    2001-06-01

    In males, aging, health and disease are processes that occur over physiologic time and involve a cascade of hormonal, biochemical and physiological changes that accompany the down-regulation of the hypothalamic-anterior pituitary-testicular axis. As aging progresses there are relative increases of body fat and decreases in muscle mass. The increased adipose tissue mass is associated with the production of a number of newly generated factors. These include aromatase, leptin, PAI-1, insulin resistance, and the dyslipidemias, all of which can lead to tissue damage. Fatty tissue becomes the focal point for study as it represents the intersection between energy storage and mobilization. The increase in adipose tissue is associated with an increase in the enzyme aromatase that converts testosterone to estradiol and leads to diminished testosterone levels that favor the preferential deposition of visceral fat. As the total body fat mass increases, hormone resistance develops for leptin and insulin. Increasing leptin fails to prevent weight gain and the hypogonadal-obesity cycle ensues causing further visceral obesity and insulin resistance. The progressive insulin resistance leads to a high triglyceride-low HDL pattern of dyslipidemia and increased cardiovascular risk. All of these factors eventually contribute to the CHAOS Complex: coronary disease, hypertension, adult-onset diabetes mellitus, obesity and/or stroke as permanent changes unfold. Other consequences of the chronic hypogonadal state include osteopenia, extreme fatigue, depression, insomnia, loss of aggressiveness and erectile dysfunction all of which develop over variable periods of time. PMID:11399122

  18. Polymerase Gamma Disease through the Ages

    ERIC Educational Resources Information Center

    Saneto, Russell P.; Naviaux, Robert K.

    2010-01-01

    The most common group of mitochondrial disease is due to mutations within the mitochondrial DNA polymerase, polymerase gamma 1 ("POLG"). This gene product is responsible for replication and repair of the small mitochondrial DNA genome. The structure-function relationship of this gene product produces a wide variety of diseases that at times, seems…

  19. Adult Stem Cells and Diseases of Aging

    PubMed Central

    Boyette, Lisa B.; Tuan, Rocky S.

    2014-01-01

    Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. PMID:24757526

  20. Adult Stem Cells and Diseases of Aging.

    PubMed

    Boyette, Lisa B; Tuan, Rocky S

    2014-01-21

    Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. PMID:24757526

  1. [Duration of effect of pulmonary rehabilitation in elderly patients with chronic obstructive pulmonary disease].

    PubMed

    Sudo, E; Ohga, E; Matsuse, T; Teramoto, S; Nagase, T; Katayama, H; Tanaka, M; Kikuchi, N; Kakurai, S; Fukuchi, Y; Ouchi, Y

    1997-09-01

    Pulmonary rehabilitation has been reported to be effective in patients with chronic obstructive pulmonary disease (COPD). To investigate the effect of a moderate period of pulmonary rehabilitation combined with inspiratory muscle training (IMT) in elderly patients with COPD, we instituted pulmonary rehabilitation for 60 weeks in five elderly patients (age: 65.4 +/- 3.7 SE years). IMT was performed for 15 min twice daily using a pressure threshold device. The inspiratory threshold was set at 15% of the maximal inspiratory pressure (PImax) of each individual. Maximal peak flow significantly increased from 3.0 +/- 0.6 (L/s) at baseline to 4.1 +/- 0.7 (L/s) after 12 weeks (p < 0.02) and was maintained at that level for 60 weeks. PImax increased significantly from 49.9 +/- 6.4 cmH2O at baseline to 67.3 +/- 3.0 cmH2O after 12 weeks (p < 0.05) and to 72.8 +/- 3.5 cmH2O (p < 0.02) after 60 weeks of rehabilitation. The 10-minute walking distance increased from 666.6 +/- 55.0 to 764.0 +/- 49.9 m (p < 0.05) after 12 weeks and was maintained at the same level. We conclude that pulmonary rehabilitation combined with IMT improves pulmonary function and inspiratory muscle strength in elderly patients with COPD between for 12 weeks after commencement, but occurs that no significant increase on lung function or 10-minute walking distance from 12 to 60 weeks. Respiratory muscle strength may further increase after 60 weeks. PMID:9430986

  2. Astroglia dynamics in ageing and Alzheimer's disease.

    PubMed

    Verkhratsky, Alexei; Zorec, Robert; Rodríguez, Jose J; Parpura, Vladimir

    2016-02-01

    Ageing of the brain is the major risk factor for neurodegenerative disorders that result in cognitive decline and senile dementia. Ageing astrocytes undergo complex and region specific remodelling which can reflect life-long adaptive plasticity. In neurodegeneration, astroglial cells are similarly a subject for morpho-functional changes hampering the homoeostasis, defence and regeneration of the central nervous system. Region-specific astroglial atrophy with the loss of function and astroglial reactivity have been reported in virtually all forms of neurodegenerative pathologies. Modulating these astroglia changes may represent a fertile ground for novel therapeutic intervention strategies to prevent, delay progression and/or ameliorate pathology. While at present this bodacious goal represents a wishful thinking, further understanding of astroglial role in ageing and neurodegeneration could bring us closer to laying the foundations for such cell-specific therapeutic approaches. PMID:26515274

  3. Ages, durations and behavioural implications of Middle Stone Age industries in southern Africa: advances in optical dating of individual grains of quartz

    NASA Astrophysics Data System (ADS)

    Jacobs, Z.

    2009-04-01

    Recent developments in OSL dating have focussed on the measurement of individual sand-sized grains of quartz. Single-grain dating allows the identification of contaminant grains in a sample and their exclusion before final age determination, and the ability to directly check the stratigraphic integrity of archaeological sequences and address concerns about post-deposition sediment mixing. These benefits result in single-grain OSL ages being both accurate and precise. Even greater precision can be attained by adopting a systematic approach to the collection and analysis of OSL data. This involves one operator using the same OSL stimulation and detection instrument, laboratory radiation sources, calibration standards, and analytical procedures for all samples. By holding these experimental parameters constant, sources of error common to all samples are removed, enabling far greater resolution of the true age structure. This approach was recently used to determine the timing and duration of two bursts of Middle Stone Age technological and behavioural innovation - the Still Bay (SB) and Howieson's Poort (HP) - in southern Africa. These distinctive artefacts are associated with the first evidence for symbols and personal ornaments, and may have been the catalyst for the expansion of Homo sapiens populations in Africa 80,000-60,000 years ago and for the subsequent migration of modern humans out of Africa. Testing such hypotheses, and the putative role of climate change, has been hampered by poor age constraints for the HP and SB industries. Previous attempts to resolve the start and end dates of these industries had been largely obscured by the chronological' haze' arising from a variety of different materials being dated by different methods using different equipment, calibration standards, measurement procedures and techniques of data analysis. By clearing this haze and placing all ages on a common timescale, we were able to constrain the timing of the SB and HP, and

  4. Impairment of age estimation from faces in Alzheimer's disease.

    PubMed

    Moyse, Evelyne; Bastin, Christine; Salmon, Eric; Brédart, Serge

    2015-01-01

    A prerequisite for any function in social cognition is the perception and processing of social cues. Age estimation is a skill that is used in everyday life and is fundamental in social interactions. This study evaluated whether facial age estimation is impaired in patients with mild to moderate Alzheimer's disease (AD). The current age of faces is known to have an impact on age estimation, and therefore stimuli belonging to different age groups (young, middle-aged, and older adults' faces) were used. As expected, an impairment of age estimation from faces was observed in mild to moderate AD patients. However, the profile of impairment depended on the age of faces and stage of the disease. Mild AD patients presented difficulties mainly in assessing the age of middle-aged adults. In moderate disease stage, these difficulties also affected the age estimation of young adult faces. Interestingly, AD patients remained relatively good at estimating the age of older adults' faces, compared to healthy controls. PMID:25589725

  5. Skin Disease in Laminopathy-Associated Premature Aging.

    PubMed

    McKenna, Tomás; Sola Carvajal, Agustín; Eriksson, Maria

    2015-11-01

    The nuclear lamina, a protein network located under the nuclear membrane, has during the past decade found increasing interest due to its significant involvement in a range of genetic diseases, including the segmental premature aging syndromes Hutchinson-Gilford progeria syndrome, restrictive dermopathy, and atypical Werner syndrome. In this review we examine these diseases, some caused by mutations in the LMNA gene, and their skin disease features. Advances within this area might also provide novel insights into the biology of skin aging, as recent data suggest that low levels of progerin are expressed in unaffected individuals and these levels increase with aging. PMID:26290387

  6. Timing the therapeutic window of opportunity in early rheumatoid arthritis: proposal for definitions of disease duration in clinical trials.

    PubMed

    Raza, Karim; Saber, Tajvur P; Kvien, Tore K; Tak, Paul P; Gerlag, Danielle M

    2012-12-01

    The effects of treatment in early rheumatoid arthritis (RA) and the consequences of delayed therapy represent important areas for research. The concept of a 'window of opportunity' is now well established and considerable attention has been paid to when it might close. However, in order to study how long the window of opportunity lasts, the timing of its opening must be precisely defined. An analysis of definitions of 'onset' in clinical studies reveals imprecision and heterogeneity, making accurate assessment of this important concept of the 'window of opportunity' very difficult. In this paper we propose that, in clinical trials in early RA, data on durations since onset of symptoms and onset of joint swelling as well as disease duration based on fulfilment of classification criteria should be routinely presented. PMID:22941769

  7. Contextual determinants of cardiovascular diseases: overcoming the residential trap by accounting for non-residential context and duration of exposure.

    PubMed

    Chum, Antony; O' Campo, Patricia

    2013-11-01

    Multilevel neighbourhood analyses rarely account for (1) non-residential exposures and (2) duration of exposure, which have the potential to improve contextual level variance explained, model fit and strength of associations. Using cross-classified logistic regressions, we evaluate the impact of socio-environmental factors at work and home on cardiovascular disease risk for 1626 adults in Toronto-Canada. In the fully-adjusted model, increased CVD risk was associated with poor food environments, lack of parks/recreational facilities, home and work proximity to a major road and noise, and working in a low-SES neighbourhood (p<0.05). Adjusting for exposure duration improved model fit and the strength of associations. PMID:24056364

  8. Interglacial Durations

    NASA Astrophysics Data System (ADS)

    Mangili, Clara; McManus, Jerry F.; Raynaud, Dominique

    2014-05-01

    In the context of future global warming induced by human activities, it is essential to assess the role of natural climatic variations. Precise knowledge of the duration of past interglacial periods is fundamental to the understanding of the potential future evolution of the Holocene. Past ice age cycles provide a natural laboratory for exploring the progression and duration of interglacial climate. Palaeorecords from ice, land and oceans extend over the last 800 ka, revealing eight glacial-interglacial cycles, with a range of insolation and greenhouse gas influences. The interglacials display a correspondingly large variety of intensity and duration, thus providing an opportunity for major insights into the mechanisms involved in the behaviour of interglacial climates. A comparison of the duration of these interglacials, however, is often difficult, as the definition of an interglacial depends on the archive that is considered. Therefore, to compare interglacial length and climate conditions from different archives, a consistent definition of interglacial conditions is required, ideally one that is not bound to the method nor to the archive under consideration. Here we present a method to identify interglacials and to calculate their length by mean of a simple statistical approach. We based our method on ~ 400 ka windows of time to determine mean climatic conditions while allowing for the possibility of long term evolution of the climatic baseline. For our study of interglacials of the past 800 ka, we used two windows that largely align with the pre- (800-430 ka ago) and post- (430-0 ka ago) mid-Brunhes event (MBE), although the resulting conclusions are not sensitive to this particular division. We applied this method to the last 800 ka of a few palaeoclimate records: the deuterium ice core (EDC) record as a climatic proxy, the benthic δ18O stack (LR04) as a proxy for sea level/ice volume, ice core (Vostok, EDC) atmospheric CO2 and additional records. Although

  9. Discover the network mechanisms underlying the connections between aging and age-related diseases

    PubMed Central

    Yang, Jialiang; Huang, Tao; Song, Won-min; Petralia, Francesca; Mobbs, Charles V.; Zhang, Bin; Zhao, Yong; Schadt, Eric E.; Zhu, Jun; Tu, Zhidong

    2016-01-01

    Although our knowledge of aging has greatly expanded in the past decades, it remains elusive why and how aging contributes to the development of age-related diseases (ARDs). In particular, a global mechanistic understanding of the connections between aging and ARDs is yet to be established. We rely on a network modelling named “GeroNet” to study the connections between aging and more than a hundred diseases. By evaluating topological connections between aging genes and disease genes in over three thousand subnetworks corresponding to various biological processes, we show that aging has stronger connections with ARD genes compared to non-ARD genes in subnetworks corresponding to “response to decreased oxygen levels”, “insulin signalling pathway”, “cell cycle”, etc. Based on subnetwork connectivity, we can correctly “predict” if a disease is age-related and prioritize the biological processes that are involved in connecting to multiple ARDs. Using Alzheimer’s disease (AD) as an example, GeroNet identifies meaningful genes that may play key roles in connecting aging and ARDs. The top modules identified by GeroNet in AD significantly overlap with modules identified from a large scale AD brain gene expression experiment, supporting that GeroNet indeed reveals the underlying biological processes involved in the disease. PMID:27582315

  10. Discover the network mechanisms underlying the connections between aging and age-related diseases.

    PubMed

    Yang, Jialiang; Huang, Tao; Song, Won-Min; Petralia, Francesca; Mobbs, Charles V; Zhang, Bin; Zhao, Yong; Schadt, Eric E; Zhu, Jun; Tu, Zhidong

    2016-01-01

    Although our knowledge of aging has greatly expanded in the past decades, it remains elusive why and how aging contributes to the development of age-related diseases (ARDs). In particular, a global mechanistic understanding of the connections between aging and ARDs is yet to be established. We rely on a network modelling named "GeroNet" to study the connections between aging and more than a hundred diseases. By evaluating topological connections between aging genes and disease genes in over three thousand subnetworks corresponding to various biological processes, we show that aging has stronger connections with ARD genes compared to non-ARD genes in subnetworks corresponding to "response to decreased oxygen levels", "insulin signalling pathway", "cell cycle", etc. Based on subnetwork connectivity, we can correctly "predict" if a disease is age-related and prioritize the biological processes that are involved in connecting to multiple ARDs. Using Alzheimer's disease (AD) as an example, GeroNet identifies meaningful genes that may play key roles in connecting aging and ARDs. The top modules identified by GeroNet in AD significantly overlap with modules identified from a large scale AD brain gene expression experiment, supporting that GeroNet indeed reveals the underlying biological processes involved in the disease. PMID:27582315

  11. Mitochondrial Acetylation and Diseases of Aging

    PubMed Central

    Wagner, Gregory R.; Payne, R. Mark

    2011-01-01

    In recent years, protein lysine acetylation has emerged as a prominent and conserved regulatory posttranslational modification that is abundant on numerous enzymes involved in the processes of intermediary metabolism. Well-characterized mitochondrial processes of carbon utilization are enriched in acetyl-lysine modifications. Although seminal discoveries have been made in the basic biology of mitochondrial acetylation, an understanding of how acetylation states influence enzyme function and metabolic reprogramming during pathological states remains largely unknown. This paper will examine our current understanding of eukaryotic acetate metabolism and present recent findings in the field of mitochondrial acetylation biology. The implications of mitochondrial acetylation for the aging process will be discussed, as well as its potential implications for the unique and localized metabolic states that occur during the aging-associated conditions of heart failure and cancer growth. PMID:21437190

  12. Hematopoiesis during development, aging, and disease.

    PubMed

    Jung, Johannes; Buisman, Sonja; de Haan, Gerald

    2016-08-01

    Hematopoietic stem cells were once considered identical. However, in the mid-1990s, it became apparent that stem cells from a person's early developmental phases are superior to those from adults, and aged stem cells are defective compared with young stem cells. It has since become clear that polycomb group proteins are important regulators of stem cell functioning. Polycomb group proteins are chromatin-associated proteins involved in writing or reading epigenetic histone modifications. Polycomb group proteins are involved in normal blood cell formation, in cancer, and possibly in aging. In this review, we describe how the different phases of hematopoietic stem cells-birth, maintenance, functional decline, derailment, and death-are continuous processes that may be controlled by polycomb group proteins. PMID:27235755

  13. Duration of Dual Antiplatelet Therapy in Coronary Artery Disease: a Review Article.

    PubMed

    Moseley, Alex D; Collado, Fareed M; Volgman, Annabelle Santos; Schaer, Gary L; Snell, R Jeffrey

    2016-07-01

    Dual antiplatelet therapy (DAPT) following an acute coronary syndrome or after placement of a coronary artery stent is superior to aspirin alone for prevention of atherothrombotic events but carries an increased bleeding risk. DAPT should be continued for at least 12 months based on current guidelines. Recent randomized trials demonstrate reduced ischemic events including myocardial infarction (MI), stroke, and death with continued DAPT for up to 30 months or longer, particularly in the post-MI population. However, this clinical benefit is accompanied by an increased risk of bleeding. Additional trials show mixed safety and efficacy with duration of DAPT of less than 12 months. The current data emphasizes the need to individualize DAPT duration at the patient level to balance the clinical benefits of a reduced risk of cardiovascular ischemic events with the greater risk of clinically significant bleeding. Patients at an increased risk of ischemic events and a lower risk of bleeding should be strongly considered for prolonged DAPT beyond the 1 year currently recommended in the practice guidelines. PMID:27260146

  14. Testing the Critical Window Hypothesis of Timing and Duration of Estradiol Treatment on Hypothalamic Gene Networks in Reproductively Mature and Aging Female Rats

    PubMed Central

    Yin, Weiling; Maguire, Sean M.; Pham, Brian; Garcia, Alexandra N.; Dang, Nguyen-Vy; Liang, Jingya; Wolfe, Andrew; Hofmann, Hans A.

    2015-01-01

    At menopause, the dramatic loss of ovarian estradiol (E2) necessitates the adaptation of estrogen-sensitive neurons in the hypothalamus to an estrogen-depleted environment. We developed a rat model to test the “critical window” hypothesis of the effects of timing and duration of E2 treatment after deprivation on the hypothalamic neuronal gene network in the arcuate nucleus and the medial preoptic area. Rats at 2 ages (reproductively mature or aging) were ovariectomized and given E2 or vehicle replacement regimes of differing timing and duration. Using a 48-gene quantitative low-density PCR array and weighted gene coexpression network analysis, we identified gene modules differentially regulated by age, timing, and duration of E2 treatment. Of particular interest, E2 status differentially affected suites of genes in the hypothalamus involved in energy balance, circadian rhythms, and reproduction. In fact, E2 status was the dominant factor in determining gene modules and hormone levels; age, timing, and duration had more subtle effects. Our results highlight the plasticity of hypothalamic neuroendocrine systems during reproductive aging and its surprising ability to adapt to diverse E2 replacement regimes. PMID:26018250

  15. Association between subjective actual sleep duration, subjective sleep need, age, body mass index, and gender in a large sample of young adults

    PubMed Central

    Kalak, Nadeem; Brand, Serge; Beck, Johannes; Holsboer-Trachsler, Edith; Wollmer, M Axel

    2015-01-01

    Background Poor sleep is a major health concern, and there is evidence that young adults are at increased risk of suffering from poor sleep. There is also evidence that sleep duration can vary as a function of gender and body mass index (BMI). We sought to replicate these findings in a large sample of young adults, and also tested the hypothesis that a smaller gap between subjective sleep duration and subjective sleep need is associated with a greater feeling of being restored. Methods A total of 2,929 university students (mean age 23.24±3.13 years, 69.1% female) took part in an Internet-based survey. They answered questions related to demographics and subjective sleep patterns. Results We found no gender differences in subjective sleep duration, subjective sleep need, BMI, age, or feeling of being restored. Nonlinear associations were observed between subjective sleep duration, BMI, and feeling of being restored. Moreover, a larger discrepancy between subjective actual sleep duration and subjective sleep need was associated with a lower feeling of being restored. Conclusion The present pattern of results from a large sample of young adults suggests that males and females do not differ with respect to subjective sleep duration, BMI, or feeling of being restored. Moreover, nonlinear correlations seemed to provide a more accurate reflection of the relationship between subjective sleep and demographic variables. PMID:25657583

  16. Water and sewage systems, socio-demographics, and duration of residence associated with endemic intestinal infectious diseases: A cohort study

    PubMed Central

    2010-01-01

    Background Studies of water-related gastrointestinal infections are usually directed at outbreaks. Few have examined endemic illness or compared rates across different water supply and sewage disposal systems. We conducted a cohort study of physician visits and hospitalizations for endemic intestinal infectious diseases in a mixed rural and urban community near Vancouver, Canada, with varied and well-characterized water and sewage systems. Methods Cohort members and their disease events were defined via universal health insurance data from 1995 through 2003. Environmental data were derived from municipal, provincial, and federal government sources. Logistic regression was used to examine associations between disease events and water and sewage systems, socio-demographic characteristics, and temporal factors. Results The cohort included 126,499 individuals and approximately 190,000,000 person-days. Crude incidence rates were 1,353 physician visits and 33.8 hospitalizations for intestinal infectious diseases per 100,000 person-years. Water supply chlorination was associated with reduced physician visit incidence (OR: 0.92, 95% CI 0.85-1.0). Two water systems with the highest proportions of surface water had increased incidence (ORs: 1.57, 95% CI 1.39-1.78; and 1.45, 95% CI 1.28-1.64). Private well water and well depth were not associated with increased risk, likely because of residents' awareness of and attention to water quality. There was increased crude incidence with increasing precipitation in the population served by surface water supplies, but this trend did not remain with adjustment for other variables. Municipal sewer systems were associated with increased risk (OR: 1.26, 95% CI 1.14-1.38). Most socio-demographic variables had predicted associations with risk: higher rates in females, in the very young and the elderly, and in residents of low income areas. Increased duration of area residence was associated with reduced risk (OR, duration ≥ 6 years: 0

  17. Use of Metformin in Diseases of Aging

    PubMed Central

    Miles, John M.; Rule, Andrew D.; Borlaug, Barry A.

    2014-01-01

    Metformin is the most commonly prescribed medication for type 2 diabetes (T2DM) in the world. It has primacy in the treatment of this disease because of its safety record and also because of evidence for reduction in the risk of cardiovascular events. Evidence has accumulated indicating that metformin is safe in people with stage 3 chronic kidney disease (CKD-3). It is estimated that roughly one-quarter of people with CKD-3 and T2DM in the United States (well over 1 million) are ineligible for metformin treatment because of elevated serum creatinine levels. This could be overcome if a scheme, perhaps based on pharmacokinetic studies, could be developed to prescribe reduced doses of metformin in these individuals. There is also substantial evidence from epidemiological studies to indicate that metformin may not only be safe, but may actually benefit people with heart failure (HF). Prospective, randomized trials of the use of metformin in HF are needed to investigate this possibility. PMID:24752835

  18. TSH receptor antibodies for confirming the diagnosis and prediction of remission duration, in newly diagnosed Graves' disease patients.

    PubMed

    Aleksić, Aleksandar; Aleksić, Zeljka; Stojanović, Miodrag

    2009-01-01

    Antibodies to TSH receptors (TRAb) have great pathogenetic importance in the development and maintenance of hyperthyroidism in Graves' disease (GD). Measurement of their serum level could be of diagnostic and prognostic importance in autoimmune hyperthyroidism and in monitoring the efficiency of thyrosuppressive drug (TSD) treatment in GD. The aim of our study was to assess the sensitivity (SN), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) of the TRAb assay in confirming the diagnosis and to define its prognostic value for remission duration in GD patients at the end of TSD treatment with thionamide derivatives, propylthiouracil or methimazole. We studied 99 patients, 65 female, 34 male, 18-76 years old; 52 GD patients and 47 as control group. We have studied frequency of relapses and remission duration in GD patients by a 2nd generation serum TRAb commercial kit. Our results showed that, the SN, SP, PPV and NPV of the TRAb test were 100%, 97%, 98% and 100%, respectively. Remission duration after TSD treatment was longer and relapses were fewer in GD patients with lower levels of TRAb before (P<0.01) and at the end of TSD treatment (P<0.05). In conclusion, our results suggest that serum TRAb is very sensitive and specific for confirming the diagnosis of GD. TRAb levels at the beginning of TSD treatment, above 5 IU/L gives 18% greater chance, and above 15 IU/L, 36% greater chance for remission, shorter than 6 months. PMID:19675869

  19. Health-and disease-related biomarkers in aging research.

    PubMed

    Thompson, Hilaire J; Voss, Joachim G

    2009-04-01

    This article focuses on a synthesis of knowledge about healthy aging research in human beings and then synthesized nurse-led research in gerontology and geriatrics that use biomarkers. Healthy aging research has attracted considerable attention in the biomedical and basic sciences within the context of four major areas: (a) genetic variations as an expression of successful or unsuccessful aging; (b) caloric restriction as an intervention to slow the progression of aging; (c) immunological aging; (d) neurobiology of the aging brain. A systematic review of the literature was performed to identify nurse-led geriatric-related biomarker research. Nurse researchers who have chosen to integrate biomarkers as part of their research studies have been working in six focal areas, which are reviewed: health promotion within risk populations, cancer, vascular disease, Alzheimer's disease, caregiving, and complementary therapies. The article provides a discussion of contributions to date, identifying existing gaps and future research opportunities. PMID:20077975

  20. 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...

  1. P Wave Dispersion and Maximum P Wave Duration Are Associated with Renal Outcomes in Chronic Kidney Disease

    PubMed Central

    Huang, Jiun-Chi; Wei, Shu-Yi; Chen, Szu-Chia; Chang, Jer-Ming; Hung, Chi-Chih; Su, Ho-Ming; Hwang, Shang-Jyh; Chen, Hung-Chun

    2014-01-01

    P wave parameters measured by 12-lead electrocardiogram (ECG) are commonly used as a noninvasive tool to evaluate left atrial enlargement. This study was designed to assess whether P wave parameters were associated with renal outcomes in chronic kidney disease (CKD) patients. This longitudinal study enrolled 439 patients with CKD stages 3–5. Renal end points were defined as the commencement of dialysis or death. Change in renal function was measured using the estimated glomerular filtration rate (eGFR) slope. We measured two ECG P wave parameters corrected for heart rate, i.e., corrected P wave dispersion and corrected maximum P wave duration. The values of P wave dispersion and maximum P wave duration were 88.8±21.7 ms and 153.3±21.7 ms, respectively. During the follow-up period (mean, 25.2 months), 95 patients (21.6%) started hemodialysis and 30 deaths (6.8%) were recorded. Multivariate Cox regression analysis identified that increased P wave dispersion [hazard ratio (HR), 1.020; 95% confidence interval (CI), 1.009–1.032; P<0.001] and maximum P wave duration (HR, 1.013; 95% CI, 1.003–1.024; P = 0.012) were associated with progression to renal end points. Furthermore, increased P wave dispersion (unstandardized coefficient β = –0.016; P = 0.037) and maximum P wave duration (unstandardized coefficient β = –0.014; P = 0.040) were negatively associated with the eGFR slope. We demonstrated that increased P wave dispersion and maximum P wave duration were associated with progression to the renal end points of dialysis or death and faster renal function decline in CKD patients. Screening CKD patients on the basis of P wave dispersion and maximum P wave duration may help identify patients at high risk for worse renal outcomes. PMID:25006682

  2. Gender ratio in a clinical population sample, age of diagnosis and duration of assessment in children and adults with autism spectrum disorder.

    PubMed

    Rutherford, Marion; McKenzie, Karen; Johnson, Tess; Catchpole, Ciara; O'Hare, Anne; McClure, Iain; Forsyth, Kirsty; McCartney, Deborah; Murray, Aja

    2016-07-01

    This article reports on gender ratio, age of diagnosis and the duration of assessment procedures in autism spectrum disorder diagnosis in a national study which included all types of clinical services for children and adults. Findings are reported from a retrospective case note analysis undertaken with a representative sample of 150 Scottish children and adults recently diagnosed with autism spectrum disorder. The study reports key findings that the gender ratio in this consecutively referred cohort is lower than anticipated in some age groups and reduces with increasing age. The gender ratio in children, together with the significant difference in the mean age of referral and diagnosis for girls compared to boys, adds evidence of delayed recognition of autism spectrum disorder in younger girls. There was no significant difference in duration of assessment for males and females suggesting that delays in diagnosis of females occur prior to referral for assessment. Implications for practice and research are considered. PMID:26825959

  3. The Impact of Alzheimer's Disease in an Aging Rural Population.

    PubMed

    Minkemeyer, Vivian; Wellman, Courtney; Goebel, Lynne

    2016-01-01

    West Virginia already has a large elderly population, and it is expected to increase along with the elderly population of the nation as a whole. Since the most important risk factor for Alzheimer's disease is older age, it is not surprising that the prevalence of Alzheimer's disease is projected to increase significantly over the next thirty-five years. This paper discusses the prevalence of Alzheimer's disease in West Virginia, programs available to assist people and caregivers affected by the disease, and the associated economic burden of the disease. PMID:27301161

  4. 40K- 40Ar dating of the Main Deccan large igneous province: Further evidence of KTB age and short duration

    NASA Astrophysics Data System (ADS)

    Chenet, Anne-Lise; Quidelleur, Xavier; Fluteau, Frédéric; Courtillot, Vincent; Bajpai, Sunil

    2007-11-01

    Most mass extinctions coincide in time with outpourings of continental flood basalts (CFB). Some 20 years ago, it was shown [Courtillot, V., Besse, J., Vandamme, D., Montigny, R., Jaeger, J.-J., Cappetta, H., 1986. Deccan flood basalts at the Cretaceous/Tertiary boundary? Earth Planet. Sci. Lett. 80, 361-374; Courtillot, V., Feraud, G., Maluski, H., Vandamme, D., Moreau, M.G., Besse, J., 1988. Deccan flood basalts and the Cretaceous/Tertiary boundary. Nature 333, 843-846; Duncan, R.A., Pyle, D.G., 1988. Rapid eruption of the Deccan flood basalts at the Cretaceous/Tertiary boundary. Nature 333 841-843] that the age of the Deccan traps was close to the Cretaceous-Tertiary (KT) boundary and its duration under 1 Myr. We have undertaken a new geochronological study, using the (unconventional) 40K- 40Ar Cassignol-Gillot technique which is particularly well suited to the potassium-poor Deccan lavas. The mean of 4 determinations from the topmost (Ambenali and Mahabaleshwar) Formations is 64.5 ± 0.6 Ma. They straddle the C29r/C29n reversal boundary for which they provide a new constraint. The mean age of 3 determinations from the oldest (Jawhar) Formation is 64.8 ± 0.6 Ma. The difference in age between top and bottom of a 3500 m composite section, probably comprising 80% of the total Deccan volume, is statistically insignificant, with the overall mean age being 64.7 ± 0.6 Ma ( N = 7). Our results are consistent with the most recent 40Ar/ 39Ar determinations [Knight, K.B., Renne, P.R., Halkett, A., White, N., 2003. 40Ar/ 39Ar dating of the Rajahmundry Traps, eastern India and their relationship to the Deccan traps. Earth Planet. Sci. Lett. 208, 85-99; Knight, K.B., Renne, P.R., Baker, J., Waight, T., White, N., 2005. Reply to '40Ar/39Ar dating of the Rajahmundry Traps, Eastern India and their relationship to the Deccan Traps: Discussion' by A.K. Baksi. Earth Planet. Sci. Lett. 239, 374-382], confirming that there should be no systematic difference between the two methods

  5. Effect of Duration of Breastfeeding on Neuropsychological Development at 10 to 12 Years of Age in a Cohort of Healthy Children

    ERIC Educational Resources Information Center

    Tozzi, Alberto Eugenio; Bisiacchi, Patrizia; Tarantino, Vincenza; Chiarotti, Flavia; D'elia, Lidia; De Mei, Barbara; Romano, Mariateresa; Gesualdo, Francesco; Salmaso, Stefania

    2012-01-01

    Aim: The aim of this article was to explore the effect of duration of breastfeeding on neurocognitive development. Method: The long-term effect of breastfeeding on neurodevelopment was examined through a battery of neuropsychological tests in 1403 children (693 females, 710 males; mean age 11y 9mo [SD 6mo], range: 10y 3mo-12y 8mo) who were…

  6. ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

    PubMed Central

    Davalli, Pierpaola; Mitic, Tijana; Caporali, Andrea; Lauriola, Angela; D'Arca, Domenico

    2016-01-01

    The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS) and/or Reactive Nitrosative Species (RNS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging. PMID:27247702

  7. 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

  8. Role of muscarinic-3 receptor antibody in systemic sclerosis: correlation with disease duration and effects of IVIG.

    PubMed

    Kumar, Sumit; Singh, Jagmohan; Kedika, Ramalinga; Mendoza, Fabian; Jimenez, Sergio A; Blomain, Erik S; DiMarino, Anthony J; Cohen, Sidney; Rattan, Satish

    2016-06-01

    Gastrointestinal dysmotility in systemic sclerosis (SSc) is associated with autoantibodies against muscarinic-3 receptor (M3-R). We investigated the temporal course of the site of action of these autoantibodies at the myenteric neurons (MN) vs. the smooth muscle (SM) M3-R in relation to disease duration, and determined the role of intravenous immunoglobulin (IVIG) in reversing these changes. Immunoglobulins purified from SSc patients (SScIgG) were used to assess their differential binding to MN and SM (from rat colon) employing immunohistochemistry (IHC). Effect of SScIgG on neural and direct muscle contraction was determined by cholinergic nerve stimulation and bethanechol-induced SM contraction. Effects of IVIG and its antigen-binding fragment F(ab')2 on SScIgG binding were studied by enzyme-linked immunosorbent assay (ELISA) of rat colonic longitudinal SM myenteric plexus (LSMMP) lysate and to second extracellular loop peptide of M3-R (M3-RL2). SScIgG from all patients demonstrated significantly higher binding to MN than to SM. With progression of SSc duration, binding at MN and SM increased in a linear fashion with a correlation coefficient of 0.696 and 0.726, respectively (P < 0.05). SScIgG-mediated attenuation of neural and direct SM contraction also increased with disease duration. ELISA analysis revealed that IVIG and F(ab')2 significantly reduced SScIgG binding to LSMMP lysate and M3-RL2. Dysmotility in SSc occurs sequentially, beginning with SScIgG-induced blockage of cholinergic neurotransmission (neuropathy), which progresses to inhibition of acetylcholine action at the SM cell (myopathy). IVIG reverses this cholinergic dysfunction at the neural and myogenic receptors by anti-idiotypic neutralization of SScIgG. PMID:27173508

  9. Telomeres in aging and disease: lessons from zebrafish

    PubMed Central

    Carneiro, Madalena C.; de Castro, Inês Pimenta

    2016-01-01

    ABSTRACT Age is the highest risk factor for some of the most prevalent human diseases, including cancer. Telomere shortening is thought to play a central role in the aging process in humans. The link between telomeres and aging is highlighted by the fact that genetic diseases causing telomerase deficiency are associated with premature aging and increased risk of cancer. For the last two decades, this link has been mostly investigated using mice that have long telomeres. However, zebrafish has recently emerged as a powerful and complementary model system to study telomere biology. Zebrafish possess human-like short telomeres that progressively decline with age, reaching lengths in old age that are observed when telomerase is mutated. The extensive characterization of its well-conserved molecular and cellular physiology makes this vertebrate an excellent model to unravel the underlying relationship between telomere shortening, tissue regeneration, aging and disease. In this Review, we explore the advantages of using zebrafish in telomere research and discuss the primary discoveries made in this model that have contributed to expanding our knowledge of how telomere attrition contributes to cellular senescence, organ dysfunction and disease. PMID:27482813

  10. Cellular senescence in aging and age-related disease: from mechanisms to therapy

    PubMed Central

    Childs, Bennett G; Durik, Matej; Baker, Darren J; van Deursen, Jan M

    2016-01-01

    Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy. PMID:26646499

  11. The role of musical aptitude and language skills in preattentive duration processing in school-aged children.

    PubMed

    Milovanov, Riia; Huotilainen, Minna; Esquef, Paulo A A; Alku, Paavo; Välimäki, Vesa; Tervaniemi, Mari

    2009-08-28

    We examined 10-12-year old elementary school children's ability to preattentively process sound durations in music and speech stimuli. In total, 40 children had either advanced foreign language production skills and higher musical aptitude or less advanced results in both musicality and linguistic tests. Event-related potential (ERP) recordings of the mismatch negativity (MMN) show that the duration changes in musical sounds are more prominently and accurately processed than changes in speech sounds. Moreover, children with advanced pronunciation and musicality skills displayed enhanced MMNs to duration changes in both speech and musical sounds. Thus, our study provides further evidence for the claim that musical aptitude and linguistic skills are interconnected and the musical features of the stimuli could have a preponderant role in preattentive duration processing. PMID:19481587

  12. Progressive decline of glucocerebrosidase in aging and Parkinson's disease

    PubMed Central

    Rocha, Emily M; Smith, Gaynor A; Park, Eric; Cao, Hongmei; Brown, Eilish; Hallett, Penelope; Isacson, Ole

    2015-01-01

    The principal risk factor for developing most adult onset neurodegenerative diseases is aging, with incidence rising significantly after age 50. Despite research efforts, the causes of Parkinson's disease (PD) remain unknown. As neurons age, they show signs of diminished lysosomal and mitochondrial function, including increased oxidative stress and accumulation of misfolded proteins, and these changes become exacerbated PD. We show that activity of the lysosomal hydrolase glucocerebrosidase gradually diminishes with age in the substantia nigra and putamen of healthy controls. This reduction is comparable to glucocerebrosidase activity in GBA1-mutation carrier PD patients. These data, demonstrate for the first time that an age-dependent reduction in glucocerebrosidase activity may lower the threshold for developing PD. PMID:25909088

  13. Lung microbiota across age and disease stage in cystic fibrosis.

    PubMed

    Coburn, Bryan; Wang, Pauline W; Diaz Caballero, Julio; Clark, Shawn T; Brahma, Vijaya; Donaldson, Sylva; Zhang, Yu; Surendra, Anu; Gong, Yunchen; Elizabeth Tullis, D; Yau, Yvonne C W; Waters, Valerie J; Hwang, David M; Guttman, David S

    2015-01-01

    Understanding the significance of bacterial species that colonize and persist in cystic fibrosis (CF) airways requires a detailed examination of bacterial community structure across a broad range of age and disease stage. We used 16S ribosomal RNA sequencing to characterize the lung microbiota in 269 CF patients spanning a 60 year age range, including 76 pediatric samples from patients of age 4-17, and a broad cross-section of disease status to identify features of bacterial community structure and their relationship to disease stage and age. The CF lung microbiota shows significant inter-individual variability in community structure, composition and diversity. The core microbiota consists of five genera - Streptococcus, Prevotella, Rothia, Veillonella and Actinomyces. CF-associated pathogens such as Pseudomonas, Burkholderia, Stenotrophomonas and Achromobacter are less prevalent than core genera, but have a strong tendency to dominate the bacterial community when present. Community diversity and lung function are greatest in patients less than 10 years of age and lower in older age groups, plateauing at approximately age 25. Lower community diversity correlates with worse lung function in a multivariate regression model. Infection by Pseudomonas correlates with age-associated trends in community diversity and lung function. PMID:25974282

  14. Lung microbiota across age and disease stage in cystic fibrosis

    PubMed Central

    Coburn, Bryan; Wang, Pauline W.; Diaz Caballero, Julio; Clark, Shawn T.; Brahma, Vijaya; Donaldson, Sylva; Zhang, Yu; Surendra, Anu; Gong, Yunchen; Elizabeth Tullis, D.; Yau, Yvonne C. W.; Waters, Valerie J.; Hwang, David M.; Guttman, David S.

    2015-01-01

    Understanding the significance of bacterial species that colonize and persist in cystic fibrosis (CF) airways requires a detailed examination of bacterial community structure across a broad range of age and disease stage. We used 16S ribosomal RNA sequencing to characterize the lung microbiota in 269 CF patients spanning a 60 year age range, including 76 pediatric samples from patients of age 4–17, and a broad cross-section of disease status to identify features of bacterial community structure and their relationship to disease stage and age. The CF lung microbiota shows significant inter-individual variability in community structure, composition and diversity. The core microbiota consists of five genera - Streptococcus, Prevotella, Rothia, Veillonella and Actinomyces. CF-associated pathogens such as Pseudomonas, Burkholderia, Stenotrophomonas and Achromobacter are less prevalent than core genera, but have a strong tendency to dominate the bacterial community when present. Community diversity and lung function are greatest in patients less than 10 years of age and lower in older age groups, plateauing at approximately age 25. Lower community diversity correlates with worse lung function in a multivariate regression model. Infection by Pseudomonas correlates with age-associated trends in community diversity and lung function. PMID:25974282

  15. Immune aging, dysmetabolism, and inflammation in neurological diseases

    PubMed Central

    Deleidi, Michela; Jäggle, Madeline; Rubino, Graziella

    2015-01-01

    As we age, the immune system undergoes a process of senescence accompanied by the increased production of proinflammatory cytokines, a chronic subclinical condition named as “inflammaging”. Emerging evidence from human and experimental models suggest that immune senescence also affects the central nervous system and promotes neuronal dysfunction, especially within susceptible neuronal populations. In this review we discuss the potential role of immune aging, inflammation and metabolic derangement in neurological diseases. The discovery of novel therapeutic strategies targeting age-linked inflammation may promote healthy brain aging and the treatment of neurodegenerative as well as neuropsychiatric disorders. PMID:26089771

  16. Prevalence of ischaemic heart disease in middle aged British men.

    PubMed Central

    Shaper, A G; Cook, D G; Walker, M; Macfarlane, P W

    1984-01-01

    The prevalence of ischaemic heart disease was determined by an administered questionnaire and electrocardiography in 7735 men aged 40-59 years drawn at random from general practices in 24 British towns. Overall, one quarter of these men had some evidence of ischaemic heart disease on questionnaire or electrocardiogram or both. On questionnaire, 14% of men had possible myocardial infarction or angina, with considerable overlap of the two syndromes. The prevalence of possible myocardial infarction combined with angina and of definite angina only showed a fourfold increase over the age range studied. Electrocardiographic evidence of ischaemic heart disease (definite or possible) was present in 15% of men, there being myocardial infarction in 4.2% and myocardial ischaemia in 10.3%. Electrocardiographic evidence of myocardial infarction increased fourfold over the age range studied. There was considerable overlap of questionnaire and electrocardiographic evidence of ischaemic heart disease. Nevertheless, more than half of those with possible myocardial infarction combined with angina had no resting electrocardiographic evidence of ischaemic heart disease, and half of those with definite myocardial infarction on electrocardiogram had no history of chest pain at any time. This national population based study strongly suggests that the prevalence of ischaemic heart disease in middle aged British men is greater than has been indicated by previous studies based on occupational groups. PMID:6732989

  17. Differences in selected medical care parameters in rheumatic disease ward patients of different ages of life

    PubMed Central

    Pobrotyn, Piotr; Susło, Robert; Milczanowski, Piotr; Drobnik, Jarosław

    2016-01-01

    Introduction Rheumatic diseases are becoming more and more common in Poland with the ageing of the population. Nearly 18% of the total hospital admissions in Poland result from rheumatic diseases, which was equivalent to 350 thousand cases in the year 2008. These diseases tend to last for many decades, decreasing both the quality of life and income of the patients as well as increasing the medical institutions’ workload and society's financial burden. The aim of the study was to determine whether the medical care parameters in a rheumatic disease hospital ward show any significant differences among different patient age groups – especially such that would support taking them into account as a basis for adjusting the financial coverage level of medical services. Material and methods Data on hospitalizations at the Rheumatic Diseases Ward of Wroclaw University Hospital in Wroclaw in the years 2009–2015 were analyzed, taking into account the age groups, number of hospital admissions, their duration and causes. Relevant statistical data analysis was performed. Discussion The study revealed that the number of old patients hospitalized at the rheumatic diseases ward increased over the last 6 years and that such statistically significant differences do exist: on average the old patients not only tend to stay much longer at the hospital, but also suffer from a different and more diverse spectrum of diseases in comparison to their younger counterparts. Conclusions The detected differences in medical care parameters support the need for more individualized medical care and increased cost of the hospital stay in the case of older patients. Consequently, those factors justify the necessity to increase the value of medical services in the case of old patients, possibly also taking into account the variation between age subgroups. PMID:27407280

  18. Oxidative Stress and Epigenetic Regulation in Ageing and Age-Related Diseases

    PubMed Central

    Cencioni, Chiara; Spallotta, Francesco; Martelli, Fabio; Valente, Sergio; Mai, Antonello; Zeiher, Andreas M.; Gaetano, Carlo

    2013-01-01

    Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations is, therefore, of the highest relevance for the development of new treatments for age-associated diseases, such as cancer, diabetes, Alzheimer and cardiovascular accidents. Mechanistically, it is well accepted that the accumulation of intracellular damage determined by reactive oxygen species (ROS) might orchestrate the progressive loss of control over biological homeostasis and the functional impairment typical of aged tissues. Here, we review how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology. Alteration of epigenetic enzyme activity, histone modifications and DNA-methylation is, in fact, typically associated with the ageing process. Specifically, ageing presents peculiar epigenetic markers that, taken altogether, form the still ill-defined “ageing epigenome”. The comprehension of mechanisms and pathways leading to epigenetic modifications associated with ageing may help the development of anti-ageing therapies. PMID:23989608

  19. Hydrogen Sulfide, the Next Potent Preventive and Therapeutic Agent in Aging and Age-Associated Diseases

    PubMed Central

    Zhang, Yuan; Tang, Zhi-Han; Ren, Zhong; Qu, Shun-Lin; Liu, Mi-Hua; Liu, Lu-Shan

    2013-01-01

    Hydrogen sulfide (H2S) is the third endogenous signaling gasotransmitter, following nitric oxide and carbon monoxide. It is physiologically generated by cystathionine-γ-lyase, cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase. H2S has been gaining increasing attention as an important endogenous signaling molecule because of its significant effects on the cardiovascular and nervous systems. Substantial evidence shows that H2S is involved in aging by inhibiting free-radical reactions, activating SIRT1, and probably interacting with the age-related gene Klotho. Moreover, H2S has been shown to have therapeutic potential in age-associated diseases. This article provides an overview of the physiological functions and effects of H2S in aging and age-associated diseases, and proposes the potential health and therapeutic benefits of H2S. PMID:23297346

  20. [Celiac disease. Risk factors for women in reproductive age].

    PubMed

    Stazi, A V; Mantovani, A

    2000-05-01

    In the past coeliac disease, or intolerance to gluten, has been considered a rare disease in infancy, whose most important signs were chronic diarrhea with malabsorption and reduced growth. However, besides this classical form, there are a number of other clinical and subclinical forms which may appear even in the adult life and without any overt intestinal sign. The alterations may affect, e.g., the liver, thyroid, skin and the female and male reproductive system. The overall prevalence of the different forms of coeliac disease in Western Europe is at least 1:300. The aim of the present paper is to describe and evaluate the effects of coeliac disease on female reproduction. Such effects include delayed menarche, amenorrhea, infertility and early menopause. Epidemiological studies show that besides reduced fertility, affected women are at higher risk of reproductive problems such as pregnancy loss, low birthweight of offspring and reduced duration of breastfeeding. There are no adequate studies to evidentiate a possible increase of birth defects; nevertheless, coeliac disease induces malabsorption, with deficiencies of nutritional factors essential to prenatal development such as iron, folic acid and vitamin K. The mechanisms underlying the reproductive alterations are still awaiting clarification; however, an interaction among specific nutritional deficiencies, endocrine imbalances and immune disturbances is suspected. As for the other effects associated to the coeliac disease, the possible prevention or treatment of the reproductive effects is only the lifelong maintenance of a gluten-free diet. PMID:11048475

  1. Assessing the Risk Factors for Multiple Sclerosis in Women of Reproductive Age Suffering the Disease in Isfahan Province

    PubMed Central

    Rejali, Mehri; Hosseini, Sayed Mohsen; Kazemi Tabaee, Maryam Sadat; Etemadifar, Masoud

    2016-01-01

    Background: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. Etiology of the disease is not well understood; however, it is more common in women than in men and occurs mainly during reproductive age. The aim of this study was to evaluate some risk factors in women of childbearing age with MS in Isfahan Province. Methods: This analytic case–control study was conducted in MS Clinic in Isfahan, 2014. The study was done on 200 patients with MS and 200 nonpatients (matched controls) that were randomly selected for inclusion in the study. The data collection tool was a researcher-designed questionnaire consisting of three parts: Demographics, disease characteristics, and some risk factors related to reproductive age. Data were analyzed by SPSS version 20, using descriptive and inferential statistics. Results: The results showed that risk of MS had a significant relationship with age at menarche (P < 0.001), prior use of oral contraceptives (OCs) (P = 0.002), duration of use of OCs (P = 0.008), and number of pregnancies (P < 0.001). However, there was no significant relationship between age of onset of use of OCs (P = 0.80) and age at the first pregnancy (P = 0.45) with the risk of MS. Conclusions: Results of this research determined that the following risk factors were associated with developing MS, age at menarche, history, and duration of use of OCs and number of pregnancies. PMID:27076896

  2. Age impact on autoimmune thyroid disease in females

    NASA Astrophysics Data System (ADS)

    Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

    2013-10-01

    Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.

  3. 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

  4. [Age at disease onset and delayed diagnosis of spondyloarthropathies].

    PubMed

    Feldtkeller, E

    1999-02-01

    A questionnaire with 78 questions concerning the situation of ankylosing spondylitis (AS) sufferers in Germany was distributed to a representative 3000 out of the more than 14,000 patient members of the German AS society; 1614 patients (54%) responded. The age distribution of these patients roughly agrees with that expected due to the distribution of the age at diagnosis and the age distribution of the German population. The group of patients more than 65 years old is, however, under-represented. It turned out that at least 28% of the patients responding do not suffer from idiopathic AS but from other spondyloarthritides (spondylitic psoriasis, spondyloarthritis combined with Crohn's disease or ulcerative colitis). The distribution of the age at disease onset agrees well with that published in 1984 by van der Linden et al.: For 4% of the patients, the age at appearance of the first spondylitic symptoms was less than 15 years, for 90% it was 15-40 years and for the remaining 6% more than 40 years. The average age at disease onset was 25.6 years. The spondyloarthritides do not differ significantly in the distribution of the age at the first spondylitic symptoms. The distribution of the age at diagnosis did not differ significantly between male and female patients, in contrast to the findings by van der Linden et al. in 1984. The average age at diagnosis was 34.3 and 35.3 years for male and female patients, respectively. The resulting mean diagnosis delay for male and female patients was 8.4 and 9.8 years, respectively. Whereas the average diagnosis delay was still 15 years for patients with disease onset in the 1950s, it was only 71/2 years for patients with disease onset in 1975-79. It is not yet possible to predict if an average diagnosis delay less than 71/2 years results for patients with a disease onset later than 1980, because the number of further diagnoses to be expected for patients with disease onset in these years is not negligible. Twenty-six percent of

  5. Loss of Intrinsic Organization of Cerebellar Networks in Spinocerebellar Ataxia Type 1: Correlates with Disease Severity and Duration

    PubMed Central

    Peri, Eitan; Chen, E. Elinor; Ben-Jacob, Eshel; Gomez, Christopher M.

    2011-01-01

    The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of cerebellar degenerative disorders, characterized by progressive gait unsteadiness, hand incoordination, and dysarthria. The mutational mechanism in SCA1, a dominantly inherited form of SCA, consists of an expanded trinucleotide CAG repeat. In SCA1, there is loss of Purkinje cells, neuronal loss in dentate nucleus, olives, and pontine nuclei. In the present study, we sought to apply intrinsic functional connectivity analysis combined with diffusion tensor imaging to define the state of cerebellar connectivity in SCA1. Our results on the intrinsic functional connectivity in lateral cerebellum and thalamus showed progressive organizational changes in SCA1 noted as a progressive increase in the absolute value of the correlation coefficients. In the lateral cerebellum, the anatomical organization of functional clusters seen as parasagittal bands in controls is lost, changing to a patchy appearance in SCA1. Lastly, only fractional anisotropy in the superior peduncle and changes in functional organization in thalamus showed a linear dependence to duration and severity of disease. The present pilot work represents an initial effort describing connectivity biomarkers of disease progression in SCA1. The functional changes detected with intrinsic functional analysis and diffusion tensor imaging suggest that disease progression can be analyzed as a disconnection syndrome. PMID:20886327

  6. REST and stress resistance in ageing and Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Lu, Tao; Aron, Liviu; Zullo, Joseph; Pan, Ying; Kim, Haeyoung; Chen, Yiwen; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek; Liu, X. Shirley; Bennett, David A.; Colaiácovo, Monica P.; Yankner, Bruce A.

    2014-03-01

    Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid β-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain.

  7. Arterial–Ventricular Coupling with Aging and Disease

    PubMed Central

    Chantler, Paul D.; Lakatta, Edward G.

    2012-01-01

    Age is the dominant risk factor for cardiovascular diseases. Understanding the coupling between the left ventricle (LV) and arterial system, termed arterial–ventricular coupling (EA/ELV), provides important mechanistic insights into the complex cardiovascular system and its changes with aging in the absence and presence of disease. EA/ELV can be indexed by the ratio of effective arterial elastance (EA; a measure of the net arterial load exerted on the LV) to left ventricular end-systolic elastance (ELV; a load-independent measure of left ventricular chamber performance). Age-associated alterations in arterial structure and function, including diameter, wall thickness, wall stiffness, and endothelial dysfunction, contribute to a gradual increase in resting EA with age. Remarkably there is a corresponding increase in resting ELV with age, due to alterations to LV remodeling (loss in myocyte number, increased collagen) and function. These age-adaptations at rest likely occur, at least, in response to the age-associated increase in EA and ensure that EA/ELV is closely maintained within a narrow range, allowing for optimal energetic efficiency at the expense of mechanical efficacy. This optimal coupling at rest is also maintained when aging is accompanied by the presence of hypertension, and obesity, despite further increases in EA and ELV in these conditions. In contrast, in heart failure patients with either reduced or preserved ejection fraction, EA/ELV at rest is impaired. During dynamic exercise, EA/ELV decreases, due to an acute mismatch between the arterial and ventricular systems as ELV increases disproportionate compared to EA (≈200 vs. 40%), to ensure that sufficient cardiac performance is achieved to meet the increased energetic requirements of the body. However, with advancing age the reduction in EA/ELV during acute maximal exercise is blunted, due to a blunted increase ELV. This impaired EA/ELV is further amplified in the presence of disease, and may

  8. We Have the Spaceship; But Where's the Start Button: Human Engineering Issues in the Age of Long Duration Space Exploration

    NASA Technical Reports Server (NTRS)

    Hamilton, George S.; Adams, Christopher W.

    2005-01-01

    As long duration space exploration and habitation becomes more commonplace, a number of Human Engineering factors (Gravitational Adaptation, 2-D to 3-D Movement Adaptation, Design Form/Function, and Space Ergonomics to name a few) will become more pronounced. More research and development is needed in these areas or the explorers may find themselves in painful or dangerous situations.

  9. The Shift in Infant Preferences for Vowel Duration and Pitch Contour between 6 and 10 Months of Age

    ERIC Educational Resources Information Center

    Kitamura, Christine; Notley, Anna

    2009-01-01

    This study investigates the influence of the acoustic properties of vowels on 6- and 10-month-old infants' speech preferences. The shape of the contour (bell or monotonic) and the duration (normal or stretched) of vowels were manipulated in words containing the vowels /i/ and /u/, and presented to infants using a two-choice preference procedure.…

  10. Demographics, Management, Preventive Health Care and Disease in Aged Horses.

    PubMed

    Ireland, Joanne L

    2016-08-01

    Gerontology has become increasingly important in equine veterinary medicine, with aged animals representing a significant proportion of the equine population. Horses are defined as geriatric or aged from age 15 years onwards but can have a life span of more than 40 years. Despite a high level of owner concern for the well-being of their geriatric animal, provision of preventive health care may be suboptimal. Owners seem to under-recognize some of the most prevalent diseases identified in geriatric horses. This review focuses on the demographic characteristics of the equine geriatric population and management and preventive care practices of older horses. PMID:27449388

  11. Diseases of Old Age in Two Paintings by Rembrandt

    PubMed Central

    Weisz, George M.; Albury, William R.

    2015-01-01

    Two paintings of older men by Rembrandt (1609–1669) are examined to demonstrate that historical attitudes toward diseases of old age and the ageing person’s response to illness can be investigated in paintings. The works selected are of different genres and date from different stages of Rembrandt’s own life, one from his youth and one from his old age. Both paintings show figures who have joint pathologies typically associated with the ageing process, the first involving the subject’s foot and the second involving the subject’s hand. Despite the sometimes painful nature of these conditions, the subjects are shown accommodating their illnesses while maintaining both their intellectual and social engagement and their emotional composure. Although the seventeenth century offered older people very little effective medical treatment in comparison with what is presently available, these paintings nevertheless present a view of illness as a subsidiary rather than a dominant feature of old age. PMID:26886771

  12. Cellular Senescence and the Biology of Aging, Disease, and Frailty.

    PubMed

    LeBrasseur, Nathan K; Tchkonia, Tamara; Kirkland, James L

    2015-01-01

    Population aging simultaneously highlights the remarkable advances in science, medicine, and public policy, and the formidable challenges facing society. Indeed, aging is the primary risk factor for many of the most common chronic diseases and frailty, which result in profound social and economic costs. Population aging also reveals an opportunity, i.e. interventions to disrupt the fundamental biology of aging could significantly delay the onset of age-related conditions as a group, and, as a result, extend the healthy life span, or health span. There is now considerable evidence that cellular senescence is an underlying mechanism of aging and age-related conditions. Cellular senescence is a process in which cells lose the ability to divide and damage neighboring cells by the factors they secrete, collectively referred to as the senescence-associated secretory phenotype (SASP). Herein, we discuss the concept of cellular senescence, review the evidence that implicates cellular senescence and SASP in age-related deterioration, hyperproliferation, and inflammation, and propose that this underlying mechanism of aging may play a fundamental role in the biology of frailty. PMID:26485647

  13. Caloric restriction: beneficial effects on brain aging and Alzheimer's disease.

    PubMed

    Van Cauwenberghe, Caroline; Vandendriessche, Charysse; Libert, Claude; Vandenbroucke, Roosmarijn E

    2016-08-01

    Dietary interventions such as caloric restriction (CR) extend lifespan and health span. Recent data from animal and human studies indicate that CR slows down the aging process, benefits general health, and improves memory performance. Caloric restriction also retards and slows down the progression of different age-related diseases, such as Alzheimer's disease. However, the specific molecular basis of these effects remains unclear. A better understanding of the pathways underlying these effects could pave the way to novel preventive or therapeutic strategies. In this review, we will discuss the mechanisms and effects of CR on aging and Alzheimer's disease. A potential alternative to CR as a lifestyle modification is the use of CR mimetics. These compounds mimic the biochemical and functional effects of CR without the need to reduce energy intake. We discuss the effect of two of the most investigated mimetics, resveratrol and rapamycin, on aging and their potential as Alzheimer's disease therapeutics. However, additional research will be needed to determine the safety, efficacy, and usability of CR and its mimetics before a general recommendation can be proposed to implement them. PMID:27240590

  14. Childhood Misfortune as a Threat to Successful Aging: Avoiding Disease

    ERIC Educational Resources Information Center

    Schafer, Markus H.; Ferraro, Kenneth F.

    2012-01-01

    Purpose: The purpose of this study was to examine whether childhood misfortune reduces the likelihood of being disease free in adulthood. Design and Methods: This article used a sample of 3,000+ American adults, aged 25-74, who were first interviewed in 1995 and reinterviewed in 2005. Logistic regression was used to estimate the odds of avoiding…

  15. Altered fractal dynamics of gait: reduced stride-interval correlations with aging and Huntington's disease

    NASA Technical Reports Server (NTRS)

    Hausdorff, J. M.; Mitchell, S. L.; Firtion, R.; Peng, C. K.; Cudkowicz, M. E.; Wei, J. Y.; Goldberger, A. L.

    1997-01-01

    Fluctuations in the duration of the gait cycle (the stride interval) display fractal dynamics and long-range correlations in healthy young adults. We hypothesized that these stride-interval correlations would be altered by changes in neurological function associated with aging and certain disease states. To test this hypothesis, we compared the stride-interval time series of 1) healthy elderly subjects and young controls and of 2) subjects with Huntington's disease and healthy controls. Using detrended fluctuation analysis we computed alpha, a measure of the degree to which one stride interval is correlated with previous and subsequent intervals over different time scales. The scaling exponent alpha was significantly lower in elderly subjects compared with young subjects (elderly: 0.68 +/- 0.14; young: 0.87 +/- 0.15; P < 0.003). The scaling exponent alpha was also smaller in the subjects with Huntington's disease compared with disease-free controls (Huntington's disease: 0.60 +/- 0.24; controls: 0.88 +/-0.17; P < 0.005). Moreover, alpha was linearly related to degree of functional impairment in subjects with Huntington's disease (r = 0.78, P < 0.0005). These findings demonstrate that strike-interval fluctuations are more random (i.e., less correlated) in elderly subjects and in subjects with Huntington's disease. Abnormal alterations in the fractal properties of gait dynamics are apparently associated with changes in central nervous system control.

  16. Innate immunity and inflammation in ageing: a key for understanding age-related diseases

    PubMed Central

    Licastro, Federico; Candore, Giuseppina; Lio, Domenico; Porcellini, Elisa; Colonna-Romano, Giuseppina; Franceschi, Claudio; Caruso, Calogero

    2005-01-01

    The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses or bacteria and other pathogens. During evolution the human organism was set to live 40 or 50 years; today, however, the immune system must remain active for much a longer time. This very long activity leads to a chronic inflammation that slowly but inexorably damages one or several organs: this is a typical phenomenon linked to ageing and it is considered the major risk factor for age-related chronic diseases. Alzheimer's disease, atherosclerosis, diabetes and even sarcopenia and cancer, just to mention a few – have an important inflammatory component, though disease progression seems also dependent on the genetic background of individuals. Emerging evidence suggests that pro-inflammatory genotypes are related to unsuccessful ageing, and, reciprocally, controlling inflammatory status may allow a better chance of successful ageing. In other words, age-related diseases are "the price we pay" for a life-long active immune system: this system has also the potential to harm us later, as its fine tuning becomes compromised. Our immune system has evolved to control pathogens, so pro-inflammatory responses are likely to be evolutionarily programmed to resist fatal infections with pathogens aggressively. Thus, inflammatory genotypes are an important and necessary part of the normal host responses to pathogens in early life, but the overproduction of inflammatory molecules might also cause immune-related inflammatory diseases and eventually death later. Therefore, low responder genotypes involved in regulation of innate defence mechanisms, might better control inflammatory responses and age-related disease development, resulting in an increased chance of long life survival

  17. NADPH oxidases: key modulators in aging and age-related cardiovascular diseases?

    PubMed Central

    Sahoo, Sanghamitra; Meijles, Daniel N.; Pagano, Patrick J.

    2016-01-01

    Reactive oxygen species (ROS) and oxidative stress have long been linked to aging and diseases prominent in the elderly such as hypertension, atherosclerosis, diabetes and atrial fibrillation (AF). NADPH oxidases (Nox) are a major source of ROS in the vasculature and are key players in mediating redox signalling under physiological and pathophysiological conditions. In this review, we focus on the Nox-mediated ROS signalling pathways involved in the regulation of ‘longevity genes’ and recapitulate their role in age-associated vascular changes and in the development of age-related cardiovascular diseases (CVDs). This review is predicated on burgeoning knowledge that Nox-derived ROS propagate tightly regulated yet varied signalling pathways, which, at the cellular level, may lead to diminished repair, the aging process and predisposition to CVDs. In addition, we briefly describe emerging Nox therapies and their potential in improving the health of the elderly population. PMID:26814203

  18. The role of telomeres and vitamin D in cellular aging and age-related diseases.

    PubMed

    Pusceddu, Irene; Farrell, Christopher-John L; Di Pierro, Angela Maria; Jani, Erika; Herrmann, Wolfgang; Herrmann, Markus

    2015-10-01

    Aging is a complex biological process characterized by a progressive decline of organ functions leading to an increased risk of age-associated diseases and death. Decades of intensive research have identified a range of molecular and biochemical pathways contributing to aging. However, many aspects regarding the regulation and interplay of these pathways are insufficiently understood. Telomere dysfunction and genomic instability appear to be of critical importance for aging at a cellular level. For example, age-related diseases and premature aging syndromes are frequently associated with telomere shortening. Telomeres are repetitive nucleotide sequences that together with the associated sheltrin complex protect the ends of chromosomes and maintain genomic stability. Recent studies suggest that micronutrients, such as vitamin D, folate and vitamin B12, are involved in telomere biology and cellular aging. In particular, vitamin D is important for a range of vital cellular processes including cellular differentiation, proliferation and apoptosis. As a result of the multiple functions of vitamin D it has been speculated that vitamin D might play a role in telomere biology and genomic stability. Here we review existing knowledge about the link between telomere biology and cellular aging with a focus on the role of vitamin D. We searched the literature up to November 2014 for human studies, animal models and in vitro experiments that addressed this topic. PMID:25803084

  19. Infectivity-associated PrPSc and disease duration-associated PrPSc of mouse BSE prions

    PubMed Central

    Miyazawa, Kohtaro; Okada, Hiroyuki; Masujin, Kentaro; Iwamaru, Yoshifumi; Yokoyama, Takashi

    2015-01-01

    ABSTRACT Disease-related prion protein (PrPSc), which is a structural isoform of the host-encoded cellular prion protein, is thought to be a causative agent of transmissible spongiform encephalopathies. However, the specific role of PrPSc in prion pathogenesis and its relationship to infectivity remain controversial. A time-course study of prion-affected mice was conducted, which showed that the prion infectivity was not simply proportional to the amount of PrPSc in the brain. Centrifugation (20,000 ×g) of the brain homogenate showed that most of the PrPSc was precipitated into the pellet, and the supernatant contained only a slight amount of PrPSc. Interestingly, mice inoculated with the obtained supernatant showed incubation periods that were approximately 15 d longer than those of mice inoculated with the crude homogenate even though both inocula contained almost the same infectivity. Our results suggest that a small population of fine PrPSc may be responsible for prion infectivity and that large, aggregated PrPSc may contribute to determining prion disease duration. PMID:26555211

  20. Oxidants, antioxidants, and the degenerative diseases of aging.

    PubMed Central

    Ames, B N; Shigenaga, M K; Hagen, T M

    1993-01-01

    Metabolism, like other aspects of life, involves tradeoffs. Oxidant by-products of normal metabolism cause extensive damage to DNA, protein, and lipid. We argue that this damage (the same as that produced by radiation) is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts. Antioxidant defenses against this damage include ascorbate, tocopherol, and carotenoids. Dietary fruits and vegetables are the principal source of ascorbate and carotenoids and are one source of tocopherol. Low dietary intake of fruits and vegetables doubles the risk of most types of cancer as compared to high intake and also markedly increases the risk of heart disease and cataracts. Since only 9% of Americans eat the recommended five servings of fruits and vegetables per day, the opportunity for improving health by improving diet is great. Images Fig. 1 PMID:8367443

  1. 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

  2. Duration of sleep at 3 years of age is associated with fat and fat-free mass at 4 years of age: the Southampton Women's Survey.

    PubMed

    Baird, Janis; Hill, Catherine M; Harvey, Nicholas C; Crozier, Sarah; Robinson, Sian M; Godfrey, Keith M; Cooper, Cyrus; Inskip, Hazel

    2016-08-01

    Many studies have shown that shorter sleep duration in childhood is associated with higher body mass index (BMI), and have proposed that it is due to an effect of sleep on adiposity. There is little evidence about the association of sleep with fat-free mass. This study examined the association between child's sleep duration at age 3 years and fat and fat-free mass at 4 years of age in a prospective cohort study of 302 boys and 285 girls. Study participants were taking part in the Southampton Women's Survey, a longitudinal study of mothers and children from preconception onwards. Total sleep duration at age 3 years was derived from parental report of night sleep and nap duration. Body composition was assessed by Dual-energy X-ray Absorptiometry (DXA) at 4 years. Mean total sleep duration was 11.5 hours. In linear regression analyses, adjusted for potentially confounding factors (maternal educational attainment, prepregnancy BMI, smoking during pregnancy, child's gestational age at birth, age at DXA, sex, age last breastfed, dietary quality at 3 years, TV watching and hours actively on the move and parental social class), shorter sleep in hours was associated with higher BMI (kg/m(2) ) [β: -0.2340, 95% confidence interval (CI): -0.373 to -0.096], a greater fat mass index (kg) (β: -0.1182, 95% CI: -0.218 to -0.018) and a greater fat-free mass index (kg) (β: -0.100, 95% CI: -0.185 to -0.015). Previous research suggested that the association between shorter sleep and higher body mass index is due to an effect on adiposity. Our findings are novel, suggesting that the relationship between sleep and BMI is also determined by an effect on muscle. PMID:26909889

  3. Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer's Disease.

    PubMed

    Smits, Fenne Margreeth; Porcaro, Camillo; Cottone, Carlo; Cancelli, Andrea; Rossini, Paolo Maria; Tecchio, Franca

    2016-01-01

    Brain activity is complex; a reflection of its structural and functional organization. Among other measures of complexity, the fractal dimension is emerging as being sensitive to neuronal damage secondary to neurological and psychiatric diseases. Here, we calculated Higuchi's fractal dimension (HFD) in resting-state eyes-closed electroencephalography (EEG) recordings from 41 healthy controls (age: 20-89 years) and 67 Alzheimer's Disease (AD) patients (age: 50-88 years), to investigate whether HFD is sensitive to brain activity changes typical in healthy aging and in AD. Additionally, we considered whether AD-accelerating effects of the copper fraction not bound to ceruloplasmin (also called "free" copper) are reflected in HFD fluctuations. The HFD measure showed an inverted U-shaped relationship with age in healthy people (R2 = .575, p < .001). Onset of HFD decline appeared around the age of 60, and was most evident in central-parietal regions. In this region, HFD decreased with aging stronger in the right than in the left hemisphere (p = .006). AD patients demonstrated reduced HFD compared to age- and education-matched healthy controls, especially in temporal-occipital regions. This was associated with decreasing cognitive status as assessed by mini-mental state examination, and with higher levels of non-ceruloplasmin copper. Taken together, our findings show that resting-state EEG complexity increases from youth to maturity and declines in healthy, aging individuals. In AD, brain activity complexity is further reduced in correlation with cognitive impairment. In addition, elevated levels of non-ceruloplasmin copper appear to accelerate the reduction of neural activity complexity. Overall, HDF appears to be a proper indicator for monitoring EEG-derived brain activity complexity in healthy and pathological aging. PMID:26872349

  4. Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases

    PubMed Central

    Smith, J. A.; Leonardi, T.; Huang, B.; Iraci, N.; Vega, B.; Pluchino, S.

    2015-01-01

    Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs—or specific EV cargoes—are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases. PMID:24973266

  5. 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

  6. Long sleep duration and afternoon napping are associated with higher risk of incident diabetes in middle-aged and older Chinese: the Dongfeng-Tongji cohort study.

    PubMed

    Han, Xu; Liu, Bing; Wang, Jing; Pan, An; Li, Yaru; Hu, Hua; Li, Xiulou; Yang, Kun; Yuan, Jing; Yao, Ping; Miao, Xiaoping; Wei, Sheng; Wang, Youjie; Liang, Yuan; Zhang, Xiaomin; Guo, Huan; Yang, Handong; Hu, Frank B; Wu, Tangchun; He, Meian

    2016-06-01

    Background In this study, we investigated the independent and combined effects of sleep duration and afternoon napping on the risk of incident diabetes among a cohort of middle-aged and older Chinese adults. Methods Information of sleep and napping was obtained by questionnaires during face-to-face interviews. We categorized sleep duration into <7 h, 7∼<8 h (reference), 8∼<9 h, 9∼<10 h, and ≥ 10 h. Afternoon napping was divided into no napping (0 min) (reference), 1-30 min, 31-60 min, 61-90 min, and > 90 min. Cox proportional hazard regression models were used. Results Compared with referential sleeping group, subjects sleeping ≥10 h had a 42% higher risk of developing diabetes. The HR was 1.28 for napping > 90 min when compared with no napping. These associations were more pronounced in individuals without hypertension. Combined effects of long sleep duration and afternoon napping were further identified. Individuals with both sleep duration ≥ 10 h and napping > 60 min had a 72% higher risk of incident diabetes than those with sleeping 7∼<8 h and napping 0 min (all above p < 0.05). Conclusions Both long sleep duration and afternoon napping were independently and jointly associated with higher risk of incident diabetes. Key messages Sleep duration was associated with diabetes, but whether it is a real cause of incident diabetes especially in Chinese still remains to be elucidated. The association of afternoon napping and diabetes was not consistent and definite, we clarified this association in a large prospective study. Long sleep duration and afternoon napping were independently and jointly associated with higher risk of incident diabetes. PMID:26969344

  7. Distinct mechanisms of impairment in cognitive ageing and Alzheimer's disease.

    PubMed

    Mapstone, Mark; Dickerson, Kathryn; Duffy, Charles J

    2008-06-01

    Similar manifestations of functional decline in ageing and Alzheimer's disease obscure differences in the underlying cognitive mechanisms of impairment. We sought to examine the contributions of top-down attentional and bottom-up perceptual factors to visual self-movement processing in ageing and Alzheimer's disease. We administered a novel heading discrimination task requiring subjects to determine direction of simulated self-movement from left or right offset optic flow fields of several sizes (25 degrees, 40 degrees or 60 degrees in diameter) to 18 Alzheimer's disease subjects (mean age = 75.3, 55% female), 21 older adult control subjects (mean age = 72.4, 67% female), and 26 younger control subjects (mean age = 26.5, 63% female). We also administered computerized measures of processing speed and divided and selective attention, and psychophysical measures of visual motion perception to all subjects. Both older groups showed significant difficulty in judging the direction of virtual self-movement [F(2,194) = 40.5, P < 0.001] and optic flow stimulus size had little effect on heading discrimination for any group. Both older groups showed impairments on measures of divided [F(2,62) = 22.2, P < 0.01] and selective [F(2,62) = 63.0, P < 0.001] attention relative to the younger adult control group, while the Alzheimer's disease group showed a selective impairment in outward optic flow perception [F(2,64) = 6.3, P = 0.003] relative to both control groups. Multiple linear regression revealed distinct attentional and perceptual contributions to heading discrimination performance for the two older groups. In older adult control subjects, poorer heading discrimination was attributable to attentional deficits (R(2) adj = 0.41, P = 0.001) whereas, in Alzheimer's disease patients, it was largely attributable to deficits of visual motion perception (R(2) adj = 0.57, P < 0.001). These findings suggest that successive attentional and perceptual deficits play independent roles in

  8. 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

  9. CHRONIC OBSTRUCTIVE PULMONARY DISEASE IS ASSOCIATED WITH MILD COGNITIVE IMPAIRMENT: THE MAYO CLINIC STUDY OF AGING

    PubMed Central

    Singh, Balwinder; Parsaik, Ajay K; Mielke, Michelle M.; Roberts, Rosebud O.; Scanlon, Paul D.; Geda, Yonas E.; Pankratz, V. Shane; Christianson, Teresa; Yawn, Barbara; Petersen, Ronald C.

    2013-01-01

    Objectives To investigate the association of chronic obstructive pulmonary disease (COPD) with mild cognitive impairment (MCI) and MCI sub-types, amnestic MCI (a-MCI) and non-amnestic MCI (na-MCI), in a population-based study of elderly. Patients and Methods Participants included 1,927 individuals, aged 70 to 89 years, enrolled in the population-based, Mayo Clinic Study of Aging. Participants were evaluated with a nurse assessment, neurological evaluation, and neuropsychological testing and the diagnosis of MCI was made according to the standardized criteria by a consensus panel. COPD was identified by the review of medical records. The study was conducted from October 1, 2004, through July 31, 2007. The associations of COPD, and disease duration with MCI, and its subtypes were evaluated using logistic regression models adjusted for potential covariates. Results Of 1,927 subjects, 288 had COPD (men vs women 17.9% vs 11.8%, p<0.001). As compared to subjects without COPD, the subjects with COPD had higher prevalence of MCI (27.1% vs 14.6%, p<0.001). The odds ratio (OR) of MCI was almost two times higher in subjects with COPD (OR =1.90, 95 %CI =1.35 – 2.65), with a similar effect in men and women. The OR for MCI increased from 1.67 (97% CI, 1.00 – 2.69) in subjects with COPD duration of ≤ 5 years to 2.08 (95% CI, 1.36 – 3.14) in subjects > 5 years. Conclusion This population-based study suggests that COPD is associated with increased odds of having MCI and its sub-types. There was a dose-response association with duration of COPD, after controlling for the potential covariates. PMID:24182702

  10. The Biology of Proteostasis in Aging and Disease

    PubMed Central

    Labbadia, Johnathan; Morimoto, Richard I.

    2015-01-01

    Loss of protein homeostasis (proteostasis) is a common feature of aging and disease that is characterized by the appearance of nonnative protein aggregates in various tissues. Protein aggregation is routinely suppressed by the proteostasis network (PN), a collection of macromolecular machines that operate in diverse ways to maintain proteome integrity across subcellular compartments and between tissues to ensure a healthy life span. Here, we review the composition, function, and organizational properties of the PN in the context of individual cells and entire organisms and discuss the mechanisms by which disruption of the PN, and related stress response pathways, contributes to the initiation and progression of disease. We explore emerging evidence that disease susceptibility arises from early changes in the composition and activity of the PN and propose that a more complete understanding of the temporal and spatial properties of the PN will enhance our ability to develop effective treatments for protein conformational diseases. PMID:25784053

  11. The biology of proteostasis in aging and disease.

    PubMed

    Labbadia, Johnathan; Morimoto, Richard I

    2015-01-01

    Loss of protein homeostasis (proteostasis) is a common feature of aging and disease that is characterized by the appearance of nonnative protein aggregates in various tissues. Protein aggregation is routinely suppressed by the proteostasis network (PN), a collection of macromolecular machines that operate in diverse ways to maintain proteome integrity across subcellular compartments and between tissues to ensure a healthy life span. Here, we review the composition, function, and organizational properties of the PN in the context of individual cells and entire organisms and discuss the mechanisms by which disruption of the PN, and related stress response pathways, contributes to the initiation and progression of disease. We explore emerging evidence that disease susceptibility arises from early changes in the composition and activity of the PN and propose that a more complete understanding of the temporal and spatial properties of the PN will enhance our ability to develop effective treatments for protein conformational diseases. PMID:25784053

  12. The role of AGEs and AGE inhibitors in diabetic cardiovascular disease.

    PubMed

    Thomas, M C; Baynes, J W; Thorpe, S R; Cooper, M E

    2005-06-01

    Prolonged hyperglycemia, dyslipidemia and oxidative stress in diabetes result in the production and accumulation of AGEs. It is now clear that AGEs contribute to the development and progression of cardiovascular disease in diabetes, as well as other complications. AGEs are thought to act through receptor-independent and dependent mechanisms to promote vascular damage, fibrosis and inflammation associated with accelerated atherogenesis. As a result, novel therapeutic agents to reduce the accumulation of AGEs in diabetes have gained interest as potential cardioprotective approaches. A variety of agents have been developed which are examined in detail in this review. These include aminoguanidine, ALT-946, pyridoxamine, benfotiamine, OPB-9195, alagebrium chloride, N-phenacylthiazolium bromide and LR-90. In addition, it has been demonstrated that a number of established therapies have the ability to reduce the accumulation of AGEs in diabetes including ACE inhibitors, angiotensin receptor antagonists, metformin, peroxisome proliferators receptor agonists, metal chelators and some antioxidants. The fact that many of these inhibitors of AGEs are effective in experimental models, despite their disparate mechanisms of action, supports the keystone role of AGEs in diabetic vascular damage. Nonetheless, the clinical utility of AGE inhibition remains to be firmly established. Optimal metabolic and blood pressure control, that is achieved early and sustained indefinitely, remains the best recourse for inhibition of AGEs until more specific interventions become a clinical reality. PMID:16026265

  13. 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

  14. Cross-sectional study of diet, physical activity, television viewing and sleep duration in 233 110 adults from the UK Biobank; the behavioural phenotype of cardiovascular disease and type 2 diabetes

    PubMed Central

    Cassidy, Sophie; Chau, Josephine Y; Catt, Michael; Bauman, Adrian; Trenell, Michael I

    2016-01-01

    Objectives Simultaneously define diet, physical activity, television (TV) viewing, and sleep duration across cardiometabolic disease groups, and investigate clustering of non-diet lifestyle behaviours. Design Cross-sectional observational study. Setting 22 UK Biobank assessment centres across the UK. Participants 502 664 adults aged 37–63 years old, 54% women. 4 groups were defined based on disease status; ‘No disease’ (n=103 993), ‘cardiovascular disease’ (CVD n=113 469), ‘Type 2 diabetes without CVD’ (n=4074) and ‘Type 2 diabetes + CVD’ (n=11 574). Main outcomes Diet, physical activity, TV viewing and sleep duration. Results People with ‘CVD’ report low levels of physical activity (<918 MET min/week, OR (95% CI) 1.23 (1.20 to 1.25)), high levels of TV viewing (>3 h/day; 1.42 (1.39 to 1.45)), and poor sleep duration (<7, >8 h/night; 1.37 (1.34 to 1.39)) relative to people without disease. People with ‘Type 2 diabetes + CVD’ were more likely to report low physical activity (1.71 (1.64 to 1.78)), high levels of TV viewing (1.92 (1.85 to 1.99)) and poor sleep duration (1.52 (1.46 to1.58)) relative to people without disease. Non-diet behaviours were clustered, with people with ‘CVD’ or ‘Type 2 diabetes + CVD’ more likely to report simultaneous low physical activity, high TV viewing and poor sleep duration than those without disease (2.15 (2.03 to 2.28) and 3.29 (3.02 to 3.58), respectively). By contrast, 3 in 4 adults with ‘Type 2 diabetes’, and 2 in 4 adults with ‘CVD’ have changed their diet in the past 5 years, compared with only 1 in 4 in the ‘No disease’ group. Models were adjusted for gender, age, body mass index, Townsend Deprivation Index, ethnicity, alcohol intake, smoking and meeting fruit/vegetable guidelines. Conclusions Low physical activity, high TV and poor sleep duration are prominent unaddressed high-risk characteristics of both CVD and type 2 diabetes, and are likely to be clustered

  15. Age-space-time CAR models in Bayesian disease mapping.

    PubMed

    Goicoa, T; Ugarte, M D; Etxeberria, J; Militino, A F

    2016-06-30

    Mortality counts are usually aggregated over age groups assuming similar effects of both time and region, yet the spatio-temporal evolution of cancer mortality rates may depend on changing age structures. In this paper, mortality rates are analyzed by region, time period and age group, and models including space-time, space-age, and age-time interactions are considered. The integrated nested Laplace approximation method, known as INLA, is adopted for model fitting and inference in order to reduce computing time in comparison with Markov chain Monte Carlo (McMC) methods. The methodology provides full posterior distributions of the quantities of interest while avoiding complex simulation techniques. The proposed models are used to analyze prostate cancer mortality data in 50 Spanish provinces over the period 1986-2010. The results reveal a decline in mortality since the late 1990s, particularly in the age group [65,70), probably because of the inclusion of the PSA (prostate-specific antigen) test and better treatment of early-stage disease. The decline is not clearly observed in the oldest age groups. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26814019

  16. Age, APOE and sex: Triad of risk of Alzheimer's disease.

    PubMed

    Riedel, Brandalyn C; Thompson, Paul M; Brinton, Roberta Diaz

    2016-06-01

    Age, apolipoprotein E ε4 (APOE) and chromosomal sex are well-established risk factors for late-onset Alzheimer's disease (LOAD; AD). Over 60% of persons with AD harbor at least one APOE-ε4 allele. The sex-based prevalence of AD is well documented with over 60% of persons with AD being female. Evidence indicates that the APOE-ε4 risk for AD is greater in women than men, which is particularly evident in heterozygous women carrying one APOE-ε4 allele. Paradoxically, men homozygous for APOE-ε4 are reported to be at greater risk for mild cognitive impairment and AD. Herein, we discuss the complex interplay between the three greatest risk factors for Alzheimer's disease, age, APOE-ε4 genotype and chromosomal sex. We propose that the convergence of these three risk factors, and specifically the bioenergetic aging perimenopause to menopause transition unique to the female, creates a risk profile for AD unique to the female. Further, we discuss the specific risk of the APOE-ε4 positive male which appears to emerge early in the aging process. Evidence for impact of the triad of AD risk factors is most evident in the temporal trajectory of AD progression and burden of pathology in relation to APOE genotype, age and sex. Collectively, the data indicate complex interactions between age, APOE genotype and gender that belies a one size fits all approach and argues for a precision medicine approach that integrates across the three main risk factors for Alzheimer's disease. PMID:26969397

  17. 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

  18. Non-coding RNA in neural function, disease, and aging

    PubMed Central

    Szafranski, Kirk; Abraham, Karan J.; Mekhail, Karim

    2015-01-01

    Declining brain and neurobiological function is arguably one of the most common features of human aging. The study of conserved aging processes as well as the characterization of various neurodegenerative diseases using different genetic models such as yeast, fly, mouse, and human systems is uncovering links to non-coding RNAs. These links implicate a variety of RNA-regulatory processes, including microRNA function, paraspeckle formation, RNA–DNA hybrid regulation, nucleolar RNAs and toxic RNA clearance, amongst others. Here we highlight these connections and reveal over-arching themes or questions related to recently appreciated roles of non-coding RNA in neural function and dysfunction across lifespan. PMID:25806046

  19. 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

  20. Paths to first treatment and duration of untreated illness in anorexia nervosa: are there differences according to age of onset?

    PubMed

    Neubauer, Karolin; Weigel, Angelika; Daubmann, Anne; Wendt, Hanna; Rossi, Maddalena; Löwe, Bernd; Gumz, Antje

    2014-07-01

    This study examined paths to first treatment and the duration of untreated illness in 140 anorexia nervosa patients using validated questionnaires and a clinical interview. The differences between individuals with an early (≤14 years, n = 40), intermediate (15-18 years, n = 53) and late onset (≥19 years, n = 47) were investigated. Participants were most commonly informed about their diagnosis and first treatment facility through general practitioners and paediatricians. The duration of untreated illness exceeded 2 years in the complete sample (25.14 months) and was longest for individuals with an early onset. The early onset group was more often externally vs. internally motivated and more frequently informed about treatment options by their social network, e.g. parents, than patients with a late onset. The results emphasize the relevance of training general practitioners and paediatricians about anorexia, the need to include parents and teachers in eating disorder prevention and to improve targeting young individuals in early interventions. PMID:24888519

  1. [The information value of the biological properties of the causative agent in the prognosis of the duration of the course of suppurative inflammatory diseases of staphylococcal etiology].

    PubMed

    Deriabin, D G; Kurlaev, P P

    1999-01-01

    The informative value of biological characteristics of Staphylococcus aureus reflecting the ability of microbes to inactivate certain factors of natural resistance (lysozyme, complement, immunoglobulins, bactericidal component of interferon) was established in determining the duration of the caused by them pyo-inflammatory diseases such as postinfection abscesses, lactation mastitis. On this basis the heterogeneous successive procedure of pattern recognition was used to develop algorithms allowing prognosis of the duration of pyo-inflammatory diseases of staphylococcal etiology in 84.6-94.4% of the patients after the quantitative and qualitative assessment of the biological properties of the pathogen with not less than 90% reliability. PMID:10491834

  2. Physiological Antioxidative Network of the Bilirubin System in Aging and Age-Related Diseases

    PubMed Central

    Kim, Sung Young; Park, Sang Chul

    2012-01-01

    Oxidative stress is detrimental to life process and is particularly responsible for aging and age-related diseases. Thus, most organisms are well equipped with a spectrum of biological defense mechanisms against oxidative stress. The major efficient antioxidative mechanism is the glutathione system, operating a redox cycling mechanism for glutathione utilization, which consists of glutathione and its peroxidase and reductase. However, this system is mainly effective for hydrophilic oxidants, while lipophilic oxidants require another scavenging system. Since many age-related pathological conditions are related to lipid peroxidation, especially in association with the aging process, the physiological role of the scavenging system for lipophilic oxidants should be considered. In this regard, the biliverdin to bilirubin conversion pathway, via biliverdin reductase (BVR), is suggested to be another major protective mechanism that scavenges lipophilic oxidants because of the lipophilic nature of bilirubin. The efficiency of this bilirubin system might be potentiated by operation of the intertwined bicyclic systems of the suggested redox metabolic cycle of biliverdin and bilirubin and the interactive control cycle of BVR and heme oxygenase. In order to combat oxidative stress, both antioxidative systems against hydrophilic and lipophilic oxidants are required to work cooperatively. In this regard, the roles of the bilirubin system in aging and age-related diseases are reassessed in this review, and their interacting networks are evaluated. PMID:22457648

  3. Evaluation of leaf wetness duration models for operational use in strawberry disease-warning systems in four US states

    NASA Astrophysics Data System (ADS)

    Montone, Verona O.; Fraisse, Clyde W.; Peres, Natalia A.; Sentelhas, Paulo C.; Gleason, Mark; Ellis, Michael; Schnabel, Guido

    2016-05-01

    Leaf wetness duration (LWD) plays a key role in disease development and is often used as an input in disease-warning systems. LWD is often estimated using mathematical models, since measurement by sensors is rarely available and/or reliable. A strawberry disease-warning system called "Strawberry Advisory System" (SAS) is used by growers in Florida, USA, in deciding when to spray their strawberry fields to control anthracnose and Botrytis fruit rot. Currently, SAS is implemented at six locations, where reliable LWD sensors are deployed. A robust LWD model would facilitate SAS expansion from Florida to other regions where reliable LW sensors are not available. The objective of this study was to evaluate the use of mathematical models to estimate LWD and time of spray recommendations in comparison to on site LWD measurements. Specific objectives were to (i) compare model estimated and observed LWD and resulting differences in timing and number of fungicide spray recommendations, (ii) evaluate the effects of weather station sensors precision on LWD models performance, and (iii) compare LWD models performance across four states in the USA. The LWD models evaluated were the classification and regression tree (CART), dew point depression (DPD), number of hours with relative humidity equal or greater than 90 % (NHRH ≥90 %), and Penman-Monteith (P-M). P-M model was expected to have the lowest errors, since it is a physically based and thus portable model. Indeed, the P-M model estimated LWD most accurately (MAE <2 h) at a weather station with high precision sensors but was the least accurate when lower precision sensors of relative humidity and estimated net radiation (based on solar radiation and temperature) were used (MAE = 3.7 h). The CART model was the most robust for estimating LWD and for advising growers on fungicide-spray timing for anthracnose and Botrytis fruit rot control and is therefore the model we recommend for expanding the strawberry disease warning

  4. Understanding Vascular Diseases: Lessons From Premature Aging Syndromes.

    PubMed

    Ikeda, Yuichi; Kumagai, Hidetoshi; Motozawa, Yoshihiro; Suzuki, Jun-Ichi; Akazawa, Hiroshi; Komuro, Issei

    2016-05-01

    Early human mummies examined recently by computed tomography demonstrated a high prevalence of vascular calcification, a pathognomonic sign of atherosclerosis, which was correlated with estimated age at death. Early populations had little exposure to modern-day metabolic risk factors: these observations thus suggest that humans have an inherent age-dependent predisposition to atherosclerosis. Premature aging syndromes are extremely rare genetic disorders that exhibit clinical phenotypes resembling accelerated aging, including severe atherosclerosis, but those phenotypes are usually segmental. Controversy persists, therefore, regarding the extent to which the molecular mechanisms underlying premature aging syndromes overlap with those of physiological aging. Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome are well-characterized premature aging syndromes. HGPS is caused by gain-of-function mutations in the LMNA gene, which result in the accumulation of a mutant nuclear protein, called "progerin," at the nuclear rim. In contrast, loss-of-function mutations in Werner syndrome ATP-dependent helicase (WRN) lead to Werner syndrome. Mesenchymal stem cells (MSCs), which can differentiate into vascular cells to maintain vascular homeostasis in response to injury, are severely affected in these syndromes. Mechanistically, either aberrant expression of progerin or loss of WRN protein in MSCs alters heterochromatin structure, resulting in premature senescence and exhaustion of functional MSCs in premature aging syndromes. Surprisingly, vascular cells and MSCs in elderly healthy individuals have shown progerin expression and decreased expression levels of WRN, respectively. Studying these rare genetic disorders could thus provide valuable insights into age-related vascular diseases that occur in the general population. PMID:26948039

  5. Effects of Aging and Idiopathic Parkinson’s Disease on Tactile Temporal Order Judgment

    PubMed Central

    Nishikawa, Natsuko; Shimo, Yasushi; Wada, Makoto; Hattori, Nobutaka; Kitazawa, Shigeru

    2015-01-01

    It is generally accepted that the basal ganglia play an important role in interval timing that requires the measurement of temporal durations. By contrast, it remains controversial whether the basal ganglia play an essential role in temporal order judgment (TOJ) of successive stimuli, a behavior that does not necessarily require the measurement of durations in time. To address this issue, we compared the effects of idiopathic Parkinson’s disease (PD) on the TOJ of two successive taps delivered to each hand, with the arms uncrossed in one condition and crossed in another. In addition to age-matched elderly participants without PD (non-PD), we examined young healthy participants so that the effect of aging could serve as a control for evaluating the effects of PD. There was no significant difference between PD and non-PD participants in any parameter of TOJ under either arm posture, although reaction time was significantly longer in PD compared with non-PD participants. By contrast, the effect of aging was apparent in both conditions. With their arms uncrossed, the temporal resolution (the interstimulus interval that yielded 84% correct responses) in elderly participants was significantly worse compared with young participants. With their arms crossed, elderly participants made more errors at longer intervals (~1 s) than young participants, although both age groups showed similar judgment reversal at moderately short intervals (~200 ms). These results indicate that the basal ganglia and dopaminergic systems do not play essential roles in tactile TOJ involving both hands and that the effect of aging on TOJ is mostly independent of the dopaminergic systems. PMID:25760621

  6. Sirtuin 1 and Aging Theory for Chronic Obstructive Pulmonary Disease

    PubMed Central

    Conti, V.; Corbi, G.; Manzo, V.; Pelaia, G.; Filippelli, A.; Vatrella, A.

    2015-01-01

    Chronic Obstructive Pulmonary disease (COPD) is an inflammatory syndrome that represents an increasing health problem, especially in the elderly population. Drug therapies are symptomatic and inadequate to contrast disease progression and mortality. Thus, there is an urgent need to clarify the molecular mechanisms responsible for this condition in order to identify new biomarkers and therapeutic targets. Processes including oxidant/antioxidant, protease/antiprotease, and proliferative/antiproliferative balance and control of inflammatory response become dysfunctional during aging as well as in COPD. Recently it was suggested that Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to oxidative stress and chronic inflammation, is implicated in both development and progression of COPD. The present review focuses on the involvement of SIRT1 in the regulation of redox state, inflammation, and premature senescence, all crucial characteristics of COPD phenotypes. Recent evidence corroborating the statement of the “aging theory for COPD” was also discussed. PMID:26236580

  7. May serum levels of advanced oxidized protein products serve as a prognostic marker of disease duration in patients with idiopathic Parkinson's disease?

    PubMed

    García-Moreno, José-Manuel; Martín de Pablos, Angel; García-Sánchez, María-Isabel; Méndez-Lucena, Carolina; Damas-Hermoso, Fátima; Rus, Macarena; Chacón, José; Fernández, Emilio

    2013-04-10

    Protein and amine halogenation is a type of oxidative stress induced by phagocytic overstimulation, and its role in Parkinson's disease (PD) has not been discerned. We have detected that advanced oxidized protein products, markers of protein halogenation, are reliably enhanced in serum of patients with PD (n=60) relative to control subjects (n=45, p<0.012), and to a lesser extent in the cerebrospinal fluid. Amine halogenation, as evaluated through 3-chlorotyrosine, is not affected. Mieloperoxidase and hydrogen peroxide levels, halogenative factors of phagocytes, are devoid of changes. Levels of advanced oxidized protein products are progressively reduced over time, and the duration of PD is larger in the Hoehn-Yahr-stage-2/3 patients (n=34) with low serum levels (R(2)=0.0145, p<0.003). Levodopa treatment contributes to this reduction (R(2)=0.259, p<0.001). These protein products are not cytotoxic, unlike 3-chlorotyrosine, but they are known to form inflammatory mediators after conjugation with serum albumin. Our observations lead to the hypothesis that the serum level of advanced oxidized protein products is a prognostic marker of PD duration, and these oxidized proteins could participate in the development of parkinsonian neurodegeneration. PMID:23121480

  8. Can we define maternal age as a genetic disease?

    PubMed Central

    Wilding, M.

    2014-01-01

    >Maternal age is strongly associated with a decrease in the probability of achieving pregnancy and the birth of a healthy child. Among current theories of the mechanism of this decrease is the hypothesis that a progressive degeneration of the respiratory capacity of mitochondria in eggs of women of advanced age leads to an energy deficit and consequent secondary effects on the oocyte and developing embryo. Mitochondria are uniquely inherited through the female germ line and these organelles contain DNA sequences that are independent from the genome. It is therefore possible that offspring born to females of advanced age inherit suboptimal mitochondria and that these persist throughout the life of the new being. This could in turn lead to long-term consequences for the offspring of females of advanced age such as a reduced potential lifespan in relation to the age of the mother at conception. In this review and hypothesis, we discuss the evidence relating to this theory and suggest that on this basis the maternal age effect could be classified as an inheritable genetic disease. PMID:25009733

  9. NF-κB in Aging and Disease

    PubMed Central

    Tilstra, Jeremy S.; Clauson, Cheryl L.; Niedernhofer, Laura J.; Robbins, Paul D.

    2011-01-01

    Stochastic damage to cellular macromolecules and organelles is thought to be a driving force behind aging and associated degenerative changes. However, stress response pathways activated by this damage may also contribute to aging. The IKK/NF-κB signaling pathway has been proposed to be one of the key mediators of aging. It is activated by genotoxic, oxidative, and inflammatory stresses and regulates expression of cytokines, growth factors, and genes that regulate apoptosis, cell cycle progression, cell senescence, and inflammation. Transcriptional activity of NF-κB is increased in a variety of tissues with aging and is associated with numerous age-related degenerative diseases including Alzheimer’s, diabetes and osteoporosis. In mouse models, inhibition of NF-κB leads to delayed onset of age-related symptoms and pathologies. In addition, NF-κB activation is linked with many of the known lifespan regulators including insulin/IGF-1, FOXO, SIRT, mTOR, and DNA damage. Thus NF-κB represents a possible therapeutic target for extending mammalian healthspan. PMID:22396894

  10. Old-age inflammatory bowel disease onset: a different problem?

    PubMed

    del Val, Joaquin Hinojosa

    2011-06-14

    Inflammatory bowel disease (IBD) in patients aged > 60 accounts for 10%-15% of cases of the disease. Diganostic methods are the same as for other age groups. Care has to be taken to distinguish an IBD colitis from other forms of colitis that can mimick clinically, endoscopically and even histologically the IBD entity. The clinical pattern in ulcerative colitis (UC) is proctitis and left-sided UC, while granulomatous colitis with an inflammatory pattern is more common in Crohn's disease (CD). The treatment options are those used in younger patients, but a series of considerations related to potential pharmacological interactions and side effects of the drugs must be taken into account. The safety profile of conventional immunomodulators and biological therapy is acceptable but more data are required on the safety of use of these drugs in the elderly population. Biological therapy has risen question on the possibility of increased side effects, however this needs to be confirmed. Adherence to performing all the test prior to biologic treatment administration is very important. The overall response to treatment is similar in the different patient age groups but elderly patients have fewer recurrences. The number of hospitalizations in patients > 65 years is greater than in younger group, accounting for 25% of all admissions for IBD. Mortality is similar in UC and slightly higher in CD, but significantly increased in hospitalized patients. Failure of medical treatment continues to be the most common indication for surgery in patients aged > 60 years. Age is not considered a contraindication for performing restorative proctocolectomy with an ileal pouch-anal anastomosis. However, incontinence evaluation should be taken into account an individualized options should be considered. PMID:21734781

  11. A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease.

    PubMed

    Brehme, Marc; Voisine, Cindy; Rolland, Thomas; Wachi, Shinichiro; Soper, James H; Zhu, Yitan; Orton, Kai; Villella, Adriana; Garza, Dan; Vidal, Marc; Ge, Hui; Morimoto, Richard I

    2014-11-01

    Chaperones are central to the proteostasis network (PN) and safeguard the proteome from misfolding, aggregation, and proteotoxicity. We categorized the human chaperome of 332 genes into network communities using function, localization, interactome, and expression data sets. During human brain aging, expression of 32% of the chaperome, corresponding to ATP-dependent chaperone machines, is repressed, whereas 19.5%, corresponding to ATP-independent chaperones and co-chaperones, are induced. These repression and induction clusters are enhanced in the brains of those with Alzheimer's, Huntington's, or Parkinson's disease. Functional properties of the chaperome were assessed by perturbation in C. elegans and human cell models expressing Aβ, polyglutamine, and Huntingtin. Of 219 C. elegans orthologs, knockdown of 16 enhanced both Aβ and polyQ-associated toxicity. These correspond to 28 human orthologs, of which 52% and 41% are repressed, respectively, in brain aging and disease and 37.5% affected Huntingtin aggregation in human cells. These results identify a critical chaperome subnetwork that functions in aging and disease. PMID:25437566

  12. Molecular insights into the premature aging disease progeria.

    PubMed

    Vidak, Sandra; Foisner, Roland

    2016-04-01

    Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare premature aging disease presenting many features resembling the normal aging process. HGPS patients die before the age of 20 years due to cardiovascular problems and heart failure. HGPS is linked to mutations in the LMNA gene encoding the intermediate filament protein lamin A. Lamin A is a major component of the nuclear lamina, a scaffold structure at the nuclear envelope that defines mechanochemical properties of the nucleus and is involved in chromatin organization and epigenetic regulation. Lamin A is also present in the nuclear interior where it fulfills lamina-independent functions in cell signaling and gene regulation. The most common LMNA mutation linked to HGPS leads to mis-splicing of the LMNA mRNA and produces a mutant lamin A protein called progerin that tightly associates with the inner nuclear membrane and affects the dynamic properties of lamins. Progerin expression impairs many important cellular processes providing insight into potential disease mechanisms. These include changes in mechanosignaling, altered chromatin organization and impaired genome stability, and changes in signaling pathways, leading to impaired regulation of adult stem cells, defective extracellular matrix production and premature cell senescence. In this review, we discuss these pathways and their potential contribution to the disease pathologies as well as therapeutic approaches used in preclinical and clinical tests. PMID:26847180

  13. The 'golden age' of DNA methylation in neurodegenerative diseases.

    PubMed

    Fuso, Andrea

    2013-03-01

    DNA methylation reactions are regulated, in the first instance, by enzymes and the intermediates that constitute the 'so called' one-carbon metabolism. This is a complex biochemical pathway, also known as the homocysteine cycle, regulated by the presence of B vitamins (folate, B6, B12) and choline, among other metabolites. One of the intermediates of this metabolism is S-adenosylmethionine, which represent the methyl donor in all the DNA methyltransferase reactions in eukaryotes. The one-carbon metabolism therefore produces the substrate necessary for the transferring of a methyl group on the cytosine residues of DNA; S-adenosylmethionine also regulates the activity of the enzymes that catalyze this reaction, namely the DNA methyltransferases (DNMTs). Alterations of this metabolic cycle can therefore be responsible for aberrant DNA methylation processes possibly leading to several human diseases. As a matter of fact, increasing evidences indicate that a number of human diseases with multifactorial origin may have an epigenetic basis. This is also due to the great technical advances in the field of epigenetic research. Among the human diseases associated with epigenetic factors, aging-related and neurodegenerative diseases are probably the object of most intense research. This review will present the main evidences linking several human diseases to DNA methylation, with particular focus on neurodegenerative diseases, together with a short description of the state-of-the-art of methylation assays. PMID:23183753

  14. Scurvy in pediatric age group - A disease often forgotten?

    PubMed

    Agarwal, Anil; Shaharyar, Abbas; Kumar, Anubrat; Bhat, Mohd Shafi; Mishra, Madhusudan

    2015-06-01

    Scurvy is caused by prolonged severe dietary deficiency of vitamin C. Being rare as compared to other nutritional deficiencies, it is seldom suspected and this frequently leads to delayed recognition of this disorder. Children with abnormal dietary habits, mental illness or physical disabilities are prone to develop this disease. The disease spectrum of scurvy is quite varied and includes dermatological, dental, bone and systemic manifestations. Subperiosteal hematoma, ring epiphysis, metaphyseal white line and rarefaction zone along with epiphyseal slips are common radiological findings. High index of suspicion, detailed history and bilateral limb radiographs aids physician in diagnosing this eternal masquerader. We searched Pubmed for recent literature (2009-2014) with search terms "scurvy" "vitamin C deficiency" "ascorbic acid deficiency" "scurvy and children" "scurvy and pediatric age group". There were a total of 36 articles relevant to pediatric scurvy in children (7 reviews and 29 case reports) which were retrieved. The review briefly recapitulates the role of vitamin C, the various disease manifestations and the treatment of scurvy to create awareness of the disease which still is reported from our country, although sporadically. The recent advances related to scurvy and its management in pediatric age group are also incorporated. PMID:25983516

  15. What has ageing to do with periodontal health and disease?

    PubMed

    Persson, G Rutger

    2006-08-01

    Periodontitis is a multi-factorial disease and in most cases also a disease with a chronic progression. Exposure to factors which contribute to periodontitis occurs over a long period, so that at the time of diagnosis it may be difficult to identify and evaluate what co-factors have contributed to its development. These include exposure to bacteria and viruses, inflammation, genetic factors, health behaviours and a variety of social factors, socio-economic status, behavioural and nutritional habits, the ability to cope with stress and the ability of the immune system to fight infections. Many patients in their 50s also experience other conditions such as heart disease, diabetes mellitus, or rheumatoid arthritis and recent reports on the associations and potential biological mechanisms by which periodontitis can be linked to other systemic diseases suggest that the patient with periodontitis is a challenged individual. Neither individuals nor their oral health care providers are currently prepared for the challenges in oral health care as the expectation of successful ageing with remaining and aesthetically functional teeth is increasing. The scientific evidence is, however, growing, and while the opportunities to prepare for successful ageing exist they must be included in the educational process of both current and future oral health care providers and their patients. PMID:16972399

  16. Scurvy in pediatric age group – A disease often forgotten?

    PubMed Central

    Agarwal, Anil; Shaharyar, Abbas; Kumar, Anubrat; Bhat, Mohd Shafi; Mishra, Madhusudan

    2015-01-01

    Scurvy is caused by prolonged severe dietary deficiency of vitamin C. Being rare as compared to other nutritional deficiencies, it is seldom suspected and this frequently leads to delayed recognition of this disorder. Children with abnormal dietary habits, mental illness or physical disabilities are prone to develop this disease. The disease spectrum of scurvy is quite varied and includes dermatological, dental, bone and systemic manifestations. Subperiosteal hematoma, ring epiphysis, metaphyseal white line and rarefaction zone along with epiphyseal slips are common radiological findings. High index of suspicion, detailed history and bilateral limb radiographs aids physician in diagnosing this eternal masquerader. We searched Pubmed for recent literature (2009–2014) with search terms “scurvy” “vitamin C deficiency” “ascorbic acid deficiency” “scurvy and children” “scurvy and pediatric age group”. There were a total of 36 articles relevant to pediatric scurvy in children (7 reviews and 29 case reports) which were retrieved. The review briefly recapitulates the role of vitamin C, the various disease manifestations and the treatment of scurvy to create awareness of the disease which still is reported from our country, although sporadically. The recent advances related to scurvy and its management in pediatric age group are also incorporated. PMID:25983516

  17. Graves' Disease Pharmacotherapy in Women of Reproductive Age.

    PubMed

    Prunty, Jeremy J; Heise, Crystal D; Chaffin, David G

    2016-01-01

    Graves' disease is an autoimmune disorder in which inappropriate stimulation of the thyroid gland results in unregulated secretion of thyroid hormones resulting in hyperthyroidism. Graves' disease is the most common cause of autoimmune hyperthyroidism during pregnancy. Treatment options for Graves' disease include thioamide therapy, partial or total thyroidectomy, and radioactive iodine. In this article, we review guideline recommendations for Graves' disease treatment in women of reproductive age including the recent guideline from the American College of Obstetricians and Gynecologists. Controversy regarding appropriate thioamide therapy before, during, and after pregnancy is reviewed. Surgical and radioactive iodine therapy considerations in this patient population are also reviewed. In patients who may find themselves pregnant during therapy or develop Graves' disease during their pregnancy, consideration should be given to the most appropriate treatment course for the mother and fetus. Thioamide therapy should be used with either propylthiouracil or methimazole at appropriate doses that target the upper range of normal to slightly hyperthyroid to avoid creating hypothyroidism in the fetus. Consideration should also be given to the adverse effects of thioamide, such as agranulocytosis and hepatotoxicity, with appropriate patient consultation regarding signs and symptoms. Individuals who wish to breastfeed their infants while taking thioamide should receive the lowest effective dose. Surgery should be reserved for extreme cases and limited to the second trimester, if possible. Radioactive iodine therapy may be used in nonpregnant individuals, with limited harm to future fertility. Radioactive iodine therapy should be withheld in pregnant women and those who are actively breastfeeding. Clinicians should keep abreast of developments in clinical trials and evidence-based recommendations regarding Graves' disease in reproductive-age women for any changes in evidence

  18. Age at disease onset: a key factor for understanding psoriatic disease.

    PubMed

    Queiro, Rubén; Tejón, Patricia; Alonso, Sara; Coto, Pablo

    2014-07-01

    Psoriasis and PsA are immune-mediated diseases with a strong genetic component. More than 20 new loci have been recently linked to these diseases. However, interactions between these genes and the phenotypic traits of both diseases are poorly understood at present. Stratification of psoriatic disease according to the sex of the patients, genetic factors or age at onset has allowed in the last few years a better understanding of the principles governing the onset and progression of these processes. The age of onset of psoriasis has been used for decades as an appropriate descriptor to define two subpopulations of psoriatic patients (types I and II) whose clinical and immunogenetic characteristics have been very well differentiated. Moreover, in patients with PsA this distinction between type I and II psoriasis also seems equally operative. In patients with PsA expressing the HLA-C*06 antigen, the latency between the onset of psoriasis and onset of joint symptoms is longer than in those without this marker. It is also known that PsA tends to appear earlier in patients with HLA-B*27 positivity, and that these patients also show a shorter interval of time between the onset of cutaneous lesions and the onset of joint disease. This review highlights the growing importance of age at disease onset as a key stratification factor in worldwide clinical and genetic studies of psoriatic disease. PMID:24273020

  19. Comparing the influences of age and disease on the Brief Assessment of Cognition in Schizophrenia in Japanese patients with schizophrenia

    PubMed Central

    Kaneda, Ayako; Katagai, Takeshi; Yasui-Furukori, Norio

    2013-01-01

    Background The Brief Assessment of Cognition in Schizophrenia (BACS) is an evaluation of cognitive function that can be completed with more cases. However, there are few studies that compare which factor, disease or aging, is a better determinant of performance on the BACS. The present study aimed to investigate the influences of disease and aging on BACS performance in schizophrenic patients using subjects with a wide range of ages. Methods Schizophrenic patients (n = 165) and a comparison group (n = 171) were recruited as subjects. All participants completed the Japanese language version of the BACS (BACS-J), and the influences of disease and aging on performance in the BACS were examined with the use of multiple regression analysis. Results There was a significant influence of diagnosis and level of education on all six tasks of the BACS and the performance and composite scores. In addition, age was found to influence five tasks and the composite score, the duration of illness influenced four tasks and the composite score, and gender influenced one task and the composite score. Conclusion The present study suggests that performance on the BACS was impaired not only by disease but also by level of education and aging. PMID:23983469

  20. Ages of celiac disease: From changing environment to improved diagnostics

    PubMed Central

    Tommasini, Alberto; Not, Tarcisio; Ventura, Alessandro

    2011-01-01

    From the time of Gee’s landmark writings, the recent history of celiac disease (CD) can be divided into many ages, each driven by a diagnostic advance and a deeper knowledge of disease pathogenesis. At the same time, these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the disease in population. In the beginning, CD was considered a chronic indigestion, even if the causative food was not known; later, the disease was proven to depend on an intolerance to wheat gliadin, leading to typical mucosal changes in the gut and to a malabsorption syndrome. This knowledge led to curing the disease with a gluten-free diet. After the identification of antibodies to gluten (AGA) in the serum of patients and the identification of gluten-specific lymphocytes in the mucosa, CD was described as an immune disorder, resembling a chronic “gluten infection”. The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presentation. More recently, the characterization of autoantibodies to endomysium and to transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disorders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of gluten reactivity and the real burden of gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further developments for the next celiac age will be proposed. PMID:21990947

  1. Management of women with Gaucher disease in the reproductive age.

    PubMed

    Rosenbaum, Hanna

    2015-02-01

    Gaucher disease (GD) is a lysosomal disorder caused by inherited deficiency of glucocerebrosidase, resulting in the accumulation of glucocerebroside in macrophages, termed "Gaucher cells" (GCs), leading to multiorgan involvement, with hepatosplenomegaly, cytopenias, pulmonary hypertension and osseous complications. The characteristic feature of GD is the organ GCs infiltration compromising their function by inducing local inflammation, infarcts and fibrosis. Enzyme replacement therapy (ERT) available for over two decades improves hematological abnormalities, reverses the visceromegaly, ameliorates bone symptoms and prevents further skeletal complications. GD affects most female events during the reproductive age, particularly, fertility, pregnancy, delivery and puerperium. While pregnancy in GD may exacerbate disease manifestations, the disease may have deleterious effect on female reproductive health milestones. ERT has a beneficial effect on the pregnancy outcome in terms of the risk of spontaneous abortion and GD-related complications, particularly bleeding during delivery and postpartum. Treatment approaches and management aspects of reproductive age events are reviewed hereby, with a focus on the outcome improvement of pregnancies, deliveries and postpartum period in GD patients. PMID:25903536

  2. Antioxidant Supplementation in the Treatment of Aging-Associated Diseases.

    PubMed

    Conti, Valeria; Izzo, Viviana; Corbi, Graziamaria; Russomanno, Giusy; Manzo, Valentina; De Lise, Federica; Di Donato, Alberto; Filippelli, Amelia

    2016-01-01

    Oxidative stress is generally considered as the consequence of an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of antioxidants supplementation therapies, which might partially depend from an underestimation of the patient specific metabolic demand and genetic background, are presented. PMID:26903869

  3. Antioxidant Supplementation in the Treatment of Aging-Associated Diseases

    PubMed Central

    Conti, Valeria; Izzo, Viviana; Corbi, Graziamaria; Russomanno, Giusy; Manzo, Valentina; De Lise, Federica; Di Donato, Alberto; Filippelli, Amelia

    2016-01-01

    Oxidative stress is generally considered as the consequence of an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of antioxidants supplementation therapies, which might partially depend from an underestimation of the patient specific metabolic demand and genetic background, are presented. PMID:26903869

  4. A mitochondrial superoxide theory for oxidative stress diseases and aging.

    PubMed

    Indo, Hiroko P; Yen, Hsiu-Chuan; Nakanishi, Ikuo; Matsumoto, Ken-Ichiro; Tamura, Masato; Nagano, Yumiko; Matsui, Hirofumi; Gusev, Oleg; Cornette, Richard; Okuda, Takashi; Minamiyama, Yukiko; Ichikawa, Hiroshi; Suenaga, Shigeaki; Oki, Misato; Sato, Tsuyoshi; Ozawa, Toshihiko; Clair, Daret K St; Majima, Hideyuki J

    2015-01-01

    Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed "the Superoxide Theory," which postulates that superoxide (O2 (•-)) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich's seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging. PMID:25834301

  5. A mitochondrial superoxide theory for oxidative stress diseases and aging

    PubMed Central

    Indo, Hiroko P.; Yen, Hsiu-Chuan; Nakanishi, Ikuo; Matsumoto, Ken-ichiro; Tamura, Masato; Nagano, Yumiko; Matsui, Hirofumi; Gusev, Oleg; Cornette, Richard; Okuda, Takashi; Minamiyama, Yukiko; Ichikawa, Hiroshi; Suenaga, Shigeaki; Oki, Misato; Sato, Tsuyoshi; Ozawa, Toshihiko; Clair, Daret K. St.; Majima, Hideyuki J.

    2015-01-01

    Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed ”the Superoxide Theory,” which postulates that superoxide (O2•−) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging. PMID:25834301

  6. Factors affecting perception thresholds of vertical whole-body vibration in recumbent subjects: Gender and age of subjects, and vibration duration

    NASA Astrophysics Data System (ADS)

    Matsumoto, Y.; Maeda, S.; Iwane, Y.; Iwata, Y.

    2011-04-01

    Some factors that may affect human perception thresholds of the vertical whole-body vibrations were investigated in two laboratory experiments with recumbent subjects. In the first experiment, the effects of gender and age of subjects on perception were investigated with three groups of 12 subjects, i.e., young males, young females and old males. For continuous sinusoidal vibrations at 2, 4, 8, 16, 31.5 and 63 Hz, there were no significant differences in the perception thresholds between male and female subjects, while the thresholds of young subjects tended to be significantly lower than the thresholds of old subjects. In the second experiment, the effect of vibration duration was investigated by using sinusoidal vibrations, at the same frequencies as above, modulated by the Hanning windows with different lengths (i.e., 0.5, 1.0, 2.0 and 4.0 s) for 12 subjects. It was found that the peak acceleration at the threshold tended to decrease with increasing duration of vibration. The perception thresholds were also evaluated by the running root-mean-square (rms) acceleration and the fourth power acceleration method defined in the current standards. The differences in the threshold of the transient vibrations for different durations were less with the fourth power acceleration method. Additionally, the effect of the integration time on the threshold was investigated for the running rms acceleration and the fourth power acceleration. It was found that the integration time that yielded less differences in the threshold of vibrations for different durations depended on the frequency of vibration.

  7. Regional placental blood oxygen level dependent (BOLD) changes with gestational age in normally developing pregnancies using long duration R2* mapping in utero

    NASA Astrophysics Data System (ADS)

    Dighe, Manjiri; Kim, Yun Jung; Seshamani, Sharmishtaa; Blazejewska, Ania I.; Mckown, Susan; Caucutt, Jason; Gatenby, Christopher; Studholme, Colin

    2016-03-01

    The aim of this study was to examine the use of R2* mapping in maternal and fetal sub-regions of the placenta with the aim of providing a reference for blood oxygenation levels during normative development. There have been a number of MR relaxation studies of placental tissues in-utero, but none have reported R2* value changes with age, or examined differences in sub-regions of the placenta. Here specialized long-duration Multi-frame R2* imaging was used to create a stable estimate for R2* values in different placental regions in healthy pregnant volunteers not imaged for clinical reasons. 27 subjects were recruited and scanned up to 3 times during their pregnancy. A multi-slice dual echo EPI based BOLD acquisition was employed and repeated between 90 and 150 times over 3 to 5 minutes to provide a high accuracy estimate of the R2* signal level. Acquisitions were also repeated in 13 cases within a visit to evaluate reproducibility of the method in a given subject. Experimental results showed R2* measurements were highly repeatable within a visit with standard deviation of (0.76). Plots of all visits against gestational age indicated clear correlations showing decreases in R2* with age. This increase was consistent was also consistent over time in multiple visits of the same volunteer during their pregnancy. Maternal and fetal regional changes with gestational age followed the same trend with increase in R2* over the gestational age.

  8. Circulating miRNAs in Ageing and Ageing-Related Diseases

    PubMed Central

    Jung, Hwa Jin; Suh, Yousin

    2015-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. They are involved in important biological processes including development, homeostasis, and ageing. Recently, extracellular miRNAs have been discovered in the bloodstream and bodily fluids. These miRNAs are shown to be secreted and circulating in microvesicles (MVs), or in complex with other factors such as RNA-binding proteins and high-density lipoprotein (HDL) particles. These cell-free, circulating miRNAs can be taken into and function as negative regulators of target genes in recipient cells. Here we review the biogenesis and uptake of circulating miRNAs as well as their profiles in ageing and ageing-related diseases. We discuss the emerging role of circulating miRNAs as biomarkers and therapeutic targets. PMID:25269672

  9. Age and duration of the Mississippi Valley-type mineralizing fluid flow event in the Viburnum Trend, southeast Missouri, USA, determined from palaeomagnetism

    USGS Publications Warehouse

    Symons, David T. A.; Lewchuk, Michael T.; Leach, D.L.

    1998-01-01

    This paper is included in the Special Publication entitled 'Dating and duration of fluid flow and fluid-rock interaction', edited by J. Parnell. The Viburnum Trend is a world-class Mississippi Valley-type (MVT) lead-zinc ore deposit in platform carbonates of the Upper Cambrian Bonneterre Dolomite in the midcontinent of the USA. Palaeomagnetic methods have been used to analyse 233 specimens from early octahedral (nine sites) and late-stage cubic (13 sites) galena ore from four mines along the c. 70 km north-south length of the Trend. The characteristic remanence is carried by single to pseudo-single domain pyrrhotite and magnetite. This is the first MVT deposit in which pyrrhotite is shown to be a remanence carrier and present in galena crystals. The remanence directions define an Early Permian mean age of 273 ?? 10 Ma for the ore-stage mineralization, a maximum duration for the mineralization event of 12 Ma, and a time difference of 5 Ma between the early octahedral and late cubic galena ore stages. The Early Permian age for the ore is consistent with models of ore genesis that invoke fluid flow from the Ouachita orogen during Ouachitan orogenesis.

  10. Picture priming in normal aging and Alzheimer's disease.

    PubMed

    Ballesteros, Soledad; Reales, José M; Mayas, Julia

    2007-05-01

    The present study investigated age invariance for naming pictures and whether implicit memory is spared in Alzheimer's disease (AD). During the study phase, young adults, AD patients, and older controls were shown outlines of familiar pictures. After a distracter task, implicit memory was assessed incidentally. The results showed similar visual priming for the three groups, although young adults responded faster than the two older groups. Moreover, the number of errors was smaller for studied than for non-studied pictures. This pattern of results was repeated across the three groups, although AD patients produced more errors than young adults and older controls, and there were no differences between these latter groups. These results confirmed previous visual and haptic findings showing unimpaired perceptual priming in normal aging and AD patients when implicit memory is assessed using identification tasks. These results are interpreted from a cognitive neuroscience perspective. PMID:17425893

  11. Age, duration of formation, and geotectonic position of the Zavitaya lithium granite-pegmatite system, Eastern Transbaikalia

    NASA Astrophysics Data System (ADS)

    Zagorsky, V. Ye.; Shokalsky, S. P.; Sergeev, S. A.

    2015-01-01

    The Zavitaya granite-pegmatite system with a lithium deposit is localized in the northern marginal part of the Onon terrane (Aginskii massif) and ajoins to the Ingoda-Shilka branch of the Mongol-Okhotsk suture in the south. This paper presents the first U-Pb (SHRIMP) age of granites and barren and spodumene pegmatites of the Zavitaya field. The Zavitaya polychronous granite-pegmatite system evolved through 40 million years: porphyritic biotite granites (169.0 ± 3 Ma), two mica granites-leucogranites (147.5 ± 3.1 Ma), muscovite leucogranites (140.0 ± 3.0 Ma), barren pegmatites (139.6 ± 3.1 Ma), and lithium spodumem pegmatites (129.6 ± 2.7 Ma). The formation of the system coincides with the change in geodynamic regimes of the region at the Middle Jurassic-Early Cretaceous boundary: the age of the early granites of the system and spodumene pegmatites corresponds to the termination of collision and to the beginning of the Early Cretaceous rifting, respectively.

  12. Factors Affecting 14C Ages of Lacustrine Carbonates: Timing and Duration of the Last Highstand Lake in the Lahontan Basin

    USGS Publications Warehouse

    Benson, L.

    1993-01-01

    Two processes contribute to inaccurate 14C age estimates of carbonates precipitated within the Lahontan basin, NevadaCalifornia: low initial 14C/C ratios in lake water (reservoir effect) and addition of modern carbon to calcium carbonate after its precipitation. The mast reliable set of 14C ages on carbonates from elevations > 1310 m in the Pyramid and Walker Lake subbasins indicate that lakes in all seven Lahontan subbasins coalesced ???14,200 14C yr B.P. forming Lake Lahontan. Lake Lahontan achieved its 1330-m highstand elevation by ???13,800 14 C yr B.P. and receded to 1310 m by ???13,700 14C yr B.P. Calculations, based on measured carbonate-accumulation rates, of the amount of time Lake Lahontan exceeded 1310 and 1330 m (500 and 50 yr) are consistent with this chronology. The timing of the Lake Lahontan highstand is of interest because of the linkage of highstand climates with proximity to the polar jet stream. The brevity of the Lahontan highstand is interpreted to indicate that the core of the southern branch of the polar jet stream remained only briefly over the Lahontan basin.

  13. Proteostasis and the Aging Proteome in Health and Disease

    PubMed Central

    2014-01-01

    The maintenance of the proteome is essential to preserve cell functionality and the ability to respond and adapt to the changing environment. This is regulated by the proteostasis network, a dedicated set of molecular components comprised of molecular chaperones and protein clearance mechanisms, regulated by cell stress signaling pathways, that prevents the toxicity associated with protein misfolding and accumulation of toxic aggregates in different subcellular compartments and tissues. The efficiency of the proteostasis network declines with age and this failure in protein homeostasis has been proposed to underlie the basis of common age-related human disorders. The current advances in the understanding of the mechanisms and regulation of proteostasis and of the different types of digressions in this process in aging have turned the attention toward the therapeutic opportunities offered by the restoration of proteostasis in age-associated degenerative diseases. Here, we discuss some of the unresolved questions on proteostasis that need to be addressed to enhance healthspan and to diminish the pathology associated with persistent protein damage. PMID:24833584

  14. Genome maintenance and transcription integrity in aging and disease

    PubMed Central

    Wolters, Stefanie; Schumacher, Björn

    2013-01-01

    DNA damage contributes to cancer development and aging. Congenital syndromes that affect DNA repair processes are characterized by cancer susceptibility, developmental defects, and accelerated aging (Schumacher et al., 2008). DNA damage interferes with DNA metabolism by blocking replication and transcription. DNA polymerase blockage leads to replication arrest and can gives rise to genome instability. Transcription, on the other hand, is an essential process for utilizing the information encoded in the genome. DNA damage that interferes with transcription can lead to apoptosis and cellular senescence. Both processes are powerful tumor suppressors (Bartek and Lukas, 2007). Cellular response mechanisms to stalled RNA polymerase II complexes have only recently started to be uncovered. Transcription-coupled DNA damage responses might thus play important roles for the adjustments to DNA damage accumulation in the aging organism (Garinis et al., 2009). Here we review human disorders that are caused by defects in genome stability to explore the role of DNA damage in aging and disease. We discuss how the nucleotide excision repair system functions at the interface of transcription and repair and conclude with concepts how therapeutic targeting of transcription might be utilized in the treatment of cancer. PMID:23443494

  15. Musculoskeletal Disease in Aged Horses and Its Management.

    PubMed

    van Weeren, Paul René; Back, Willem

    2016-08-01

    Musculoskeletal disorders are the most prevalent health problem in aging horses. They are not life threatening, but are painful and an important welfare issue. Chronic joint disease (osteoarthritis) and chronic laminitis are the most prevalent. Treating osteoarthritis in the elderly horse is similar to treating performance horses, but aims at providing a stable situation with optimal comfort. Immediate medical treatment of flare-ups, long-term pain management, and adaptation of exercise and living conditions are the mainstays of treatment. Laminitis in the geriatric horse is related often to pituitary pars intermedia dysfunction, which may be treated with additional pergolide. PMID:27449390

  16. Chronic hepatitis C: an age wave of disease burden.

    PubMed

    McHutchison, John G; Bacon, Bruce R

    2005-10-01

    There are at least 2.7 million individuals in the United States, most of them in their 40s and 50s, who are chronically infected with hepatitis C virus (HCV). As these infected individuals get older, about 20% will develop cirrhosis, and a significant fraction of those with cirrhosis (about 1 in 10) will then develop serious decompensated liver disease or hepatocellular carcinoma. Currently, HCV is the primary cause of death in 8000 to 12 000 people every year; the virus is also the primary reason for liver transplantation in the United States. Although the number of new cases of HCV infection has been dropping steadily since the introduction of improved blood-supply screening, the "age wave" of existing chronic HCV in baby boomers is expected to contribute to a substantial rise in morbidity, mortality, and costs over the next 2 decades. Although it is difficult to predict which HCV-infected patients will progress to serious liver disease, the availability of a combination drug regimen (peginterferon alfa plus ribavirin) that essentially "cures" the disease in more than half of treated patients now provides clinicians and pharmacists in managed care settings with the tools needed to diminish the impact of the anticipated wave of liver disease. This article reviews the epidemiology, natural history, clinical and economic burden, and screening and treatment options for HCV. PMID:16232012

  17. Radiocarbon ages of terrestrial gastropods extend duration of ice-free conditions at the Two Creeks forest bed, Wisconsin, USA

    USGS Publications Warehouse

    Rech, Jason A.; Nekola, Jeffrey C.; Pigati, Jeffrey S.

    2012-01-01

    Analysis of terrestrial gastropods that underlie the late Pleistocene Two Creeks forest bed (~ 13,800–13,500 cal yr BP) in eastern Wisconsin, USA provides evidence for a mixed tundra-taiga environment prior to formation of the taiga forest bed. Ten new AMS 14C analyses on terrestrial gastropod shells indicate the mixed tundra-taiga environment persisted from ~ 14,500 to 13,900 cal yr BP. The Twocreekan climatic substage, representing ice-free conditions on the shore of Lake Michigan, therefore began near the onset of peak warming conditions during the Bølling–Allerød interstadial and lasted ~ 1000 yr, nearly 600 yr longer than previously thought. These results provide important data for understanding the response of continental ice sheets to global climate forcing and demonstrate the potential of using terrestrial gastropod fossils for both environmental reconstruction and age control in late Quaternary sediments.

  18. Circulating inflamma-miRs in aging and age-related diseases

    PubMed Central

    Olivieri, Fabiola; Rippo, Maria R.; Procopio, Antonio D.; Fazioli, Francesca

    2013-01-01

    Evidence on circulating microRNAs (miRNAs) is indisputably opening a new era in systemic and tissue-specific biomarker research, highlighting new inter-cellular and inter-organ communication mechanisms. Circulating miRNAs might be active messengers eliciting a systemic response as well as non-specific “by-products” of cell activity and even of cell death; in either case they have the potential to be clinically relevant biomarkers for a number of physiopathological processes, including inflammatory responses and inflammation-related conditions. A large amount of evidence indicates that miRNAs can exert two opposite roles, activating as well as inhibiting inflammatory pathways. The inhibitory action probably relates to the need for activating anti-inflammatory mechanisms to counter potent proinflammatory signals, like the nuclear factor kappaB (NF-κB) pathway, to prevent cell and tissue destruction. MiRNA-based anti-inflammatory mechanisms may acquire a crucial role during aging, where a chronic, low-level proinflammatory status is likely sustained by the cell senescence secretome and by progressive activation of immune cells over time. This process entails age-related changes, especially in extremely old age, in those circulating miRNAs that are capable of modulating the inflammatory status (inflamma-miRs). Interestingly, a number of such circulating miRNAs seem to be promising biomarkers for the major age-related diseases that share a common chronic, low-level proinflammatory status, such as cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), Alzheimer Disease (AD), rheumatoid arthritis (RA), and cancers. PMID:23805154

  19. Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases

    PubMed Central

    Sallam, Nada

    2016-01-01

    Despite the wealth of epidemiological and experimental studies indicating the protective role of regular physical activity/exercise training against the sequels of aging and cardiovascular diseases, the molecular transducers of exercise/physical activity benefits are not fully identified but should be further investigated in more integrative and innovative approaches, as they bear the potential for transformative discoveries of novel therapeutic targets. As aging and cardiovascular diseases are associated with a chronic state of oxidative stress and inflammation mediated via complex and interconnected pathways, we will focus in this review on the antioxidant and anti-inflammatory actions of exercise, mainly exerted on adipose tissue, skeletal muscles, immune system, and cardiovascular system by modulating anti-inflammatory/proinflammatory cytokines profile, redox-sensitive transcription factors such as nuclear factor kappa B, activator protein-1, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, antioxidant and prooxidant enzymes, and repair proteins such as heat shock proteins, proteasome complex, oxoguanine DNA glycosylase, uracil DNA glycosylase, and telomerase. It is important to note that the effects of exercise vary depending on the type, intensity, frequency, and duration of exercise as well as on the individual's characteristics; therefore, the development of personalized exercise programs is essential. PMID:26823952

  20. The hippocampus in aging and disease: From plasticity to vulnerability.

    PubMed

    Bartsch, T; Wulff, P

    2015-11-19

    The hippocampus has a pivotal role in learning and in the formation and consolidation of memory and is critically involved in the regulation of emotion, fear, anxiety, and stress. Studies of the hippocampus have been central to the study of memory in humans and in recent years, the regional specialization and organization of hippocampal functions have been elucidated in experimental models and in human neurological and psychiatric diseases. The hippocampus has long been considered a classic model for the study of neuroplasticity as many examples of synaptic plasticity such as long-term potentiation and -depression have been identified and demonstrated in hippocampal circuits. Neuroplasticity is the ability to adapt and reorganize the structure or function to internal or external stimuli and occurs at the cellular, population, network or behavioral level and is reflected in the cytological and network architecture as well as in intrinsic properties of hippocampal neurons and circuits. The high degree of hippocampal neuroplasticity might, however, be also negatively reflected in the pronounced vulnerability of the hippocampus to deleterious conditions such as ischemia, epilepsy, chronic stress, neurodegeneration and aging targeting hippocampal structure and function and leading to cognitive deficits. Considering this framework of plasticity and vulnerability, we here review basic principles of hippocampal anatomy and neuroplasticity on various levels as well as recent findings regarding the functional organization of the hippocampus in light of the regional vulnerability in Alzheimer's disease, ischemia, epilepsy, neuroinflammation and aging. PMID:26241337

  1. Dermatological disease in the older age group: a cross-sectional study in aged care facilities

    PubMed Central

    Deo, Maneka S; Vandal, Alain C; Jarrett, Paul

    2015-01-01

    Objectives To estimate the prevalence of dermatological disease in aged care facilities, and the relationship between cognitive or physical disability and significant disease. Setting 2 large aged care facilities in Auckland, New Zealand, each providing low and high level care. Participants All 161 residents of the facilities were invited to participate. The only exclusion criterion was inability to obtain consent from the individual or designated guardian. 88 participants were recruited—66 females (75%), 22 males (25%) with average age 87.1 years (SD 5.5 years). Primary and secondary outcome measures Primary—presence of significant skin disease (defined as that which in the opinion of the investigators needed treatment or was identified as a patient concern) diagnosed clinically on full dermatological examination by a dermatologist or dermatology trainee. Secondary—functional and cognitive status (Rehabilitation Complexity Scale and Abbreviated Mental Test Score). Results 81.8% were found to have at least one significant condition. The most common disorders were onychomycosis 42 (47.7%), basal cell carcinoma 13 (14.8%), asteototic eczema 11 (12.5%) and squamous cell carcinoma in situ 9 (10.2%). Other findings were invasive squamous cell carcinoma 7 (8%), bullous pemphigoid 2 (2.3%), melanoma 2 (2.3%), lichen sclerosus 2 (2.3%) and carcinoma of the breast 1 (1.1%). Inflammatory disease was more common in those with little physical disability compared with those with serious physical disability (OR 3.69; 95% CI 1.1 to 12.6, p=0.04). No significant association was found between skin disease and cognitive impairment. Conclusions A high rate of dermatological disease was found. Findings ranged from frequent but not life-threatening conditions (eg, onychomycosis), to those associated with a significant morbidity (eg, eczema, lichen sclerosus and bullous pemphigoid), to potentially life-threatening (eg, squamous cell carcinoma, melanoma and breast cancer

  2. The school age child with congenital heart disease.

    PubMed

    Boyle, Lynn; Kelly, Michelle M; Reynolds, Kathryn; Conlan, Misty; Taylor, Felisha

    2015-01-01

    Currently, in the United States, there are approximately 1 in 150 adults living with congenital heart disease (CHD) (). Infant and childhood mortality related to CHD decreased by 31% between 1987 and 2005 (). This survival trend is predicted to increase each year due to advancements in treatment and management of CHD. This significant shift in the epidemiology of CHD requires nurses to take action in preparing children with CHD and their families for their teenage years and young adulthood. The school-age child is the ideal age to begin teaching the child about their healthcare needs and how to care for themselves in preparation for the future. The school-age child with CHD has specific physical, intellectual, emotional, and developmental needs that must be considered and managed using a multidisciplinary approach. Pediatric nurses must be aware of these needs as they help the child and their family seamlessly and successfully transition into young adulthood as a happy and healthy CHD survivor. PMID:25330332

  3. Translational Research Involving Oxidative Stress and Diseases of Aging

    PubMed Central

    Floyd, Robert A.; Towner, Rheal A.; He, Ting; Hensley, Kenneth; Maples, Kirk R.

    2011-01-01

    There is ample mounting evidence that reactive oxidant species are exacerbated in inflammatory processes, many pathological conditions and underlying processes of chronic age-related diseases. Therefore there is increased expectation that therapeutics can be developed which act in some fashion to suppress reactive oxidant species and ameliorate the condition. This has turned out to be more difficult than at first expected. Developing therapeutics for indications where reactive oxidant species is an important consideration presents some unique challenges. We discuss important questions including whether reactive oxidant species should be a therapeutic target and the need to recognize the fact that an antioxidant in a defined chemical system may be a poor antioxidant operationally in a biological system and the importance of considering the fact that reactive oxidant species may accompany the disease or pathological system rather than being a causative factor. We also discuss the value of having preclinical models to determine if the processes which are important in causing the disease under study is critically dependent on reactive oxidant species events and if the therapeutic under consideration quells these processes. In addition we discuss measures of success that must be met in commercial research and development in preclinical and clinical trials and discuss as examples our translational research effort in developing nitrones for the treatment of acute ischemic stroke and as anti-cancer agents. PMID:21549833

  4. Hypoxia-Inducible Histone Lysine Demethylases: Impact on the Aging Process and Age-Related Diseases

    PubMed Central

    Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

    2016-01-01

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

  5. Hypoxia-Inducible Histone Lysine Demethylases: Impact on the Aging Process and Age-Related Diseases.

    PubMed

    Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

    2016-03-01

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

  6. Mixing in age-structured population models of infectious diseases.

    PubMed

    Glasser, John; Feng, Zhilan; Moylan, Andrew; Del Valle, Sara; Castillo-Chavez, Carlos

    2012-01-01

    Infectious diseases are controlled by reducing pathogen replication within or transmission between hosts. Models can reliably evaluate alternative strategies for curtailing transmission, but only if interpersonal mixing is represented realistically. Compartmental modelers commonly use convex combinations of contacts within and among groups of similarly aged individuals, respectively termed preferential and proportionate mixing. Recently published face-to-face conversation and time-use studies suggest that parents and children and co-workers also mix preferentially. As indirect effects arise from the off-diagonal elements of mixing matrices, these observations are exceedingly important. Accordingly, we refined the formula published by Jacquez et al. [19] to account for these newly-observed patterns and estimated age-specific fractions of contacts with each preferred group. As the ages of contemporaries need not be identical nor those of parents and children to differ by exactly the generation time, we also estimated the variances of the Gaussian distributions with which we replaced the Kronecker delta commonly used in theoretical studies. Our formulae reproduce observed patterns and can be used, given contacts, to estimate probabilities of infection on contact, infection rates, and reproduction numbers. As examples, we illustrate these calculations for influenza based on "attack rates" from a prospective household study during the 1957 pandemic and for varicella based on cumulative incidence estimated from a cross-sectional serological survey conducted from 1988-94, together with contact rates from the several face-to-face conversation and time-use studies. Susceptibility to infection on contact generally declines with age, but may be elevated among adolescents and adults with young children. PMID:22037144

  7. Analytical approaches to the diagnosis and treatment of aging and aging-related disease: redox status and proteomics.

    PubMed

    Calabrese, V; Dattilo, S; Petralia, A; Parenti, R; Pennisi, M; Koverech, G; Calabrese, V; Graziano, A; Monte, I; Maiolino, L; Ferreri, T; Calabrese, E J

    2015-05-01

    Basal levels of oxidants are indispensible for redox signaling to produce adaptive cellular responses such as vitagenes linked to cell survival; however, at higher levels, they are detrimental to cells, contributing to aging and to the pathogenesis of numerous age-related diseases. Aging is a complex systemic process and the major gap in aging research reminds the insufficient knowledge about pathways shifting from normal "healthy" aging to disease-associated pathological aging. The major complication of normal "healthy" aging is in fact the increasing risk of age-related diseases such as cardiovascular diseases, diabetes mellitus, and neurodegenerative pathologies that can adversely affect the quality of life in general, with enhanced incidences of comorbidities and mortality. In this context, global "omics" approaches may help to dissect and fully study the cellular and molecular mechanisms of aging and age-associated processes. The proteome, being more close to the phenotype than the transcriptome and more stable than the metabolome, represents the most promising "omics" field in aging research. In the present study, we exploit recent advances in the redox biology of aging and discuss the potential of proteomics approaches as innovative tools for monitoring at the proteome level the extent of protein oxidative insult and related modifications with the identification of targeted proteins. PMID:25824967

  8. Regenerating skeletal muscle in the face of aging and disease.

    PubMed

    Jasuja, Ravi; LeBrasseur, Nathan K

    2014-11-01

    Skeletal muscle is a fundamental organ in the generation of force and movement, the regulation of whole-body metabolism, and the provision of resiliency. Indeed, physical medicine and rehabilitation is recognized for optimizing skeletal muscle health in the context of aging (sarcopenia) and disease (cachexia). Exercise is, and will remain, the cornerstone of therapies to improve skeletal muscle health. However, there are now a number of promising biologic and small molecule interventions currently under development to rejuvenate skeletal muscle, including myostatin inhibitors, selective androgen receptor modulators, and an activator of the fast skeletal muscle troponin complex. The opportunities for skeletal muscle-based regenerative therapies and a selection of emerging pharmacologic interventions are discussed in this review. PMID:24879554

  9. [Sleep quality in aged patients with peripheral vascular diseases].

    PubMed

    Corrêa, Karina; Ceolim, Maria Filomena

    2008-03-01

    Peripheral vascular diseases (PVD) are prevalent among the elderly, and, due to their chronic character, result in poor quality of life and poor sleep quality. This study aimed at evaluating sleep quality of elderly people diagnosed with PVD who undergo clinical ambulatory treatment in a university hospital in Campinas, in the State of São Paulo. Subjects (n=50, aged 74 +/- 8 years old) answered the Pittsburgh Sleep Quality Index (PSQI) and provided basic demographic data and PVD history (35 subjects had arterial blockage in lower limbs). Results showed that 34 subjects presented bad sleep quality; sleep length was 5.8 (+/- 2.3) hours, and, according to 23 subjects, night sleep was frequently disturbed by pain (thrice a week or more). Eighteen subjects took analgesics; four took sleep medicines. Findings may have important implications for nurses working with PVD patients, stressing the need to take into account consequences of PVD on sleep disturbances when planning their interventions. PMID:18450142

  10. Effects of promoting increased duration and exclusivity of breastfeeding on adiposity and insulin-like growth factor-I at age 11.5 years: a randomized trial

    PubMed Central

    Martin, Richard M; Patel, Rita; Kramer, Michael S.; Guthrie, Lauren; Vilchuck, Konstantin; Bogdanovich, Natalia; Sergeichick, Natalia; Gusina, Nina; Foo, Ying; Palmer, Tom; Rifas-Shiman, Sheryl L.; Gillman, Matthew W; Davey Smith, George; Oken, Emily

    2013-01-01

    Importance Evidence that increased duration and exclusivity of breastfeeding reduces child obesity risk is based on observational studies that are prone to confounding. Objective To investigate effects of an intervention to promote increased duration and exclusivity of breastfeeding on child adiposity and circulating insulin-like growth factor (IGF)-I (which regulates growth). Design Cluster-randomized controlled trial. Setting 31 Belarusian maternity hospitals and their affiliated polyclinics, randomized to usual practices (n=15) or a breastfeeding promotion intervention (n=16). Participants 17,046 breastfeeding mother-infant pairs enrolled in 1996/7, of whom 13,879 (81.4%) were followed-up between January 2008 and December 2010 at a median age of 11.5 years. Intervention Breastfeeding promotion intervention modeled on the WHO/UNICEF Baby Friendly Hospital Initiative. Main outcome measures Body mass index (BMI), fat and fat-free mass indices (FMI and FFMI), percent body fat, waist circumference, triceps and subscapular skinfold thicknesses, overweight and obesity, and whole-blood IGF-I. Primary analysis was based on modified intention-to-treat (without imputation), accounting for clustering within hospitals/clinics. Results The experimental intervention substantially increased breastfeeding duration and exclusivity (43% vs. 6% and 7.9% vs. 0.6% exclusively breastfed at 3 and 6 months, respectively) versus the control intervention. Cluster-adjusted mean differences in outcomes at 11.5 years between experimental vs. control groups were: 0.19 kg/m2 (95% 4 CI: −0.09, 0.46) for BMI; 0.12 kg/m2 (−0.03, 0.28) for FMI; 0.04 kg/m2 (−0.11, 0.18) for FFMI; 0.47% (−0.11, 1.05) for % body fat; 0.30 cm (−1.41, 2.01) for waist circumference; −0.07 mm (−1.71, 1.57) for triceps and −0.02 mm (−0.79, 0.75) for subscapular skinfold thicknesses; and −0.02 standard deviations (−0.12, 0.08) for IGF-I. The cluster-adjusted odds ratio for overweight / obesity (BMI

  11. Aberrant subcellular neuronal calcium regulation in aging and Alzheimer's disease.

    PubMed

    Camandola, Simonetta; Mattson, Mark P

    2011-05-01

    In this mini-review/opinion article we describe evidence that multiple cellular and molecular alterations in Alzheimer's disease (AD) pathogenesis involve perturbed cellular calcium regulation, and that alterations in synaptic calcium handling may be early and pivotal events in the disease process. With advancing age neurons encounter increased oxidative stress and impaired energy metabolism, which compromise the function of proteins that control membrane excitability and subcellular calcium dynamics. Altered proteolytic cleavage of the β-amyloid precursor protein (APP) in response to the aging process in combination with genetic and environmental factors results in the production and accumulation of neurotoxic forms of amyloid β-peptide (Aβ). Aβ undergoes a self-aggregation process and concomitantly generates reactive oxygen species that can trigger membrane-associated oxidative stress which, in turn, impairs the functions of ion-motive ATPases and glutamate and glucose transporters thereby rendering neurons vulnerable to excitotoxicity and apoptosis. Mutations in presenilin-1 that cause early-onset AD increase Aβ production, but also result in an abnormal increase in the size of endoplasmic reticulum calcium stores. Some of the events in the neurodegenerative cascade can be counteracted in animal models by manipulations that stabilize neuronal calcium homeostasis including dietary energy restriction, agonists of glucagon-like peptide 1 receptors and drugs that activate mitochondrial potassium channels. Emerging knowledge of the actions of calcium upstream and downstream of Aβ provides opportunities to develop novel preventative and therapeutic interventions for AD. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. PMID:20950656

  12. [Dental caries of the developmental age as a civilization disease].

    PubMed

    Wójcicka, Anna; Zalewska, Magdalena; Czerech, Ewa; Jabłoński, Robert; Grabowska, Stanisława Zyta; Maciorkowska, Elzbieta

    2012-01-01

    According to the definition of the World Health Organization (WHO), dental caries is a local pathological process of the extrasomatic background, leading to enamel decalcification, decomposition of dental hard tissue, and in consequence to formation of a dental cavity. Morbidity of dental caries increases with age, reaching 100% of children, aged from 6 to 7. Poland is one of few European countries where the incidence of dental caries in children did not decrease, despite recommendations of WHO for 2000 year, aimed at the decrease in the incidence of dental caries among 6-year-old children to the level of 50%. The recommendation of WHO for 2015 year is to reduce the incidence of dental caries to 30% among 6-year-olds, i.e., 70% of 6 year-old children should be free of dental caries. Apart from genetic conditioning, inappropriate health behaviors, nutritional habits and gastroesophageal reflux disease influence the development of dental caries. Consumption of 'fast food' and drinking sweetened beverages of low pH contribute markedly to the development of dental caries, decreasing simultaneously consumption of pro healthy foods, including milk and cereals. Taking into consideration perspective clinical examinations of children and adolescents, evaluating the relationship between dental caries and nutritional habits as well as environmental conditioning, the study shows current data about factors, contributing to the incidence of dental caries in children, collected from the literature. The attention was paid to the relationship between dental caries and gastroesophageal reflux disease and the necessity of its early diagnostics and proper treatment. PMID:23484402

  13. Sympathetic regulation during thermal stress in human aging and disease.

    PubMed

    Greaney, Jody L; Kenney, W Larry; Alexander, Lacy M

    2016-04-01

    Humans control their core temperature within a narrow range via precise adjustments of the autonomic nervous system. In response to changing core and/or skin temperature, several critical thermoregulatory reflex effector responses are initiated and include shivering, sweating, and changes in cutaneous blood flow. Cutaneous vasomotor adjustments, mediated by modulations in sympathetic nerve activity (SNA), aid in the maintenance of thermal homeostasis during cold and heat stress since (1) they serve as the first line of defense of body temperature and are initiated before other thermoregulatory effectors, and (2) they are on the efferent arm of non-thermoregulatory reflex systems, aiding in the maintenance of blood pressure and organ perfusion. This review article highlights the sympathetic responses of humans to thermal stress, with a specific focus on primary aging as well as impairments that occur in both heart disease and type 2 diabetes mellitus. Age- and pathology-related changes in efferent muscle and skin SNA during cold and heat stress, measured directly in humans using microneurography, are discussed. PMID:26627337

  14. Cerebrovascular contributions to aging and Alzheimer's disease in Down syndrome.

    PubMed

    Wilcock, Donna M; Schmitt, Frederick A; Head, Elizabeth

    2016-05-01

    Down syndrome (DS) is a common cause of intellectual disability and is also associated with early age of onset of Alzheimer's disease (AD). Due to an extra copy of chromosome 21, most adults over 40years old with DS have beta-amyloid plaques as a result of overexpression of the amyloid precursor protein. Cerebrovascular pathology may also be a significant contributor to neuropathology observed in the brains of adults with DS. This review describes the features of cardiovascular dysfunction and cerebrovascular pathology in DS that may be modifiable risk factors and thus targets for interventions. We will describe cerebrovascular pathology, the role of co-morbidities, imaging studies indicating vascular pathology and the possible consequences. It is clear that our understanding of aging and AD in people with DS will benefit from further studies to determine the role that cerebrovascular dysfunction contributes to cognitive health. 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:26593849

  15. [Metabolic abnormalities as a basis for age-dependent diseases and aging? State of the art].

    PubMed

    Tereshina, E V

    2009-01-01

    Metabolic syndrome (MS) is a number of certain criteria reflecting abnormalities in lipid and glucose metabolism. These abnormalities are considered to be a reason for atherosclerosis, cardiovascular diseases (CVD) and diabetes mellitus type 2. The prevalence of CVD among those with diabetes is 3-5 folds higher than without diabetes. MS demonstrates ethnic and gender variants, its frequency depends on the lifestyle and age. Attention to MS has been attracted in the last decades induced by the obesity epidemic in US. The adipose tissue and high triglyceride blood levels have been regarded as hallmark of MS. It has appeared that metabolic ways of cholesterol, fat and glucose were tightly connected and united in a system of energy expenditure and reproduction. The high prevalence of MS, heart attacks and diabetes in the elderly population makes the evidence of age to be an independent risk factor of the development of metabolic abnormalities. But this problem is still out of the field of interest in gerontology. There exist a number of unsolved questions concerning the function of visceral adipose tissue, the role of free fatty acids in the insulin resistance, mechanisms of inflammation in the old age and so on that can be an object of gerontology. So, a program of advanced researches in this field is discussed. PMID:19827683

  16. Valve repair in rheumatic heart disease in pediatric age group.

    PubMed

    Reddy, Pramod K; Dharmapuram, Anil K; Swain, Sunil K; Ramdoss, Nagarajan; Raghavan, Sreekanth S; Murthy, Kona S

    2008-04-01

    Valve repair in children is technically demanding but more desirable than valve replacement. From April 2004 to September 2005, 1 boy and 8 girls with rheumatic heart disease, aged 2-13 years (median, 9 years), underwent valve repair for isolated mitral regurgitation in 5, combined mitral and aortic regurgitation in 2, mitral stenosis in 1, and mitral regurgitation associated with atrial septal defect in 1. Chordal shortening in 7, annular plication in 6, commissurotomy in 1, reconstruction of commissural leaflets in 7 were performed for mitral valve disease. Plication and reattachment of the aortic cusps was carried out in 2 patients. Annuloplasty rings were not used. All patients survived the operation, 8 had trivial or mild residual mitral regurgitation, and 1 had trivial aortic regurgitation. Mean left atrial pressure decreased from 14 to 7 mm Hg postoperatively. During follow-up of 3-18 months, all children were asymptomatic and enjoyed normal activity. None required reoperation. In addition to chordal shortening and annular plication, reconstruction of the commissural leaflets is considered the most important aspect of valve repair. It can be achieved without annuloplasty rings, giving good early and midterm results. PMID:18381871

  17. Nonalcoholic fatty liver disease and aging: Epidemiology to management

    PubMed Central

    Bertolotti, Marco; Lonardo, Amedeo; Mussi, Chiara; Baldelli, Enrica; Pellegrini, Elisa; Ballestri, Stefano; Romagnoli, Dante; Loria, Paola

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic (nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications (cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment (diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients. PMID:25339806

  18. Polygenic risk of Parkinson disease is correlated with disease age at onset

    PubMed Central

    Escott‐Price, Valentina; Nalls, Mike A.; Morris, Huw R.; Lubbe, Steven; Brice, Alexis; Gasser, Thomas; Heutink, Peter; Wood, Nicholas W.; Hardy, John; Singleton, Andrew B.

    2015-01-01

    Objective We have investigated the polygenic architecture of Parkinson disease (PD) and have also explored the potential relationship between an individual's polygenic risk score and their disease age at onset. Methods This study used genotypic data from 4,294 cases and 10,340 controls obtained from the meta‐analysis of PD genome‐wide association studies. Polygenic score analysis was performed as previously described by the International Schizophrenia Consortium, testing whether the polygenic score alleles identified in 1 association study were significantly enriched in the cases relative to the controls of 3 independent studies. Linear regression was used to investigate the relationship between an individual's polygenic score for PD risk alleles and disease age at onset. Results Our polygenic score analysis has identified significant evidence for a polygenic component enriched in the cases of each of 3 independent PD genome‐wide association cohorts (minimum p = 3.76 × 10−6). Further analysis identified compelling evidence that the average polygenic score in patients with an early disease age at onset was significantly higher than in those with a late age at onset (p = 0.00014). Interpretation This provides strong support for a large polygenic contribution to the overall heritable risk of PD and also suggests that early onset forms of the illness are not exclusively caused by highly penetrant Mendelian mutations, but can also be contributed to by an accumulation of common polygenic alleles with relatively low effect sizes. Ann Neurol 2015;77:582–591 PMID:25773351

  19. The association between Kawasaki disease and allergic diseases, from infancy to school age.

    PubMed

    Tsai, Yi-Jing; Lin, Ching-Heng; Fu, Lin-Shien; Fu, Yun-Ching; Lin, Ming-Chih; Jan, Sheng-Ling

    2013-01-01

    Kawasaki disease (KD) is the most common acquired heart disease among preschool children in most industrialized countries. An atopic trend after KD illness has been observed in epidemiological studies. This is consistent with the findings of elevated IgE levels and increased IL-4 in KD patients. However, studies on the early allergic association among children with KD are still limited. This study aimed to evaluate the association between KD and allergic diseases, from infancy to school age. Allergic diseases included atopic dermatitis, allergic rhinitis (AR), asthma, and urticaria. This matched case-control study used the National Health Insurance Research Database of Taiwan as its data source. Patients born between 1997 and 2004 and with a main diagnosis of KD were retrieved for analysis. A 1:4 matched control group was selected by zip code, gender, and age. The prevalence rates and progression sequence of allergic manifestations were analyzed. During the first 5 years of life, children with KD had higher rates of allergic manifestations. Both groups have similar atopic march. In 2010, at the age of 6-13 years, there were 7072 children with KD and 27,265 children without KD. Children with KD had more AR (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.22-1.38) and asthma (OR, 1.16; 95% CI, 1.05-1.27) than controls. Children with KD have a higher allergic susceptibility recognized from their 1st year of life. The atopic tendency persists until school age. Additional studies are needed to elucidate the underlying determinants of this distinct immune phenotype. PMID:23998245

  20. Glutathione as a Biomarker in Parkinson's Disease: Associations with Aging and Disease Severity

    PubMed Central

    Mischley, Laurie K.; Standish, Leanna J.; Weiss, Noel S.; Padowski, Jeannie M.; Kavanagh, Terrance J.; White, Collin C.; Rosenfeld, Michael E.

    2016-01-01

    Objectives. Oxidative stress contributes to Parkinson's disease (PD) pathophysiology and progression. The objective was to describe central and peripheral metabolites of redox metabolism and to describe correlations between glutathione (Glu) status, age, and disease severity. Methods. 58 otherwise healthy individuals with PD were examined during a single study visit. Descriptive statistics and scatterplots were used to evaluate normality and distribution of this cross-sectional sample. Blood tests and magnetic resonance spectroscopy (MRS) were used to collect biologic data. Spearman's rank-order correlation coefficients were used to evaluate the strength and direction of the association. The Unified PD Rating Scale (UPDRS) and the Patient-Reported Outcomes in PD (PRO-PD) were used to rate disease severity using regression analysis. Results. Blood measures of Glu decreased with age, although there was no age-related decline in MRS Glu. The lower the blood Glu concentration, the more severe the UPDRS (P = 0.02, 95% CI: −13.96, −1.14) and the PRO-PD (P = 0.01, 95% CI: −0.83, −0.11) scores. Discussion. These data suggest whole blood Glu may have utility as a biomarker in PD. Future studies should evaluate whether it is a modifiable risk factor for PD progression and whether Glu fortification improves PD outcomes.

  1. College Students' Ageist Behavior: The Role of Aging Knowledge and Perceived Vulnerability to Disease

    ERIC Educational Resources Information Center

    Stahl, Sarah T.; Metzger, Aaron

    2013-01-01

    This cross-sectional study examined the associations among perceived vulnerability to disease, aging knowledge, and ageism (positive and negative) in a sample of undergraduate students enrolled in a human development course (N = 649; M age = 19.94 years, SD = 2.84 years). Perceived vulnerability to disease and aging knowledge were associated with…

  2. Knowledge about Aging and Alzheimer Disease: A Comparison of Professional Caregivers and Noncaregivers

    ERIC Educational Resources Information Center

    Rust, Tiana B.; See, Sheree Kwong

    2007-01-01

    This study assessed professional caregivers of persons with Alzheimer disease (AD) and non-caregivers' knowledge about aging and AD. Participants completed modified versions of the Alzheimer Disease Knowledge Test and the multiple-choice version of the Facts on Aging Quiz #1. Overall, knowledge levels about AD and aging were low. Caregivers were…

  3. TDP-43 in aging and Alzheimer's disease - a review.

    PubMed

    Wilson, Andrea C; Dugger, Brittany N; Dickson, Dennis W; Wang, Deng-Shun

    2011-01-01

    Transactive response DNA-binding protein of 43 kDa (TDP-43), an RNA and DNA binding protein involved in transcriptional repression, RNA splicing and RNA metabolism during the stress response, is the major component of neuronal inclusions in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions, now referred to as FTLD-TDP. While initially thought to be relatively specific to ALS and FTLD-TDP, TDP-43 pathology has now been detected in a number of other neurodegenerative diseases, many associated with tau pathology, including Guam Parkinson dementia complex and Alzheimer's disease (AD). TDP-43 pathology is detected in 25% to 50% of AD cases, especially those with more severe clinical phenotype and greater Alzheimer type pathology, as well as AD cases with hippocampal sclerosis (HS). HS is characterized by selective neuronal loss affecting CA1 sector of the hippocampus, and most cases of HS, with or without AD, have TDP-43 pathology. Whether TDP-43 pathology is merely an incidental finding in AD or actually contributing to the more severe clinical phenotype remains unresolved. Presence of TDP-43 in normal elderly, who are at increased risk for AD, would strengthen the argument that it is not merely a secondary or incidental finding in end stage AD. Limited studies suggest that TDP-43 pathology is infrequent in neurologically normal elderly (3% or less). We provide an overview of what is known about TDP-43 in AD, normal aging and in other disorders and suggest that TDP-43 proteinopathies be considered in two classes - primary and secondary. PMID:21326809

  4. The role of sirtuins in aging and age-related diseases.

    PubMed

    Wątroba, Mateusz; Szukiewicz, Dariusz

    2016-03-01

    Sirtuins, initially described as histone deacetylases and gene silencers in yeast, are now known to have much more functions and to be much more abundant in living organisms. Sirtuins gained much attention when they were first acknowledged to be responsible for some beneficial and longevity-promoting effects of calorie restriction in many species of animals - from fruit flies to mammals. In this paper, we discuss some detailed molecular mechanisms of inducing these effects, and wonder if they could be possibly mimicked without actually applying calorie restriction, through induction of sirtuin activity. It is known now that sirtuins, when adjusting the pattern of cellular metabolism to nutrient availability, can regulate many metabolic functions significant from the standpoint of aging research - including DNA repair, genome stability, inflammatory response, apoptosis, cell cycle, and mitochondrial functions. While carrying out these regulations, sirtuins cooperate with many transcription factors, including PGC-1a, NFKB, p53 and FoxO. This paper contains some considerations about possible use of facilitating activity of the sirtuins in prevention of aging, metabolic syndrome, chronic inflammation, and other diseases. PMID:26521204

  5. [Musculoskeletal pathology in occupational risks and common degenerative disease: reflections on the intensity and duration of the risk].

    PubMed

    Bergamini, Roberta; Astengo, Rossana

    2014-01-01

    Nowadays, in Italy the reports of mnusculoskeletal diseases increase as confirmed in the last INAIL (national insurance for occupational diseases and injuries) annual report. The Emilia-Ronmagna is one of the region with the highest number of reports: 15.9% of the total in 2012. The decree no. 81/08 has partially simplified the medico-legal activities related to musculoskeletal diseases; however, the medico-legal physicians have still to deal with some issues such as risk assessment quality, economic crisis, and specific work environments (e.g. agriculture and many handicraft activities). Tire risk factors of musculoskeletal diseases and their assessments are quite well studied. The latency period of these diseases needs to be investigated, since it could be a relevant aspect for legal medical judgment, insurance protection and prevention. Based on literature data and INAIL experience, authors propose some considerations useful for a scientific debate. PMID:25558730

  6. Specificity of inhibitory deficits in normal aging and Alzheimer's disease.

    PubMed

    Collette, Fabienne; Schmidt, Christina; Scherrer, Christine; Adam, Stéphane; Salmon, Eric

    2009-06-01

    Deficits of suppression abilities are frequently observed in normal aging and Alzheimer's disease. However, few studies have explored these deficits in the two populations simultaneously using a large battery of tasks. The aim of the present study was to explore if the pattern of performance presented by elderly subjects and AD patients is in agreement with theoretical frameworks [Wilson, S.P., Harnishfeger, K.K., 1998. The development of efficient inhibition: Evidence from directed forgetting tasks. Dev. Rev. 18, 86-123; see also Nigg J.T., 2000. On inhibition/disinhibition in developmental psychopathology: views from cognitive and personality psychology and a working inhibition taxonomy. Psychol. Bull. 126, 220-246], distinguishing between the concepts of inhibition (a voluntary suppression of irrelevant information) and interference (an automatic suppression process occurring prior to conscious awareness). The results obtained demonstrated that (1) there is an alteration of the inhibitory process in normal elderly subjects; (2) inhibitory and interference resolution processes are quantitately less efficient in AD, since these patients present a correct performance only for information which leaves weak traces in memory. PMID:18029058

  7. The Impact of HCV Infection Duration on HIV Disease Progression and Response to cART amongst HIV Seroconverters in the UK

    PubMed Central

    Inshaw, Jamie; Leen, Clifford; Gilson, Richard; Hawkins, David; Collins, Simon; Fox, Julie; McLean, Ken; Fidler, Sarah; Phillips, Andrew; Lattimore, Sam; Babiker, Abdel; Porter, Kholoud

    2015-01-01

    Introduction The effect of HCV infection on HIV disease progression remains unclear; the effect of HCV infection duration on HIV disease progression is unknown. Methods We used data from a cohort of HIV seroconverters to investigate the effect of HCV infection duration on time from HIV seroconversion to CD4 <350cells/mm3, AIDS or death, censoring at the earlier of cART initiation or last clinic visit, adjusting for confounders and splitting data into follow up periods from HIV seroconversion (<2, 2–4 and >4 years). We additionally compared CD4 cell decline following HCV infection to that of mono-infected individuals with similar HIV infection duration by fitting a random effects model. In a separate analysis, we used linear mixed models to we examine the effect of HCV infection and its duration on CD4 increase over 48 weeks following cART. Results Of 1655 individuals, 97 (5.9%) were HCV co-infected. HCV<1 year was associated with a higher risk of endpoint in each follow-up period from HIV seroconversion (HR [95% CI] 2.58 [1.51, 4.41], p = 0.001; 3.80 [1.20, 12.03], p = 0.023; 2.03 [0.88, 4.71], p = 0.098 for <2, 2–4 and >4 years respectively), compared to mono-infected individuals. However, we found no evidence of an association for those with HCV>2 years (all p>0.89). Individuals experienced a somewhat greater decrease in CD4 count following HCV infection lasting 13 months, relative to individuals with HIV alone, (estimate = -3.33, 95% CI [-7.29, 0.63] cells/mm3 per month, p = 0.099). Of 1502 initiating cART, 106 (7.1%) were HCV co-infected, with no evidence of HCV duration at cART being associated with immunological response (p = 0.45). Conclusions The impact of HCV co-infection on HIV disease progression appears to be restricted to the first year after HCV infection. PMID:26225723

  8. Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.

    PubMed

    Bousquet, Jean; Jorgensen, Christian; Dauzat, Michel; Cesario, Alfredo; Camuzat, Thierry; Bourret, Rodolphe; Best, Nicolas; Anto, Josep M; Abecassis, Frederic; Aubas, Pierre; Avignon, Antoine; Badin, Melanie; Bedbrook, Anna; Blain, Hubert; Bourdin, Arnaud; Bringer, Jacques; Camu, William; Cayla, Guilhaume; Costa, David J; Courtet, Philippe; Cristol, Jean-Paul; Demoly, Pascal; de la Coussaye, Jean-Emmanuel; Fesler, Pierre; Gouzi, Fares; Gris, Jean-Christophe; Guillot, Bernard; Hayot, Maurice; Jeandel, Claude; Jonquet, Olivier; Journot, Laurent; Lehmann, Sylvain; Mathieu, Gwenaelle; Morel, Jacques; Ninot, Gregory; Pelissier, Jacques; Picot, Marie-Christine; Radier-Pontal, Francoise; Robine, Jean-Marie; Rodier, Michel; Roubille, Francois; Sultan, Ariane; Wojtusciszyn, Anne; Auffray, Charles; Balling, Rudi; Barbara, Cristina; Cambon-Thomsen, Anne; Chavannes, Niels H; Chuchalin, Alexander; Crooks, George; Dedeu, Antoni; Fabbri, Leonardo M; Garcia-Aymerich, Judith; Hajjam, Jawad; Melo Gomes, Elisabete; Palkonen, Susana; Piette, Francois; Pison, Christophe; Price, David; Samolinski, Boleslaw; Schunemann, Holger J; Sterk, Peter J; Yiallouros, Panayiotis; Roca, Josep; Van de Perre, Philippe; Mercier, Jacques

    2014-01-01

    Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council. The novel trend for the management of NCDs is evolving towards integrative, holistic approaches. NCDs are intertwined with ageing. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has prioritised NCDs. To tackle them in their totality in order to reduce their burden and societal impact, it is proposed that NCDs should be considered as a single expression of disease with different risk factors and entities. An innovative integrated health system built around systems medicine and strategic partnerships is proposed to combat NCDs. It includes (i) understanding the social, economic, environmental, genetic determinants, as well as the molecular and cellular mechanisms underlying NCDs; (ii) primary care and practice-based interprofessional collaboration; (iii) carefully phenotyped patients; (iv) development of unbiased and accurate biomarkers for comorbidities, severity and follow up of patients; (v) socio-economic science; (vi) development of guidelines; (vii) training; and (viii) policy decisions. The results could be applicable to all countries and adapted to local needs, economy and health systems. This paper reviews the complexity of NCDs intertwined with ageing. It gives an overview of the problem and proposes two practical examples of systems medicine (MeDALL) applied to allergy and to NCD co-morbidities (MACVIA-LR, Reference Site of the European Innovation Partnership on Active and Healthy Ageing). PMID:24641234

  9. Estimation of Heterogeneity in Diagnostic Parameters of Age-related Diseases.

    PubMed

    Blokh, David; Stambler, Ilia

    2014-08-01

    The heterogeneity of parameters is a ubiquitous biological phenomenon, with critical implications for biological systems functioning in normal and diseased states. We developed a method to estimate the level of objects set heterogeneity with reference to particular parameters and applied it to type II diabetes and heart disease, as examples of age-related systemic dysfunctions. The Friedman test was used to establish the existence of heterogeneity. The Newman-Keuls multiple comparison method was used to determine clusters. The normalized Shannon entropy was used to provide the quantitative evaluation of heterogeneity. There was obtained an estimate for the heterogeneity of the diagnostic parameters in healthy subjects, as well as in heart disease and type II diabetes patients, which was strongly related to their age. With aging, as with the diseases, the level of heterogeneity (entropy) was reduced, indicating a formal analogy between these phenomena. The similarity of the patterns in aging and disease suggested a kind of "early aging" of the diseased subjects, or alternatively a "disease-like" aging process, with reference to these particular parameters. The proposed method and its validation on the chronic age-related disease samples may support a way toward a formal mathematical relation between aging and chronic diseases and a formal definition of aging and disease, as determined by particular heterogeneity (entropy) changes. PMID:25110613

  10. Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration

    PubMed Central

    Swaroop, Anand; Chew, Emily Y.; Rickman, Catherine Bowes; Abecasis, Gonçalo R.

    2012-01-01

    Aging-associated neurodegenerative diseases significantly influence the quality of life of affected individuals. Genetic approaches, combined with genomic technology, have provided powerful insights into common late-onset diseases, such as age-related macular degeneration (AMD). Here, we discuss current findings on the genetics of AMD to highlight areas of rapid progress and new challenges. We also attempt to integrate available genetic and biochemical data with cellular pathways involved in aging to formulate an integrated model of AMD pathogenesis. PMID:19405847

  11. The AGE-RAGE pathway and its relation to cardiovascular disease in patients with chronic kidney disease.

    PubMed

    Leurs, Paul; Lindholm, Bengt

    2013-11-01

    Chronic kidney disease (CKD) carries an unequivocal high risk for cardiovascular disease (CVD) contributing to high morbimortality; however, the underlying reasons are not fully known. Among mechanisms involved in the pathophysiology of CVD, chronic overstimulation of the advanced glycation end-products (AGE)-receptor for AGE (RAGE) pathway is likely a major contributor in patients with CKD. This review describes briefly some of the components of this pathway, highlighting especially differences between circulating AGE and tissue AGE and how activation of the AGE-RAGE pathway may promote CVD in CKD. PMID:24231387

  12. Generative FDG-PET and MRI model of aging and disease progression in Alzheimer's disease.

    PubMed

    Dukart, Juergen; Kherif, Ferath; Mueller, Karsten; Adaszewski, Stanislaw; Schroeter, Matthias L; Frackowiak, Richard S J; Draganski, Bogdan

    2013-04-01

    The failure of current strategies to provide an explanation for controversial findings on the pattern of pathophysiological changes in Alzheimer's Disease (AD) motivates the necessity to develop new integrative approaches based on multi-modal neuroimaging data that captures various aspects of disease pathology. Previous studies using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (sMRI) report controversial results about time-line, spatial extent and magnitude of glucose hypometabolism and atrophy in AD that depend on clinical and demographic characteristics of the studied populations. Here, we provide and validate at a group level a generative anatomical model of glucose hypo-metabolism and atrophy progression in AD based on FDG-PET and sMRI data of 80 patients and 79 healthy controls to describe expected age and symptom severity related changes in AD relative to a baseline provided by healthy aging. We demonstrate a high level of anatomical accuracy for both modalities yielding strongly age- and symptom-severity- dependant glucose hypometabolism in temporal, parietal and precuneal regions and a more extensive network of atrophy in hippocampal, temporal, parietal, occipital and posterior caudate regions. The model suggests greater and more consistent changes in FDG-PET compared to sMRI at earlier and the inversion of this pattern at more advanced AD stages. Our model describes, integrates and predicts characteristic patterns of AD related pathology, uncontaminated by normal age effects, derived from multi-modal data. It further provides an integrative explanation for findings suggesting a dissociation between early- and late-onset AD. The generative model offers a basis for further development of individualized biomarkers allowing accurate early diagnosis and treatment evaluation. PMID:23592957

  13. The Interleukin-6 inflammation pathway from cholesterol to aging – Role of statins, bisphosphonates and plant polyphenols in aging and age-related diseases

    PubMed Central

    Omoigui, Sota

    2007-01-01

    We describe the inflammation pathway from Cholesterol to Aging. Interleukin 6 mediated inflammation is implicated in age-related disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimer's disease and some forms of Arthritis and Cancer. Statins and Bisphosphonates inhibit Interleukin 6 mediated inflammation indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion. Polyphenolic compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated inflammation by direct inhibition of the signal transduction pathway. Therapeutic targets for the control of all the above diseases should include inhibition of Interleukin-6 mediated inflammation. PMID:17374166

  14. Brain Na(+), K(+)-ATPase Activity In Aging and Disease.

    PubMed

    de Lores Arnaiz, Georgina Rodríguez; Ordieres, María Graciela López

    2014-06-01

    in signaling pathways, enzyme changes in diverse neurological diseases as well as during aging, have been summarized. Issues refer mainly to Na(+), K(+)-ATPase studies in ischemia, brain injury, depression and mood disorders, mania, stress, Alzheimer´s disease, learning and memory, and neuronal hyperexcitability and epilepsy. PMID:25018677

  15. Brain Na+, K+-ATPase Activity In Aging and Disease

    PubMed Central

    de Lores Arnaiz, Georgina Rodríguez; Ordieres, María Graciela López

    2014-01-01

    , enzyme changes in diverse neurological diseases as well as during aging, have been summarized. Issues refer mainly to Na+, K+-ATPase studies in ischemia, brain injury, depression and mood disorders, mania, stress, Alzheimer´s disease, learning and memory, and neuronal hyperexcitability and epilepsy. PMID:25018677

  16. 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

  17. Age-specific Parkinson disease risk in GBA mutation carriers: information for genetic counseling

    PubMed Central

    Rana, Huma Q.; Balwani, Manisha; Bier, Louise; Alcalay, Roy N.

    2012-01-01

    Purpose We sought to estimate age-specific risk of Parkinson disease in relatives of patients with Gaucher disease, who are obligate carriers of GBA mutations and who were not ascertained by family history of Parkinson disease. Methods A validated family history of Parkinson disease questionnaire was administered to 119 patients with Gaucher disease who were evaluated at the Mount Sinai School of Medicine from 2009 to 2012; the ages of their parents, siblings, and children, history of Parkinson disease, age at onset of Parkinson disease, and ethnic background were obtained. Kaplan–Meier survival curves were used to estimate age-specific Parkinson disease penetrance among parents of patients with Gaucher disease, who are obligatory GBA mutation carriers. Results Two participants with Gaucher disease were affected by Parkinson disease (5.4% of those who were 60 years or older). Of the 224 informative parents of patients with Gaucher disease, 11 had Parkinson disease (4.9%). Among the parents (obligatory carriers), cumulative risk of Parkinson disease by ages 65 and 85 was estimated to be 2.2% ±2.1% and 10.9% ±7.2%, respectively. Conclusion We provide useful age-specific estimates of Parkinson disease penetrance in patients with Gaucher disease and GBA heterozygous carriers for genetic counseling. Although GBA mutations may increase the risk for PD, the vast majority of patients with Gaucher disease and heterozygotes may not develop the disease. Further studies are needed to identify what modifies the risk of Parkinson disease in GBA mutation carriers. PMID:22935721

  18. Accelerated Vascular Aging as a Paradigm for Hypertensive Vascular Disease: Prevention and Therapy.

    PubMed

    Barton, Matthias; Husmann, Marc; Meyer, Matthias R

    2016-05-01

    Aging is considered the most important nonmodifiable risk factor for cardiovascular disease and death after age 28 years. Because of demographic changes the world population is expected to increase to 9 billion by the year 2050 and up to 12 billion by 2100, with several-fold increases among those 65 years of age and older. Healthy aging and prevention of aging-related diseases and associated health costs have become part of political agendas of governments around the world. Atherosclerotic vascular burden increases with age; accordingly, patients with progeria (premature aging) syndromes die from myocardial infarctions or stroke as teenagers or young adults. The incidence and prevalence of arterial hypertension also increases with age. Arterial hypertension-like diabetes and chronic renal failure-shares numerous pathologies and underlying mechanisms with the vascular aging process. In this article, we review how arterial hypertension resembles premature vascular aging, including the mechanisms by which arterial hypertension (as well as other risk factors such as diabetes mellitus, dyslipidemia, or chronic renal failure) accelerates the vascular aging process. We will also address the importance of cardiovascular risk factor control-including antihypertensive therapy-as a powerful intervention to interfere with premature vascular aging to reduce the age-associated prevalence of diseases such as myocardial infarction, heart failure, hypertensive nephropathy, and vascular dementia due to cerebrovascular disease. Finally, we will discuss the implementation of endothelial therapy, which aims at active patient participation to improve primary and secondary prevention of cardiovascular disease. PMID:27118295

  19. Adenoviral-based foot-and-mouth disease virus vaccine: effect of duration of antigen expression on immunogenicity in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An adenoviral (Ad5)-based foot-and-mouth disease virus (FMDV) subunit vaccine, Ad5-A24, is an effective alternative to the current inactivated whole virus vaccine and has a number of advantages including no requirement for infectious FMDV and DIVA (Differentiation of Infected from Vaccinated Animals...

  20. Mitochondrial and Ubiquitin Proteasome System Dysfunction in Ageing and Disease: Two Sides of the Same Coin?

    PubMed Central

    Ross, Jaime M.; Olson, Lars; Coppotelli, Giuseppe

    2015-01-01

    Mitochondrial dysfunction and impairment of the ubiquitin proteasome system have been described as two hallmarks of the ageing process. Additionally, both systems have been implicated in the etiopathogenesis of many age-related diseases, particularly neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. Interestingly, these two systems are closely interconnected, with the ubiquitin proteasome system maintaining mitochondrial homeostasis by regulating organelle dynamics, the proteome, and mitophagy, and mitochondrial dysfunction impairing cellular protein homeostasis by oxidative damage. Here, we review the current literature and argue that the interplay of the two systems should be considered in order to better understand the cellular dysfunction observed in ageing and age-related diseases. Such an approach may provide valuable insights into molecular mechanisms underlying the ageing process, and further discovery of treatments to counteract ageing and its associated diseases. Furthermore, we provide a hypothetical model for the heterogeneity described among individuals during ageing. PMID:26287188

  1. FUS/TLS-immunoreactive neuronal and glial cell inclusions increase with disease duration in familial amyotrophic lateral sclerosis with an R521C FUS/TLS mutation.

    PubMed

    Suzuki, Naoki; Kato, Shinsuke; Kato, Masako; Warita, Hitoshi; Mizuno, Hideki; Kato, Masaaki; Shimakura, Naoko; Akiyama, Haruhiko; Kobayashi, Zen; Konno, Hidehiko; Aoki, Masashi

    2012-09-01

    Basophilic inclusions (BIs) are pathological features of a subset of frontotemporal lobar degeneration disorders, including sporadic amyotrophic lateral sclerosis (ALS) and familial ALS (FALS). Mutations in the fused in sarcoma/translocated in liposarcoma (FUS/TLS) gene have recently been identified as a cause of FALS. The FUS/TLS-immunoreactive inclusions are consistently found in cases of frontotemporal lobar degeneration with BIs; however, the association between ALS cases with BIs and FUS/TLS accumulation is not well understood. We used immunohistochemistry to analyze 3 autopsy cases of FALS with the FUS/TLS mutation and with BIs using anti-FUS/TLS antibodies. The disease durations were 1, 3, and 9 years. As the disease duration becomes longer, there were broader distributions of neuronal and glial FUS/TLS-immunoreactive inclusions. As early as 1 year after the onset, BIs, neuronal cytoplasmic inclusions and glial cytoplasmic inclusions were found in the substantia nigra in addition to the anterior horn of the spinal cord. Glial cytoplasmic inclusions are found earlier and in a wider distribution than neuronal cytoplasmic inclusions. The distribution of FUS/TLS-immunoreactive inclusions in FUS/TLS-mutated FALS with BIs was broader than that of BIs alone, suggesting that the pathogenetic mechanism may have originated from the FUS/TLS proteinopathy. PMID:22878663

  2. Treatment of cytomegalovirus infection and disease pre- and post-quantitative nucleic acid test standardization: does use of a more sensitive assay lead to longer treatment duration?

    PubMed

    Dioverti, M Veronica; Lahr, Brian; Razonable, Raymund R

    2016-02-01

    Quantitative cytomegalovirus (CMV) nucleic acid testing (NAT) has been standardized using the World Health Organization (WHO) international calibration standard. A new FDA-approved WHO-calibrated assay (CA) was found to be more sensitive than a laboratory-developed test (LDT). We hypothesized that monitoring therapeutic response using a more sensitive assay may lead to longer antiviral therapy in solid organ and hematopoietic stem cell transplant patients with CMV infection. We reviewed transplant patients with CMV disease retrospectively, and divided them into two groups: those diagnosed and managed based on LDT and those managed using WHO-CA. Compared to patients monitored by LDT, the time to reach an undetectable viral load was significantly longer in the group monitored by the WHO-CA. However, a trend toward shorter duration of antiviral treatment was observed (median, 34 vs. 41 d; p = 0.058), with earlier discontinuation of induction antiviral therapy upon reaching undetectable viral load using WHO-CA (11 vs. 18 d; p = 002). We concluded that despite using a more sensitive CMV NAT, the total duration of antiviral treatment was not significantly prolonged in transplant patients with CMV infection and disease. Relapse rates did not differ between the two groups. PMID:26589482

  3. Movement Preparation and Bilateral Modulation of Beta Activity in Aging and Parkinson’s Disease

    PubMed Central

    Meziane, Hadj Boumediene; Moisello, Clara; Perfetti, Bernardo; Kvint, Svetlana; Isaias, Ioannis Ugo; Quartarone, Angelo; Di Rocco, Alessandro; Ghilardi, Maria Felice

    2015-01-01

    In previous studies of young subjects performing a reaction-time reaching task, we found that faster reaction times are associated with increased suppression of beta power over primary sensorimotor areas just before target presentation. Here we ascertain whether such beta decrease similarly occurs in normally aging subjects and also in patients with Parkinson’s disease (PD), where deficits in movement execution and abnormalities of beta power are usually present. We found that in both groups, beta power decreased during the motor task in the electrodes over the two primary sensorimotor areas. However, before target presentation, beta decreases in PD were significantly smaller over the right than over the left areas, while they were symmetrical in controls. In both groups, functional connectivity between the two regions, measured with imaginary coherence, increased before the target appearance; however, in PD, it decreased immediately after, while in controls, it remained elevated throughout motor planning. As in previous studies with young subjects, the degree of beta power before target appearance correlated with reaction time. The values of coherence during motor planning, instead, correlated with movement time, peak velocity and acceleration. We conclude that planning of prompt and fast movements partially depends on coordinated beta activity of both sensorimotor areas, already at the time of target presentation. The delayed onset of beta decreases over the right region observed in PD is possibly related to a decreased functional connectivity between the two areas, and this might account for deficits in force programming, movement duration and velocity modulation. PMID:25635777

  4. The Effect of Parkinson's Disease on Time Estimation as a Function of Stimulus Duration Range and Modality

    ERIC Educational Resources Information Center

    Smith, Jared G.; Harper, David N.; Gittings, David; Abernethy, David

    2007-01-01

    The present research sought to investigate the role of the basal ganglia in timing of sub- and supra-second intervals via an examination of the ability of people with Parkinson's disease (PD) to make temporal judgments in two ranges, 100-500 ms, and 1-5 s. Eighteen non-demented medicated patients with PD were compared with 14 matched controls on a…

  5. 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...

  6. The developmental aging and origins of health and disease hypotheses explained by different protein networks.

    PubMed

    Feltes, Bruno César; de Faria Poloni, Joice; Bonatto, Diego

    2011-08-01

    One theory that attempts to explain how and why an organism ages is the developmental hypothesis of aging (DevAge), which describes how developmental programming leads to aging in adults. Interestingly, the developmental origins of health and disease hypothesis (DOHaD) asserts that some aging-associated diseases that occur in adults are closely related to development and to conditions in the intrauterine environment. Thus, both aging and aging-associated diseases can be viewed, at least in part, as the result of a developmental program that is activated early in embryogenesis and persists throughout the lifespan of the organism. We would expect this developmental program to be regulated by a set of interacting protein networks that connect environmental and molecular signals. However, the connection between aging and development is not clear. Thus, a systems biology approach that incorporates different "omic" databases for two mammalian models, Homo sapiens and Mus musculus, was used to evaluate how development and aging are interconnected. Interestingly, three major, evolutionarily conserved processes, namely the immune system, epigenetics, and aerobic metabolism, appear to regulate aging and development in both H. sapiens and M. musculus. Considering that these three processes are essential to embryogenesis, the protein networks within these processes are subjected to strong selective pressure to eliminate gross developmental abnormalities in early embryogenesis. This selective pressure becomes more relaxed in the adult organism, permitting the onset of aging-associated diseases and inflammation-related aging; this concept echoes the antagonistic pleiotropy hypothesis of aging. PMID:21380541

  7. Morbidity risks among older adults with pre-existing age-related diseases.

    PubMed

    Akushevich, Igor; Kravchenko, Julia; Ukraintseva, Svetlana; Arbeev, Konstantin; Kulminski, Alexander; Yashin, Anatoliy I

    2013-12-01

    Multi-morbidity is common among older adults; however, for many aging-related diseases there is no information for U.S. elderly population on how earlier-manifested disease affects the risk of another disease manifested later during patient's lifetime. Quantitative evaluation of risks of cancer and non-cancer diseases for older adults with pre-existing conditions is performed using the Surveillance, Epidemiology, and End Results (SEER) Registry data linked to the Medicare Files of Service Use (MFSU). Using the SEER-Medicare data containing individual records for 2,154,598 individuals, we empirically evaluated age patterns of incidence of age-associated diseases diagnosed after the onset of earlier manifested disease and compared these patterns with those in general population. Individual medical histories were reconstructed using information on diagnoses coded in MFSU, dates of medical services/procedures, and Medicare enrollment/disenrollment. More than threefold increase of subsequent diseases risk was observed for 15 disease pairs, majority of them were i) diseases of the same organ and/or system (e.g., Parkinson disease for patients with Alzheimer disease, HR=3.77, kidney cancer for patients with renal failure, HR=3.28) or ii) disease pairs with primary diseases being fast-progressive cancers (i.e., lung, kidney, and pancreas), e.g., ulcer (HR=4.68) and melanoma (HR=4.15) for patients with pancreatic cancer. Lower risk of subsequent disease was registered for 20 disease pairs, mostly among patients with Alzheimer's or Parkinson's disease, e.g., decreased lung cancer risk among patients with Alzheimer's (HR=0.64) and Parkinson's (HR=0.60) disease. Synergistic and antagonistic dependences in geriatric disease risks were observed among US elderly confirming known and detecting new associations of wide spectrum of age-associated diseases. The results can be used in optimization of screening, prevention and treatment strategies of chronic diseases among U.S. elderly

  8. Telomeres and telomerase as therapeutic targets to prevent and treat age-related diseases

    PubMed Central

    Bär, Christian; Blasco, Maria A.

    2016-01-01

    Telomeres, the protective ends of linear chromosomes, shorten throughout an individual’s lifetime. Telomere shortening is a hallmark of molecular aging and is associated with premature appearance of diseases associated with aging. Here, we discuss the role of telomere shortening as a direct cause for aging and age-related diseases. In particular, we draw attention to the fact that telomere length influences longevity. Furthermore, we discuss intrinsic and environmental factors that can impact on human telomere erosion. Finally, we highlight recent advances in telomerase-based therapeutic strategies for the treatment of diseases associated with extremely short telomeres owing to mutations in telomerase, as well as age-related diseases, and ultimately aging itself. PMID:27081482

  9. Normal aging in rats and pathological aging in human Alzheimer's disease decrease FAAH activity: modulation by cannabinoid agonists.

    PubMed

    Pascual, A C; Martín-Moreno, A M; Giusto, N M; de Ceballos, M L; Pasquaré, S J

    2014-12-01

    Anandamide is an endocannabinoid involved in several physiological functions including neuroprotection. Anandamide is synthesized on demand and its endogenous level is regulated through its degradation, where fatty acid amide hydrolase plays a major role. The aim of this study was to characterize anandamide breakdown in physiological and pathological aging and its regulation by CB1 and CB2 receptor agonists. Fatty acid amide hydrolase activity was analyzed in an independent cohort of human cortical membrane samples from control and Alzheimer's disease patients, and in membrane and synaptosomes from adult and aged rat cerebral cortex. Our results demonstrate that fatty acid amide hydrolase activity decreases in the frontal cortex from human patients with Alzheimer's disease and this effect is mimicked by Aβ(1-40) peptide. This activity increases and decreases in aged rat cerebrocortical membranes and synaptosomes, respectively. Also, while the presence of JWH-133, a CB2 selective agonist, slightly increases anandamide hydrolysis in human controls, it decreases this activity in adults and aged rat cerebrocortical membranes and synaptosomes. In the presence of WIN55,212-2, a mixed CB1/CB2 agonist, anandamide hydrolysis increases in Alzheimer's disease patients but decreases in human controls as well as in adult and aged rat cerebrocortical membranes and synaptosomes. Although a similar profile is observed in fatty acid amide hydrolase activity between aged rat synaptic endings and human Alzheimer's disease brains, it is differently modulated by CB1/CB2 agonists. This modulation leads to a reduced availability of anandamide in Alzheimer's disease and to an increased availability of this endocannabinoid in aging. PMID:25456842

  10. Similarly Strong Purifying Selection Acts on Human Disease Genes of All Evolutionary Ages

    PubMed Central

    Cai, James J.; Borenstein, Elhanan; Chen, Rong

    2009-01-01

    A number of studies have showed that recently created genes differ from the genes created in deep evolutionary past in many aspects. Here, we determined the age of emergence and propensity for gene loss (PGL) of all human protein–coding genes and compared disease genes with non-disease genes in terms of their evolutionary rate, strength of purifying selection, mRNA expression, and genetic redundancy. The older and the less prone to loss, non-disease genes have been evolving 1.5- to 3-fold slower between humans and chimps than young non-disease genes, whereas Mendelian disease genes have been evolving very slowly regardless of their ages and PGL. Complex disease genes showed an intermediate pattern. Disease genes also have higher mRNA expression heterogeneity across multiple tissues than non-disease genes regardless of age and PGL. Young and middle-aged disease genes have fewer similar paralogs as non-disease genes of the same age. We reasoned that genes were more likely to be involved in human disease if they were under a strong functional constraint, expressed heterogeneously across tissues, and lacked genetic redundancy. Young human genes that have been evolving under strong constraint between humans and chimps might also be enriched for genes that encode important primate or even human-specific functions. PMID:20333184

  11. Impact of Typical Aging and Parkinson's Disease on the Relationship among Breath Pausing, Syntax, and Punctuation

    ERIC Educational Resources Information Center

    Huber, Jessica E.; Darling, Meghan; Francis, Elaine J.; Zhang, Dabao

    2012-01-01

    Purpose: The present study examines the impact of typical aging and Parkinson's disease (PD) on the relationship among breath pausing, syntax, and punctuation. Method: Thirty young adults, 25 typically aging older adults, and 15 individuals with PD participated. Fifteen participants were age- and sex-matched to the individuals with PD.…

  12. Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) in Aging Populations.

    PubMed

    Fragoso, Carlos A Vaz

    2016-01-01

    Current epidemiologic practice evaluates COPD based on self-reported symptoms of chronic bronchitis, self-reported physician-diagnosed COPD, spirometry confirmed airflow obstruction, or emphysema diagnosed by volumetric computed chest tomography (CT). Because the highest risk population for having COPD includes a predominance of middle-aged or older persons, aging related changes must also be considered, including: 1) increased multimorbidity, polypharmacy, and severe deconditioning, as these identify mechanisms that underlie respiratory symptoms and can impart a complex differential diagnosis; 2) increased airflow limitation, as this impacts the interpretation of spirometry confirmed airflow obstruction; and 3) "senile" emphysema, as this impacts the specificity of CT-diagnosed emphysema. Accordingly, in an era of rapidly aging populations worldwide, the use of epidemiologic criteria that do not rigorously consider aging related changes will result in increased misidentification of COPD and may, in turn, misinform public health policy and patient care. PMID:26629987

  13. Nutrition and age-associated inflammation: implications for disease prevention

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accumulating evidence suggests that aging is associated with dysregulated immune and inflammatory responses. Investigation into the cellular and molecular mechanisms underlying this phenomenon suggests that an up-regulated cyclooxygenase (COX)-2 expression, and resulting increase in production of pr...

  14. Age-by-disease biological interactions: implications for late-life depression

    PubMed Central

    McKinney, Brandon C.; Oh, Hyunjung; Sibille, Etienne

    2012-01-01

    Onset of depressive symptoms after the age of 65, or late-life depression (LLD), is common and poses a significant burden on affected individuals, caretakers, and society. Evidence suggests a unique biological basis for LLD, but current hypotheses do not account for its pathophysiological complexity. Here we propose a novel etiological framework for LLD, the age-by-disease biological interaction hypothesis, based on the observations that the subset of genes that undergoes lifelong progressive changes in expression is restricted to a specific set of biological processes, and that a disproportionate number of these age-dependent genes have been previously and similarly implicated in neurodegenerative and neuropsychiatric disorders, including depression. The age-by-disease biological interaction hypothesis posits that age-dependent biological processes (i) are “pushed” in LLD-promoting directions by changes in gene expression naturally occurring during brain aging, which (ii) directly contribute to pathophysiological mechanisms of LLD, and (iii) that individual variability in rates of age-dependent changes determines risk or resiliency to develop age-related disorders, including LLD. We review observations supporting this hypothesis, including consistent and specific age-dependent changes in brain gene expression and their overlap with neuropsychiatric and neurodegenerative disease pathways. We then review preliminary reports supporting the genetic component of this hypothesis. Other potential biological mediators of age-dependent gene changes are proposed. We speculate that studies examining the relative contribution of these mechanisms to age-dependent changes and related disease mechanisms will not only provide critical information on the biology of normal aging of the human brain, but will inform our understanding of age-dependent diseases, in time fostering the development of new interventions for prevention and treatment of age-dependent diseases, including

  15. Oxidative Stress, Aging and CNS disease in the Canine Model of Human Brain Aging

    PubMed Central

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    SYNOPSIS Decline in cognitive functions that accompany aging in dogs may have a biological basis, and many of the disorders associated with aging in canines may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of both laboratory and clinical studies – antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs. However, determining all effective compounds and combinations, dosage ranges, as well as when to initiate intervention and long term effects constitute gaps in our current knowledge. PMID:18249248

  16. Classifying aging as a disease in the context of ICD-11.

    PubMed

    Zhavoronkov, Alex; Bhullar, Bhupinder

    2015-01-01

    Aging is a complex continuous multifactorial process leading to loss of function and crystalizing into the many age-related diseases. Here, we explore the arguments for classifying aging as a disease in the context of the upcoming World Health Organization's 11th International Statistical Classification of Diseases and Related Health Problems (ICD-11), expected to be finalized in 2018. We hypothesize that classifying aging as a disease with a "non-garbage" set of codes will result in new approaches and business models for addressing aging as a treatable condition, which will lead to both economic and healthcare benefits for all stakeholders. Actionable classification of aging as a disease may lead to more efficient allocation of resources by enabling funding bodies and other stakeholders to use quality-adjusted life years (QALYs) and healthy-years equivalent (HYE) as metrics when evaluating both research and clinical programs. We propose forming a Task Force to interface the WHO in order to develop a multidisciplinary framework for classifying aging as a disease with multiple disease codes facilitating for therapeutic interventions and preventative strategies. PMID:26583032

  17. Classifying aging as a disease in the context of ICD-11

    PubMed Central

    Zhavoronkov, Alex; Bhullar, Bhupinder

    2015-01-01

    Aging is a complex continuous multifactorial process leading to loss of function and crystalizing into the many age-related diseases. Here, we explore the arguments for classifying aging as a disease in the context of the upcoming World Health Organization’s 11th International Statistical Classification of Diseases and Related Health Problems (ICD-11), expected to be finalized in 2018. We hypothesize that classifying aging as a disease with a “non-garbage” set of codes will result in new approaches and business models for addressing aging as a treatable condition, which will lead to both economic and healthcare benefits for all stakeholders. Actionable classification of aging as a disease may lead to more efficient allocation of resources by enabling funding bodies and other stakeholders to use quality-adjusted life years (QALYs) and healthy-years equivalent (HYE) as metrics when evaluating both research and clinical programs. We propose forming a Task Force to interface the WHO in order to develop a multidisciplinary framework for classifying aging as a disease with multiple disease codes facilitating for therapeutic interventions and preventative strategies. PMID:26583032

  18. Aging and Lung Disease. Clinical Impact and Cellular and Molecular Pathways.

    PubMed

    Rojas, Mauricio; Mora, Ana L; Kapetanaki, Maria; Weathington, Nathaniel; Gladwin, Mark; Eickelberg, Oliver

    2015-12-01

    With the expected rapid growth of the aging population worldwide, there is a clear need to understand the complex process of aging to develop interventions that might extend the health span in this group of patients. Aging is associated with increased susceptibility to a variety of chronic diseases, and lung pathologies are no exception. The prevalence of lung diseases such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease has been found to increase considerably with age. In October 2014, the Division of Pulmonary, Allergy, and Critical Care of the University of Pittsburgh cohosted the Pittsburgh-Munich Lung Conference focused in aging and lung disease with the Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Ludwig-Maximilians University and Helmholtz Zentrum Munich Germany. The purpose of the conference was to disseminate novel concepts in aging mechanisms that have an impact in lung physiology and pathogenesis of pulmonary diseases that commonly occur in older populations. The conference included 28 presentations on diverse topics, which are summarized in this report. The participants identified priorities for future basic and translational investigations that will assist in the identification of molecular insights involved in the pathogenesis of age-related pulmonary diseases and the design of therapeutic interventions for these lung conditions. PMID:26653202

  19. Dental Disease in Aged Horses and Its Management.

    PubMed

    Nicholls, Victoria M; Townsend, Neil

    2016-08-01

    Improved recognition of equine geriatric conditions has resulted in a surge in our aged population with a concurrent escalation of many age-related dental pathologies. Prevention of these disorder is the ultimate aim but early identification and appropriate management can increase an animal's oral comfort and maximise its masticatory ability. There is only a finite amount of tooth available for eruption in the horse and therefore as the teeth become worn and less efficient as a grinding unit, dietary modification becomes a paramount consideration to accommodate this. Geriatric animals have differing requirements for restraint and sedation with treatment of coexisting disorders also an important requirement. PMID:27449389

  20. 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...

  1. The voices of Iris: Cinematic representations of the aged woman and Alzheimer's disease in Iris (2001).

    PubMed

    Graham, Megan E

    2014-11-01

    Audiences must be critical of film representations of the aged woman living with Alzheimer's disease and of dangerous reinscriptions of stereotypical equations about ageing as deterioration. This paper analyses the representation and decline of the aged woman through the different voices of Iris Murdoch in Richard Eyre's film Iris (2001). Key vocal scenes are considered: On-screen encounters between young and aged Iris, vocal representations of dementia symptoms and silencing Iris as her disease progresses. Further, Iris' recurrent unaccompanied song, "The Lark in the Clear Air," compels audiences to "see" Iris with their ears more than with their eyes, exemplifying the representational power of sound in film. This paper is an appeal for increased debate about sonic representations of aged women, ageing and Alzheimer's disease and dementia in film. The significance of audiences' critical awareness and understanding about the social implications of these representations is discussed. PMID:25370076

  2. 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

  3. Chronic Diseases in the Pediatric Age Group. Matrix No. 7.

    ERIC Educational Resources Information Center

    Katz, Michael

    This paper briefly outlines current problems associated with chronic diseases in children and youth and provides indications for the types of future research and analysis needed to facilitate the development of solutions. In general, these problems are associated with the following: malignancies, hereditary anemias, cystic fibrosis, other chronic…

  4. The Effect of Alzheimer's Disease and Aging on Conceptual Combination

    ERIC Educational Resources Information Center

    Taler, Vanessa; Chertkow, Howard; Saumier, Daniel

    2005-01-01

    Alzheimer's disease (AD) subjects, healthy elderly, and young adults interpreted a series of novel noun-noun expressions composed of familiar object words. Subjects interpreted each item by selecting one of three possible definitions: a definition in which the referents of each noun were associated together in a particular context (e.g., rabbit…

  5. Aging Stereotypes Must be Taken Into Account for the Diagnosis of Prodromal and Early Alzheimer Disease.

    PubMed

    Régner, Isabelle; Mazerolle, Marie; Alescio-Lautier, Béatrice; Clarys, David; Michel, Bernard; Paccalin, Marc; Piolino, Pascale; Rigalleau, François; Sambuchi, Nathalie; Huguet, Pascal

    2016-01-01

    Because of a dramatic increase of older people worldwide, screening for prodromal state of Alzheimer disease (AD) is a major societal challenge. Many individuals diagnosed with prodromal AD, do not convert to AD, some remaining stable and others reversing back to normal. We argue that an important source of this overdiagnosis comes from negative aging stereotypes (eg, the culturally shared beliefs that aging inescapably causes severe cognitive decline and diseases). Many laboratory studies show that such stereotypes impair memory performance in healthy older adults, producing inflated age differences. Research is needed to examine how aging stereotypes implicitly permeate neuropsychological testing and contribute to false positives. PMID:26650879

  6. What determines age-related disease: do we know all the right questions?

    PubMed Central

    2009-01-01

    The average human lifespan has increased throughout the last century due to the mitigation of many infectious diseases. More people now die of age-related diseases than ever before, but these diseases have been resistant to elimination. Progress has been made in treatments and preventative measures to delay the onsets of these diseases, but most cancers and vascular diseases are still with us and they kill about the same fraction of the population year after year. For example, US Caucasian female deaths from breast plus genital cancers have remained a fairly constant ~7% of the age-related disease deaths from 1938 to 1998 and have been consistently ~2-fold greater than female colon plus rectal cancer deaths over that span. This type of stability pattern pervades the age-related diseases and suggests that intrinsic properties within populations determine these fractions. Recognizing this pattern and deciphering its origin will be necessary for the complete understanding of these major causes of death. It would appear that more than the random processes of aging drive this effect. The question is how to meaningfully approach this problem. This commentary discusses the epidemiological and aging perspectives and their current limitations in providing an explanation. The age of bioinformatics offers hope, but only if creative systems approaches are forthcoming. PMID:19904627

  7. What determines age-related disease: do we know all the right questions?

    PubMed

    Juckett, David A

    2010-06-01

    The average human lifespan has increased throughout the last century due to the mitigation of many infectious diseases. More people now die of age-related diseases than ever before, but these diseases have been resistant to elimination. Progress has been made in treatments and preventative measures to delay the onsets of these diseases, but most cancers and vascular diseases are still with us and they kill about the same fraction of the population year after year. For example, US Caucasian female deaths from breast plus genital cancers have remained a fairly constant approximately 7% of the age-related disease deaths from 1938 to 1998 and have been consistently approximately 2-fold greater than female colon plus rectal cancer deaths over that span. This type of stability pattern pervades the age-related diseases and suggests that intrinsic properties within populations determine these fractions. Recognizing this pattern and deciphering its origin will be necessary for the complete understanding of these major causes of death. It would appear that more than the random processes of aging drive this effect. The question is how to meaningfully approach this problem. This commentary discusses the epidemiological and aging perspectives and their current limitations in providing an explanation. The age of bioinformatics offers hope, but only if creative systems approaches are forthcoming. PMID:19904627

  8. 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

  9. We Have the Spaceship; But Where's the Start Button: Human Engineering Issues in the Age of Long Duration Space Exploration - Presentation

    NASA Technical Reports Server (NTRS)

    Hamilton, George; Adams, Chris

    2005-01-01

    This viewgraph presentation addresses the following considerations for human factors engineering during long duration human space flight: gravitational adaptation, 2-D to 3-D adaptation, handles, exercise posture, and space ergonomics. The presentation argues that there is an urgent need to advance research is these areas in preparation for future manned missions.

  10. Telomere Length in Epidemiology: A Biomarker of Aging, Age-Related Disease, Both, or Neither?

    PubMed Central

    Sanders, Jason L.; Newman, Anne B.

    2013-01-01

    Telomeres are nucleoprotein caps flanking DNA. They are shortened by cell division and oxidative stress and are lengthened by the enzyme telomerase and DNA exchange during mitosis. Short telomeres induce cellular senescence. As an indicator of oxidative stress and senescence (2 processes thought to be fundamental to aging), telomere length is hypothesized to be a biomarker of aging. This hypothesis has been tested for more than a decade with epidemiologic study methods. In cross-sectional studies, researchers have investigated whether leukocyte telomere length (LTL) is associated with demographic, behavioral, and health variables. In prospective studies, baseline LTL has been used to predict mortality and occasionally other adverse health outcomes. Conflicting data have generated heated debate about the value of LTL as a biomarker of overall aging. In this review, we address the epidemiologic data on LTL and demonstrate that shorter LTL is associated with older age, male gender, Caucasian race, and possibly atherosclerosis; associations with other markers of health are equivocal. We discuss the reasons for discrepancy across studies, including a detailed review of methods for measuring telomere length as they apply to epidemiology. Finally, we conclude with questions about LTL as a biomarker of aging and how epidemiology can be used to answer these questions. PMID:23302541

  11. Mitochondria in Ageing and Diseases: The Super Trouper of the Cell.

    PubMed

    Coppotelli, Giuseppe; Ross, Jaime M

    2016-01-01

    The past decade has witnessed an explosion of knowledge regarding how mitochondrial dysfunction may translate into ageing and disease phenotypes, as well as how it is modulated by genetic and lifestyle factors.[...]. PMID:27187361

  12. Lung and Heart Diseases Are Better Predicted by Pack-Years than by Smoking Status or Duration of Smoking Cessation in HIV Patients

    PubMed Central

    Guaraldi, Giovanni; Raggi, Paolo; Gomes, André; Zona, Stefano; Marchi, Enrico; Santoro, Antonella; Besutti, Giulia; Scaglioni, Riccardo; Ligabue, Guido; Leipsic, Jonathon; Man, Paul; Sin, Don

    2015-01-01

    Background The objective of this study was to assess the relationship of pack-years smoking and time since smoking cessation with risk of lung and heart disease. Methods We investigated the history of lung and heart disease in 903 HIV-infected patients who had undergone thoracic computed tomography (CT) imaging stratified by smoking history. Multimorbidity lung and heart disease (MLHD) was defined as the presence of ≥ 2 clinical or subclinical lung abnormalities and at least one heart abnormality. Results Among 903 patients, 23.7% had never smoked, 28.7% were former smokers and 47.6% were current smokers. Spirometry indicated chronic obstructive pulmonary disease in 11.4% of patients and MLHD was present in 53.6%. Age, male sex, greater pack-years smoking history and smoking cessation less than 5 years earlier vs. more than 10 years earlier (OR 2.59, 95% CI 1.27–5.29, p = 0.009) were independently associated with CT detected subclinical lung and heart disease. Pack-years smoking history was more strongly associated with MLHD than smoking status (p<0.001). Conclusions MLHD is common even among HIV-infected patients who never smoked and pack- years smoking history is a stronger predictor than current smoking status of MLHD. A detailed pack-years smoking history should be routinely obtained and smoking cessation strategies implemented. PMID:26650682

  13. From cellular senescence to age-associated diseases: the miRNA connection

    PubMed Central

    2012-01-01

    Cellular senescence has evolved from an in-vitro model system to study aging in vitro to a multifaceted phenomenon of in-vivo importance as senescent cells in vivo have been identified and their removal delays the onset of age-associated diseases in a mouse model system. From the large emerging class of non-coding RNAs, miRNAs have only recently been functionally implied in the regulatory networks that are modified during the aging process. Here we summarize examples of similarities between the differential expression of miRNAs during senescence and age-associated diseases and suggest that these similarities might emphasize the importance of senescence for the pathogenesis of age-associated diseases. Understanding such a connection on the level of miRNAs might offer valuable opportunities for designing novel diagnostic and therapeutic strategies. PMID:24472232

  14. Glycated Lysine Residues: A Marker for Non-Enzymatic Protein Glycation in Age-Related Diseases

    PubMed Central

    Ansari, Nadeem A.; Moinuddin; Ali, Rashid

    2011-01-01

    Nonenzymatic glycosylation or glycation of macromolecules, especially proteins leading to their oxidation, play an important role in diseases. Glycation of proteins primarily results in the formation of an early stage and stable Amadori-lysine product which undergo further irreversible chemical reactions to form advanced glycation endproducts (AGEs). This review focuses these products in lysine rich proteins such as collagen and human serum albumin for their role in aging and age-related diseases. Antigenic characteristics of glycated lysine residues in proteins together with the presence of serum autoantibodies to the glycated lysine products and lysine-rich proteins in diabetes and arthritis patients indicates that these modified lysine residues may be a novel biomarker for protein glycation in aging and age-related diseases. PMID:21725160

  15. Impact of Air Pollutants on Oxidative Stress in Common Autophagy-Mediated Aging Diseases

    PubMed Central

    Numan, Mohamed Saber; Brown, Jacques P.; Michou, Laëtitia

    2015-01-01

    Atmospheric pollution-induced cellular oxidative stress is probably one of the pathogenic mechanisms involved in most of the common autophagy-mediated aging diseases, including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s, disease, as well as Paget’s disease of bone with or without frontotemporal dementia and inclusion body myopathy. Oxidative stress has serious damaging effects on the cellular contents: DNA, RNA, cellular proteins, and cellular organelles. Autophagy has a pivotal role in recycling these damaged non-functional organelles and misfolded or unfolded proteins. In this paper, we highlight, through a narrative review of the literature, that when autophagy processes are impaired during aging, in presence of cumulative air pollution-induced cellular oxidative stress and due to a direct effect on air pollutant, autophagy-mediated aging diseases may occur. PMID:25690002

  16. Potential Therapeutical Contributions of the Endocannabinoid System towards Aging and Alzheimer’s Disease

    PubMed Central

    Bonnet, Amandine E; Marchalant, Yannick

    2015-01-01

    Aging can lead to decline in cognition, notably due to neurodegenerative processes overwhelming the brain over time. As people live longer, numerous concerns are rightfully raised toward long-term slowly incapacitating diseases with no cure, such as Alzheimer’s disease. Since the early 2000’s, the role of neuroinflammation has been scrutinized for its potential role in the development of diverse neurodegenerative diseases notably because of its slow onset and chronic nature in aging. Despite the lack of success yet, treatment of chronic neuroinflammation could help alleviate process implicated in neurodegenerative disease. A growing number of studies including our own have aimed at the endocannabinoid system and unfolded unique effects of this system on neuroinflammation, neurogenesis and hallmarks of Alzheimer’s disease and made it a reasonable target in the context of normal and pathological brain aging. PMID:26425394

  17. Validating chronic disease ascertainment algorithms for use in the Canadian longitudinal study on aging.

    PubMed

    Oremus, Mark; Postuma, Ronald; Griffith, Lauren; Balion, Cynthia; Wolfson, Christina; Kirkland, Susan; Patterson, Christopher; Shannon, Harry S; Raina, Parminder

    2013-09-01

    We validated seven chronic disease ascertainment algorithms for use in the Canadian Longitudinal Study on Aging. The algorithms pertained to diabetes mellitus type 2, parkinsonism, chronic airflow obstruction (CAO), hand osteoarthritis (OA), hip OA, knee OA, and ischemic heart disease. Our target recruitment was 20 cases and controls per disease; some cases were controls for unrelated diseases. Participants completed interviewer-administered disease symptom and medication use questionnaires. Diabetes cases and controls underwent fasting glucose testing; CAO cases and controls underwent spirometry testing. For each disease, the appropriate algorithm was used to classify participants' disease status (positive or negative for disease). We also calculated sensitivity and specificity using physician diagnosis as the reference standard. The final sample involved 176 participants recruited in three Canadian cities between 2009 and 2011. Most estimated sensitivities and specificities were 80 per cent or more, indicating that the seven algorithms correctly identified individuals with the target disease. PMID:23924995

  18. Prophylaxis in von Willebrand Disease: Coming of Age?

    PubMed

    Saccullo, Giorgia; Makris, Mike

    2016-07-01

    Although in most cases von Willebrand disease (VWD) is a mild disorder, a subgroup of patients experience frequent bleeding. In contrast to severe hemophilia in which prophylaxis is the accepted standard of care, this is less frequently used in VWD. Most type 1 VWD patients can be adequately managed with episodic desmopressin and tranexamic acid. In patients with more severe disease, especially those with type 3 VWD, joint bleeds, epistaxis, menorrhagia, and gastrointestinal bleeding are problematic and usually require treatment with von Willebrand factor/factor VIII (VWF/FVIII) concentrate. While in the past these patients were managed with on-demand VWF/FVIII concentrate, several recent reports have demonstrated the value of prophylactic treatment. Despite some uncertainties about the economic impact of treatment of severe VWD, prophylaxis with VWF concentrate should now be considered as the standard of care for the more severe end of the spectrum of affected individuals. The recent introduction of recombinant VWF concentrate is likely to improve the acceptability of prophylaxis in VWD. PMID:27253087

  19. Rejuvenation of senescent cells-the road to postponing human aging and age-related disease?

    PubMed

    Sikora, Ewa

    2013-07-01

    Cellular senescence is the state of permanent inhibition of cell proliferation. Replicative senescence occurs due to the end replication problem and shortening telomeres with each cell division leading to DNA damage response (DDR). The number of short telomeres increases with age and age-related pathologies. Stress induced senescence, although not accompanied by attrition of telomeres, is also attributed to the DDR induced by irreparable DNA lesions in telomeric DNA. Senescent cells characterized by the presence of γH2AX, the common marker of double DNA strand breaks, and other senescence markers including activity of SA-β-gal, accumulate in tissues of aged animals and humans as well as at sites of pathology. It is believed that cellular senescence evolved as a cancer barrier since non-proliferating senescent cells cannot be transformed to neoplastic cells. On the other hand senescent cells favor cancer development, just like other age-related pathologies, by creating a low grade inflammatory state due to senescence associated secretory phenotype (SASP). Reversal/inhibition of cellular senescence could prolong healthy life span, thus many attempts have been undertaken to influence cellular senescence. The two main approaches are genetic and pharmacological/nutritional modifications of cell fate. The first one concerns cell reprogramming by induced pluripotent stem cells (iPSCs), which in vitro is effective even in cells undergoing senescence, or derived from very old or progeroid patients. The second approach concerns modification of senescence signaling pathways just like TOR-induced by pharmacological or with natural agents. However, knowing that aging is unavoidable we cannot expect its elimination, but prolonging healthy life span is a goal worth serious consideration. PMID:23064316

  20. The involvement of BDNF, NGF and GDNF in aging and Alzheimer’s disease

    PubMed Central

    Budni, Josiane; Bellettini-Santos, Tatiani; Mina, Francielle; Garcez, Michelle Lima; Zugno, Alexandra Ioppi

    2015-01-01

    Aging is a normal physiological process accompanied by cognitive decline. This aging process has been the primary risk factor for development of aging-related diseases such as Alzheimer’s disease (AD). Cognitive deficit is related to alterations of neurotrophic factors level such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF). These strong relationship between aging and AD is important to investigate the time which they overlap, as well as, the pathophysiological mechanism in each event. Considering that aging and AD are related to cognitive impairment, here we discuss the involving these neurotrophic factors in the aging process and AD. PMID:26425388

  1. Human iPSC-based modeling of late-onset disease via progerin-induced aging.

    PubMed

    Miller, Justine D; Ganat, Yosif M; Kishinevsky, Sarah; Bowman, Robert L; Liu, Becky; Tu, Edmund Y; Mandal, Pankaj K; Vera, Elsa; Shim, Jae-won; Kriks, Sonja; Taldone, Tony; Fusaki, Noemi; Tomishima, Mark J; Krainc, Dimitri; Milner, Teresa A; Rossi, Derrick J; Studer, Lorenz

    2013-12-01

    Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) resets their identity back to an embryonic age and, thus, presents a significant hurdle for modeling late-onset disorders. In this study, we describe a strategy for inducing aging-related features in human iPSC-derived lineages and apply it to the modeling of Parkinson's disease (PD). Our approach involves expression of progerin, a truncated form of lamin A associated with premature aging. We found that expression of progerin in iPSC-derived fibroblasts and neurons induces multiple aging-related markers and characteristics, including dopamine-specific phenotypes such as neuromelanin accumulation. Induced aging in PD iPSC-derived dopamine neurons revealed disease phenotypes that require both aging and genetic susceptibility, such as pronounced dendrite degeneration, progressive loss of tyrosine hydroxylase (TH) expression, and enlarged mitochondria or Lewy-body-precursor inclusions. Thus, our study suggests that progerin-induced aging can be used to reveal late-onset age-related disease features in hiPSC-based disease models. PMID:24315443

  2. Human iPSC-based Modeling of Late-Onset Disease via Progerin-induced Aging

    PubMed Central

    Miller, Justine D.; Ganat, Yosif M.; Kishinevsky, Sarah; Bowman, Robert L.; Liu, Becky; Tu, Edmund Y.; Mandal, Pankaj; Vera, Elsa; Shim, Jae-won; Kriks, Sonja; Taldone, Tony; Fusaki, Noemi; Tomishima, Mark J.; Krainc, Dimitri; Milner, Teresa A.; Rossi, Derrick J.; Studer, Lorenz

    2014-01-01

    Summary Reprogramming somatic cells to induced pluripotent stem cells (iPSCs), resets their identity back to an embryonic age, and thus presents a significant hurdle for modeling late-onset disorders. In this study, we describe a strategy for inducing aging-related features in human iPSC-derived lineages and apply it to the modeling of Parkinson’s disease (PD). Our approach involves expression of progerin, a truncated form of lamin A associated with premature aging. We found that expression of progerin in iPSC-derived fibroblasts and neurons induces multiple aging-related markers and characteristics, including dopamine-specific phenotypes such as neuromelanin accumulation. Induced aging in PD-iPSC-derived dopamine neurons revealed disease phenotypes that require both aging and genetic susceptibility, such as pronounced dendrite degeneration, progressive loss of tyrosine-hydroxylase (TH) expression and enlarged mitochondria or Lewy body-precursor inclusions. Thus, our study suggests that progerin-induced aging can be used to reveal late-onset age-related disease features in hiPSC-based disease models. PMID:24315443

  3. Impaired Word Recognition in Alzheimer's Disease: The Role of Age of Acquisition

    ERIC Educational Resources Information Center

    Cuetos, Fernando; Herrera, Elena; Ellis, Andrew W.

    2010-01-01

    Studies of word production in patients with Alzheimer's disease have identified the age of acquisition of words as an important predictor of retention or loss, with early acquired words remaining accessible for longer than later acquired words. If, as proposed by current theories, effects of age of acquisition reflect the involvement of semantic…

  4. The African Turquoise Killifish: A Model for Exploring Vertebrate Aging and Diseases in the Fast Lane.

    PubMed

    Harel, Itamar; Brunet, Anne

    2015-01-01

    Why and how organisms age remains a mystery, and it defines one of the biggest challenges in biology. Aging is also the primary risk factor for many human pathologies, such as cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. Thus, manipulating the aging rate and potentially postponing the onset of these devastating diseases could have a tremendous impact on human health. Recent studies, relying primarily on nonvertebrate short-lived model systems, have shown the importance of both genetic and environmental factors in modulating the aging rate. However, relatively little is known about aging in vertebrates or what processes may be unique and specific to these complex organisms. Here we discuss how advances in genomics and genome editing have significantly expanded our ability to probe the aging process in a vertebrate system. We highlight recent findings from a naturally short-lived vertebrate, the African turquoise killifish, which provides an attractive platform for exploring mechanisms underlying vertebrate aging and age-related diseases. PMID:26642856

  5. Speech monitoring skills in Alzheimer's disease, Parkinson's disease, and normal aging.

    PubMed

    McNamara, P; Obler, L K; Au, R; Durso, R; Albert, M L

    1992-01-01

    We examined the abilities of 15 patients with dementia of the Alzheimer type (DAT), 22 patients with Parkinson's Disease (PD), and 141 healthy subjects (ranging in age from 30 to 79 years) to detect and correct their own speech errors. Each subject was shown the Cookie Theft picture of the BDAE (Goodglass & Kaplan, 1972. The assessment of aphasia and related disorders. Philadelphia: Lea & Febiger.) and instructed to tell the examiner the "...story of what's happening in the picture." Self-monitoring performance was assessed by tabulating the number of uncorrected errors as well as repaired errors. We divided repairs into two types based on the psycholinguistics literature (van Wijk & Kempen, 1987. Cognitive Psychology, 19, 403-440). Speech corrections were judged to be lemma repairs when the reparandum was a single word, and reformulation repairs when a new syntactic constituent was added to the reparandum. Patients with DAT corrected only 24% of their total errors and patients with PD only 25%. Healthy subjects, by contrast, corrected from 72 to 92% of their total errors. Patients with DAT tended to rely on reformulation repairs while patients with PD used both repair types about equally often. While healthy elderly Ss (in the 70s group) utilized lemma repairs more often than the reformulation strategy, all other healthy Ss used both strategies about equally often. Across all groups naming performance correlated negatively with numbers of undetected errors. Results point to a previously unrecognized communication disorder associated with PD and DAT and manifested by an impairment in the ability to correct output errors. This impairment may be related to attentional and frontal dysfunction in the two patient groups. PMID:1547468

  6. Evidence for the timing and duration of the last interglacial period from high-precision uranium-series ages of corals on tectonically stable coastlines

    USGS Publications Warehouse

    Muhs, D.R.

    2002-01-01

    The last interglacial period has a timing and duration that can be estimated from U-series dating of emergent, coral-bearing deposits on tectonically stable coastlines. High-precision dating from Bermuda, the Bahamas, Hawaii, and Australia suggests that the last interglacial period had a sea level at least as high as present from ???128,000 to 116,000 yr B.P. Sea level reached a near-present level more quickly after the close of the penultimate glacial period than at the close of the last glacial period and the duration of high sea level is longer than that implied by the deep-sea record. ?? 2002 University of Washington.

  7. [Hearing disorders in peripheral arterial vascular diseases. A contribution on hearing loss in the aged].

    PubMed

    Böhme, G

    1987-12-01

    Otologic-audiologic examination was carried out in 171 patients (aged between 37-86; average age 64) with confirmed internal angiologic peripheral arterial vascular disease. Additional findings were observed in 94 of these patients who revealed an obliteration of the internal carotid artery or cerebral ischaemic stroke. Diseases of the ear were excluded clinically and audiologically. The mean hearing loss shows a sensory-neural high-tone loss in the tone audiogram. The range of scatter increases proportionately to the increase in tone loss. If compared with the physiologic examination of geriatric patients, the total word comprehension and minimal discrimination loss in the speech audiogram point towards a pathologic impairment of hearing in old age. The total word comprehension amounts to 251.20% in the 51-60 age group, 250.40% in the persons 61-70 years of age, 180.96% for the 71-80 age group and 131.67% for those over 80 years of age. The minimal discrimination loss comprises 4.00% for the 51-60 age group, 4.19% for the 61-70 group, 21.35% for 71-80 age bracket and 35.62% for those over 80. On the strength of these findings, an arterial sclerotic vascular disease should be considered as one of the multifactorial genesis of hearing impairment in old age. Special attention should be focussed on decompensation of the total word comprehension and minimal discrimination loss before the age of eighty. This would contribute towards a differentiation of physiologic and pathologic hearing diseases in old age. PMID:3431312

  8. "I'm Not Going to Die from the AIDS": Resilience in Aging with HIV Disease

    ERIC Educational Resources Information Center

    Emlet, Charles A.; Tozay, Shakima; Raveis, Victoria H.

    2011-01-01

    Purpose: Adults aging with HIV/AIDS can experience resilience in spite of the deleterious affects of the disease. This study seeks to examine the lived experiences of older adults with HIV/AIDS as it relates to strengths and resilience in dealing with this devastating disease. Design and methods: Semistructured in-depth interviews were conducted…

  9. Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development

    PubMed Central

    Trotter, Caroline L.; Ramsay, Mary E.; Chandra, Manosree; Jolley, Keith A.; van der Ende, Arie; Carion, Françoise; Berthelsen, Lene; Hoffmann, Steen; Harðardóttir, Hjördís; Vazquez, Julio A.; Murphy, Karen; Toropainen, Maija; Caniça, Manuela; Ferreira, Eugenia; Diggle, Mathew; Edwards, Giles F.; Taha, Muhamed-Kheir; Stefanelli, Paola; Kriz, Paula; Gray, Steve J.; Fox, Andrew J.; Jacobsson, Susanne; Claus, Heike; Vogel, Ulrich; Tzanakaki, Georgina; Heuberger, Sigrid; Caugant, Dominique A.; Frosch, Matthias; Maiden, Martin C. J.

    2014-01-01

    New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and ≥25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups. PMID:24695776

  10. The emerging role of Notch pathway in ageing: Focus on the related mechanisms in age-related diseases.

    PubMed

    Balistreri, Carmela Rita; Madonna, Rosalinda; Melino, Gerry; Caruso, Calogero

    2016-08-01

    Notch signaling is an evolutionarily conserved pathway, which is fundamental for the development of all tissues, organs and systems of human body. Recently, a considerable and still growing number of studies have highlighted the contribution of Notch signaling in various pathological processes of the adult life, such as age-related diseases. In particular, the Notch pathway has emerged as major player in the maintenance of tissue specific homeostasis, through the control of proliferation, migration, phenotypes and functions of tissue cells, as well as in the cross-talk between inflammatory cells and the innate immune system, and in onset of inflammatory age-related diseases. However, until now there is a confounding evidence about the related mechanisms. Here, we discuss mechanisms through which Notch signaling acts in a very complex network of pathways, where it seems to have the crucial role of hub. Thus, we stress the possibility to use Notch pathway, the related molecules and pathways constituting this network, both as innovative (predictive, diagnostic and prognostic) biomarkers and targets for personalised treatments for age-related diseases. PMID:27328278

  11. 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

  12. Knowledge of memory aging and Alzheimer's disease in college students and mental health professionals.

    PubMed

    Jackson, Erin M; Cherry, Katie E; Smitherman, Emily A; Hawley, Karri S

    2008-03-01

    In this study, college students and mental health professionals completed the Knowledge of Memory Aging Questionnaire, Alzheimer's Disease Knowledge Test and the Fraboni Scale of Ageism before and after a lecture on normal and pathological memory issues in adulthood. Results confirmed that professionals were more knowledgeable about memory aging and Alzheimer's disease (AD) and less ageist than college students. Analyses of pre- and post-lecture response accuracy yielded comparable benefits in memory aging and AD knowledge for both groups. Correlation analyses provided modest evidence for the influence of ageist attitudes on the knowledge measures. Implications for memory education programs and psychology curriculum are considered. PMID:18389407

  13. Attention and driving skills in aging and Alzheimer's disease.

    PubMed

    Parasuraman, R; Nestor, P G

    1991-10-01

    The number of older drivers with dementia is rising with the aging of the adult population. A public health issue is growing because of concerns about the motor vehicle accident risk posed by drivers with dementia of the Alzheimer's type (DAT) and other progressive, degenerative dementias. However, little is known about the specific perceptual/cognitive deficits contributing to impaired driving in DAT. The present paper proposes, on both theoretical and empirical grounds, that attentional skills in relation to driving should be examined in older adults with and without DAT. Such investigations should focus on normal older adults and those in the mild, early stages of dementia because the latter are the most likely among the dementia population to be still driving. Evidence is presented indicating (1) that motor vehicle accident rates are related to performance on information-processing measures of different components of attention; (2) that this relationship is greatest for measures of the switching of selective attention and less for that of divided and sustained attention (vigilance); and (3) that many of these same attentional functions, and particularly the switching of visual selective attention, are impaired in the early stages of DAT and thus may contribute to increased accident risk. Further studies of cognitive and driving performance in older drivers are necessary to establish that the attentional impairments found in mild DAT contribute to increased accident risk. Implications of these findings for driver assessment, education, and training are discussed. PMID:1769674

  14. Hair trace elementary profiles in aging rodents and primates: links to altered cell homeodynamics and disease.

    PubMed

    Ambeskovic, Mirela; Fuchs, Eberhard; Beaumier, Pierre; Gerken, Michael; Metz, Gerlinde A

    2013-10-01

    Aging is associated with an increased incidence of pathological conditions such as neurodegeneration, cardiovascular and renal disease, and cancer. These conditions are believed to be linked to a disruption in cell homeodynamics, which is regulated by essential trace elements. In this study we used hair elementary analysis by inductively coupled plasma mass spectrometry (ICPMS) to examine age-related profiles of 47 elements in both rats and common marmoset monkeys. Hair was collected from young adult (6 months) and aged (18 months) Long-Evans male rats, and young adult (2 years), middle-aged (4 years) and aged (>8 years) marmosets. The results revealed that aging reduces content levels of cobalt, potassium and selenium while content levels of aluminium, arsenic, boron, mercury, molybdenum, and titanium were elevated in aged rats. Similarly, aged marmosets showed reduced levels of cobalt and elevated levels of aluminium. Case studies in aged rats revealed that myocardial infarction was associated with elevated levels of sodium, potassium and cadmium and reduced zinc, while renal failure was linked to elevated content of potassium, chloride and boron and reduced contents of manganese. Carcinoma was linked to elevated arsenic and reduced selenium levels. These findings indicate that hair elementary profiles in healthy aging and age-related diseases reflect altered cell and organ metabolic functions. Cobalt and aluminium in particular may serve as biomarkers of aging in animal models. Thus, elementary deposition in hair may have predictive and diagnostic value in age-related pathological conditions, including cardiovascular and kidney disease and cancer. PMID:24057279

  15. 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...

  16. The effect of aging on brain barriers and the consequences for Alzheimer's disease development.

    PubMed

    Gorlé, Nina; Van Cauwenberghe, Caroline; Libert, Claude; Vandenbroucke, Roosmarijn E

    2016-08-01

    Life expectancy has increased in most developed countries, which has led to an increase in the proportion of elderly people in the world's population. However, this increase in life expectancy is not accompanied by a lengthening of the health span since aging is characterized with progressive deterioration in cellular and organ functions. The brain is particularly vulnerable to disease, and this is reflected in the onset of age-related neurodegenerative diseases such as Alzheimer's disease. Research shows that dysfunction of two barriers in the central nervous system (CNS), the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB), plays an important role in the progression of these neurodegenerative diseases. The BBB is formed by the endothelial cells of the blood capillaries, whereas the BCSFB is formed by the epithelial cells of the choroid plexus (CP), both of which are affected during aging. Here, we give an overview of how these barriers undergo changes during aging and in Alzheimer's disease, thereby disturbing brain homeostasis. Studying these changes is needed in order to gain a better understanding of the mechanisms of aging at the brain barriers, which might lead to the development of new therapies to lengthen the health span (including mental health) and reduce the chances of developing Alzheimer's disease. PMID:27143113

  17. UPS Activation in the Battle Against Aging and Aggregation-Related Diseases: An Extended Review.

    PubMed

    Papaevgeniou, Nikoletta; Chondrogianni, Niki

    2016-01-01

    Aging is a biological process accompanied by gradual increase of damage in all cellular macromolecules, i.e., nucleic acids, lipids, and proteins. When the proteostasis network (chaperones and proteolytic systems) cannot reverse the damage load due to its excess as compared to cellular repair/regeneration capacity, failure of homeostasis is established. This failure is a major hallmark of aging and/or aggregation-related diseases. Dysfunction of the major cellular proteolytic machineries, namely the proteasome and the lysosome, has been reported during the progression of aging and aggregation-prone diseases. Therefore, activation of these pathways is considered as a possible preventive or therapeutic approach against the progression of these processes. This chapter focuses on UPS activation studies in cellular and organismal models and the effects of such activation on aging, longevity and disease prevention or reversal. PMID:27613027

  18. Decreased plasma cholesterol levels during aging in transgenic mouse models of Alzheimer's disease.

    PubMed

    Wirths, Oliver; Thelen, Karin; Breyhan, Henning; Luzón-Toro, Berta; Hoffmann, Karl-Heinz; Falkai, Peter; Lütjohann, Dieter; Bayer, Thomas A

    2006-02-01

    A large number of studies deals with the association of cholesterol and Abeta levels, however, the results are so far controversial. Whereas some studies report on increased cholesterol levels, other authors refer to an association of decreased peripheral cholesterol and the incidence of Alzheimer's disease. It is also questionable whether plasma cholesterol levels could be used as a predictive biomarker for the incidence of Alzheimer's disease. In the present report, we studied the relationship between these two parameters during aging in different transgenic mouse models of Alzheimer's disease, expressing both mutant human amyloid precursor protein and mutant human presenilin-1. Measurements of plasma cholesterol levels revealed a significant reduction in aged APP/PS1 and APP/PS1ki mice, whereas plasma levels in young and aged control mice remained almost unchanged. Furthermore, statistical analysis revealed a significant negative correlation between plasma cholesterol and brain Abeta42 levels during aging in the mice expressing both APP and PS1. PMID:16307858

  19. Retirement Age and the Age of Onset of Alzheimer’s Disease: Results from the ICTUS Study

    PubMed Central

    Grotz, Catherine; Letenneur, Luc; Bonsang, Eric; Amieva, Hélène; Meillon, Céline; Quertemont, Etienne; Salmon, Eric; Adam, Stéphane

    2015-01-01

    Objectives To test whether deferred retirement is associated with delayed onset of Alzheimer’s disease (AD), and, if so, to determine whether retirement age still predicts the age at onset of AD when two potential biases are considered. Methods The study sample was gathered from the Impact of Cholinergic Treatment Use/Data Sharing Alzheimer cohort (ICTUS/DSA), a European study of 1,380 AD patients. Information regarding retirement age, onset of symptoms and covariates was collected at baseline whereas age at diagnosis was gathered from the patient’s medical record prior to study entry. Linear mixed models, adjusted for gender, education, occupation, center, country, household income, depression and cardiovascular risk factors were conducted on 815 patients. Results (1) The global analyses (n = 815) revealed that later age at retirement was associated with later age at diagnosis (β = 0.31, p < 0.0001); (2) once the selection bias was considered (n = 637), results showed that this association was weaker but remained significant (β = 0.15, p = 0.004); (3) once the bias of the reverse causality (i.e., the possibility that subjects may have left the workforce due to prior cognitive impairment) was considered (n = 447), the effect was no longer significant (β = 0.06, p = 0.18). Conclusion The present study supports that there is an association between retirement age and age at onset of AD. However, the strength of this association appears to be overestimated due to the selection bias. Moreover, the causality issue remains unresolved. Further prospective investigations are mandatory in order to correctly address this question. PMID:25714815

  20. U-Pb garnet, sphene, monazite, and rutile ages: Implications for the duration of high-grade metamorphism and cooling histories, Adirondack Mts. , New York

    SciTech Connect

    Mezger, K.; Rawnsley, C.M.; Hanson, G.N. ); Bohlen, S.R. )

    1991-05-01

    Garnet ages for the Lowlands range from 1,168-1,127 Ma, those from the central and southern Highlands from 1,154-1,013 Ma. Metamorphism in the Highlands may not have occurred as a single event but rather in several discrete thermal pulses. An age of 1,153 {plus minus} 3 Ma was determined for garnets in the syn-regional metamorphic contact aureole of the Diana syenite, consistent with that of the syenite intrusion, 1 155 {plus minus} 4 Ma. Garnets just outside the contact aureole give an age of 1,168 {plus minus} 6 Ma. In the Lowlands, monazite yielded an age of 1,161 {plus minus} 1 Ma, rutiles yielded ages of 1,005 {plus minus} 2 Ma and 953 {plus minus} 4 Ma, and sphene ages range from 1,156 to 1,103 Ma. In the Highlands, monazite yielded an age of 1,033 {plus minus} 1 Ma, rutiles yielded ages of 911 {plus minus} 2 Ma and 885 {plus minus} 2 and sphenes from 1,033 Ma to 991 Ma. The rutile and monazite ages indicate that both terranes cooled at time-integrated rates of ca. 1.5C/Ma for at least 150 Ma following the last phase of high-grade metamorphism. The Lowlands cooled to ca. 400C by ca. 1,000 Ma and the Highlands by ca. 900 Ma. The mineral ages indicate that metamorphic pressures and temperatures recorded by thermobarometry correspond to conditions attained polychronically over 150 Ma or more. Mineral ages combined with temperature estimates for peak metamorphism indicate that the closure temperature for the U-Pb system is >800C in garnet, 640-730C in monazite, and 500-670C in sphene.

  1. Neuropathology and apolipoprotein E profile of aged chimpanzees: implications for Alzheimer disease.

    PubMed Central

    Gearing, M; Rebeck, G W; Hyman, B T; Tigges, J; Mirra, S S

    1994-01-01

    Neuropathological findings in three aged chimpanzees were compared with those in rhesus monkeys and individuals with Alzheimer disease. Senile plaques and blood vessels were immunoreactive for amyloid beta-protein and apolipoprotein E (apoE) in the nonhuman primates, recapitulating findings in human aging and Alzheimer disease. Neurofibrillary tangles, another hallmark of Alzheimer disease, were absent. PCR/restriction-enzyme analysis in chimpanzees revealed an APOE profile similar to the human APOE type 4 allele associated with an increased risk of Alzheimer disease. These findings militate against the hypothesis that the absence of APOE type 3 allele predisposes to neurofibrillary tangle formation and support the value of aged primates for exploring mechanisms of amyloid processing and the role of apoE. Images PMID:7937774

  2. Age at onset of Alzheimer's disease: clue to the relative importance of etiologic factors

    SciTech Connect

    Horner, R.D.

    1987-09-01

    Clues to the relative importance of possible etiologic factors for dementia of the Alzheimer type may be gained by examining the fit of case series to Sartwell's model of the distribution of incubation periods. If age at disease onset is used as the incubation period of this disease, a genetic or environmental factor acting during the prenatal period is suggested if the distribution of these ages fits the lognormal curve; otherwise, environmental factors acting after birth are implicated. Case series were identified from the literature. Four case series were found which contained sufficiently detailed data to permit this secondary analysis; only one case series was population-based. The distribution of age at disease onset for each series was graphically and statistically assessed for fit to the logarithmic normal distribution. Each case series fit the lognormal curve well. This suggests that research into the etiology of dementia of the Alzheimer type should focus on the prenatal experiences of patients with this disease.

  3. 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

  4. Influence of disease duration, continued followup and further antiphospholipid testing on the frequency and classification category of antiphospholipid syndrome in a cohort of patients with systemic lupus erythematosus.

    PubMed

    Pérez-Vázquez, M E; Villa, A R; Drenkard, C; Cabiedes, J; Alarcón-Segovia, D

    1993-03-01

    In an earlier study of a cohort of 667 patients with systemic lupus erythematosus (SLE) followed for 7.5 months with mean antiphospholipid (aPL) testing 2.5 times, we found a 10% prevalence of definite antiphospholipid syndrome (APS) (2 clinical manifestations and high aPL levels). To determine if more followup and aPL testing increased such prevalence we restudied the cohort after a mean followup of 3.1 years and a mean aPL testing of 5.6 times and found a 15% prevalence of definite APS. Another 21% of patients with SLE had probable APS with either high titers of aPL but only one clinical manifestation or low titers with 2 clinical manifestations. The prevalence of high titer positivity of aPL (IgG and/or IgM isotype) reached 41%. One aPL related feature that increased significantly was livedo reticularis possibly from increased awareness. Factors that influenced significantly the mobility upwards in APS category were more pregnancies and further aPL testing. Conversely, immunosuppressive treatment decreased higher aPL levels. The large number of patients with long disease duration in our cohort showed that the maximum prevalence of definite APS is reached after 15-18 years and is 23%. This might be the highest prevalence of definite APS within SLE. PMID:8478848

  5. The Duration of an Exposure Response Gradient between Incident Obstructive Airways Disease and Work at the World Trade Center Site: 2001-2011

    PubMed Central

    Hall, Charles B.; Liu, Xiaoxue; Zeig-Owens, Rachel; Webber, Mayris P.; Aldrich, Thomas K.; Weakley, Jessica; Schwartz, Theresa; Cohen, Hillel W.; Glaser, Michelle S.; Olivieri, Brianne L.; Weiden, Michael D.; Nolan, Anna; Kelly, Kerry J.; Prezant, David J.

    2015-01-01

    Background: Adverse respiratory effects of World Trade Center (WTC) exposure have been widely documented, but the length of time that exposure remains associated with disease is uncertain. We estimate the incidence of new cases of physician-diagnosed obstructive airway disease (OAD) as a function of time since 9/11/2001 in WTC-exposed firefighters. Methods: Exposure was categorized by first WTC arrival time: high (9/11/2001 AM); moderate (9/11/2001 PM or 9/12/2001); or low (9/13-24/2001). We modeled relative rates (RR) and 95% confidence intervals (CI) of OAD incidence by exposure over the first 10 years post-9/11/2001, estimating the time(s) of change in the RR with change point models. We further examined the relationship between self-reported lower respiratory symptoms and physician diagnoses. Results: Change points were observed at 15 and 84 months post-9/11/2001, with relative incidence rates for the high versus low exposure group of 4.02 (95% CI 2.62-6.16) prior to 15 months, 1.90 (95% CI 1.49-2.44) from months 16 to 84, and 1.20 (95% CI 0.92-1.56) thereafter. Incidence in all exposure groups increased after the WTC health program began to offer free coverage of OAD medications in month 63. Self-reported lower respiratory symptoms in the first 15 months had 80.6% sensitivity, but only 35.9% specificity, for eventual OAD diagnoses. Conclusions: New OAD diagnoses are associated with WTC exposure for at least seven years. Some portion of the extended duration of that association may be due to delayed diagnoses. Nevertheless, our results support recognizing OAD among rescue workers as WTC-related even when diagnosed years after exposure. PMID:26064784

  6. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

    PubMed

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

    2016-07-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. PMID:27479945

  7. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels

    PubMed Central

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F.; Eszes, Marika; Faull, Richard L.M.; Curtis, Maurice A.; Waldvogel, Henry J.; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V.; Coppola, Giovanni; Yang, X. William

    2016-01-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=−0.41, p=5.5×10−8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. PMID:27479945

  8. Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer.

    PubMed

    Conti, Simon L; Eisenberg, Michael L

    2016-01-01

    As couples are increasingly delaying parenthood, the effect of the aging men and women on reproductive outcomes has been an area of increased interest. Advanced paternal age has been shown to independently affect the entire spectrum of male fertility as assessed by reductions in sperm quality and fertilization (both assisted and unassisted). Moreover, epidemiological data suggest that paternal age can lead to higher rates of adverse birth outcomes and congenital anomalies. Mounting evidence also suggests increased risk of specific pediatric and adult disease states ranging from cancer to behavioral traits. While disease states associated with advancing paternal age have been well described, consensus recommendations for neonatal screening have not been as widely implemented as have been with advanced maternal age. PMID:26975491

  9. Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer

    PubMed Central

    Conti, Simon L; Eisenberg, Michael L

    2016-01-01

    As couples are increasingly delaying parenthood, the effect of the aging men and women on reproductive outcomes has been an area of increased interest. Advanced paternal age has been shown to independently affect the entire spectrum of male fertility as assessed by reductions in sperm quality and fertilization (both assisted and unassisted). Moreover, epidemiological data suggest that paternal age can lead to higher rates of adverse birth outcomes and congenital anomalies. Mounting evidence also suggests increased risk of specific pediatric and adult disease states ranging from cancer to behavioral traits. While disease states associated with advancing paternal age have been well described, consensus recommendations for neonatal screening have not been as widely implemented as have been with advanced maternal age. PMID:26975491

  10. Diabetes mellitus Type II and cognitive capacity in healthy aging, mild cognitive impairment and Alzheimer's disease.

    PubMed

    Degen, Christina; Toro, Pablo; Schönknecht, Peter; Sattler, Christine; Schröder, Johannes

    2016-06-30

    While diabetes mellitus (DM) Type II has repeatedly been linked to Alzheimer´s disease (AD) and mild cognitive impairment (MCI), longitudinal research is scarce and disease duration has not always been taken into account. In a birth cohort born between 1930 and 1932 we investigated the influence of DM Type II and disease duration on neuropsychological functioning (memory/learning, attention, verbal fluency, visuospatial thinking and abstract thinking) across 14 years. Subjects who developed MCI or AD performed significantly poorer on all neuropsychological tests applied. While significant main effects DM Type II did not arise, its presence led to a significant deterioration of performance in the digit symbol test and visuospatial thinking over time. Additionally, in visuospatial thinking this change was more pronounced for individuals suffering from MCI/AD. We found that, as a concomitant disease DM Type II does not affect memory functioning, which is typically compromised in MCI and early AD. Rather, it may lead to deficits in cognitive flexibility and visuospatial thinking. DM Type II can be considered a frequent comorbid condition which can aggravate the course of MCI and AD. In this respect it may serve as a model for other comorbid conditions in AD. PMID:27082868

  11. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease

    PubMed Central

    Moskalev, Alexey; Chernyagina, Elizaveta; de Magalhães, João Pedro; Barardo, Diogo; Thoppil, Harikrishnan; Shaposhnikov, Mikhail; Budovsky, Arie; Fraifeld, Vadim E.; Garazha, Andrew; Tsvetkov, Vasily; Bronovitsky, Evgeny; Bogomolov, Vladislav; Scerbacov, Alexei; Kuryan, Oleg; Gurinovich, Roman; Jellen, Leslie C.; Kennedy, Brian; Mamoshina, Polina; Dobrovolskaya, Evgeniya; Aliper, Alex; Kaminsky, Dmitry; Zhavoronkov, Alex

    2015-01-01

    As the level of interest in aging research increases, there is a growing number of geroprotectors, or therapeutic interventions that aim to extend the healthy lifespan and repair or reduce aging-related damage in model organisms and, eventually, in humans. There is a clear need for a manually-curated database of geroprotectors to compile and index their effects on aging and age-related diseases and link these effects to relevant studies and multiple biochemical and drug databases. Here, we introduce the first such resource, Geroprotectors (http://geroprotectors.org). Geroprotectors is a public, rapidly explorable database that catalogs over 250 experiments involving over 200 known or candidate geroprotectors that extend lifespan in model organisms. Each compound has a comprehensive profile complete with biochemistry, mechanisms, and lifespan effects in various model organisms, along with information ranging from chemical structure, side effects, and toxicity to FDA drug status. These are presented in a visually intuitive, efficient framework fit for casual browsing or in-depth research alike. Data are linked to the source studies or databases, providing quick and convenient access to original data. The Geroprotectors database facilitates cross-study, cross-organism, and cross-discipline analysis and saves countless hours of inefficient literature and web searching. Geroprotectors is a one-stop, knowledge-sharing, time-saving resource for researchers seeking healthy aging solutions. PMID:26342919

  12. Aging with a disability: A systematic review of cardiovascular disease and osteoporosis among women aging with a physical disability

    PubMed Central

    Rosso, Andrea L.; Wisdom, Jennifer Pelt; Horner-Johnson, Willi; McGee, Marjorie G.; Michael, Yvonne L.

    2016-01-01

    Compared to men, women live longer but experience greater morbidity as they age. However, little is known about the rapidly growing population of women aging with disability. Women aging with disabilities may encounter barriers that increase risk of morbidity, including lack of access to medical care or inadequate assistance, equipment, or services. To evaluate risks of morbidity in this group, we conducted a systematic review focused on two important and prevalent conditions: cardiovascular disease (CVD) and osteoporosis. MEDLINE was searched for reports published between January 1, 1990 and August 6, 2010 and additional studies were identified through searches of bibliographies. 9,156 abstracts and 93 articles were reviewed to identify empirical studies of women with physical disability who were 45 years or older and that reported CVD or osteoporosis as an outcome and not a cause of the disability. Articles meeting inclusion criteria were then critically appraised to exclude poor quality studies. In seven articles that evaluated CVD outcomes, we found limited evidence to support an increased risk of prevalence of CVD or risk factors for CVD in women aging with physical disabilities compared to non-disabled control populations. The literature is limited by small sample sizes that reduced statistical power to detect true differences. No articles meeting inclusion criteria were identified to evaluate osteoporosis risk in this group. This review is limited by the narrow focus on physical disabilities and two health outcomes. Additional high quality empirical research is necessary to understand the risks to health of women aging with disabilities. PMID:21075569

  13. Epigenetic Control of Stem Cell Potential During Homeostasis, Aging, and Disease

    PubMed Central

    Beerman, Isabel; Rossi, Derrick J.

    2015-01-01

    Stem cell decline is an important cellular driver of aging-associated pathophysiology in multiple tissues. Epigenetic regulation is central to establishing and maintaining stem cell function, and emerging evidence indicates that epigenetic dysregulation contributes to the altered potential of stem cells during aging. Unlike terminally differentiated cells, the impact of epigenetic dysregulation in stem cells is propagated beyond self; alterations can be heritably transmitted to differentiated progeny, in addition to being perpetuated and amplified within the stem cell pool through self-renewal divisions. This review focuses on recent studies examining epigenetic regulation of tissue-specific stem cells in homeostasis, aging, and aging-related disease. PMID:26046761

  14. First episodes of behavioral symptoms in Alzheimer's disease patients at age 90 and over, and early-onset Alzheimer's disease: comparison with senile dementia of Alzheimer's type.

    PubMed

    Hori, Koji; Oda, Tatsuro; Asaoka, Toshiyasu; Yoshida, Masahiro; Watanabe, Shoichi; Oyamada, Reiko; Tominaga, Itaru; Inada, Toshiya

    2005-12-01

    We evaluated dementia symptoms to clarify the character of dementia with Alzheimer's disease (AD) observed in the oldest old patients and that of dementia with early-onset AD. Subjects were consecutive AD inpatients admitted for the first time at age of 90 years and over because of behavioral symptoms (demented nonagenarian group: D90G; n=18) and those with 24 consecutive inpatients with AD with early-onset (EOG). The Gottfries, Brane and Steen's scale and the Dementia Behavior Disturbance scale were used to evaluate the symptoms and troublesome behaviors. The scores of these scales in D90G and in EOG were compared with those of 26 sex distribution-, severity of dementia-, and disease duration-matched inpatients with AD with late-onset (LOG). Compared with LOG, wakefulness was more impaired and waking up at night was more frequent in D90G, while memory, orientation and inappropriate behaviors were more severe in EOG. These results suggest that the clinical features of dementia in EOG were quantitatively different from those of LOG. In contrast, the clinical feature of dementia of D90G were sleep-wake pattern disturbance and were qualitatively different from those of LOG. PMID:16401251

  15. Mass spectrometric analysis of protein tyrosine nitration in aging and neurodegenerative diseases.

    PubMed

    Yeo, Woon-Seok; Kim, Young Jun; Kabir, Mohammad Humayun; Kang, Jeong Won; Ahsan-Ul-Bari, Md; Kim, Kwang Pyo

    2015-01-01

    This review highlights the significance of protein tyrosine nitration (PTN) in signal transduction pathways, the progress achieved in analytical methods, and the implication of nitration in the cellular pathophysiology of aging and age-related neurodegenerative diseases. Although mass spectrometry of nitrated peptides has become a powerful tool for the characterization of nitrated peptides, the low stoichiometry of this modification clearly necessitates the use of affinity chromatography to enrich modified peptides. Analysis of nitropeptides involves identification of endogenous, intact modification as well as chemical conversion of the nitro group to a chemically reactive amine group and further modifications that enable affinity capture and enhance detectability by altering molecular properties. In this review, we focus on the recent progress in chemical derivatization of nitropeptides for enrichment and mass analysis, and for detection and quantification using various analytical tools. PTN participates in physiological processes, such as aging and neurodegenerative diseases. Accumulation of 3-nitrotyrosine has been found to occur during the aging process; this was identified through mass spectrometry. Further, there are several studies implicating the presence of nitrated tyrosine in age-related diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. PMID:24889964

  16. The Association of Smoking and Surgery in Inflammatory Bowel Disease is Modified by Age at Diagnosis

    PubMed Central

    Frolkis, Alexandra D; de Bruyn, Jennifer; Jette, Nathalie; Lowerison, Mark; Engbers, Jordan; Ghali, William; Lewis, James D; Vallerand, Isabelle; Patten, Scott; Eksteen, Bertus; Barnabe, Cheryl; Panaccione, Remo; Ghosh, Subrata; Wiebe, Samuel; Kaplan, Gilaad G

    2016-01-01

    Objectives: We assessed the association of smoking at diagnosis of inflammatory bowel disease (IBD) on the need for an intestinal resection. Methods: The Health Improvement Network was used to identify an inception cohort of Crohn's disease (n=1519) and ulcerative colitis (n=3600) patients from 1999–2009. Poisson regression explored temporal trends for the proportion of newly diagnosed IBD patients who never smoked before their diagnosis and the risk of surgery within 3 years of diagnosis. Cox proportional hazard models assessed the association between smoking and surgery, and effect modification was explored for age at diagnosis. Results: The rate of never smokers increased by 3% per year for newly diagnosed Crohn's disease patients (incidence rate ratio (IRR) 1.03; 95% confidence interval (CI): 1.02–1.05), but not for ulcerative colitis. The rate of surgery decreased among Crohn's disease patients aged 17–40 years (IRR 0.96; 95% CI: 0.93–0.98), but not for ulcerative colitis. Smoking at diagnosis increased the risk of surgery for Crohn's disease patients diagnosed after the age of 40 (hazard ratio (HR) 2.99; 95% CI: 1.52–5.92), but not for those diagnosed before age 40. Ulcerative colitis patients diagnosed between the ages of 17 and 40 years and who quit smoking before their diagnosis were more likely to undergo a colectomy (ex-smoker vs. never smoker: HR 1.66; 95% CI: 1.04–2.66). The age-specific findings were consistent across sensitivity analyses for Crohn's disease, but not ulcerative colitis. Conclusions: In this study, the association of smoking and surgical resection was dependent on the age at diagnosis of IBD. PMID:27101004

  17. Recent Developments in Understanding Brain Aging: Implications for Alzheimer's Disease and Vascular Cognitive Impairment.

    PubMed

    Deak, Ferenc; Freeman, Willard M; Ungvari, Zoltan; Csiszar, Anna; Sonntag, William E

    2016-01-01

    As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease. PMID:26590911

  18. A novel diagnostic tool reveals mitochondrial pathology in human diseases and aging

    PubMed Central

    Scheibye-Knudsen, Morten; Scheibye-Alsing, Karsten; Canugovi, Chandrika; Croteau, Deborah L.; Bohr, Vilhelm A.

    2013-01-01

    The inherent complex and pleiotropic phenotype of mitochondrial diseases poses a significant diagnostic challenge for clinicians as well as an analytical barrier for scientists. To overcome these obstacles we compiled a novel database, www.mitodb.com, containing the clinical features of primary mitochondrial diseases. Based on this we developed a number of qualitative and quantitative measures, enabling us to determine whether a disorder can be characterized as mitochondrial. These included a clustering algorithm, a disease network, a mitochondrial barcode and two scoring algorithms. Using these tools we detected mitochondrial involvement in a number of diseases not previously recorded as mitochondrial. As a proof of principle Cockayne syndrome, ataxia with oculomotor apraxia 1 (AOA1), spinocerebellar ataxia with axonal neuropathy 1 (SCAN1) and ataxia-telangiectasia have recently been shown to have mitochondrial dysfunction and those diseases showed strong association with mitochondrial disorders. We next evaluated mitochondrial involvement in aging and detected two distinct categories of accelerated aging disorders, one of them being associated with mitochondrial dysfunction. Normal aging seemed to associate stronger with the mitochondrial diseases than the non-mitochondrial partially supporting a mitochondrial theory of aging. PMID:23524341

  19. Respiratory Sinus Arrhythmia and Diseases of Aging: Obesity, Diabetes Mellitus, and Hypertension.

    PubMed Central

    Masi, Christopher M.; Hawkley, Louise C.; Rickett, Edith M.; Cacioppo, John T.

    2007-01-01

    Associations between respiratory sinus arrhythmia (RSA) and several chronic diseases, including obesity, diabetes mellitus, and hypertension, have been documented in recent years. Although most evidence suggests reduced RSA is the result of chronic disease rather than the cause, some studies have documented reduced RSA among at-risk individuals prior to disease onset. These results raise the possibility that decreased vagal tone may play a role in the pathogenesis of certain chronic diseases. Presented here is a brief overview of studies which examine the relationship between vagal tone, as measured by RSA and baroreflex gain, and diseases of aging, including obesity, diabetes mellitus, and hypertension. Mechanisms by which vagal tone may be related to disease processes are discussed. In addition, we present results from a population-based study of RSA and hypertension in older adults. Consistent with previous studies, we found an inverse relationship between RSA and age, cigarette use, and diabetes. In logistic regression models which control for age, cigarette use, and diabetes, we found RSA was a significant negative predictor of hypertension. We conclude that the relationship between RSA and hypertension is somewhat independent of the age-related decline in parasympathetic activity. PMID:17034928

  20. Is pathological aging a successful resistance against amyloid-beta or preclinical Alzheimer's disease?

    PubMed

    Murray, Melissa E; Dickson, Dennis W

    2014-01-01

    Individuals with pathological aging, a form of cerebral amyloidosis in older people, have widespread extracellular amyloid-beta (Aβ) senile plaque deposits in the setting of limited neurofibrillary tau pathology. Unlike the characteristic finding of antemortem cognitive impairment in Alzheimer's disease patients, individuals with pathological aging usually lack cognitive impairment despite similar Aβ senile plaque burdens. It has been hypothesized that protective or resistance factors may underlie pathological aging, thus minimizing or preventing deleterious effects on cognition. Despite increasing interest and recognition, a review of the literature remains challenging given the range of terms used to describe pathological aging. This debate briefly reviews neuropathologic and biochemical evidence that pathological aging individuals have resistance factors to Aβ plaque pathology. Additionally, we will discuss evidence of pathological aging as an intermediate between normal individuals and Alzheimer's disease patients, and discuss protective or resistance factors against vascular disease and neurofibrillary pathology. Lastly, we will emphasize the need for longitudinal biomarker evidence using amyloid positron emission tomography, which will provide a better understanding of the kinetics of Aβ deposition in pathological aging. PMID:25031637

  1. Young systemic factors as a medicine for age-related neurodegenerative diseases

    PubMed Central

    Katsimpardi, Lida; Rubin, Lee L

    2015-01-01

    It is widely known that neurogenesis, brain function and cognition decline with aging. Increasing evidence suggests that cerebrovascular dysfunction is a major cause of cognitive impairment in the elderly but is also involved in age-related neurodegenerative diseases. Finding ways and molecules that reverse this process and ameliorate age- and disease-related cognitive impairment by targeting vascular and neurogenic deterioration would be of great therapeutic value. In Katsimpardi et al. we reported that young blood has a dual beneficial effect in the aged brain by restoring age-related decline in neurogenesis as well as inducing a striking remodeling of the aged vasculature and restoring blood flow to youthful levels. Additionally, we identified a youthful systemic factor, GDF11 that recapitulates these beneficial effects of young blood. We believe that the identification of young systemic factors that can rejuvenate the aged brain opens new roads to therapeutic intervention for neurodegenerative diseases by targeting both neural stem cells and neurogenesis as well as at the vasculature.

  2. Emerging roles of frailty and inflammaging in risk assessment of age-related chronic diseases in older adults: the intersection between aging biology and personalized medicine.

    PubMed

    Wu, I-Chien; Lin, Cheng-Chieh; Hsiung, Chao A

    2015-01-01

    A chronic disease in older adults usually runs a course that is less predictable than in younger individuals. Unexplained variations in disease incidence, prognosis, therapeutic responses, and toxicity are frequently observed among older adults. This heterogeneity poses huge challenges to the current one-size-fits-all health care systems, and calls for more personalized managements of chronic diseases in older adults. Aging is characterized by progressive deterioration of bodily functions with increasing risk of failure over time. The entire process is hierarchically organized, and progresses from intracellular events to changes at systemic and ultimately organism levels at different rates among different individuals. Aging biology exerts great influences on the development and progression of most age-related chronic diseases. Thus, aging biology could contribute to the complexity of illnesses that increase with age, and aging biomarkers possess a great potential to enable personalized health risk assessment and health care. We review evidences supporting the roles of aging biomarkers in risk assessment of prevalent age-related diseases. Frailty phenotype is an objectively measured indicator of advanced-stage aging that is characterized by organism-level dysfunction. In contrast, altered inflammation markers level signifies an earlier stage between cellular abnormalities and systems dysfunction. Results of human observational studies and randomized controlled trials indicate that these measures, albeit simple, greatly facilitate classification of older patients with cancer, chronic kidney disease, cardiovascular diseases and type 2 diabetes mellitus into groups that vary in disease incidence, prognosis and therapeutic response/toxicity. As the detailed mechanisms underlying the complex biologic process of aging are unraveled in the future, a larger array of biomarkers that correlate with biologic aging at different stages will be discovered. Following the

  3. Infectious disease burden and cognitive function in young to middle-aged adults.

    PubMed

    Gale, Shawn D; Erickson, Lance D; Berrett, Andrew; Brown, Bruce L; Hedges, Dawson W

    2016-02-01

    Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults. PMID:26598104

  4. Forecasting and Analyzing the Disease Burden of Aged Population in China, Based on the 2010 Global Burden of Disease Study

    PubMed Central

    Bao, Chengzhen; Mayila, Mamat; Ye, Zhenhua; Wang, Jianbing; Jin, Mingjuan; He, Wenjiong; Chen, Kun

    2015-01-01

    Background: Forecasting the disease burden of the elderly will contribute to make a comprehensive assessment about physical and mental status of the elderly in China and provide a basis for reducing the negative consequences of aging society to a minimum. Methods: This study collected data from a public database online provided by Global Burden of Disease Study 2010. Grey model GM (1, 1) was used to forecast all-cause and disease-specific rates of disability adjusted life years (DALYs) in 2015 and 2020. Results: After cross-sectional and longitudinal analysis, we found that non-communicable diseases (NCDs) were still the greatest threats in the elderly, followed by injuries. As for 136 predicted causes, more than half of NCDs increased obviously with age, less than a quarter of communicable, material, neonatal, and nutritional disorders or injuries had uptrend. Conclusions: The findings display the health condition of the Chinese elderly in the future, which will provide critical information for scientific and sociological researches on preventing and reducing the risks of aging society. PMID:26121188

  5. Evolution of the human lifespan and diseases of aging: Roles of infection, inflammation, and nutrition

    PubMed Central

    Finch, Caleb E.

    2009-01-01

    Humans have evolved much longer lifespans than the great apes, which rarely exceed 50 years. Since 1800, lifespans have doubled again, largely due to improvements in environment, food, and medicine that minimized mortality at earlier ages. Infections cause most mortality in wild chimpanzees and in traditional forager-farmers with limited access to modern medicine. Although we know little of the diseases of aging under premodern conditions, in captivity, chimpanzees present a lower incidence of cancer, ischemic heart disease, and neurodegeneration than current human populations. These major differences in pathology of aging are discussed in terms of genes that mediate infection, inflammation, and nutrition. Apolipoprotein E alleles are proposed as a prototype of pleiotropic genes, which influence immune responses, arterial and Alzheimer’s disease, and brain development. PMID:19966301

  6. Micronutrient (Zn, Cu, Fe)-gene interactions in ageing and inflammatory age-related diseases: implications for treatments.

    PubMed

    Mocchegiani, Eugenio; Costarelli, Laura; Giacconi, Robertina; Piacenza, Francesco; Basso, Andrea; Malavolta, Marco

    2012-04-01

    In ageing, alterations in inflammatory/immune response and antioxidant capacity lead to increased susceptibility to diseases and loss of mobility and agility. Various essential micronutrients in the diet are involved in age-altered biological functions. Micronutrients (zinc, copper, iron) play a pivotal role either in maintaining and reinforcing the immune and antioxidant performances or in affecting the complex network of genes (nutrigenomic approach) involved in encoding proteins for a correct inflammatory/immune response. By the other side, the genetic inter-individual variability may affect the absorption and uptake of the micronutrients (nutrigenetic approach) with subsequent altered effects on inflammatory/immune response and antioxidant activity. Therefore, the individual micronutrient-gene interactions are fundamental to achieve healthy ageing. In this review, we report and discuss the role of micronutrients (Zn, Cu, Fe)-gene interactions in relation to the inflammatory status and the possibility of a supplement in the event of a micronutrient deficiency or chelation in presence of micronutrient overload in relation to specific polymorphisms of inflammatory proteins or proteins related of the delivery of the micronutriemts to various organs and tissues. In this last context, we report the protein-metal speciation analysis in order to have, coupled with micronutrient-gene interactions, a more complete picture of the individual need in micronutrient supplementation or chelation to achieve healthy ageing and longevity. PMID:22322094

  7. Age-at-Onset in Late Onset Alzheimer Disease is Modified by Multiple Genetic Loci

    PubMed Central

    Naj, Adam C.; Jun, Gyungah; Reitz, Christiane; Kunkle, Brian W.; Perry, William; Park, YoSon; Beecham, Gary W.; Rajbhandary, Ruchita A.; Hamilton-Nelson, Kara L.; Wang, Li-San; Kauwe, John S.K.; Huentelman, Matthew J.; Myers, Amanda J.; Bird, Thomas D.; Boeve, Bradley F.; Baldwin, Clinton T.; Jarvik, Gail P.; Crane, Paul K.; Rogaeva, Ekaterina; Barmada, Michael M.; Demirci, F. Yesim; Cruchaga, Carlos; Kramer, Patricia; Ertekin-Taner, Nilufer; Hardy, John; Graff-Radford, Neill R.; Green, Robert C.; Larson, Eric B.; St George-Hyslop, Peter; Buxbaum, Joseph D.; Evans, Denis; Schneider, Julie A.; Lunetta, Kathryn L.; Kamboh, M. Ilyas; Saykin, Andrew J.; Reiman, Eric M.; De Jager, Philip L.; Bennett, David A.; Morris, John C.; Montine, Thomas J.; Goate, Alison M.; Blacker, Deborah; Tsuang, Debby W.; Hakonarson, Hakon; Kukull, Walter A.; Foroud, Tatiana M.; Martin, Eden R.; Haines, Jonathan L.; Mayeux, Richard; Farrer, Lindsay A.; Schellenberg, Gerard D.; Pericak-Vance, Margaret A.

    2015-01-01

    Importance As APOE locus variants contribute to both risk of late-onset Alzheimer disease and differences in age-at-onset, it is important to know if other established late-onset Alzheimer disease risk loci also affect age-at-onset in cases. Objectives To investigate the effects of known Alzheimer disease risk loci in modifying age-at-onset, and to estimate their cumulative effect on age-at-onset variation, using data from genome-wide association studies in the Alzheimer’s Disease Genetics Consortium (ADGC). Design, Setting and Participants The ADGC comprises 14 case-control, prospective, and family-based datasets with data on 9,162 Caucasian participants with Alzheimer’s occurring after age 60 who also had complete age-at-onset information, gathered between 1989 and 2011 at multiple sites by participating studies. Data on genotyped or imputed single nucleotide polymorphisms (SNPs) most significantly associated with risk at ten confirmed LOAD loci were examined in linear modeling of AAO, and individual dataset results were combined using a random effects, inverse variance-weighted meta-analysis approach to determine if they contribute to variation in age-at-onset. Aggregate effects of all risk loci on AAO were examined in a burden analysis using genotype scores weighted by risk effect sizes. Main Outcomes and Measures Age at disease onset abstracted from medical records among participants with late-onset Alzheimer disease diagnosed per standard criteria. Results Analysis confirmed association of APOE with age-at-onset (rs6857, P=3.30×10−96), with associations in CR1 (rs6701713, P=7.17×10−4), BIN1 (rs7561528, P=4.78×10−4), and PICALM (rs561655, P=2.23×10−3) reaching statistical significance (P<0.005). Risk alleles individually reduced age-at-onset by 3-6 months. Burden analyses demonstrated that APOE contributes to 3.9% of variation in age-at-onset (R2=0.220) over baseline (R2=0.189) whereas the other nine loci together contribute to 1.1% of

  8. Beyond and behind the fingerprints of oxidative stress in age-related diseases: Secrets of successful aging.

    PubMed

    Polidori, M Cristina; Scholtes, Marlies

    2016-04-01

    Several years after the first publication of the definition of oxidative stress by Helmut Sies, this topic is still focus of a large body of attention and research in the field of aging, neurodegeneration and disease prevention. The conduction of clinical and epidemiological research without a solid biochemical rationale has led to largely frustrating results without being able to disprove the oxidative stress hypothesis. The present work is dedicated to Helmut Sies and describes the successful scientific approach to bench-to-bedside (-to-behavior) oxidative stress clinical research. PMID:27095215

  9. Cardiac Aging: From Molecular Mechanisms to Significance in Human Health and Disease

    PubMed Central

    Dai, Dao-Fu; Chen, Tony; Johnson, Simon C.; Szeto, Hazel

    2012-01-01

    Abstract Cardiovascular diseases (CVDs) are the major causes of death in the western world. The incidence of cardiovascular disease as well as the rate of cardiovascular mortality and morbidity increase exponentially in the elderly population, suggesting that age per se is a major risk factor of CVDs. The physiologic changes of human cardiac aging mainly include left ventricular hypertrophy, diastolic dysfunction, valvular degeneration, increased cardiac fibrosis, increased prevalence of atrial fibrillation, and decreased maximal exercise capacity. Many of these changes are closely recapitulated in animal models commonly used in an aging study, including rodents, flies, and monkeys. The application of genetically modified aged mice has provided direct evidence of several critical molecular mechanisms involved in cardiac aging, such as mitochondrial oxidative stress, insulin/insulin-like growth factor/PI3K pathway, adrenergic and renin angiotensin II signaling, and nutrient signaling pathways. This article also reviews the central role of mitochondrial oxidative stress in CVDs and the plausible mechanisms underlying the progression toward heart failure in the susceptible aging hearts. Finally, the understanding of the molecular mechanisms of cardiac aging may support the potential clinical application of several “anti-aging” strategies that treat CVDs and improve healthy cardiac aging. PMID:22229339

  10. 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

  11. Association between Age and Striatal Volume Stratified by CAG Repeat Length in Prodromal Huntington Disease

    PubMed Central

    Aylward, Elizabeth; Mills, James; Liu, Dawei; Nopoulos, Peggy; Ross, Christopher A.; Pierson, Ronald; Paulsen, Jane S.

    2011-01-01

    Background: Longer CAG repeat length is associated with faster clinical progression in Huntington disease, although the effect of higher repeat length on brain atrophy is not well documented. Method: Striatal volumes were obtained from MRI scans of 720 individuals with prodromal Huntington disease. Striatal volume was plotted against age separately for groups with CAG repeat lengths of 38–39, 40, 41, 42, 43, 44, 45, 46, and 47–54. Results: Slopes representing the association between age and striatal volume were significantly steeper as CAG repeat length increased. Discussion: Although cross-sectional, these data suggest that striatal atrophy, like clinical progression, may occur faster with higher CAG repeat lengths. PMID:21593963

  12. 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

  13. 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

  14. The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer’s Disease

    PubMed Central

    Ko, Shun-Yao; Ko, Hshin-An; Chu, Kuo-Hsiung; Shieh, Tzong-Ming; Chi, Tzong-Cherng; Chen, Hong-I; Chang, Weng-Cheng; Chang, Shu-Shing

    2015-01-01

    Amyloid precursor protein (APP) has been modified by β and γ-secretase that cause amyloid deposits (plaques) in neuronal cells. Glyceraldhyde-derived AGEs has been identified as a major source of neurotoxicity in Alzheimer’s disease (AD). In a previous study, we demonstrated that glyceraldehyde-derived AGEs increase APP and Aβ via ROS. Furthermore, the combination of AGEs and Aβ has been shown to enhance neurotoxicity. In mice, APP expression is increased by tail vein injection of AGEs. This evidence suggests a correlation between AGEs and the development of AD. However, the role played by AGEs in the pathogenesis of AD remains unclear. In this report, we demonstrate that AGEs up-regulate APP processing protein (BACE and PS1) and Sirt1 expression via ROS, but do not affect the expression of downstream antioxidant genes HO-1 and NQO-1. Moreover, we found that AGEs increase GRP78 expression and enhance the cell death-related pathway p53, bcl-2/bax ratio, caspase 3. These results indicate that AGEs impair the neuroprotective effects of Sirt1 and lead to neuronal cell death via ER stress. Our findings suggest that AGEs increase ROS production, which stimulates downstream pathways related to APP processing, Aβ production, Sirt1, and GRP78, resulting in the up-regulation of cell death related pathway. This in-turn enhances neuronal cell death, which leads to the development of AD. PMID:26587989

  15. Expression and localization of aging markers in lacrimal gland of chronic graft-versus-host disease

    NASA Astrophysics Data System (ADS)

    Kawai, Masataka; Ogawa, Yoko; Shimmura, Shigeto; Ohta, Shigeki; Suzuki, Takanori; Kawamura, Naoshi; Kuwana, Masataka; Kawakami, Yutaka; Tsubota, Kazuo

    2013-08-01

    Aging is commonly defined as the accumulation of diverse deleterious changes in cells and tissues with advancing age. To investigate whether aging changes are involved in the lacrimal glands of chronic graft-versus-host disease (cGVHD) model mice, we obtained the specimens from cGVHD model mice, untreated aged and young mice, and examined by histopathology, and immunoblotting. Oxidative stress markers, 8-OHdG, 4-HNE, and hexonoyl lesion (HEL), and other aging markers, p16 and p38, were used to assess the samples. The infiltrating mononuclear cells and endothelia of capillaries in the cGVHD and aged mice expressed the oxidative stress markers and other aging markers, but not in the young mice. Histological changes and the expression of aging markers in the samples from cGVHD mice exhibited similar features to those in aging mice. These results suggest that changes that typically appear with advanced age occur earlier in the lives of mice with lacrimal gland cGVHD.

  16. BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer’s Disease

    PubMed Central

    Klöppel, Stefan; Koutsouleris, Nikolaos; Sauer, Heinrich

    2013-01-01

    Alzheimer’s disease (AD), the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI)-based biomarker that predicts the individual progression of mild cognitive impairment (MCI) to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE) score indicates accelerated atrophy and is considered a risk factor for conversion to AD. Here, the BrainAGE framework was applied to predict the individual brain ages of 195 subjects with MCI at baseline, of which a total of 133 developed AD during 36 months of follow-up (corresponding to a pre-test probability of 68%). The ability of the BrainAGE framework to correctly identify MCI-converters was compared with the performance of commonly used cognitive scales, hippocampus volume, and state-of-the-art biomarkers derived from cerebrospinal fluid (CSF). With accuracy rates of up to 81%, BrainAGE outperformed all cognitive scales and CSF biomarkers in predicting conversion of MCI to AD within 3 years of follow-up. Each additional year in the BrainAGE score was associated with a 10% greater risk of developing AD (hazard rate: 1.10 [CI: 1.07–1.13]). Furthermore, the post-test probability was increased to 90% when using baseline BrainAGE scores to predict conversion to AD. The presented framework allows an accurate prediction even with multicenter data. Its fast and fully automated nature facilitates the integration into the clinical workflow. It can be exploited as a tool for screening as well as for monitoring treatment options. PMID:23826273

  17. Neural stem cells could serve as a therapeutic material for age-related neurodegenerative diseases

    PubMed Central

    Suksuphew, Sarawut; Noisa, Parinya

    2015-01-01

    Progressively loss of neural and glial cells is the key event that leads to nervous system dysfunctions and diseases. Several neurodegenerative diseases, for instance Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, are associated to aging and suggested to be a consequence of deficiency of neural stem cell pool in the affected brain regions. Endogenous neural stem cells exist throughout life and are found in specific niches of human brain. These neural stem cells are responsible for the regeneration of new neurons to restore, in the normal circumstance, the functions of the brain. Endogenous neural stem cells can be isolated, propagated, and, notably, differentiated to most cell types of the brain. On the other hand, other types of stem cells, such as mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells can also serve as a source for neural stem cell production, that hold a great promise for regeneration of the brain. The replacement of neural stem cells, either endogenous or stem cell-derived neural stem cells, into impaired brain is highly expected as a possible therapeutic mean for neurodegenerative diseases. In this review, clinical features and current routinely treatments of age-related neurodegenerative diseases are documented. Noteworthy, we presented the promising evidence of neural stem cells and their derivatives in curing such diseases, together with the remaining challenges to achieve the best outcome for patients. PMID:25815135

  18. Age-sex distribution of various diseases with particular reference to toxoplasmic lymphadenopathy.

    PubMed Central

    Beverley, J. K.; Fleck, D. G.; Kwantes, W.; Ludlam, G. B.

    1976-01-01

    An account is given of some human diseases which affect one sex more than the other. An age-sex realtionship has been noted among British patients with acquired toxoplasmic lymphadenopathy. This is compared with the findings of other European workers. A possible explanation is offered taking all these diseases into consideration together with some of the experimental work done in animals and some of the variations in immunological responses by man. PMID:1063216

  19. [Fifth revolution in medicine: on the role of infections in pathogenesis of aging and chronic diseases].

    PubMed

    Alibek, K; Grechanyĭ, L; Klimenko, T; Pashkova, A

    2008-01-01

    The XXth century is marked by the substantial increase in human life expectancy. Historically, main reasons for that are four achievements of medicine: (1) improvements in common hygiene, such as waste disposal and water purification which led to the significant reduction of communicable diseases; (2) common recognition of Pasteur's Germ Theory followed by improvements in occupational and personal hygiene as well as introduction of antiseptic and aseptic measures; (3) decrease in childhood mortality due to the discovery and widespread application of vaccination; and (4) the discovery and clinical application of antibiotics. An epidemiological transition took place, i.e. the shift from communicable infectious diseases, as a main cause of morbidity and mortality, to chronic degenerative diseases, mainly considered non-infectious. Experimental evidence has been accumulated on a significant number of microorganisms, including viruses (such as a group of herpes viruses, hepatitis viruses, etc.), bacteria (Chlamydia, Helicobacter, periodontal pathogens, etc.), fungi and parasites, as an underlying reason for many of diseases, such as atherosclerosis, various cancers, type 1 and 2 diabetes, neurodegenerative and some psychiatric diseases, osteoporosis, autoimmune diseases and others. On the other hand, most of these diseases have been traditionally associated with age, together with other "age-related" disorders, such as immune system suppression, thymus involution, pathologic calcification, etc. Taken together, these facts suggest that aging, among others, has infectious origins, and that burden of infections may lead to enhanced senescence and premature death. In fact, infections may serve as a trigger of senescence, presumably via the mechanisms of chronic oxidative stress, low-grade inflammation, telomere shortening, and autoimmune processes due to the molecular mimicry. We believe that next step in human longevity increase can be possible by common appreciation of

  20. Age-related differences in celiac disease: Specific characteristics of adult presentation

    PubMed Central

    Vivas, Santiago; Vaquero, Luis; Rodríguez-Martín, Laura; Caminero, Alberto

    2015-01-01

    Celiac disease may appear both in early childhood and in elderly subjects. Current knowledge of the disease has revealed some differences associated to the age of presentation. Furthermore, monitoring and prognosis of celiac subjects can vary depending on the pediatric or adult stage. The main objective of this review is to provide guidance for the adult diagnostic and follow-up processes, which must be tailored specifically for adults and be different from pediatric patients. PMID:26558154

  1. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease.

    PubMed

    Klosinski, Lauren P; Yao, Jia; Yin, Fei; Fonteh, Alfred N; Harrington, Michael G; Christensen, Trace A; Trushina, Eugenia; Brinton, Roberta Diaz

    2015-12-01

    White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical. PMID:26844268

  2. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease

    PubMed Central

    Klosinski, Lauren P.; Yao, Jia; Yin, Fei; Fonteh, Alfred N.; Harrington, Michael G.; Christensen, Trace A.; Trushina, Eugenia; Brinton, Roberta Diaz

    2015-01-01

    White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical. PMID:26844268

  3. A platform for rapid exploration of aging and diseases in a naturally short-lived vertebrate

    PubMed Central

    Harel, Itamar; Benayoun, Bérénice A.; Machado, Ben; Singh, Param Priya; Hu, Chi-Kuo; Pech, Matthew F.; Valenzano, Dario R.; Zhang, Elisa; Sharp, Sabrina C.; Artandi, Steven E.; Brunet, Anne

    2015-01-01

    Summary Aging is a complex process that affects multiple organs. Modeling aging and age-related diseases in the lab is challenging because classical vertebrate models have relatively long lifespans. Here we develop the first platform for rapid exploration of age-dependent traits and diseases in vertebrates, using the naturally short-lived African turquoise killifish. We provide an integrative genomic and genome-editing toolkit in this organism using our de novo-assembled genome and the CRISPR/Cas9 technology. We mutate many genes encompassing the hallmarks of aging, and for a subset, we produce stable lines within 2–3 months. As a proof-of-principle, we show that fish deficient for the protein subunit of telomerase exhibit the fastest onset of telomere-related pathologies among vertebrates. We further demonstrate the feasibility of creating specific genetic variants. This genome-to-phenotype platform represents a unique resource for studying vertebrate aging and disease in a high throughput manner and for investigating candidates arising from human genome-wide studies. PMID:25684364

  4. The impact of dysphagia on quality of life in ageing and Parkinson's disease as measured by the swallowing quality of life (SWAL-QOL) questionnaire.

    PubMed

    Leow, Li Pyn; Huckabee, Maggie-Lee; Anderson, Tim; Beckert, Lutz

    2010-09-01

    This prospective, cross-sectional study evaluated the impact of dysphagia on quality of life in healthy ageing and in subjects with Parkinson's disease (PD) using the Swallowing Quality of Life (SWAL-QOL) questionnaire. Sixteen healthy young adults (8 males, mean age = 25.1 years) and 16 healthy elders (8 males, mean age = 72.8 years) were recruited. Thirty-two subjects with idiopathic PD (mean age = 68.5 years) were recruited from a movement disorders clinic. The severity of PD was staged using the Hoehn and Yahr scale. Results revealed that elders experienced symptoms of dysphagia more frequently than young adults but the overall SWAL-QOL scores were not significantly different. Subjects with PD who experienced dysphagia reported greatly reduced QOL, and significant differences were found in all but one subsection of the SWAL-QOL. Disease progression detrimentally impacts QOL, with subjects in later-stage PD experiencing further reduction in the desire to eat, difficulty with food selection, and prolonged eating duration. These features, which increase with disease severity, are likely to impact negatively upon nutritional status, which is already under threat from PD-related dysphagia. PMID:19680723

  5. Age-related changes and diseases of the ocular surface and cornea.

    PubMed

    Gipson, Ilene K

    2013-12-01

    Aging of the ocular surface and corneal tissues, major components of the visual system, causes major eye disease and results in substantial cost in medical and social terms. These diseases include the highly prevalent dry eye disease that affects the ocular surface and its glands, leading to tear film alterations, discomfort, and decreased vision. Studies show that 14.4% of the population in the United States older than 50 years have dry eye disease and demonstrate that it is particularly prevalent among women. Annual medical costs per patient with dry eye in the United States are estimated at $783 per year, with an overall medical cost adjusted to prevalence of $3.84 billion per year. Societal costs, which include loss of productivity, are estimated per patient at $11,302 per year, with overall costs adjusted to prevalence of $55.4 billion per year. Because there are few effective treatments for the disease, more research on its etiology and mechanisms is warranted and needed. Increased public education about risk factors for the disease is also required. Another major age-related eye disease of the cornea that leads to vision impairment and potentially blindness if left untreated is Fuchs' endothelial corneal dystrophy. This disease leads to loss of the endothelial cells on the internal side of the cornea that are responsible for keeping the cornea in the proper hydration state to ensure its transparency to light. The mechanism of cell loss is unknown, and the only treatment available to date is surgical transplantation of the cornea or inner part of the cornea. These medically costly procedures require donor corneas, eye banking, and medical follow-up, with accrued costs. Fuchs' endothelial corneal dystrophy is a major cause of corneal transplantation in the United States; therefore, research support is needed to determine the mechanism of this age-related disease, to develop medical, nonsurgical methods for treatment. PMID:24335068

  6. Patients Presenting with Advanced Human Immunodeficiency Virus Disease: Epidemiological Features by Age Group

    PubMed Central

    2016-01-01

    We explored factors influencing presentation with advanced human immunodeficiency virus (HIV) disease by age group. Data were derived from a city-wide cross-sectional survey of 759 HIV-infected adults living in Seoul, Korea. The significance of each observed factor was assessed via multivariate logistic regression. Of subjects aged 20-34 years, lower educational level had a positive influence on presentation with advanced HIV disease (adjusted odds ratio [aOR], 2.43; 95% confidence interval [CI], 1.36-4.34); those recently diagnosed with HIV were more likely to be presented with advanced HIV disease (aOR, 3.17; 95% CI, 0.99-10.2). Of the subjects aged 35-49 years, those w ith advanced HIV disease were more likely to have been diagnosed during health check-ups (aOR, 2.91; 95% CI, 1.15-7.32) or via clinical manifestations (aOR, 3.61; 95% CI, 1.39-9.36). Of the subjects aged ≥ 50 years, presentation with advanced HIV disease was significantly more common in older subjects (aOR per increment of 5 years, 2.06; 95% CI, 1.32-3.23) and less common among individuals diagnosed with HIV in 2000-2006 (aOR, 0.18; 95% CI, 0.04-0.83). In conclusion, a lower educational level in younger subjects and more advanced age in older subjects positively influence the presentation of advanced HIV disease. PMID:26839469

  7. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

    PubMed

    Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

    2016-05-31

    The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD. PMID:27210754

  8. Age-Related Changes in Immunological Factors and Their Relevance in Allergic Disease Development During Childhood

    PubMed Central

    Chang, Woo-Sung; Kim, Eun-Jin; Lim, Yeon-Mi; Yoon, Dankyu; Son, Jo-Young; Park, Jung-Won; Hong, Soo-Jong; Cho, Sang-Heon

    2016-01-01

    Purpose Allergic diseases are triggered by Th2-mediated immune reactions to allergens and orchestrated by various immunological factors, including immune cells and cytokines. Although many reports have suggested that childhood is the critical period in the onset of allergic diseases and aging leads to alter the susceptibility of an individual to allergic diseases, age-related changes in various immunological factors in healthy individuals as well as their difference between healthy and allergic children have not yet been established. Methods We investigated the ratio of Th1/Th2 cells and the levels of 22 allergy-related cytokines across all age groups in individuals who were classified as clinically non-atopic and healthy. We also examined their differences between healthy and allergic children to evaluate immunological changes induced by the development of allergic diseases during childhood. Results The Th1/Th2 ratio rose gradually during the growth period including childhood, reaching peak values in the twenties-thirties age group. Th1/Th2 ratios were significantly lower in allergic children than in healthy controls, whereas 14 of 22 cytokines were significantly higher in allergic children than in healthy controls. On the other hand, there were no differences in Th1/Th2 ratios and cytokines between healthy and allergic adolescents. Conclusions In this study, age-related changes in Th1/Th2 ratios were found in normal controls across all age groups, and decreases in Th1/Th2 ratio were observed with increasing of 14 cytokines in allergic children. The results of this study may be helpful as reference values for both monitoring immunological changes according to aging in healthy individuals and distinguishing between normal and allergic subjects in terms of immune cells and soluble factors. PMID:27126727

  9. 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

  10. 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

  11. The zebrafish as a gerontology model in nervous system aging, disease, and repair.

    PubMed

    Van Houcke, Jessie; De Groef, Lies; Dekeyster, Eline; Moons, Lieve

    2015-11-01

    Considering the increasing number of elderly in the world's population today, developing effective treatments for age-related pathologies is one of the biggest challenges in modern medical research. Age-related neurodegeneration, in particular, significantly impacts important sensory, motor, and cognitive functions, seriously constraining life quality of many patients. Although our understanding of the causal mechanisms of aging has greatly improved in recent years, animal model systems still have much to tell us about this complex process. Zebrafish (Danio rerio) have gained enormous popularity for this research topic over the past decade, since their life span is relatively short but, like humans, they are still subject to gradual aging. In addition, the extensive characterization of its well-conserved molecular and cellular physiology makes the zebrafish an excellent model to unravel the underlying mechanisms of aging, disease, and repair. This review provides a comprehensive overview of the progress made in zebrafish gerontology, with special emphasis on nervous system aging. We review the evidence that classic hallmarks of aging can also be recognized within this small vertebrate, both at the molecular and cellular level. Moreover, we illustrate the high level of similarity with age-associated human pathologies through a survey of the functional deficits that arise as zebrafish age. PMID:26538520

  12. Common DNA methylation alterations of Alzheimer's disease and aging in peripheral whole blood

    PubMed Central

    Li, Hongdong; Guo, Zheng; Guo, You; Li, Mengyao; Yan, Haidan; Cheng, Jun; Wang, Chenguang; Hong, Guini

    2016-01-01

    Alzheimer's disease (AD) is a common aging-related neurodegenerative illness. Recently, many studies have tried to identify AD- or aging-related DNA methylation (DNAm) biomarkers from peripheral whole blood (PWB). However, the origin of PWB biomarkers is still controversial. In this study, by analyzing 2565 DNAm profiles for PWB and brain tissue, we showed that aging-related DNAm CpGs (Age-CpGs) and AD-related DNAm CpGs (AD-CpGs) observable in PWB both mainly reflected DNAm alterations intrinsic in leukocyte subtypes rather than methylation differences introduced by the increased ratio of myeloid to lymphoid cells during aging or AD progression. The PWB Age-CpGs and AD-CpGs significantly overlapped 107 sites (P-value = 2.61×10−12) and 97 had significantly concordant methylation alterations in AD and aging (P-value < 2.2×10−16), which were significantly enriched in nervous system development, neuron differentiation and neurogenesis. More than 60.8% of these 97 concordant sites were found to be significantly correlated with age in normal peripheral CD4+ T cells and CD14+ monocytes as well as in four brain regions, and 44 sites were also significantly differentially methylated in different regions of AD brain tissue. Taken together, the PWB DNAm alterations related to both aging and AD could be exploited for identification of AD biomarkers. PMID:26943045

  13. Visual cortex in aging and Alzheimer's disease: changes in visual field maps and population receptive fields

    PubMed Central

    Brewer, Alyssa A.; Barton, Brian

    2012-01-01

    Although several studies have suggested that cortical alterations underlie such age-related visual deficits as decreased acuity, little is known about what changes actually occur in visual cortex during healthy aging. Two recent studies showed changes in primary visual cortex (V1) during normal aging; however, no studies have characterized the effects of aging on visual cortex beyond V1, important measurements both for understanding the aging process and for comparison to changes in age-related diseases. Similarly, there is almost no information about changes in visual cortex in Alzheimer's disease (AD), the most common form of dementia. Because visual deficits are often reported as one of the first symptoms of AD, measurements of such changes in the visual cortex of AD patients might improve our understanding of how the visual system is affected by neurodegeneration as well as aid early detection, accurate diagnosis and timely treatment of AD. Here we use fMRI to first compare the visual field map (VFM) organization and population receptive fields (pRFs) between young adults and healthy aging subjects for occipital VFMs V1, V2, V3, and hV4. Healthy aging subjects do not show major VFM organizational deficits, but do have reduced surface area and increased pRF sizes in the foveal representations of V1, V2, and hV4 relative to healthy young control subjects. These measurements are consistent with behavioral deficits seen in healthy aging. We then demonstrate the feasibility and first characterization of these measurements in two patients with mild AD, which reveal potential changes in visual cortex as part of the pathophysiology of AD. Our data aid in our understanding of the changes in the visual processing pathways in normal aging and provide the foundation for future research into earlier and more definitive detection of AD. PMID:24570669

  14. [Depressive frustration at vascular diseases of a brain in patients of elderly and senile age].

    PubMed

    Kudrina, P I; Ar'ev, A L; Titkov, Iu S

    2012-01-01

    According to inspection of 206 patients of 60 years old and elder on the basis of neurologic department of the Geriatric Center of Republican Hospital No 3 high prevalence of depression of small and average degree in the persons of advanced age suffering from cerebrovascular diseases is revealed. To estimate the expressiveness of depression the Hamilton's scale including 17 parameters was used. PMID:23130521

  15. Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome.

    PubMed

    Kho, Alvin T; Chhabra, Divya; Sharma, Sunita; Qiu, Weiliang; Carey, Vincent J; Gaedigk, Roger; Vyhlidal, Carrie A; Leeder, J Steven; Tantisira, Kelan G; Weiss, Scott T

    2016-06-01

    The fetal origins of disease hypothesis suggests that variations in the course of prenatal lung development may affect life-long pulmonary function growth, decline, and pathobiology. Many studies support the existence of differences in the developing lung trajectory in males and females, and sex-specific differences in the prevalence of chronic lung diseases, such as asthma and bronchopulmonary dysplasia. The objectives of this study were to investigate the early developing fetal lung for transcriptomic correlates of postconception age (maturity) and sex, and their associations with chronic lung diseases. We analyzed whole-lung transcriptome profiles of 61 females and 78 males at 54-127 days postconception (dpc) from nonsmoking mothers using unsupervised principal component analysis and supervised linear regression models. We identified dominant transcriptomic correlates for postconception age and sex with corresponding gene sets that were enriched for developing lung structural and functional ontologies. We observed that the transcriptomic sex difference was not a uniform global time shift/lag, rather, lungs of males appear to be more mature than those of females before 96 dpc, and females appear to be more mature than males after 96 dpc. The age correlate gene set was consistently enriched for asthma and bronchopulmonary dysplasia genes, but the sex correlate gene sets were not. Despite sex differences in the developing fetal lung transcriptome, postconception age appears to be more dominant than sex in the effect of early fetal lung developments on disease risk during this early pseudoglandular phase of development. PMID:26584061

  16. Sex, Aging, and Preexisting Cerebral Ischemic Disease in Patients With Aortic Stenosis

    PubMed Central

    Wang, Ping; Acker, Michael A.; Bilello, Michel; Melhem, Elias R.; Stambrook, Elizabeth; Ratcliffe, Sarah J.; Floyd, Thomas F.

    2011-01-01

    Background Patients undergoing cardiac surgery have a high frequency of preexisting cerebral ischemic lesions, the presence of which appears to predict cognitive sequelae. Patients undergoing aortic valve replacement for aortic stenosis (AS) incur an exceptionally high risk for perioperative cerebral ischemia. The extreme risk in this subgroup may arise from the preexisting burden of cerebral ischemic disease. We tested the hypotheses that increasing age, female sex, coronary artery disease, and the severity of AS are predictive of the severity of preexisting cerebral ischemic lesions. Methods A total of 95 subjects were included in this study. Subjects were imaged on 1.5 Tesla magnetic resonance imaging scanners to obtain multimodal image sets which were used for the automatic segmentation of cerebral lesion volume. The dependence of lesion volume upon age, sex, coronary artery disease, and the severity of AS were tested. Results The results demonstrate a strong correlation between aging, female sex, and white matter and ischemia-like lesion volume in patients with aortic stenosis. Conclusions Women and those of advanced age presenting for aortic valve replacement for AS may incur a particularly high risk for postoperative neurologic sequelae due to an exceptional preexisting burden of cerebral ischemic disease. PMID:20868818

  17. Psychosocial Factors Associated with Risk Perceptions for Chronic Diseases in Younger and Middle-Aged Women

    PubMed Central

    Hamilton, Jada G.; Lobel, Marci

    2016-01-01

    Perceptions of disease risk play an important role in motivating people to adopt healthy behaviors. However, little is known about psychosocial factors that influence women’s perceived risk for developing disease. The present study investigated the extent to which individual traits, social influences, objective risk factors, and demographic characteristics were associated with women’s risk perceptions for cardiovascular disease, breast cancer, and lung cancer. Using structural equation modeling, we examined hypothesized associations among 452 younger (ages 18-25 years) and 167 middle-aged (ages 40-64 years) women. A greater number and variety of factors were associated with middle-aged women’s risk perceptions compared to younger women. For both groups, some objective risk factors were associated with risk perceptions; yet, associations also existed between multiple psychosocial variables (optimism, health locus of control, social exposure to disease, perceived stigma) and risk perceptions. Results suggested that women may base their risk estimates on factors beyond those considered important by healthcare providers. PMID:26110993

  18. Can Neglected Tropical Diseases Compromise Human Wellbeing in Sex-, Age-, and Trait-Specific Ways?

    PubMed Central

    Geary, David C.

    2016-01-01

    Traits that facilitate competition for reproductive resources or that influence mate choice have evolved to signal resilience to infectious disease and other stressors. As a result, the dynamics of competition and choice can, in theory, be used to generate predictions about sex-, age-, and trait-specific vulnerabilities for any sexually reproducing species, including humans. These dynamics and associated vulnerabilities are reviewed for nonhuman species, focusing on traits that are compromised by exposure to parasites. Using the same approach, sex-, age-, and trait-specific vulnerabilities to parasitic disease are illustrated for children’s and adolescent’s physical growth and fitness. Suggestions are then provided for widening the assessment of human vulnerabilities to include age-appropriate measures of behavioral (e.g., children’s play) and cognitive (e.g., language fluency) traits. These are traits that are likely to be compromised by infection in age- and sex-specific ways. Inclusion of these types of measures in studies of neglected tropic diseases has the potential to provide a more nuanced understanding of how these diseases undermine human wellbeing and may provide a useful means to study the efficacy of associated treatments. PMID:27077746

  19. Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset

    SciTech Connect

    Small, G.W.; Kuhl, D.E.; Riege, W.H.; Fujikawa, D.G.; Ashford, J.W.; Metter, E.J.; Mazziotta, J.C.

    1989-06-01

    No previous study of Alzheimer's disease has, to our knowledge, assessed the effect of both age at dementia onset and gender on cerebral glucose metabolic patterns. To this end, we used positron emission tomography (fludeoxyglucose F 18 method) to study 24 patients with clinical diagnoses of probable Alzheimer's disease. Comparisons of the 13 patients with early-onset dementia (less than 65 years of age) with the 11 patients with late-onset dementia (greater than 65 years of age) revealed significantly lower left parietal metabolic ratios (left posterior parietal region divided by the hemispheric average) in the early-onset group. The metabolic ratio of posterior parietal cortex divided by the relatively disease-stable average of caudate and thalamus also separated patients with early-onset dementia from those with late-onset dementia, but not men from women. Further comparisons between sexes showed that, in all brain regions studied, the 9 postmenopausal women had higher nonweighted mean metabolic rates than the 15 men from the same age group, with hemispheric sex differences of 9% on the right and 7% on the left. These results demonstrate decreased parietal ratios in early-onset dementia of Alzheimer's disease, independent of a gender effect.

  20. Age Differences in Understandings of Disease Causality: AIDS, Colds, and Cancer.

    ERIC Educational Resources Information Center

    Sigelman, Carol; And Others

    1993-01-01

    Asked 9, 11, and 13 year olds and college students about risk factors for AIDS, colds, and cancer. Found that knowledge of risk factors became more accurate with age; knowledge of risk factors was largely independent of knowledge of nonrisk factors; and knowledge about 1 disease was largely independent of knowledge about another. (MDM)

  1. 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

  2. Chronic and progressive Parkinson's disease MPTP model in adult and aged mice.

    PubMed

    Muñoz-Manchado, Ana B; Villadiego, Javier; Romo-Madero, Sonia; Suárez-Luna, Nela; Bermejo-Navas, Alfonso; Rodríguez-Gómez, José A; Garrido-Gil, Pablo; Labandeira-García, José L; Echevarría, Miriam; López-Barneo, José; Toledo-Aral, Juan J

    2016-01-01

    Despite the different animal models of Parkinson's disease developed during the last years, they still present limitations modelling the slow and progressive process of neurodegeneration. Here, we undertook a histological, neurochemical and behavioural analysis of a new chronic parkinsonian mouse model generated by the subcutaneous administration of low doses of MPTP (20 mg/kg, 3 times per week) for 3 months, using both young adult and aged mice. The MPTP-induced nigrostriatal neurodegeneration was progressive and was accompanied by a decrease in striatal dopamine levels and motor impairment. We also demonstrated the characteristic neuroinflammatory changes (microglial activation and astrogliosis) associated with the neurodegenerative process. Aged animals showed both a faster time course of neurodegeneration and an altered neuroinflammatory response. The long-term systemic application of low MPTP doses did not induce any increase in mortality in either young adult or aged mice and better resembles the slow evolution of the neurodegenerative process. This treatment could be useful to model different stages of Parkinson's disease, providing a better understanding of the pathophysiology of the disease and facilitating the testing of both protective and restorative treatments. Here, we show a new chronic and progressive parkinsonian mouse model, in young and aged mice. This model produces a stable degeneration of the dopaminergic nigrostriatal pathway, continuous neuroinflammatory reaction and motor deficits. Aged animals showed a faster neurodegeneration and an altered neuroinflammatory response. This treatment could be useful to model different stages of PD and to test both protective and restorative therapeutic approaches. PMID:26500044

  3. 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

  4. Well-Being and Chronic Disease Incidence: The English Longitudinal Study of Ageing

    PubMed Central

    Okely, Judith A.; Gale, Catharine R.

    2016-01-01

    ABSTRACT Background Previous research suggests that greater well-being may protect against onset of chronic disease. However, it is unclear whether this association is similar across different types of disease. Method We used Cox proportional hazards regression to examine the prospective relationship between well-being (measured using the CASP-19 quality of life questionnaire) and incidence of arthritis, cancer, stroke, diabetes, myocardial infarction, and chronic lung disease over 8 years. The sample consisted of 8182 participants 50 years or older from the English Longitudinal Study of Ageing. Results After adjustments for established risk factors, a standard deviation increase in CASP-19 score was associated with a decrease in arthritis risk (hazard ratio [HR] = 0.89, 95% confidence interval [CI] = 0.83–0.96) and, in those younger than 65 years, a decrease in diabetes risk (HR = 0.82, 95% CI = 0.70–0.95) and chronic lung disease risk (HR = 0.80, 95% CI = 0.66–0.97). Higher CASP-19 scores were associated with reduced risk for stroke and myocardial infarction; however, these associations were no longer significant after adjustments for established risk factors. No association was observed for cancer incidence. An age interaction was observed for diabetes, myocardial infarction, and chronic lung disease, with a stronger association between CASP-19 score and disease incidence at younger ages. Conclusions The extent of association between well-being and incident disease risk is not consistent across different chronic diseases. Future studies should examine the cause of this variation. PMID:26569542

  5. Synchronizing an aging brain: can entraining circadian clocks by food slow Alzheimer’s disease?

    PubMed Central

    Kent, Brianne A.

    2014-01-01

    Alzheimer’s disease (AD) is a global epidemic. Unfortunately, we are still without effective treatments or a cure for this disease, which is having devastating consequences for patients, their families, and societies around the world. Until effective treatments are developed, promoting overall health may hold potential for delaying the onset or preventing neurodegenerative diseases such as AD. In particular, chronobiological concepts may provide a useful framework for identifying the earliest signs of age-related disease as well as inexpensive and noninvasive methods for promoting health. It is well reported that AD is associated with disrupted circadian functioning to a greater extent than normal aging. However, it is unclear if the central circadian clock (i.e., the suprachiasmatic nucleus) is dysfunctioning, or whether the synchrony between the central and peripheral clocks that control behavior and metabolic processes are becoming uncoupled. Desynchrony of rhythms can negatively affect health, increasing morbidity and mortality in both animal models and humans. If the uncoupling of rhythms is contributing to AD progression or exacerbating symptoms, then it may be possible to draw from the food-entrainment literature to identify mechanisms for re-synchronizing rhythms to improve overall health and reduce the severity of symptoms. The following review will briefly summarize the circadian system, its potential role in AD, and propose using a feeding-related neuropeptide, such as ghrelin, to synchronize uncoupled rhythms. Synchronizing rhythms may be an inexpensive way to promote healthy aging and delay the onset of neurodegenerative disease such as AD. PMID:25225484

  6. Synchronizing an aging brain: can entraining circadian clocks by food slow Alzheimer's disease?

    PubMed

    Kent, Brianne A

    2014-01-01

    Alzheimer's disease (AD) is a global epidemic. Unfortunately, we are still without effective treatments or a cure for this disease, which is having devastating consequences for patients, their families, and societies around the world. Until effective treatments are developed, promoting overall health may hold potential for delaying the onset or preventing neurodegenerative diseases such as AD. In particular, chronobiological concepts may provide a useful framework for identifying the earliest signs of age-related disease as well as inexpensive and noninvasive methods for promoting health. It is well reported that AD is associated with disrupted circadian functioning to a greater extent than normal aging. However, it is unclear if the central circadian clock (i.e., the suprachiasmatic nucleus) is dysfunctioning, or whether the synchrony between the central and peripheral clocks that control behavior and metabolic processes are becoming uncoupled. Desynchrony of rhythms can negatively affect health, increasing morbidity and mortality in both animal models and humans. If the uncoupling of rhythms is contributing to AD progression or exacerbating symptoms, then it may be possible to draw from the food-entrainment literature to identify mechanisms for re-synchronizing rhythms to improve overall health and reduce the severity of symptoms. The following review will briefly summarize the circadian system, its potential role in AD, and propose using a feeding-related neuropeptide, such as ghrelin, to synchronize uncoupled rhythms. Synchronizing rhythms may be an inexpensive way to promote healthy aging and delay the onset of neurodegenerative disease such as AD. PMID:25225484

  7. The use of mature zebrafish (Danio rerio) as a model for human aging and disease.

    PubMed

    Keller, Evan T; Murtha, Jill M

    2004-07-01

    Zebrafish (Danio rerio) have been extensively utilized for understanding mechanisms of development. These studies have led to a wealth of resources including genetic tools, informational databases, and husbandry methods. In spite of all these resources, zebrafish have been underutilized for exploring pathophysiology of disease and the aging process. Zebrafish offer several advantages over mammalian models for these studies, including the ability to perform saturation mutagenesis and the capability to contain thousands of animals in a small space. In this review, we will discuss the use of mature zebrafish as an animal model and provide specific examples to support this novel use of zebrafish. Examples include demonstrating that clinical pathology can be performed in mature zebrafish and that age-associated changes in heat shock response can be observed in zebrafish. These highlights demonstrate the utility of zebrafish as a model for disease and aging. PMID:15533791

  8. Aging, Neurodegenerative Disease, and Traumatic Brain Injury: The Role of Neuroimaging

    PubMed Central

    Levine, Brian

    2015-01-01

    Abstract Traumatic brain injury (TBI) is a highly prevalent condition with significant effects on cognition and behavior. While the acute and sub-acute effects of TBI recover over time, relatively little is known about the long-term effects of TBI in relation to neurodegenerative disease. This issue has recently garnered a great deal of attention due to publicity surrounding chronic traumatic encephalopathy (CTE) in professional athletes, although CTE is but one of several neurodegenerative disorders associated with a history of TBI. Here, we review the literative on neurodegenerative disorders linked to remote TBI. We also review the evidence for neuroimaging changes associated with unhealthy brain aging in the context of remote TBI. We conclude that neuroimaging biomarkers have significant potential to increase understanding of the mechanisms of unhealthy brain aging and neurodegeneration following TBI, with potential for identifying those at risk for unhealthy brain aging prior to the clinical manifestation of neurodegenerative disease. PMID:25192426

  9. Lessons from the analysis of nonhuman primates for understanding human aging and neurodegenerative diseases

    PubMed Central

    Verdier, Jean-Michel; Acquatella, Isabelle; Lautier, Corinne; Devau, Gina; Trouche, Stéphanie; Lasbleiz, Christelle; Mestre-Francés, Nadine

    2015-01-01

    Animal models are necessary tools for solving the most serious challenges facing medical research. In aging and neurodegenerative disease studies, rodents occupy a place of choice. However, the most challenging questions about longevity, the complexity and functioning of brain networks or social intelligence can almost only be investigated in nonhuman primates. Beside the fact that their brain structure is much closer to that of humans, they develop highly complex cognitive strategies and they are visually-oriented like humans. For these reasons, they deserve consideration, although their management and care are more complicated and the related costs much higher. Despite these caveats, considerable scientific advances have been possible using nonhuman primates. This review concisely summarizes their role in the study of aging and of the mechanisms involved in neurodegenerative disorders associated mainly with cognitive dysfunctions (Alzheimer's and prion diseases) or motor deficits (Parkinson's and related diseases). PMID:25788873

  10. Cortical neurons express nerve growth factor receptors in advanced age and Alzheimer disease.

    PubMed Central

    Mufson, E J; Kordower, J H

    1992-01-01

    Using a monoclonal antibody directed against the primate nerve growth factor (NGF) receptor, we examined the expression of NGF receptors within neuronal perikarya of normal adult human cerebral cortex (27-98 years old) and individuals with Alzheimer disease (AD). This expression of cortical NGF receptors was compared with that seen in other neurological diseases and normal human development as well as in young and aged nonhuman primates. NGF receptor-containing cortical neurons were not observed in young adults (less than 50 years old) and were observed only infrequently in non-demented elderly individuals (50-80 years old). In contrast, numerous NGF receptor-containing cortical neurons were seen in AD patients of all ages and in one 98-year-old nondemented patient. In advanced age and AD, numerous NGF receptor-positive neurons were located within laminae II-VI of temporal association cortices whereas only a few were seen in the subicular complex, entorhinal cortex, parahippocampal gyrus, and amygdaloid complex. These perikarya appeared healthy, with bipolar, fusiform, or multipolar morphologies and extended varicose dendritic arbors. These neurons failed to express neurofibrillary tangle-bearing material. In contrast to AD, NGF receptor-containing cortical neurons were not observed in Parkinson disease, Pick disease, or Shy-Drager syndrome. The NGF receptor-containing cortical neurons seen in advanced age and AD were similar in morphology to those observed in human fetal cortex. No NGF receptor-containing cortical neurons were observed in young or aged nonhuman primates. These findings suggest that neurons within the human cerebral cortex exhibit plasticity in their expression of NGF receptors in AD and extreme advanced aging. Images PMID:1309947

  11. Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer’s Disease

    PubMed Central

    Cottone, Carlo; Cancelli, Andrea; Rossini, Paolo Maria; Tecchio, Franca

    2016-01-01

    Brain activity is complex; a reflection of its structural and functional organization. Among other measures of complexity, the fractal dimension is emerging as being sensitive to neuronal damage secondary to neurological and psychiatric diseases. Here, we calculated Higuchi’s fractal dimension (HFD) in resting-state eyes-closed electroencephalography (EEG) recordings from 41 healthy controls (age: 20–89 years) and 67 Alzheimer’s Disease (AD) patients (age: 50–88 years), to investigate whether HFD is sensitive to brain activity changes typical in healthy aging and in AD. Additionally, we considered whether AD-accelerating effects of the copper fraction not bound to ceruloplasmin (also called “free” copper) are reflected in HFD fluctuations. The HFD measure showed an inverted U-shaped relationship with age in healthy people (R2 = .575, p < .001). Onset of HFD decline appeared around the age of 60, and was most evident in central-parietal regions. In this region, HFD decreased with aging stronger in the right than in the left hemisphere (p = .006). AD patients demonstrated reduced HFD compared to age- and education-matched healthy controls, especially in temporal-occipital regions. This was associated with decreasing cognitive status as assessed by mini-mental state examination, and with higher levels of non-ceruloplasmin copper. Taken together, our findings show that resting-state EEG complexity increases from youth to maturity and declines in healthy, aging individuals. In AD, brain activity complexity is further reduced in correlation with cognitive impairment. In addition, elevated levels of non-ceruloplasmin copper appear to accelerate the reduction of neural activity complexity. Overall, HDF appears to be a proper indicator for monitoring EEG-derived brain activity complexity in healthy and pathological aging. PMID:26872349

  12. Abnormal brain aging as a radical-related disease: A new target for nuclear medicine

    SciTech Connect

    Fujibayashi, Y.; Yamamoto, S.; Waki, A. |

    1996-05-01

    DNA damages caused by endogenously produced radicals are closely correlated with aging. Among them, mitochondrial DNA (mtDNA) deletions have been reported as a memory of DNA damage by oxygen radicals. In fact, clinical as well as experimental studies indicated the accumulation of deleted mtDNA in the brain, myocardium and son on, in aged subjects. In our previous work, radioiodinated radical trapping agent, p-iodophenyl-N-t-butylnitrone, and hypoxia imaging agent, Cu-62 diacetyl-bis-N-4-methyl-thiosemicarbazone have been developed for the diagnosis of radical-related diseases, such as ischemic, inflammation, cancer or aging. The aim of the present work was to evaluate these agents for brain aging studies. In our university, an unique animal model, a senescence accelerated model mouse (SAM), has been established. Among the various substrains, SAMP8 showing memory deterioration in its young age ({approximately}3 month) was basically evaluated as an abnormal brain aging model with mtDNA deletion. As controls, SAMR1 showing normal aging and ddY mice were used. MtDNA deletion n the brain was analyzed with polymerase-chain reaction (PCR) method, and relationship between mtDNA deletion and brain uptake of IPBN or Cu-62-ATSM was studied. In 1-3 month old SAMP8 brain, multiple mtDNa deletions were already found and their content was significantly higher than that of SAMR1 or age-matched ddY control. Thus, it was cleared that SAMP8 brain has high tendency to be attacked by endogenously produced oxygen radicals, possibly from its birth. Both IPBN and Cu-ATSM showed significantly higher accumulation in the SAMP8 brain than in the SAMR1 brain, indicating that these agents have high possibility for the early detection of abnormal brain aging as a radical-related disease.

  13. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease.

    PubMed

    Allison, Beth J; Kaandorp, Joepe J; Kane, Andrew D; Camm, Emily J; Lusby, Ciara; Cross, Christine M; Nevin-Dolan, Rhianon; Thakor, Avnesh S; Derks, Jan B; Tarry-Adkins, Jane L; Ozanne, Susan E; Giussani, Dino A

    2016-05-01

    Aging and developmental programming are both associated with oxidative stress and endothelial dysfunction, suggesting common mechanistic origins. However, their interrelationship has been little explored. In a rodent model of programmed cardiovascular dysfunction we determined endothelial function and vascular telomere length in young (4 mo) and aged (15 mo) adult offspring of normoxic or hypoxic pregnancy with or without maternal antioxidant treatment. We show loss of endothelial function [maximal arterial relaxation to acetylcholine (71 ± 3 vs. 55 ± 3%) and increased vascular short telomere abundance (4.2-1.3 kb) 43.0 ± 1.5 vs. 55.1 ± 3.8%) in aged vs. young offspring of normoxic pregnancy (P < 0.05). Hypoxic pregnancy in young offspring accelerated endothelial dysfunction (maximal arterial relaxation to acetylcholine: 42 ± 1%, P < 0.05) but this was dissociated from increased vascular short telomere length abundance. Maternal allopurinol rescued maximal arterial relaxation to acetylcholine in aged offspring of normoxic or hypoxic pregnancy but not in young offspring of hypoxic pregnancy. Aged offspring of hypoxic allopurinol pregnancy compared with aged offspring of untreated hypoxic pregnancy had lower levels of short telomeres (vascular short telomere length abundance 35.1 ± 2.5 vs. 48.2 ± 2.6%) and of plasma proinflammatory chemokine (24.6 ± 2.8 vs. 36.8 ± 5.5 pg/ml, P < 0.05). These data provide evidence for divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease, and aging being decelerated by antioxidants even prior to birth.-Allison, B. J., Kaandorp, J. J., Kane, A. D., Camm, E. J., Lusby, C., Cross, C. M., Nevin-Dolan, R., Thakor, A. S., Derks, J. B., Tarry-Adkins, J. L., Ozanne, S. E., Giussani, D. A. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease. PMID:26932929

  14. Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity.

    PubMed

    Wang, S-M; Ho, T-S; Lin, H-C; Lei, H-Y; Wang, J-R; Liu, C-C

    2012-06-01

    Enterovirus 71 (EV71) infection commonly strike children under the age of 3 years, with an occasionally unfavorable outcome in children. This study was designed to explore the relationship between age and the severity of complications, which may associate with antibody-dependent enhancement (ADE) in EV71. All EV71-infected patients during the outbreak of 2008 were recruited. In total, 134 patients were enrolled and categorized into two age groups, 0-12 months (n = 18) and >12 months (n = 116). Pulmonary edema/hemorrhage more commonly occur in patients younger than 12 months. No difference in the occurrence of herpangina/hand-foot-and-mouth disease (HFMD), uncomplicated brainstem encephalitis (BE), or autonomic nervous system (ANS) dysregulation was noted between the two age groups. Patients with pulmonary edema/hemorrhage (11.9 ± 14.7 months) were younger than patients with herpangina/HFMD (35.8 ± 26.4 months) or ANS dysregulation (33.9 ± 20.9 months). Our findings are in agreement with the data regarding the outbreak in Taiwan, in which a decrease in age corresponded to an increase in disease severity with regard to central nervous system complications. A reduction of maternal antibodies to the subneutralizing level within 1 year of age may be associated with the ADE of the infection. This study could provide possible clinical significance with regard to ADE phenomena in young infants infected by EV71. PMID:21983920

  15. Cardiovascular disease and type 1 diabetes: prevalence, prediction and management in an ageing population.

    PubMed

    Lee, Siang Ing; Patel, Mitesh; Jones, Christopher M; Narendran, Parth

    2015-11-01

    Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes mellitus (T1D). However, evidence of its risks and management is often extrapolated from studies in type 2 diabetic (T2D) patients or the general population. This approach is unsatisfactory given that the underlying pathology, demographics and natural history of the disease differ between T1D and T2D. Furthermore, with a rising life expectancy, a greater number of T1D patients are exposed to the cardiovascular (CV) risk factors associated with an ageing population. The aim of this review is to examine the existing literature around CVD in T1D. We pay particular attention to CVD prevalence, how well we manage risk, potential biomarkers, and whether the studies included the older aged patients (defined as aged over 65). We also discuss approaches to the management of CV risk in the older aged. The available data suggest a significant CVD burden in patients with T1D and poor management of CV risk factors. This is underpinned by a poor evidence base for therapeutic management of CV risk specifically for patients with T1D, and in the most relevant population - the older aged patients. We would suggest that important areas remain to be addressed, particularly exploring the risks and benefits of therapeutic approaches to CVD management in the older aged. PMID:26568811

  16. Cardiovascular disease and type 1 diabetes: prevalence, prediction and management in an ageing population

    PubMed Central

    Lee, Siang Ing; Patel, Mitesh; Jones, Christopher M.; Narendran, Parth

    2015-01-01

    Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes mellitus (T1D). However, evidence of its risks and management is often extrapolated from studies in type 2 diabetic (T2D) patients or the general population. This approach is unsatisfactory given that the underlying pathology, demographics and natural history of the disease differ between T1D and T2D. Furthermore, with a rising life expectancy, a greater number of T1D patients are exposed to the cardiovascular (CV) risk factors associated with an ageing population. The aim of this review is to examine the existing literature around CVD in T1D. We pay particular attention to CVD prevalence, how well we manage risk, potential biomarkers, and whether the studies included the older aged patients (defined as aged over 65). We also discuss approaches to the management of CV risk in the older aged. The available data suggest a significant CVD burden in patients with T1D and poor management of CV risk factors. This is underpinned by a poor evidence base for therapeutic management of CV risk specifically for patients with T1D, and in the most relevant population – the older aged patients. We would suggest that important areas remain to be addressed, particularly exploring the risks and benefits of therapeutic approaches to CVD management in the older aged. PMID:26568811

  17. Natural Antibodies as Rheostats for Susceptibility to Chronic Diseases in the Aged.

    PubMed

    Rothstein, Thomas L

    2016-01-01

    Natural antibodies are spontaneously produced in the absence of infection or immunization, and are both anti-microbial and autoreactive. Autoreactive natural antibodies can bind noxious molecules, such as those involved in clinical situations of atherosclerosis (oxLDL), malignancy (NGcGM3), and neurodegeneration (amyloid, tau) and can affect the fate of their targets or the cells bearing them to maintain homeostasis. Clinically relevant natural antibodies have been shown to decline with advancing age in those few situations where measurements have been made. Consistent with this, human B-1 cells that are thought to be responsible for generating natural antibodies also decline with advancing age. These findings together suggest that an age-related decline in amount or efficacy of homeostatic natural antibodies is associated with relative loss of protection against molecules involved in several diseases whose incidence rises in the older age population, and that those individuals experiencing greatest loss are at greatest risk. In this view, natural antibodies act as rheostats for susceptibility to several age-related diseases. These considerations suggest that administration of natural antibodies, or of factors that maintain B-1 cells and/or enhance production of natural antibodies by B-1 cells, may serve to counteract the onset or progression of age-related chronic illness. PMID:27092140

  18. Natural Antibodies as Rheostats for Susceptibility to Chronic Diseases in the Aged

    PubMed Central

    Rothstein, Thomas L.

    2016-01-01

    Natural antibodies are spontaneously produced in the absence of infection or immunization, and are both anti-microbial and autoreactive. Autoreactive natural antibodies can bind noxious molecules, such as those involved in clinical situations of atherosclerosis (oxLDL), malignancy (NGcGM3), and neurodegeneration (amyloid, tau) and can affect the fate of their targets or the cells bearing them to maintain homeostasis. Clinically relevant natural antibodies have been shown to decline with advancing age in those few situations where measurements have been made. Consistent with this, human B-1 cells that are thought to be responsible for generating natural antibodies also decline with advancing age. These findings together suggest that an age-related decline in amount or efficacy of homeostatic natural antibodies is associated with relative loss of protection against molecules involved in several diseases whose incidence rises in the older age population, and that those individuals experiencing greatest loss are at greatest risk. In this view, natural antibodies act as rheostats for susceptibility to several age-related diseases. These considerations suggest that administration of natural antibodies, or of factors that maintain B-1 cells and/or enhance production of natural antibodies by B-1 cells, may serve to counteract the onset or progression of age-related chronic illness. PMID:27092140

  19. Increased epigenetic age and granulocyte counts in the blood of Parkinson's disease patients

    PubMed Central

    Horvath, Steve; Ritz, Beate R.

    2015-01-01

    It has been a long standing hypothesis that blood tissue of PD Parkinson's disease (PD) patients may exhibit signs of accelerated aging. Here we use DNA methylation based biomarkers of aging (“epigenetic clock”) to assess the aging rate of blood in two ethnically distinct case-control data sets. Using n=508 Caucasian and n=84 Hispanic blood samples, we assess a) the intrinsic epigenetic age acceleration of blood (IEAA), which is independent of blood cell counts, and b) the extrinsic epigenetic age acceleration rate of blood (EEAA) which is associated with age dependent changes in blood cell counts. Blood of PD subjects exhibits increased age acceleration according to both IEAA (p=0.019) and EEAA (p=6.1×10−3). We find striking differences in imputed blood cell counts between PD cases and controls. Compared to control subjects, PD subjects contains more granulocytes (p=1.0×10−9 in Caucasians, p=0.00066 in Hispanics) but fewer T helper cells (p=1.4×10−6 in Caucasians, p=0.0024 in Hispanics) and fewer B cells (p=1.6×10−5 in Caucasians, p=4.5×10−5 in Hispanics). Overall, this study shows that the epigenetic age of the immune system is significantly increased in PD patients and that granulocytes play a significant role. PMID:26655927

  20. The Age-by-Disease Interaction Hypothesis of Late-Life Depression

    PubMed Central

    McKinney, Brandon Chad; Sibille, Etienne

    2012-01-01

    The phenomenological diagnosis of depression is successful in increasing diagnostic reliability, but it is a classification scheme without biological bases. One subtype of depression for which evidence suggests a unique biological basis is late-life depression (LLD), with first onset of symptoms after the age of 65. LLD is common and poses a significant burden on affected individuals, caretakers, and society. The pathophysiology of LLD includes disruptions of the neural network underlying mood, which can be conceptualized as the result of dysfunction in multiple underlying biological processes. Here, we briefly review current LLD hypotheses and then describe the characteristics of molecular brain aging and their overlap with disease processes. Further, we propose a new hypothesis for LLD, the Age-by-Disease Interaction hypothesis, which posits that the clinical presentation of LLD is the integrated output of specific biological processes that are pushed in LLD-promoting directions by changes in gene expression naturally occurring during brain aging, hence leading the brain to a physiological state that is more susceptible to LLD, since additional pushes by genetic, environmental and biochemical factors may now be sufficient to generate dysfunctional states that produce depressive symptoms. We put our propositions together into a decanalization model to aid in illustrating how age-related biological changes of the brain can shift the repertoire of available functional states in a pro-depression direction, and how additional factors can readily lead the system into distinct and stable maladaptive phenotypes, including LLD. This model brings together basic research on neuropsychiatric and neurodegenerative diseases more closely with the investigation of normal aging. Specifically, identifying biological processes affected during normal aging may inform the development of new interventions for the prevention and treatment of LLD. PMID:23570886

  1. Molecular and Chemical Genetic Approaches to Developmental Origins of Aging and Disease in Zebrafish

    PubMed Central

    Sasaki, Tomoyuki; Kishi, Shuji

    2013-01-01

    The incidence of diseases increases rapidly with age, accompanied by progressive deteriorations of physiological functions in organisms. Aging-associated diseases are sporadic but mostly inevitable complications arising from senescence. Senescence is often considered the antithesis of early development, but yet there may be factors and mechanisms in common between these two phenomena over the dynamic process of aging. The association between early development and late-onset disease with advancing age is thought to come from a consequence of developmental plasticity, the phenomenon by which one genotype can give rise to a range of physiologically and/or morphologically adaptive states in response to different environmental or genetic perturbations. On the one hand, we hypothesized that the future aging process can be predictive based on adaptivity during the early developmental period. Modulating the thresholds of adaptive plasticity by chemical genetic approaches, we have been investigating whether any relationship exists between the regulatory mechanisms that function in early development and in senescence using the zebrafish (Danio rerio), a small freshwater fish and a useful model animal for genetic studies. We have successfully conducted experiments to isolate zebrafish mutants expressing apparently altered senescence phenotypes during embryogenesis (“embryonic senescence”), subsequently showing shortened lifespan in adulthoods. We anticipate that previously uncharacterized developmental genes may mediate the aging process and play a pivotal role in senescence. On the other hand, unexpected senescence-related genes might also be involved in the early developmental process and regulation. The ease of manipulation using the zebrafish system allows us to conduct an exhaustive exploration of novel genes and small molecular compounds that can be linked to the senescence phenotype, and thereby facilitates searching for the evolutionary and developmental origins

  2. How Do Immune Cells Support and Shape the Brain in Health, Disease, and Aging?

    PubMed Central

    Kipnis, Jonathan; Rivest, Serge; Prat, Alexandre

    2013-01-01

    For decades, several axioms have prevailed with respect to the relationships between the CNS and circulating immune cells. Specifically, immune cell entry was largely considered to be pathological or to mark the beginning of pathology within the brain. Moreover, local inflammation associated with neurodegenerative diseases such Alzheimer's disease or amyotrophic lateral sclerosis, were considered similar in their etiology to inflammatory diseases, such as remitting relapsing-multiple sclerosis. The ensuing confusion reflected a lack of awareness that the etiology of the disease as well as the origin of the immune cells determines the nature of the inflammatory response, and that inflammation resolution is an active cellular process. The last two decades have seen a revolution in these prevailing dogmas, with a significant contribution made by the authors. Microglia and infiltrating monocyte-derived macrophages are now known to be functionally distinct and of separate origin. Innate and adaptive immune cells are now known to have protective/healing properties in the CNS, as long as their activity is regulated, and their recruitment is well controlled; their role is appreciated in maintenance of brain plasticity in health, aging, and chronic neurodevelopmental and neurodegenerative diseases. Moreover, it is now understood that the barriers of the brain are not uniform in their interactions with the circulating immune cells. The implications of these new findings to the basic understanding of CNS repair processes, brain aging, and a wide spectrum of CNS disorders, including acute injuries, Rett syndrome, Alzheimer's disease, and multiple sclerosis, will be discussed. PMID:24198349

  3. Common Aging Signature in the Peripheral Blood of Vascular Dementia and Alzheimer's Disease.

    PubMed

    Luo, Hongbo; Han, Guangchun; Wang, Jiajia; Zeng, Fan; Li, Yuanming; Shao, Shaoju; Song, Fuhai; Bai, Zhouxian; Peng, Xing; Wang, Yan-Jiang; Shi, Xiangqun; Lei, Hongxing

    2016-08-01

    Alzheimer's disease (AD) and vascular dementia (VaD) are the two most dominant forms of dementia in elderly people. Due to the large overlap between AD and VaD in clinical observations, great controversies exist regarding the distinction and connection between these two types of senile dementia. Here for the first time, we resort to the gene expression pattern of the peripheral blood to compare AD and VaD objectively. In our previous work, we have demonstrated that the dysregulation of gene expression in AD is unique among the examined diseases including neurological diseases, cancer, and metabolic diseases. In this study, we found that the dysregulation of gene expression in AD and VaD is quite similar to each other at both functional and gene levels. Interestingly, the dysregulation started at the early stages of the diseases, namely mild cognitive impairment (MCI) and vascular cognitive impairment (VCI). We have also shown that this signature is distinctive from that of peripheral vascular diseases. Comparison with aging studies revealed that the most profound change in AD and VaD, namely ribosome, is consistent with the accelerated aging scenario. This study may have implications to the common mechanism between AD and VaD. PMID:26099307

  4. Genome-Wide Scan Informed by Age-Related Disease Identifies Loci for Exceptional Human Longevity

    PubMed Central

    Fortney, Kristen; Dobriban, Edgar; Garagnani, Paolo; Pirazzini, Chiara; Monti, Daniela; Mari, Daniela; Atzmon, Gil; Barzilai, Nir; Franceschi, Claudio; Owen, Art B.; Kim, Stuart K.

    2015-01-01

    We developed a new statistical framework to find genetic variants associated with extreme longevity. The method, informed GWAS (iGWAS), takes advantage of knowledge from large studies of age-related disease in order to narrow the search for SNPs associated with longevity. To gain support for our approach, we first show there is an overlap between loci involved in disease and loci associated with extreme longevity. These results indicate that several disease variants may be depleted in centenarians versus the general population. Next, we used iGWAS to harness information from 14 meta-analyses of disease and trait GWAS to identify longevity loci in two studies of long-lived humans. In a standard GWAS analysis, only one locus in these studies is significant (APOE/TOMM40) when controlling the false discovery rate (FDR) at 10%. With iGWAS, we identify eight genetic loci to associate significantly with exceptional human longevity at FDR < 10%. We followed up the eight lead SNPs in independent cohorts, and found replication evidence of four loci and suggestive evidence for one more with exceptional longevity. The loci that replicated (FDR < 5%) included APOE/TOMM40 (associated with Alzheimer’s disease), CDKN2B/ANRIL (implicated in the regulation of cellular senescence), ABO (tags the O blood group), and SH2B3/ATXN2 (a signaling gene that extends lifespan in Drosophila and a gene involved in neurological disease). Our results implicate new loci in longevity and reveal a genetic overlap between longevity and age-related diseases and traits, including coronary artery disease and Alzheimer’s disease. iGWAS provides a new analytical strategy for uncovering SNPs that influence extreme longevity, and can be applied more broadly to boost power in other studies of complex phenotypes. PMID:26677855

  5. Effect of Educational Outreach Timing and Duration on Facility Performance for Infectious Disease Care in Uganda: A Trial with Pre-Post and Cluster Randomized Controlled Components

    PubMed Central

    Burnett, Sarah M.; Mbonye, Martin K.; Naikoba, Sarah; Zawedde-Muyanja, Stella; Kinoti, Stephen N.; Ronald, Allan; Rubashembusya, Timothy; Willis, Kelly S.; Colebunders, Robert; Manabe, Yukari C.; Weaver, Marcia R.

    2015-01-01

    Background Classroom-based learning is often insufficient to ensure high quality care and application of health care guidelines. Educational outreach is garnering attention as a supplemental method to enhance health care worker capacity, yet there is little information about the timing and duration required to improve facility performance. We sought to evaluate the effects of an infectious disease training program followed by either immediate or delayed on-site support (OSS), an educational outreach approach, on nine facility performance indicators for emergency triage, assessment, and treatment; malaria; and pneumonia. We also compared the effects of nine monthly OSS visits to extended OSS, with three additional visits over six months. Methods This study was conducted at 36 health facilities in Uganda, covering 1,275,960 outpatient visits over 23 months. From April 2010 to December 2010, 36 sites received infectious disease training; 18 randomly selected sites in arm A received nine monthly OSS visits (immediate OSS) and 18 sites in arm B did not. From March 2011 to September 2011, arm A sites received three additional visits every two months (extended OSS), while the arm B sites received eight monthly OSS visits (delayed OSS). We compared the combined effect of training and delayed OSS to training followed by immediate OSS to determine the effect of delaying OSS implementation by nine months. We also compared facility performance in arm A during the extended OSS to immediate OSS to examine the effect of additional, less frequent OSS. Results Delayed OSS, when combined with training, was associated with significant pre/post improvements in four indicators: outpatients triaged (44% vs. 87%, aRR = 1.54, 99% CI = 1.11, 2.15); emergency and priority patients admitted, detained, or referred (16% vs. 31%, aRR = 1.74, 99% CI = 1.10, 2.75); patients with a negative malaria test result