Science.gov

Sample records for age underlying disease

  1. 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

  2. Mechanisms underlying the production of false memories for famous people's names in aging and Alzheimer's disease.

    PubMed

    Plancher, Gaën; Guyard, Anne; Nicolas, Serge; Piolino, Pascale

    2009-10-01

    It is well known that the occurrence of false memories increases with aging, but the results remain inconsistent concerning Alzheimer's disease (AD). Moreover, the mechanisms underlying the production of false memories are still unclear. Using an experimental episodic memory test with material based on the names of famous people in a procedure derived from the DRM paradigm [Roediger, H. L., III, & McDermott, K. B. (1995). Creating false memories: Remembering words not presented in lists. Journal of Experimental Psychology: Learning, Memory & Cognition, 21, 803-814], we examined correct and false recall and recognition in 30 young adults, 40 healthy older adults, and 30 patients with AD. Moreover, we evaluated the relationships between false memory performance, correct episodic memory performance, and a set of neuropsychological assessments evaluating the semantic memory and executive functions. The results clearly indicated that correct recall and recognition performance decreased with the subjects' age, but it decreased even more with AD. In addition, semantically related false recalls and false recognitions increased with age but not with dementia. On the contrary, non-semantically related false recalls and false recognitions increased with AD. Finally, the regression analyses showed that executive functions mediated related false memories and episodic memory mediated related and unrelated false memories in aging. Moreover, executive functions predicted related and unrelated false memories in AD, and episodic and semantic memory predicted semantically related and unrelated false memories in AD. In conclusion, the results obtained are consistent with the current constructive models of memory suggesting that false memory creation depends on different cognitive functions and, consequently, that the impairments of these functions influence the production of false memories.

  3. Alzheimer's Disease as Subcellular `Cancer' --- The Scale-Invariant Principles Underlying the Mechanisms of Aging ---

    NASA Astrophysics Data System (ADS)

    Murase, M.

    1996-01-01

    Alzheimer's disease (AD) is characterized by the slow onset of neurodegeneration leading to dementia in many elderly people. The pathological hallmarks of AD are: the extracellular β-amyloid deposition in the senile plaques; the β-amyloid deposition in cerebral blood vessel walls especially in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D); the intracellular neurofibrillary tangle formation composed of paired helical filaments (PHF), the principal component of which is a hyperphosphorylated form of the microtubule-binding protein, tau; and neurological dysfuction and neuronal cell death in limited regions and pathways of the central nervous system. Note that β-amyloid is a truncated form of a cell surface integral membrane glycoprotein: amyloid precursor protein (APP). Despite these hallmarks, the pathogenesis of AD has been poorly understood. In the present paper, a theory of aging is proposed to give a coherent account of the origins and causes of neurodegeneration common to the diverse neurodegenerative disorders such as AD and prion (proteinaceous infectious particles) diseases in comparison with the pathogenesis of cancers. Surprisingly, the self-aggregation of denatured proteins -- such as β-amyloid, PHF and prions -- responsible for neuronal cell death resembles, in many respects, the development (or the clonal evolution) of malignant cells at the expense of the entire organism harboring them. Although neurodegenerative disorders and cancers apparently differe in pathology, they nevertheless seem to follow the same priciples regardless of the level and scale of the biological organization. It is the general principles of heritable variations and natural selection as well as the general principles of self-organization that operate, not only on different molecules, but also at different hierarchical levels and scales of the biological organizaiton, independent of the details of diseases. Traditionally, natural selection, along

  4. Mild cognitive impairment due to alzheimer disease is less likely under the age of 65.

    PubMed

    Shin, Soojeong; Kim, Jong Hun; Cho, Jeong Hee; Kim, Gyu Sik; Choi, Sun-Ah; Lee, Jun Hong

    2015-01-01

    Patients with amnestic mild cognitive impairment (aMCI) are considered to have a high risk for Alzheimer dementia (AD). Even high positive predictive values, however, cannot be guaranteed even by tests with high sensitivity and specificity when disease prevalence is low. If we regard the clinical criteria for aMCI as a test for predicting aMCI due to AD, the positive predictive value of the criteria will be low by definition in young patients with aMCI (age below 65 years) because of the low prevalence of AD in this age group. To test this hypothesis, we compared CSF biomarkers for AD between young (age below 65 years) and old (age 65 years or older) age groups of normal cognition, aMCI, and AD of the Alzheimer's Disease Neuroimaging Initiative database. Using these biomarkers, we observed that the prevalence of aMCI due to AD differed significantly between the young and the old. For example, only 28.2% young aMCI, but 63.2% old aMCI, had abnormal CSF amyloid measures consistent with AD pathology. As posited, the presence of aMCI due to AD was lower in young aMCI than in old aMCI. Given that the likelihood of aMCI due to AD is reduced in younger subjects, more attention to and evaluation of alternative diagnoses need to be considered in this group.

  5. Ageing and neurodegenerative diseases.

    PubMed

    Hung, Chia-Wei; Chen, Yu-Chih; Hsieh, Wan-Ling; Chiou, Shih-Hwa; Kao, Chung-Lan

    2010-11-01

    Ageing, which all creatures must encounter, is a challenge to every living organism. In the human body, it is estimated that cell division and metabolism occurs exuberantly until about 25 years of age. Beyond this age, subsidiary products of metabolism and cell damage accumulate, and the phenotypes of ageing appear, causing disease formation. Among these age-related diseases, neurodegenerative diseases have drawn a lot of attention due to their irreversibility, lack of effective treatment, and accompanied social and economical burdens. In seeking to ameliorate ageing and age-related diseases, the search for anti-ageing drugs has been of much interest. Numerous studies have shown that the plant polyphenol, resveratrol (3,5,4'-trihydroxystilbene), extends the lifespan of several species, prevents age-related diseases, and possesses anti-inflammatory, and anti-cancer properties. The beneficial effects of resveratrol are believed to be associated with the activation of a longevity gene, SirT1. In this review, we discuss the pathogenesis of age-related neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and cerebrovascular disease. The therapeutic potential of resveratrol, diet and the roles of stem cell therapy are discussed to provide a better understanding of the ageing mystery.

  6. Disease drivers of aging

    PubMed Central

    Hodes, Richard J.; Sierra, Felipe; Austad, Steven N.; Epel, Elissa; Neigh, Gretchen N.; Erlandson, Kristine M.; Schafer, Marissa J.; LeBrasseur, Nathan K.; Wiley, Christopher; Campisi, Judith; Sehl, Mary E.; Scalia, Rosario; Eguchi, Satoru; Kasinath, Balakuntalam S.; Halter, Jeffrey B.; Cohen, Harvey Jay; Demark-Wahnefried, Wendy; Ahles, Tim A.; Barzilai, Nir; Hurria, Arti; Hunt, Peter W.

    2017-01-01

    It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship—the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging. PMID:27943360

  7. Aging as disease.

    PubMed

    De Winter, Gunnar

    2015-05-01

    In this paper, I will argue that ageing can be construed as disease. First, the concept of disease is discussed, where the distinction is made between two lines of thought, an objectivist and a subjectivist one. After determining the disease conception to be used throughout the argument, it is proposed that senescence could be seen as disease. Three common counterarguments are discussed, none of which appears strong enough to effectively counter the advocated view. In the third section, two potential implications of the view advocated here will be briefly touched upon. These are the quest for a cure or treatment for ageing and the general attitude towards the elderly. It is concluded that, utilizing an objective disease concept, ageing could be seen as a disease. None of the considered counterarguments packs enough of a punch to discard this. The implications are complex and intertwined, but need not be negative.

  8. Senescence, aging, and disease.

    PubMed

    Crews, Douglas E

    2007-05-01

    All over the world people are surviving into their seventh and later decades of life more frequently today than ever before in human history. Some remain in good health, while others show chronic degenerative conditions (CDCs), frailty, and relatively rapid mortality. Thereafter, multiple factors promoting health and well-being become ever more complex as we age. After attainment of reproductive maturation, many physiological decrements occurring in concert with age reflect both senescent and disease processes, not simply the passage of time. Senescence is a process that begins with DNA, molecules and cells and ultimately terminates in cellular death, loss of organ function, and somatic frailty. These changes are different from benign changes with age that do not alter function. Both differ from the pathological processes represented by disease. Either disease or senescence may be age-related, but neither is age-determined. Disease results from pathological alterations and it affects all age groups. Diseases need not be related to senescence, which includes alterations due to inherent aspects of organismal biology. Distinctions among senescence, aging, and disease blur for the late-life CDCs because, in addition to disease processes, many CDCs are phenotypic manifestations of senescing DNA, organelles, cells, and organs. During earlier epochs of human evolution, greater environmental exposures and fewer cultural buffers likely lead to greater frailty and mortality before senescence progressed greatly, as they still do for most animals. In modern-day settings, culturally patterned behaviors have allowed human frailty to become disconnected somewhat from mortality, unlike non-human species.

  9. Hospitalizations and Deaths Because of Respiratory and Diarrheal Diseases Among Haitian Children Under Five Years of Age, 2011–2013

    PubMed Central

    Vinekar, Kavita; Schaad, Nicolas; Lucien, Mentor Ali Ber; Leshem, Eyal; Oboho, Ikwo K.; Joseph, Gerard; Juin, Stanley; Dawood, Fatimah S.; Parashar, Umesh; Katz, Mark A.; Tohme, Rania A.

    2015-01-01

    Background Respiratory and diarrheal diseases are leading causes of morbidity and mortality among children younger than 5 years in developing countries. Data on the burden of these diseases in Haiti are scarce. Methods We conducted a retrospective review of hospital admission registries during January 1, 2011–December 31, 2013 for children younger than 5 years in 6 hospitals in Haiti. We recorded the number of all-cause, respiratory and diarrheal disease admissions and deaths by epidemiologic week and age. Results A total of 31,565 hospital admissions and 1763 deaths were recorded among children aged <5 years during the study period. Respiratory diseases accounted for 9183 (29%) hospitalizations and 301 (17%) deaths. Children aged 6–23 months had the highest percentage of hospitalizations attributable to respiratory diseases (38%), whereas children aged 36–47 months had the highest proportion of deaths attributable to respiratory diseases (37%). Respiratory disease hospitalizations followed a bimodal seasonal pattern, with peaks during May–June and October–December. Diarrheal diseases accounted for 8063 (26%) hospitalizations and 224 (13%) deaths. Children aged 6–11 months had the highest percentage of diarrhea-associated hospitalizations (39%) and deaths (29%). Diarrheal disease admissions peaked in January–April before the rainy season. Conclusions Respiratory and diarrheal diseases contributed to more than half of hospitalizations and almost a third of deaths in children younger than 5 years in Haiti. These data are essential to assess the impact of pneumococcal and rotavirus vaccines and other interventions in Haiti. PMID:26244833

  10. Ageing with Muscular Disease

    PubMed Central

    Martinsen, Bente; Dreyer, Pia

    2016-01-01

    Background: The demographic development with an ageing population is predicted to be the next global public health challenge. Advances in medicine and the socioeconomic development have reduced mortality and morbidity due to infectious conditions and non-communicable diseases. The increase in longevity will not be restricted to healthy people. Objective: To understand how people with muscular diseases experience ageing. Method: A literature review was conducted using the Matrix Method developed by Garrard (2007). This systematic method was used to identify, describe and interpret studies, irrespective of the methods applied. To avoid the exclusion of important sources, experiences and topics, we chose an integrative approach that accommodates the inclusion of studies with different methodologies. People with MD have gradually extended their life expectancy during the last 30 years. Thus, we reviewed the literature regarding MD and ageing without time limit. Results: We identified three themes: 1) Slowing down early 2) Accepting lifelong deterioration and 3) Striving for normality. Conclusion: People with MD live in a field of tension between a feeling of autonomy and normality and difficulties coping with reduced physical abilities. Getting older accentuates this tension since the physical strength diminishes and it is harder to maintain autonomy. The bodily challenges may coincide with the end of the rehabilitation people living with MD have received. Seemingly, no age-related rehabilitation is offered, and people living with MD are thus at risk of an unnecessarily passive life. PMID:28144383

  11. 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

  12. Chronic kidney disease and premature ageing.

    PubMed

    Kooman, Jeroen P; Kotanko, Peter; Schols, Annemie M W J; Shiels, Paul G; Stenvinkel, Peter

    2014-12-01

    Chronic kidney disease (CKD) shares many phenotypic similarities with other chronic diseases, including heart failure, chronic obstructive pulmonary disease, HIV infection and rheumatoid arthritis. The most apparent similarity is premature ageing, involving accelerated vascular disease and muscle wasting. We propose that in addition to a sedentary lifestyle and psychosocial and socioeconomic determinants, four major disease-induced mechanisms underlie premature ageing in CKD: an increase in allostatic load, activation of the 'stress resistance response', activation of age-promoting mechanisms and impairment of anti-ageing pathways. The most effective current interventions to modulate premature ageing-treatment of the underlying disease, optimal nutrition, correction of the internal environment and exercise training-reduce systemic inflammation and oxidative stress and induce muscle anabolism. Deeper mechanistic insight into the phenomena of premature ageing as well as early diagnosis of CKD might improve the application and efficacy of these interventions and provide novel leads to combat muscle wasting and vascular impairment in chronic diseases.

  13. Acute diarrhoeal disease in children under 7 years of age in a peri-urban slum of Santiago, Chile.

    PubMed Central

    Araya, M.; Figueroa, G.; Espinoza, J.; Montesinos, N.; Spencer, E.; Brunser, O.

    1985-01-01

    A group of 168 families who lived in a peri-urban slum in Santiago were surveyed for 9 months. All of them had a child under 7 years of age. Medical activities and data collection were carried out at a Field Station and by means of twice-weekly visits to each home, at which time cases of diarrhoea were recorded and investigated. Faecal samples for bacteriological, parasitological and rotavirus studies were obtained during each episode. The characteristics of clinical course, hygienic practices in the family, and monthly anthropometric measurements of infants and toddlers were also recorded. The mean monthly incidence of diarrhoea was 7.1 episodes per 100 children. Of the episodes, 44.2% were associated with pathogenic bacteria, 14.4% with rotavirus, 38.4% with parasites and in 27.9% no enteropathogens were identified. It was found that adequate hygienic habits were not associated with a decreased risk of developing diarrhoea and that about 60% of children did not have diarrhoea throughout the study period. The nutritional status was adequate in most cases: weight-for-age was below the 5th percentile in 11.5% of subjects and the height-for-age was normal in all. No moderate or severe cases of malnutrition were detected. PMID:4067299

  14. The emergence of the mitochondrial genome as a partial regulator of nuclear function is providing new insights into the genetic mechanisms underlying age-related complex disease.

    PubMed

    Horan, Martin P; Cooper, David N

    2014-04-01

    Mitochondrial malfunction appears to be intimately associated with age and age-related complex disorders but the precise pathological relevance of such malfunction remains unclear. Mitochondrial, and more specifically bioenergetic, malfunction is commonly encountered in cancer, degenerative disorders and aging. The identification of a mitochondrial-nuclear retrograde signaling pathway in yeast has facilitated the study of the corresponding retrograde signaling mechanisms induced in response to mitochondrial malfunction in mammals including human. Mitochondrial-nuclear crosstalk is critical for the maintenance of cellular homeostasis, and some mitochondrial DNA mutations may perturb crosstalk signaling. However, ascertaining whether mitochondrial malfunction is a cause or a consequence of disease development will be key to determining whether or not impaired crosstalk signaling is of direct pathological and hence therapeutic relevance. Here, we review what is known about the nuclear adaptive compensatory mechanisms induced in response to mitochondrial malfunction. We discuss the role of mitochondrial DNA variants in modulating the penetrance of human inherited disease caused by mutations in the nuclear genome and explore the underlying mechanisms by which they influence the retrograde response. We conclude that mitochondrial DNA variants have the potential to induce molecular signals through the mitochondrial-nuclear crosstalk mechanism, thereby promoting nuclear compensation in response to mitochondrial malfunction. The implications for the development of genetic or pharmaceutical interventions for the treatment of mitochondrial malfunction in complex disease are also explored.

  15. Effect of Aging in the Perception of Health-Related Quality of Life in End-Stage Renal Disease Patients under Online-Hemodiafiltration

    PubMed Central

    Moura, Alexandra; Madureira, José; Alija, Pablo; Fernandes, João Carlos; Oliveira, José Gerardo; Lopez, Martin; Filgueiras, Madalena; Amado, Leonilde; Sameiro-Faria, Maria; Miranda, Vasco; Santos-Silva, Alice; Costa, Elísio

    2015-01-01

    This work aimed to evaluate how aging could influence patients’ perception of health quality of life (HRQOL), as well as, the effect of aging on dialysis adequacy and in hematological, iron status, inflammatory and nutritional markers. In this transversal study were enrolled 305 ESRD patients under online-hemodiafiltration (OL-HDF) (59.67% males; 64.9 ± 14.3 years old). Data about comorbidities, hematological data, iron status, dialysis adequacy, nutritional and inflammatory markers were collected from patient’s records. Moreover, HRQOL score, by using the Kidney Disease Quality of Life-Short Form (KDQOL-SF), was assessed. Analyzing the results according to quartiles of age, significant differences were found for some parameters evaluated by the KDQOL-SF instrument, namely for work status, physical functioning and role-physical, which decreased with increasing age. We also found a higher proportion of diabetic patients, a decrease in creatinine, iron, albumin serum levels, transferrin saturation and nPCR, with increasing age. Moreover, significant negative correlations were found between age and mean cell hemoglobin concentration, iron, transferrin saturation, albumin, nPCR, work status, physical functioning and role-physical. In conclusion, our results showed that aging is associated with a decreased work status, physical functioning and role-physical, with a decreased dialysis adequacy, iron availability and nutritional status, and with an increased proportion of diabetic patients and of patients using central venous catheter, as the vascular access. The knowledge of these changes associated with aging, which have impact in the quality of life of the patients, could be useful in their management. PMID:25657849

  16. 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.

  17. 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

  18. Age-related eye disease.

    PubMed

    Voleti, Vinod B; Hubschman, Jean-Pierre

    2013-05-01

    As with many organs, compromised function of the eye is accompanied with age and has become increasingly prevalent with the aging population. When decreased visual loss becomes significant, patients' ability to perform activities of daily living becomes compromised. This decrease in function is met with morbidity and mortality, as well as a large socioeconomic burden throughout the world. This review summarizes the most common age-related eye diseases, including cataract, glaucoma, diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration. Although our understanding of the genetic and biochemical pathways of these diseases is sill at its primitive stages, we have become able to help our patients improve the quality of life as they age.

  19. Aortic valve replacement in children under 16 years of age with congenital or rheumatic valvular disease. A study of 64 cases.

    PubMed

    Abid, F; Abid, A; Fekih, M; Zaouali, R M; Ben Ismail, M

    1992-01-01

    Sixty-four children have had a single aortic valve replacement under 16 years of age, 50 for rheumatic disease (47) or bacterial endocarditis (3) (group I) and 14 for a congenital aortic valve lesion (group II), 38 were disk prostheses and 26 were ball prostheses. Associated procedures had to be performed 31 times, with widening of a small aortic annulus by a patch in 7 patients. The early mortality was 12.5%. Of 56 survivors, 55 were followed postoperatively for a mean period of 7 years (group I: 44, group II: 11). Forty of the 55 patients were anticoagulated (correctly maintained in only 24 patients), 15 were not anticoagulated. A high rate of late complications was observed. Thrombo-embolic accidents in 5 patients with inefficient anticoagulant treatment, 2 haemorrhagic episodes, 7 prosthetic leaks; specific problems related to this group of young patients were: recurrence of rheumatic fever with increasing severity of mitral valve disease requiring mitral valve replacement in 5 patients and outgrowth of the prosthesis, which affected 7 patients; this complication is the result of either fibrous deposit around the valve annulus or such a small annulus that the surgeon could only implant a small prosthesis. Ten patients required 11 reoperations for various reasons. The main reason for reoperation was mitral valve replacement for worsening of mitral valve disease caused by recurrence of rheumatic fever. A high late mortality 10/55 (18%) was noted. The main cause of death was a perivalvular leak (5); 1 late death was caused by a stenotic number 17 Björk-Shiley valve.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. 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.

  1. [Aging and retinal vascular diseases].

    PubMed

    Takagi, Hitoshi

    2007-03-01

    Ocular vascular diseases such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration, whose population increases along with aging, have become leading causes of severe visual disturbance. Macular edema and serous retinal detachment are associated with abnormal vascular leakage and tractional retinal detachment, and neovascular glaucoma is caused by retinal neovascularization. Such ocular vascular diseases are caused by vascular cell aging and vascular damage associated with lifestyle-related diseases including diabetes mellitus, hypertension, hyperlipidemia, and obesity. In the present study, we investigated molecular mechanisms in such vascular deficiencies using vascular cell biology methodology, and we propose novel strategies for the treatment of such vascular diseases. Along with aging, oxidative stress and physical stress, such as mechanical stretch, continuously and directly insult vascular cells. Such stress induces apoptosis by intracellular signaling through stress kinases in cultured retinal vascular cells. Inhibition of such stress kinases could be an effective treatment to protect the vascular cells against age-related damage. In a retinal vascular developmental model, pericyte loss causes pathology mimicking macular edema and proliferative diabetic retinopathy. Angiopoietin 1 (Ang 1) secreted by pericytes suppresses oxidative stress-induced intracellular signaling through stress kinases linked to cell apoptosis and normalizes such retinal pathology. This suggests that the paracrine action of Ang 1 in the pericytes is necessary to sustain normal retinal vasculature, and that Ang 1-triggered intracellular signaling is useful for the treatment of vascular cell pathology associated with pericyte loss. In diabetic retinopathy and retinal vein occlusion, retinal vessels regress along with retinal vascular cell apoptosis, and the retina becomes ischemic followed by pathological retinal neovascularization. VEGF has been

  2. Epigenetics of Aging and Aging-related Disease

    PubMed Central

    2014-01-01

    Aging is associated with a wide range of human disorders, including cancer, diabetes, cardiovascular, and neurodegenerative diseases. Long thought to be an inexorable road toward decline and diseases, aging is in fact remarkably plastic. Such plasticity could be harnessed to approach age-related diseases from a novel perspective. Although many studies have focused on the genes that impact aging, the nongenetic regulation of aging is gaining increasing attention. Specifically, aging is associated with profound epigenetic changes, resulting in alterations of gene expression and disturbances in broad genome architecture and the epigenomic landscape. The potential reversibility of these epigenetic changes that occur as a hallmark of aging offers exciting opportunities to alter the trajectory of age-related diseases. This short review highlights key epigenetic players in the regulation of aging, as well as both future goals and challenges to the utilization of epigenetic strategies to delay and reverse the main diseases of aging. PMID:24833581

  3. Epigenetics of aging and aging-related disease.

    PubMed

    Brunet, Anne; Berger, Shelley L

    2014-06-01

    Aging is associated with a wide range of human disorders, including cancer, diabetes, cardiovascular, and neurodegenerative diseases. Long thought to be an inexorable road toward decline and diseases, aging is in fact remarkably plastic. Such plasticity could be harnessed to approach age-related diseases from a novel perspective. Although many studies have focused on the genes that impact aging, the nongenetic regulation of aging is gaining increasing attention. Specifically, aging is associated with profound epigenetic changes, resulting in alterations of gene expression and disturbances in broad genome architecture and the epigenomic landscape. The potential reversibility of these epigenetic changes that occur as a hallmark of aging offers exciting opportunities to alter the trajectory of age-related diseases. This short review highlights key epigenetic players in the regulation of aging, as well as both future goals and challenges to the utilization of epigenetic strategies to delay and reverse the main diseases of aging.

  4. Aging Changes in Retinal Microglia and their Relevance to Age-related Retinal Disease.

    PubMed

    Ma, Wenxin; Wong, Wai T

    2016-01-01

    Age-related retinal diseases, such as age-related macular degeneration (AMD) and glaucoma, contain features of chronic retinal inflammation that may promote disease progression. However, the relationship between aging and neuroinflammation is unclear. Microglia are long-lived, resident immune cells of the retina, and mediate local neuroinflammatory reactions. We hypothesize that aging changes in microglia may be causally linked to neuroinflammatory changes underlying age-dependent retinal diseases. Here, we review the evidence for (1) how the retinal microglial phenotype changes with aging, (2) the factors that drive microglial aging in the retina, and (3) aging-related changes in microglial gene expression. We examine how these aspects of microglial aging changes may relate to pathogenic mechanisms of immune dysregulation driving the progression of age-related retinal disease. These relationships can highlight microglial aging as a novel target for the prevention and treatment of retinal disease.

  5. [Neurological diseases in the aged].

    PubMed

    Kameyama, M

    1990-12-01

    In this paper, I described clinical and basic problems on neurology of the aged patients. These studies have been done in various institutions with many co-workers. 1) A PET study revealed some age differences on CBF, CMRO2, or CMRgl. But these results are not so rigid in which much of individual variations should be considered in interpretation. Calendar age is not always compatible to biological age. 2) Saccular aneurysms in the brain artery were found in 7.3% of 1200 routine autopsy series of the aged subjects. Aneurysms with external diameter exceeding 6 mm had been fatally ruptured in 14 (78%) of 18 subjects. 3) Variations of the pyramidal crossing are found responsible for bizarre clinical manifestations. Non-crossing component was more prominent in the right pyramidal tract; consequently, right pyramidal tracts including ventral and lateral one seemed to have more extensive representation in the spinal cord level. 4) I123-IMP SPECT study showed a reduced uptake in the area 4 or area 4-6 of the ALS patients. 5) I introduced a new simplified Wartenberg's maneuver, which is useful for detection of subtle pyramidal dysfunctions. 6) Cases with central pontine myelinolysis and those of paraneoplastic syndrome were presented with an emphasis on their patho-chemical mechanisms. 7) Lewis-Sumner syndrome showing multifocal persistent conduction block is not rare in the aged, in which we have already had some useful therapeutic methods. 8) Dementia complicated with neurodegenerative disease was discussed on its clinical and chemical features of mental disturbances. In ALS-dementia, CSF-homovanilic acid reduced significantly than in the control and L-dopa was effective in some patients. 9) Vascular and Alzheimer-type dementias were presented and discussed on their pathogenetic mechanism according to our recent studies with review of literature.

  6. When neurogenesis encounters aging and disease.

    PubMed

    Lazarov, Orly; Mattson, Mark P; Peterson, Daniel A; Pimplikar, Sanjay W; van Praag, Henriette

    2010-12-01

    In this review, we consider the evidence that a reduction in neurogenesis underlies aging-related cognitive deficits and impairments in disorders such as Alzheimer's disease (AD). The molecular and cellular alterations associated with impaired neurogenesis in the aging brain are discussed. Dysfunction of presenilin-1, misprocessing of amyloid precursor protein and toxic effects of hyperphosphorylated tau and β-amyloid probably contribute to impaired neurogenesis in AD. Because factors such as exercise, environmental enrichment and dietary energy restriction enhance neurogenesis, and protect against age-related cognitive decline and AD, knowledge of the underlying neurogenic signaling pathways could lead to novel therapeutic strategies for preserving brain function. In addition, manipulation of endogenous neural stem cells and stem cell transplantation, as stand-alone or adjunct treatments, seems promising.

  7. When Neurogenesis Encounters Aging and Disease

    PubMed Central

    Lazarov, Orly; Mattson, Mark P.; Peterson, Daniel A.; Pimplikar, Sanjay W.; van Praag, Henriette

    2010-01-01

    In this review, we consider the evidence that a reduction in neurogenesis underlies aging-related cognitive deficits, and impairments in disorders such as Alzheimer's disease (AD). The molecular and cellular alterations associated with impaired neurogenesis in the aging brain are discussed. Dysfunction of presenilin-1, misprocessing of amyloid precursor protein and toxic effects of hyperphosphorylated tau and β-amyloid likely contribute to impaired neurogenesis in AD. Since factors such as exercise, enrichment and dietary energy restriction enhance neurogenesis, and protect against age-related cognitive decline and AD, knowledge of the underlying neurogenic signaling pathways could lead to novel therapeutic strategies for preserving brain function. In addition, manipulation of endogenous neural stem cells and stem cell transplantation, as stand-alone or adjunct treatments, seem promising. PMID:20961627

  8. 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

  9. Epigenetic alterations underlying autoimmune diseases.

    PubMed

    Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein

    2016-01-01

    Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases.

  10. Prognostic factors for disease progression in advanced Hodgkin's disease: an analysis of patients aged under 60 years showing no progression in the first 6 months after starting primary chemotherapy.

    PubMed Central

    Lee, S. M.; Radford, J. A.; Ryder, W. D.; Collins, C. D.; Deakin, D. P.; Crowther, D.

    1997-01-01

    The aim of this study was to determine whether a very high-risk group based on presenting characteristics could be identified in patients with advanced Hodgkin's disease who may benefit from high-dose chemotherapy (HDCT). Between 1975 and 1992, 453 previously untreated patients aged under 60 years who did not progress in the first 6 months after the start of standard chemotherapy had their hospital notes reviewed. The outcomes analysed were early disease progression (in the 6- to 18-month window following the start of chemotherapy) and disease progression in the whole of the follow-up period. A Cox regression analysis was used to investigate the combined effects of a number of presenting characteristics on these outcomes. Despite the presence of factors with significant effects on the relative rate of progression, the absolute effects in a group identified as having the poorest prognosis were not especially poor. No group could be defined with a freedom from progression rate of less than 70% over 6-18 months, and the worst prognostic group, which included only 53 patients, had an overall freedom from progression rate of 57% at 5 years. Four other reported prognostic indices were evaluated using our data set, but none of the indices was more successful in identifying a very high-risk group. It has not been possible to define a sufficiently high-risk group of patients with Hodgkin's disease based on presenting characteristics for whom HDCT could be advised as part of primary treatment. The search for more discriminating prognostic factors identifying vulnerable patients with a high risk of relapse must continue before a role can be found for HDCT following conventional chemotherapy in patients without disease progression. PMID:9000607

  11. 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…

  12. 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...

  13. Disease spread in age structured populations with maternal age effects.

    PubMed

    Clark, Jessica; Garbutt, Jennie S; McNally, Luke; Little, Tom J

    2017-04-01

    Fundamental ecological processes, such as extrinsic mortality, determine population age structure. This influences disease spread when individuals of different ages differ in susceptibility or when maternal age determines offspring susceptibility. We show that Daphnia magna offspring born to young mothers are more susceptible than those born to older mothers, and consider this alongside previous observations that susceptibility declines with age in this system. We used a susceptible-infected compartmental model to investigate how age-specific susceptibility and maternal age effects on offspring susceptibility interact with demographic factors affecting disease spread. Our results show a scenario where an increase in extrinsic mortality drives an increase in transmission potential. Thus, we identify a realistic context in which age effects and maternal effects produce conditions favouring disease transmission.

  14. 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

  15. Heart Disease Affects Women of All Ages

    MedlinePlus

    ... Home Current Issue Past Issues Heart Disease Affects Women of All Ages Past Issues / Winter 2007 Table ... of this page please turn Javascript on. Young Women: Lifestyle-related factors that increase heart disease risk ...

  16. 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.

  17. Mechanisms Underlying T Cell Immunosenescence: Aging and Cytomegalovirus Infection

    PubMed Central

    Tu, Wenjuan; Rao, Sudha

    2016-01-01

    The ability of the human immune system to protect against infectious disease declines with age and efficacy of vaccination reduces significantly in the elderly. Aging of the immune system, also termed as immunosenescence, involves many changes in human T cell immunity that is characterized by a loss in naïve T cell population and an increase in highly differentiated CD28- memory T cell subset. There is extensive data showing that latent persistent human cytomegalovirus (HCMV) infection is also associated with age-related immune dysfunction in the T cells, which might enhance immunosenescence. Understanding the molecular mechanisms underlying age-related and HCMV-related immunosenescence is critical for the development of effective age-targeted vaccines and immunotherapies. In this review, we will address the role of both aging and HCMV infection that contribute to the T cell senescence and discuss the potential molecular mechanisms in aged T cells. PMID:28082969

  18. Molecular Diagnostics of Ageing and Tackling Age-related Disease.

    PubMed

    Timmons, James A

    2017-01-01

    As average life expectancy increases there is a greater focus on health-span and, in particular, how to treat or prevent chronic age-associated diseases. Therapies which were able to control 'biological age' with the aim of postponing chronic and costly diseases of old age require an entirely new approach to drug development. Molecular technologies and machine-learning methods have already yielded diagnostics that help guide cancer treatment and cardiovascular procedures. Discovery of valid and clinically informative diagnostics of human biological age (combined with disease-specific biomarkers) has the potential to alter current drug-discovery strategies, aid clinical trial recruitment and maximize healthy ageing. I will review some basic principles that govern the development of 'ageing' diagnostics, how such assays could be used during the drug-discovery or development process. Important logistical and statistical considerations are illustrated by reviewing recent biomarker activity in the field of Alzheimer's disease, as dementia represents the most pressing of priorities for the pharmaceutical industry, as well as the chronic disease in humans most associated with age.

  19. 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...

  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. Leprosy among children under 15 years of age: literature review*

    PubMed Central

    de Oliveira, Marcela Bahia Barretto; Diniz, Lucia Martins

    2016-01-01

    Leprosy is a chronic infectious disease caused by Mycobacterium leprae, representing a public health issue in some countries. Though more prevalent in adults, the detection of new cases in children under 15 years of age reveals an active circulation of bacillus, continued transmission and lack of disease control by the health system, as well as aiding in the monitoring of the endemic. Among patients under 15 years of age, the most affected age group is children between 10 and 14 years of age, although cases of patients of younger than 1 year of age have also been reported. Household contacts are the primary source of infection, given that caretakers, such as babysitters and others, must be considered in this scenario. Paucibacillary forms of the disease prevailed, especially borderline-tuberculoid leprosy, with a single lesion in exposed areas of the body representing the main clinical manifestation. Reactional states: Lepra reactions are rare, although some authors have reported high frequencies of this phenomenon, the most frequent of which is Type 1 Lepra Reaction. Peripheral nerve involvement has been described at alarming rates in some studies, which increases the chance of deformities, a serious problem, especially if one considers the age of these patients. The protective effect of BCG vaccination was found in some studies, but no consensus has been reached among different authors. Children must receive the same multidrug therapy regimen and the doses should, ideally, be calculated based on the child´s weight. Adverse reactions to this therapy are rare within this age group. This article aims to review epidemiological, clinical, and therapeutic aspects of leprosy in patients under 15 years of age. PMID:27192519

  2. Aging - RNA in Development and Disease

    PubMed Central

    Cookson, Mark R

    2011-01-01

    Given that RNA is involved in virtually all biological processes, it is perhaps not surprising that several RNA binding proteins are associated with aging and with different age related disorders. Other chapters in this volume will discuss some specific examples of diseases where RNA plays a role that are also associated with aging, such as cancer and inflammation, so here I will discuss some general aspects of how RNA changes with the aging process. I will also discuss some specific examples of RNA binding proteins that are associated with age-dependent neurological diseases as these provide an interesting framework to examine how lifetime mutations might lead to a late onset disease, although the answers to these questions are still not well understood. PMID:21898829

  3. The application of information theory for the research of aging and aging-related diseases.

    PubMed

    Blokh, David; Stambler, Ilia

    2016-03-19

    This article reviews the application of information-theoretical analysis, employing measures of entropy and mutual information, for the study of aging and aging-related diseases. The research of aging and aging-related diseases is particularly suitable for the application of information theory methods, as aging processes and related diseases are multi-parametric, with continuous parameters coexisting alongside discrete parameters, and with the relations between the parameters being as a rule non-linear. Information theory provides unique analytical capabilities for the solution of such problems, with unique advantages over common linear biostatistics. Among the age-related diseases, information theory has been used in the study of neurodegenerative diseases (particularly using EEG time series for diagnosis and prediction), cancer (particularly for establishing individual and combined cancer biomarkers), diabetes (mainly utilizing mutual information to characterize the diseased and aging states), and heart disease (mainly for the analysis of heart rate variability). Few works have employed information theory for the analysis of general aging processes and frailty, as underlying determinants and possible early preclinical diagnostic measures for aging-related diseases. Generally, the use of information-theoretical analysis permits not only establishing the (non-linear) correlations between diagnostic or therapeutic parameters of interest, but may also provide a theoretical insight into the nature of aging and related diseases by establishing the measures of variability, adaptation, regulation or homeostasis, within a system of interest. It may be hoped that the increased use of such measures in research may considerably increase diagnostic and therapeutic capabilities and the fundamental theoretical mathematical understanding of aging and disease.

  4. Neuroglia in ageing and disease.

    PubMed

    Verkhratsky, Alexei; Rodríguez, José J; Parpura, Vladimir

    2014-08-01

    The proper operation of the mammalian brain requires dynamic interactions between neurones and glial cells. Various types of glial cells are susceptible to morpho-functional changes in a variety of brain pathological states, including toxicity, neurodevelopmental, neurodegenerative and psychiatric disorders. Morphological modifications include a change in the glial cell size and shape; the latter is evident by changes of the appearance and number of peripheral processes. The most blatant morphological change is associated with the alteration of the sheer number of neuroglia cells in the brain. Functionally, glial cells can undergo various metabolic and biochemical changes, the majority of which reflect upon homeostasis of neurotransmitters, in particular that of glutamate, as well as on defence mechanisms provided by neuroglia. Not only glial cells exhibit changes associated with the pathology of the brain but they also change with brain aging.

  5. NAD+ and Sirtuins in Aging and Disease

    PubMed Central

    Imai, Shin-ichiro; Guarente, Leonard

    2014-01-01

    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 anti-aging intervention, providing hope to aging societies worldwide. PMID:24786309

  6. 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

  7. Mitochondrial Medicine for Aging and Neurodegenerative Diseases

    PubMed Central

    2011-01-01

    Mitochondria are key cytoplasmic organelles, responsible for generating cellular energy, regulating intracellular calcium levels, altering the reduction-oxidation potential of cells, and regulating cell death. Increasing evidence suggests that mitochondria play a central role in aging and in neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and Freidriech ataxia. Further, several lines of evidence suggest that mitochondrial dysfunction is an early event in most late-onset neurodegenerative diseases. Biochemical and animal model studies of inherited neurodegenerative diseases have revealed that mutant proteins of these diseases are associated with mitochondria. Mutant proteins are reported to block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins and disrupt the electron transport chain, induce free radicals, cause mitochondrial dysfunction, and, ultimately, damage neurons. This article discusses critical issues of mitochondria causing dysfunction in aging and neurodegenerative diseases, and discusses the potential of developing mitochondrial medicine, particularly mitochondrially targeted antioxidants, to treat aging and neurodegenerative diseases. PMID:18566920

  8. Nutrition and AGE-ing: Focusing on Alzheimer's Disease.

    PubMed

    Abate, Giulia; Marziano, Mariagrazia; Rungratanawanich, Wiramon; Memo, Maurizio; Uberti, Daniela

    2017-01-01

    Recently, the role of food and nutrition in preventing or delaying chronic disability in the elderly population has received great attention. Thanks to their ability to influence biochemical and biological processes, bioactive nutrients are considered modifiable factors capable of preserving a healthy brain status. A diet rich in vitamins and polyphenols and poor in saturated fatty acids has been recommended. In the prospective of a healthy diet, cooking methods should be also considered. In fact, cooking procedures can modify the original dietary content, contributing not only to the loss of healthy nutrients, but also to the formation of toxins, including advanced glycation end products (AGEs). These harmful compounds are adsorbed at intestinal levels and can contribute to the ageing process. The accumulation of AGEs in ageing ("AGE-ing") is further involved in the exacerbation of neurodegenerative and many other chronic diseases. In this review, we discuss food's dual role as both source of bioactive nutrients and reservoir for potential toxic compounds-paying particular attention to the importance of proper nutrition in preventing/delaying Alzheimer's disease. In addition, we focus on the importance of a good education in processing food in order to benefit from the nutritional properties of an optimal diet.

  9. 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.

  10. Nutrition and AGE-ing: Focusing on Alzheimer's Disease

    PubMed Central

    Marziano, Mariagrazia; Rungratanawanich, Wiramon; Memo, Maurizio

    2017-01-01

    Recently, the role of food and nutrition in preventing or delaying chronic disability in the elderly population has received great attention. Thanks to their ability to influence biochemical and biological processes, bioactive nutrients are considered modifiable factors capable of preserving a healthy brain status. A diet rich in vitamins and polyphenols and poor in saturated fatty acids has been recommended. In the prospective of a healthy diet, cooking methods should be also considered. In fact, cooking procedures can modify the original dietary content, contributing not only to the loss of healthy nutrients, but also to the formation of toxins, including advanced glycation end products (AGEs). These harmful compounds are adsorbed at intestinal levels and can contribute to the ageing process. The accumulation of AGEs in ageing (“AGE-ing”) is further involved in the exacerbation of neurodegenerative and many other chronic diseases. In this review, we discuss food's dual role as both source of bioactive nutrients and reservoir for potential toxic compounds—paying particular attention to the importance of proper nutrition in preventing/delaying Alzheimer's disease. In addition, we focus on the importance of a good education in processing food in order to benefit from the nutritional properties of an optimal diet. PMID:28168012

  11. Seasonal changes in circadian peripheral plasma concentrations of melatonin, serotonin, dopamine and cortisol in aged horses with Cushing's disease under natural photoperiod.

    PubMed

    Haritou, S J A; Zylstra, R; Ralli, C; Turner, S; Tortonese, D J

    2008-08-01

    Equine pituitary pars intermedia dysfunction (PPID) is a common and serious condition that gives rise to Cushing's disease. In the older horse, it results in hyperadrenocorticism and disrupted energy metabolism, the severity of which varies with the time of year. To gain insight into the mechanism of its pathogenesis, 24-h profiles for peripheral plasma melatonin, serotonin, dopamine and cortisol concentrations were determined at the winter and summer solstices, and the autumn and spring equinoxes in six horses diagnosed with Cushing's disease and six matched controls. The nocturnal rises in plasma melatonin concentrations, although different across seasons, were broadly of the same duration and similar amplitude in both groups of animals (P > 0.05). The plasma concentrations of cortisol did not show seasonal variation and were different in diseased horses only in the summer when they were higher across the entire 24-h period (P < 0.05). Serotonin concentrations were not significantly affected by time of year but tended to be lower in Cushingoid horses (P = 0.07). By contrast, dopamine output showed seasonal variation and was significantly lower in the Cushing's group in the summer and autumn (P < 0.05). The finding that the profiles of circulating melatonin are similar in Cushingoid and control horses reveals that the inability to read time of year by animals suffering from Cushing's syndrome is an unlikely reason for the disease. In addition, the results provide evidence that alterations in the dopaminergic and serotoninergic systems may participate in the pathogenesis of PPID.

  12. Seasonal Changes in Circadian Peripheral Plasma Concentrations of Melatonin, Serotonin, Dopamine and Cortisol in Aged Horses with Cushing’s Disease under Natural Photoperiod

    PubMed Central

    Haritou, S J A; Zylstra, R; Ralli, C; Turner, S; Tortonese, D J

    2008-01-01

    Equine pituitary pars intermedia dysfunction (PPID) is a common and serious condition that gives rise to Cushing’s disease. In the older horse, it results in hyperadrenocorticism and disrupted energy metabolism, the severity of which varies with the time of year. To gain insight into the mechanism of its pathogenesis, 24-h profiles for peripheral plasma melatonin, serotonin, dopamine and cortisol concentrations were determined at the winter and summer solstices, and the autumn and spring equinoxes in six horses diagnosed with Cushing’s disease and six matched controls. The nocturnal rises in plasma melatonin concentrations, although different across seasons, were broadly of the same duration and similar amplitude in both groups of animals (P > 0.05). The plasma concentrations of cortisol did not show seasonal variation and were different in diseased horses only in the summer when they were higher across the entire 24-h period (P < 0.05). Serotonin concentrations were not significantly affected by time of year but tended to be lower in Cushingoid horses (P = 0.07). By contrast, dopamine output showed seasonal variation and was significantly lower in the Cushing’s group in the summer and autumn (P < 0.05). The finding that the profiles of circulating melatonin are similar in Cushingoid and control horses reveals that the inability to read time of year by animals suffering from Cushing’s syndrome is an unlikely reason for the disease. In addition, the results provide evidence that alterations in the dopaminergic and serotoninergic systems may participate in the pathogenesis of PPID. PMID:18540997

  13. Introduction to Aging, Cancer, and Age-related Diseases.

    PubMed

    Perry, Daniel P

    2010-06-01

    A rising tide of chronic age-dependent diseases, co-morbidities, and geriatric syndromes--a veritable Silver Tsunami--will soon present serious challenges for North America, Europe, Japan, and other industrialized nations. Meanwhile, a growing number of scientists, led by biogerontologists, maintain that the key to blunting the societal impact of large-scale decline and disability among older populations lies with better understanding and potential manipulation of biological mechanisms of aging itself. Well-characterized interventions that slow aging and extend health and vigor in animal models may be forerunners of technologies that preserve additional years of healthy productive life in humans. What will it take to validate these momentous insights from biogerontology and their potential applications for human populations? What are the points of resistance for key opinion leaders and policy makers? And how can biogerontologists make common cause with those outside the discipline to inform larger and more politically powerful audiences?

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

    PubMed Central

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

    2015-01-01

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

  15. Pathophysiology of age-related diseases

    PubMed Central

    Campisi, Giuseppina; Chiappelli, Martina; De Martinis, Massimo; Franco, Vito; Ginaldi, Lia; Guiglia, Rosario; Licastro, Federico; Lio, Domenico

    2009-01-01

    A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy on 7-8 April 2009. Three lectures from that Symposium by G. Campisi, L. Ginaldi and F. Licastro are here summarized. Ageing is a complex process which negatively impacts on the development of various bodily systems and its ability to function. A long life in a healthy, vigorous, youthful body has always been one of humanity's greatest dreams. Thus, a better understanding of the pathophysiology of age-related diseases is urgently required to improve our understanding of maintaining good health in the elderly and to program possible therapeutic intervention. PMID:19737378

  16. Aging and endothelin: determinants of disease.

    PubMed

    Barton, Matthias

    2014-11-24

    Since the beginning of the 20th century human life expectancy has doubled to more than 80 years, and growth and aging of the world population now represent major challenges for healthcare providers, political decision makers, and societies. Cellular senescence is associated with a general, pro-inflammatory state, which represents the common denominator between aging and chronic diseases and their progression. Approaches to interfere with these changes and to allow healthy aging involve modulation of the cellular activity of modifiable molecular mediators (MMMs), such as signaling molecules and growth factors. ET-1 - the biologically predominant member of the endothelin peptide family - is an endothelial cell-derived peptide with a wide variety of developmental and physiological functions, which include embryogenesis, nociception, and natriuresis. In addition, ET-1 is a cytokine-like, multifunctional peptide with pro-inflammatory, mitogenic, and vasoconstrictor properties. If produced in excess amounts ET-1 promotes disease - mainly via activation of its ETA receptor. Because of its multiple disease-promoting functions ET-1 represents an ideal target MMM. Preclinical studies targeting either activity or production of ET-1 - utilizing ERAs, ARBs, or ACEIs, respectively - have demonstrated that partial regression of aging-associated changes in vasculature and kidney is possible. In this article I will review the molecular regulation of ET-1 and its role in the physiology of vascular homeostasis, aging, and cellular senescence. The clinical implications of activators of ET-1 overproduction, modalities for delaying or reversing aging-related cellular changes, as well as interventions to promote healthy aging and early disease prevention - particularly physical activity - are discussed.

  17. 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

  18. 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

  19. 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.

  20. Chronic kidney Disease and the Aging Population.

    PubMed

    Tonelli, Marcello; Riellae, Miguel

    2014-01-01

    Youth, which is forgiven everything, forgives itself nothing: age, which forgives itself everything, is forgiven nothing. George Bernard Shaw The proportion of older people in the general population is steadily increasing worldwide, with the most rapid growth in low-and middle-income countries [1]. This demographic change is to be celebrated, because it is the consequence of socioeconomic development and better life expectancy. However, population aging also has important implications for society - in diverse areas including health systems, labor markets, public policy, social programs, and family dynamics [2]. A successful response to the aging population will require capitalizing on the opportunities that this transition offers, as well as effectively addressing its challenges. Chronic kidney disease (CKD) is an important public health problem that is characterized by poor health outcomes and very high health care costs. CKD is a major risk multiplier in patients with diabetes, hypertension, heart disease and stroke - all of which are key causes of death and disability in older people [3]. Since the prevalence of CKD is higher in older people, the health impact of population aging will depend in part on how the kidney community responds. March 13, 2014 will mark the celebration of the 9th World Kidney Day (WKD), an annual event jointly sponsored by the International Society of Nephrology and the International Federation of Kidney Foundations. Since its inception in 2006, WKD has become the most successful effort to raise awareness among policymakers and the general public about the importance of kidney disease. The topic for WKD 2014 is "CKD in older people". This article reviews the key links between kidney function, age, health and illness - and discusses the implications of the aging population for the care of people with CKD.

  1. Life stress, glucocorticoid signaling, and the aging epigenome: Implications for aging-related diseases.

    PubMed

    Gassen, Nils C; Chrousos, George P; Binder, Elisabeth B; Zannas, Anthony S

    2017-03-01

    Life stress has been associated with accelerated cellular aging and increased risk for developing aging-related diseases; however, the underlying molecular mechanisms remain elusive. A highly relevant process that may underlie this association is epigenetic regulation. In this review, we build upon existing evidence to propose a model whereby exposure to life stress, in part via its effects on the hypothalamic-pituitary axis and the glucocorticoid signaling system, may alter the epigenetic landscape across the lifespan and, consequently, influence genomic regulation and function in ways that are conducive to the development of aging-related diseases. This model is supported by recent studies showing that life stressors and stress-related phenotypes can accelerate epigenetic aging, a measure that is based on DNA methylation prediction of chronological age and has been associated with several aging-related disease phenotypes. We discuss the implications of this model for the prevention and treatment of aging-related diseases, as well as the challenges and limitations of this line of research.

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

    PubMed Central

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

    2016-01-01

    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 have profound social and economic costs. Population aging also reveals an opportunity; that is, 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 healthy lifespan, or healthspan. 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 the 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

  3. 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.

  4. 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

  5. Breast cancer under age 40: a different approach.

    PubMed

    Ribnikar, D; Ribeiro, J M; Pinto, D; Sousa, B; Pinto, A C; Gomes, E; Moser, E C; Cardoso, M J; Cardoso, F

    2015-04-01

    Breast cancer (BC) under age 40 is a complex disease to manage due to the additionally fertility-related factors to be taken in consideration. More than 90% of young patients with BC are symptomatic. Women<40 years are more likely to develop BC with worse clinicopathological features and more aggressive subtype. This has been frequently associated with inferior outcomes. Recently, the prognostic significance of age<40 has been shown to differ according to the BC subtype, being associated with worst recurrence-free survival (RFS) and overall survival (OS) for luminal BC. The biology of BC<40 has also been explored through analysis of large genomic data set, and specific pathways overexpressed in these tumors have been identified which can lead to the development of targeted therapy in the future. A multidisciplinary tumor board should determine the optimal locoregional and systemic management strategies for every individual patient with BC before the start of any therapy including surgery. This applies to both early (early breast cancer (EBC)) and advanced (advanced breast cancer (ABC)) disease, before the start of any therapy. Mastectomy even in young patients confers no overall survival advantage when compared to breast-conserving treatment (BCT), followed by radiotherapy. Regarding axillary approach, indications are identical to other age groups. Young age is one of the most important risk factors for local recurrence after both breast-conserving surgery (BCS) and mastectomy, associated with a higher risk of distant metastasis and death. Radiation after BCS reduces local recurrence from 19.5 to 10.2% in BC patients 40 years and younger. The indications for and the choice of systemic treatment for invasive BC (both early and advanced disease) should not be based on age alone but driven by the biological characteristics of the individual tumor (including hormone receptor status, human epidermal growth factor receptor 2 (HER-2) status, grade, and proliferative

  6. Geriatric surgery is about disease, not age

    PubMed Central

    Preston, Stephen D; Southall, Ashley RD; Nel, Mark; Das, Saroj K

    2008-01-01

    Summary Maintaining life span and quality of life remains a valid aim of surgery in elderly people. Surgery can be an effective way of restoring both length and quality of life to older people. Minimally invasive techniques and surgery under local anaesthesia make fewer demands on geriatric physiology; given that co-morbidity is a stronger predictor of outcome from surgery than age, this is a significant consideration. PMID:18687864

  7. Cellular Regulation of Amyloid Formation in Aging and Disease

    PubMed Central

    Stroo, Esther; Koopman, Mandy; Nollen, Ellen A. A.; Mata-Cabana, Alejandro

    2017-01-01

    As the population is aging, the incidence of age-related neurodegenerative diseases, such as Alzheimer and Parkinson disease, is growing. The pathology of neurodegenerative diseases is characterized by the presence of protein aggregates of disease specific proteins in the brain of patients. Under certain conditions these disease proteins can undergo structural rearrangements resulting in misfolded proteins that can lead to the formation of aggregates with a fibrillar amyloid-like structure. Cells have different mechanisms to deal with this protein aggregation, where the molecular chaperone machinery constitutes the first line of defense against misfolded proteins. Proteins that cannot be refolded are subjected to degradation and compartmentalization processes. Amyloid formation has traditionally been described as responsible for the proteotoxicity associated with different neurodegenerative disorders. Several mechanisms have been suggested to explain such toxicity, including the sequestration of key proteins and the overload of the protein quality control system. Here, we review different aspects of the involvement of amyloid-forming proteins in disease, mechanisms of toxicity, structural features, and biological functions of amyloids, as well as the cellular mechanisms that modulate and regulate protein aggregation, including the presence of enhancers and suppressors of aggregation, and how aging impacts the functioning of these mechanisms, with special attention to the molecular chaperones. PMID:28261044

  8. Chronic depression as a model disease for cerebral aging.

    PubMed

    Bewernick, Bettina H; Schlaepfer, Thomas E

    2013-03-01

    Conceptualizations of the underlying neurobiology of major depression have changed their focus from dysfunctions of neurotransmission to dysfunctions of neurogenesis and neuroprotection. The "neurogenesis hypothesis of depression" posits that changes in the rate of neurogenesis are the underlying mechanism in the pathology and treatment of major depression. Stress, neuroinflammation, dysfunctional insulin regulation, oxidative stress, and alterations in neurotrophic factors possibly contribute to the development of depression. The influence of antidepressant therapies, namely pharmacotherapy and neuroprotectants, on cellular plasticity are summarized. A dysfunction of complex neuronal networks as a consequence of neural degeneration in neuropsychiatric diseases has led to the application of deep brain stimulation. We discuss the way depression seen in the light of the neurogenesis hypothesis can be used as a model disease for cerebral aging. A common pathological mechanism in depression and cerebral aging-a dysfunction of neuroprotection and neurogenesis-is discussed. This has implications for new treatment methods.

  9. 20 CFR 404.1038 - Domestic employees under age 18.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Domestic employees under age 18. 404.1038 Section 404.1038 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... from Employment § 404.1038 Domestic employees under age 18. Domestic services you perform in a...

  10. 20 CFR 404.1038 - Domestic employees under age 18.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Domestic employees under age 18. 404.1038 Section 404.1038 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... from Employment § 404.1038 Domestic employees under age 18. Domestic services you perform in a...

  11. 20 CFR 404.1038 - Domestic employees under age 18.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Domestic employees under age 18. 404.1038 Section 404.1038 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... from Employment § 404.1038 Domestic employees under age 18. Domestic services you perform in a...

  12. 20 CFR 404.1038 - Domestic employees under age 18.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Domestic employees under age 18. 404.1038 Section 404.1038 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... from Employment § 404.1038 Domestic employees under age 18. Domestic services you perform in a...

  13. 20 CFR 404.1038 - Domestic employees under age 18.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Domestic employees under age 18. 404.1038 Section 404.1038 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... from Employment § 404.1038 Domestic employees under age 18. Domestic services you perform in a...

  14. Age, dental infections, and coronary heart disease.

    PubMed

    Mattila, K J; Asikainen, S; Wolf, J; Jousimies-Somer, H; Valtonen, V; Nieminen, M

    2000-02-01

    Epidemiological and intervention studies have suggested that infections are risk factors for coronary heart disease (CHD). Dental infections have appeared as cardiovascular risk factors in cross-sectional and in follow-up studies, and the association has been independent of the "classic" coronary risk factors. This case-control study aimed at detailed assessment of the dental pathology found in various CHD categories (including elderly patients). Altogether, 85 patients with proven coronary heart disease and 53 random controls, matched for sex, age, geographic area, and socio-economic status, were compared with regard to dental status, assessed blindly with four separate scores, and to the "classic" coronary risk factors (seven of the controls had CHD, and they were not included in the analyses). The dental indices were higher among CHD patients than in the controls, but, contrary to previous studies, the differences were not significant (between the CHD patients and their matched controls or among the different CHD categories). This result could not be explained by potential confounding factors. The participants in the present study were older and had more often undergone recent dental treatment in comparison with subjects in our earlier studies. Age correlated with the severity of dental infections only in the random controls but not in the coronary patients who, although young, already had high dental scores. We believe that the higher age of the participants in the present study is the most likely reason for the results. Other possible explanations include an age-related selection bias among older CHD patients, and the fact that those participating in studies like this may have better general health and thus also less severe dental infections. Thus, the role of dental infections as a coronary risk factor varies according to the characteristics of the population studied.

  15. 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

  16. 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

  17. The role of macroautophagy in the ageing process, anti-ageing intervention and age-associated diseases.

    PubMed

    Bergamini, E; Cavallini, G; Donati, A; Gori, Z

    2004-12-01

    Macroautophagy is a degradation/recycling system ubiquitous in eukariotic cells, which generates nutrients during fasting under the control of amino acids and hormones, and contributes to the turnover and rejuvenation of cellular components (long-lived proteins, cytomembranes and organelles). Tight coupling between these two functions may be the weak point in cell housekeeping. Ageing denotes a post-maturational deterioration of tissues and organs with the passage of time, due to the progressive accumulation of the misfunctioning cell components because of oxidative damage and an age-dependent decline of turnover rate and housekeeping. Caloric restriction (CR) and lower insulin levels may slow down many age-dependent processes and extend lifespan. Recent evidence is reviewed showing that autophagy is involved in ageing and in the anti-ageing action of anti-ageing calorie restriction: function of autophagy declines during adulthood and is almost negligible at older age; CR prevents the age-dependent decline of autophagic proteolysis and improves the sensitivity of liver cells to stimulation of lysosomal degradation; protection of autophagic proteolysis from the age-related decline co-varies with the duration and level of anti-ageing food restriction like the effects of CR extending lifespan; the pharmacological stimulation of macroautophagy has anti-ageing effects. Besides the involvement in ageing, macroautophagy may have an essential role in the pathogenesis of many age-associated diseases. Higher protein turnover may not fully account for the anti-ageing effects of macroautophagy, and effects of macroautophagy on housekeeping of the cell organelles, antioxidant machinery of cell membranes and transmembrane cell signaling should also be considered.

  18. Sirtuins and renal diseases: relationship with aging and diabetic nephropathy.

    PubMed

    Kitada, Munehiro; Kume, Shinji; Takeda-Watanabe, Ai; Kanasaki, Keizo; Koya, Daisuke

    2013-02-01

    Sirtuins are members of the Sir2 (silent information regulator 2) family, a group of class III deacetylases. Mammals have seven different sirtuins, SIRT1-SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules. SIRT1 has been the most extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. SIRT1 deficiency under various stress conditions, such as metabolic or oxidative stress or hypoxia, is implicated in the pathophysiologies of age-related diseases including diabetes, cardiovascular diseases, neurodegenerative disorders and renal diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation and fibrosis, and may regulate lipid metabolism, autophagy, blood pressure and sodium balance. Therefore the activation of SIRT1 in the kidney may be a new therapeutic target to increase resistance to many causal factors in the development of renal diseases, including diabetic nephropathy. In addition, SIRT3 and SIRT6 are implicated in age-related disorders or longevity. In the present review, we discuss the protective functions of sirtuins and the association of sirtuins with the pathophysiology of renal diseases, including diabetic nephropathy.

  19. 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

  20. 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.

  1. The aged gut in inflammatory bowel diseases.

    PubMed

    Ardesia, M; Villanacci, V; Fries, W

    2015-12-01

    Senescence is accompanied by various anatomical and functional alterations starting from mastication and deglutition and consequent modifications of nutrition. In addition, the widespread use of proton pump inhibitors and non-steroidal anti-inflammatory drugs in aged subjects weakens the gastric barrier, thus contributing to easier entry of microbes into the gastrointestinal tract. The microbiota of the elderly is less stable than that of younger adults, therefore, gut dysbiosis is more frequent. Dysbiosis represents a key factor for infections, e.g. Clostridium difficile, especially after antibiotic treatment, but also represents an important step for the development of inflammatory bowel diseases (IBD). IBD onset in the elderly needs careful evaluation in order to distinguish this entity from other pathologies that may affect the gut in senescence. Colitis associated with diverticula, drug-induced, ischemic, and microscopic colitides are among the possible diseases and, therefore, a careful macroscopic and histologic evaluation is mandatory. Finally, late onset IBD represents an important challenge for physicians since it occurs in subjects with frequent comorbidities and relative concomitant treatments. Although there is some evidence that disease course of elderly-onset IBD follows a milder course, overall morbidity, hospitalization rates and even mortality, the latter mostly due to comorbidities, are increased, especially in emergency settings.

  2. Motives and methods of under-age casino gamblers.

    PubMed

    Giacopassi, David; Stitt, B Grant; Nichols, Mark

    2006-12-01

    Numerous studies have documented that under-age gambling is quite common. The present study employs interviews of 48 university students who gambled under-age to determine the motives and methods associated with casino gambling by minors. The information gathered in these interviews indicates that access to casinos is easily attained, that the risk of exposure once gambling is minimal, and the motivations of under-age gamblers differ in important ways from that of adults, as access to alcohol, accompanying parents, and the desire to experience the "forbidden fruit" of casino gambling are commonly mentioned motivations by under-age gamblers.

  3. 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.

  4. Control of mitochondrial integrity in ageing and disease.

    PubMed

    Szklarczyk, Radek; Nooteboom, Marco; Osiewacz, Heinz D

    2014-07-05

    Various molecular and cellular pathways are active in eukaryotes to control the quality and integrity of mitochondria. These pathways are involved in keeping a 'healthy' population of this essential organelle during the lifetime of the organism. Quality control (QC) systems counteract processes that lead to organellar dysfunction manifesting as degenerative diseases and ageing. We discuss disease- and ageing-related pathways involved in mitochondrial QC: mtDNA repair and reorganization, regeneration of oxidized amino acids, refolding and degradation of severely damaged proteins, degradation of whole mitochondria by mitophagy and finally programmed cell death. The control of the integrity of mtDNA and regulation of its expression is essential to remodel single proteins as well as mitochondrial complexes that determine mitochondrial functions. The redundancy of components, such as proteases, and the hierarchies of the QC raise questions about crosstalk between systems and their precise regulation. The understanding of the underlying mechanisms on the genomic, proteomic, organellar and cellular levels holds the key for the development of interventions for mitochondrial dysfunctions, degenerative processes, ageing and age-related diseases resulting from impairments of mitochondria.

  5. Age and diagnostic performance of Alzheimer disease CSF biomarkers

    PubMed Central

    Rosén, E.; Hansson, O.; Andreasen, N.; Parnetti, L.; Jonsson, M.; Herukka, S.-K.; van der Flier, W.M.; Blankenstein, M.A.; Ewers, M.; Rich, K.; Kaiser, E.; Verbeek, M.M.; Olde Rikkert, M.; Tsolaki, M.; Mulugeta, E.; Aarsland, D.; Visser, P.J.; Schröder, J.; Marcusson, J.; de Leon, M.; Hampel, H.; Scheltens, P.; Wallin, A.; Eriksdotter-Jönhagen, M.; Minthon, L.; Winblad, B.; Blennow, K.; Zetterberg, H.

    2012-01-01

    Objectives: Core CSF changes in Alzheimer disease (AD) are decreased amyloid β1–42, increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly. Methods: We investigated effects of age on the diagnostic performance of CSF biomarkers in a uniquely large multicenter study population, including a cross-sectional cohort of 529 patients with AD dementia (median age 71, range 43–89 years) and 304 controls (67, 44–91 years), and a longitudinal cohort of 750 subjects without dementia with mild cognitive impairment (69, 43–89 years) followed for at least 2 years, or until dementia diagnosis. Results: The specificities for subjects without AD and the areas under the receiver operating characteristics curves decreased with age. However, the positive predictive value for a combination of biomarkers remained stable, while the negative predictive value decreased only slightly in old subjects, as an effect of the high AD prevalence in older ages. Conclusion: Although the diagnostic accuracies for AD decreased with age, the predictive values for a combination of biomarkers remained essentially stable. The findings highlight biomarker variability across ages, but support the use of CSF biomarkers for AD even in older populations. PMID:22302554

  6. Differential Effects of Aging on Processes Underlying Task Switching

    ERIC Educational Resources Information Center

    West, Robert; Travers, Stephanie

    2008-01-01

    In this study, we used event-related brain potentials (ERPs) to examine the effects of aging on processes underlying task switching. The response time data revealed an age-related increase in mixing costs before controlling for general slowing and no effect of aging on switching costs. In the cue-locked epoch, the ERP data revealed little effect…

  7. 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

  8. 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.

  9. Genetic evidence for common pathways in human age-related diseases

    PubMed Central

    Johnson, Simon C; Dong, Xiao; Vijg, Jan; Suh, Yousin

    2015-01-01

    Aging is the single largest risk factor for chronic disease. Studies in model organisms have identified conserved pathways that modulate aging rate and the onset and progression of multiple age-related diseases, suggesting that common pathways of aging may influence age-related diseases in humans as well. To determine whether there is genetic evidence supporting the notion of common pathways underlying age-related diseases, we analyzed the genes and pathways found to be associated with five major categories of age-related disease using a total of 410 genomewide association studies (GWAS). While only a small number of genes are shared among all five disease categories, those found in at least three of the five major age-related disease categories are highly enriched for apoliprotein metabolism genes. We found that a more substantial number of gene ontology (GO) terms are shared among the 5 age-related disease categories and shared GO terms include canonical aging pathways identified in model organisms, such as nutrient-sensing signaling, translation, proteostasis, stress responses, and genome maintenance. Taking advantage of the vast amount of genetic data from the GWAS, our findings provide the first direct evidence that conserved pathways of aging simultaneously influence multiple age-related diseases in humans as has been demonstrated in model organisms. PMID:26077337

  10. Validation of anti-aging drugs by treating age-related diseases.

    PubMed

    Blagosklonny, Mikhail V

    2009-03-28

    Humans die from age-related diseases, which are deadly manifestations of the aging process. In order to extend life span, an anti-aging drug must delay age-related diseases. All together age-related diseases are the best biomarker of aging. Once a drug is used for treatment of any one chronic disease, its effect against other diseases (atherosclerosis, cancer, prostate enlargement, osteoporosis, insulin resistance, Alzheimer's and Parkinson's diseases, age-related macular degeneration) may be evaluated in the same group of patients. If the group is large, then the anti-aging effect could be validated in a couple of years. Startlingly, retrospective analysis of clinical and preclinical data reveals four potential anti-aging modalities.

  11. 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.

  12. Huntington's Disease: Nuclear Gatekeepers Under Attack.

    PubMed

    Veldman, Matthew B; Yang, X William

    2017-04-05

    In this issue of Neuron, Gasset-Rosa et al. (2017) and Grima et al. (2017) describe defects in the nuclear pore complex and impaired nucleocytoplasmic transport in Huntington's disease (HD). The findings suggest that erosion of nuclear gatekeeping function, which is found in normal brain aging, may play an important role in the pathogenesis of multiple neurodegenerative disorders, including HD.

  13. [Pregnancy in patients with underlying renal disease].

    PubMed

    Golshayan, D; Mathieu, C; Burnier, M

    2007-03-07

    Pregnancy has generally been regarded as very high risk in women with chronic renal insufficiency. In this review, we describe the physiologic changes in systemic and renal haemodynamics during pregnancy, as well as the nature and severity of possible maternal and foetal complications in the setting of underlying renal disease. The risks are proportional to the degree of functional renal impairment, the presence or not of proteinuria and/or arterial hypertension at the time of conception, and are related to the type of underlying nephropathy or systemic disease in the mother. Furthermore, if the renal disease has been diagnosed before pregnancy, a better planning of the moment of conception, as well as a tight follow-up, allow for a better maternal and obstetrical outcome.

  14. 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.

  15. [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.

  16. Aging is not a disease: distinguishing age-related macular degeneration from aging.

    PubMed

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-11-01

    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.

  17. 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

  18. 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)

  19. 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

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

    PubMed

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

    2015-08-17

    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.

  1. Regulation of muscle atrophy in aging and disease.

    PubMed

    Vinciguerra, Manlio; Musaro, Antonio; Rosenthal, Nadia

    2010-01-01

    Muscle aging is characterized by a decline in functional performance and restriction of adaptability, due to progressive loss of muscle tissue coupled with a decrease in strength and force output. Together with selective activation ofapoptotic pathways, a hallmark of age-related muscle loss or sarcopenia is the progressive incapacity of regeneration machinery to replace damaged muscle. These characteristics are shared by pathologies involving muscle wasting, such as muscular dystrophies or amyotrophic lateral sclerosis, cancer and AIDS, all characterized by alterations in metabolic and physiological parameters, progressive weakness in specific muscle groups. Modulation ofextracellular agonists, receptors, protein kinases, intermediate molecules, transcription factors and tissue-specific gene expression collectively compromise the functionality of skeletal muscle tissue, leading to muscle degeneration and persistent protein degradation through activation ofproteolytic systems, such as calpain, ubiquitin-proteasome and caspase. Additional decrements in muscle growth factors compromise skeletal muscle growth, differentiation, survival and regeneration. A better understanding of the mechanisms underlying the pathogenesis of muscle atrophy and wasting associated with different diseases has been the objective of numerous studies and represents an important first step for the development of therapeutic approaches. Among these, insulin-like growth factor-1 (IGF-1) has emerged as a growth factor with a remarkably wide range of actions and a tremendous potential as a therapeutic in attenuating the atrophy and frailty associated with muscle aging and diseases. In this chapter we provide an overview of current concepts in muscle atrophy, focusing specifically on the molecular basis of IGF-1 action and survey current gene and cell therapeutic approaches to rescue muscle atrophy in aging and disease.

  2. Stem cell transplantation improves aging-related diseases

    PubMed Central

    Ikehara, Susumu; Li, Ming

    2014-01-01

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

  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. Impact of pregnancy on underlying renal disease.

    PubMed

    Baylis, Chris

    2003-01-01

    Normal pregnancy involves marked renal vasodilation and large increases in glomerular filtration rate (GFR). Studies in rats reveal that the gestational renal vasodilation is achieved by parallel reductions in tone in afferent and efferent arterioles so GFR rises without a change in glomerular blood pressure. There is some evidence from animal studies that increased renal generation of nitric oxide (NO) may be involved. Although chronic renal vasodilation has been implicated in causing progression of renal disease in nonpregnant states by glomerular hypertension, there are no long-term deleterious effects of pregnancies on the kidney when maternal renal function is normal because glomerular blood pressure remains normal. When maternal renal function is compromised before conception, there are no long-term adverse effects on renal function in most types of renal disease, providing that the GFR is well maintained before conception. When serum creatinine exceeds approximately 1.4 mg/dL, pregnancy may accelerate the renal disease increases and when serum creatinine >2 mg/dL, the chances are greater than 1 in 3 that pregnancy will hasten the progression of the renal disease. The available animal studies suggest that glomerular hypertension does not occur despite diverse injuries. Thus, the mechanisms of the adverse interaction between pregnancy and underlying renal disease remain unknown.

  5. Redefining meaningful age groups in the context of disease.

    PubMed

    Geifman, Nophar; Cohen, Raphael; Rubin, Eitan

    2013-12-01

    Age is an important factor when considering phenotypic changes in health and disease. Currently, the use of age information in medicine is somewhat simplistic, with ages commonly being grouped into a small number of crude ranges reflecting the major stages of development and aging, such as childhood or adolescence. Here, we investigate the possibility of redefining age groups using the recently developed Age-Phenome Knowledge-base (APK) that holds over 35,000 literature-derived entries describing relationships between age and phenotype. Clustering of APK data suggests 13 new, partially overlapping, age groups. The diseases that define these groups suggest that the proposed divisions are biologically meaningful. We further show that the number of different age ranges that should be considered depends on the type of disease being evaluated. This finding was further strengthened by similar results obtained from clinical blood measurement data. The grouping of diseases that share a similar pattern of disease-related reports directly mirrors, in some cases, medical knowledge of disease-age relationships. In other cases, our results may be used to generate new and reasonable hypotheses regarding links between diseases.

  6. Langerhans cell histiocytosis in children under 2 years of age.

    PubMed

    Rivera-Luna, R; Alter-Molchadsky, N; Cardenas-Cardos, R; Martínez-Guerra, G

    1996-05-01

    This is a retrospective study of 55 children under the age of 2 years diagnosed with Langerhans cell histiocytosis (LCH). They were classified according to age and organ function and dysfunction following Lahey's criteria. The studied population was divided into four groups by age of diagnosis (0-6, 7-12, 13-18, and 19-24 months). Statistical analysis showed no significant difference in outcome between age groups, although the population under 6 months had a 81.3% fatality rate. The presence of organ dysfunction was a major cause of death in all age groups, being statistically significant in outcome (P > 0.005) compared with patients without organ dysfunction. The presence of thrombocytopenia and/or respiratory dysfunction was also highly associated with a fatal outcome. In the surviving population, no second malignancies have been reported. The late secondary effects of therapy include endocrine, orofacial, and osseous pathologies.

  7. Cell-Nonautonomous Mechanisms Underlying Cellular and Organismal Aging.

    PubMed

    Medkour, Younes; Svistkova, Veronika; Titorenko, Vladimir I

    2016-01-01

    Cell-autonomous mechanisms underlying cellular and organismal aging in evolutionarily distant eukaryotes have been established; these mechanisms regulate longevity-defining processes within a single eukaryotic cell. Recent findings have provided valuable insight into cell-nonautonomous mechanisms modulating cellular and organismal aging in eukaryotes across phyla; these mechanisms involve a transmission of various longevity factors between different cells, tissues, and organisms. Herein, we review such cell-nonautonomous mechanisms of aging in eukaryotes. We discuss the following: (1) how low molecular weight transmissible longevity factors modulate aging and define longevity of cells in yeast populations cultured in liquid media or on solid surfaces, (2) how communications between proteostasis stress networks operating in neurons and nonneuronal somatic tissues define longevity of the nematode Caenorhabditis elegans by modulating the rates of aging in different tissues, and (3) how different bacterial species colonizing the gut lumen of C. elegans define nematode longevity by modulating the rate of organismal aging.

  8. Blue journal conference. Aging and susceptibility to lung disease.

    PubMed

    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; Budinger, G R Scott

    2015-02-01

    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.

  9. 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)

  10. 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

  11. 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…

  12. 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

  13. Mitochondria and PGC-1α in Aging and Age-Associated Diseases

    PubMed Central

    Wenz, Tina

    2011-01-01

    Aging is the most significant risk factor for a range of degenerative disease such as cardiovascular, neurodegenerative and metabolic disorders. While the cause of aging and its associated diseases is multifactorial, mitochondrial dysfunction has been implicated in the aging process and the onset and progression of age-associated disorders. Recent studies indicate that maintenance of mitochondrial function is beneficial in the prevention or delay of age-associated diseases. A central molecule seems to be the peroxisome proliferator-activated receptor γ coactivator α (PGC-1α), which is the key regulator of mitochondrial biogenesis. Besides regulating mitochondrial function, PGC-1α targets several other cellular processes and thereby influences cell fate on multiple levels. This paper discusses how mitochondrial function and PGC-1α are affected in age-associated diseases and how modulation of PGC-1α might offer a therapeutic potential for age-related pathology. PMID:21629705

  14. Mitochondria and PGC-1α in Aging and Age-Associated Diseases.

    PubMed

    Wenz, Tina

    2011-01-01

    Aging is the most significant risk factor for a range of degenerative disease such as cardiovascular, neurodegenerative and metabolic disorders. While the cause of aging and its associated diseases is multifactorial, mitochondrial dysfunction has been implicated in the aging process and the onset and progression of age-associated disorders. Recent studies indicate that maintenance of mitochondrial function is beneficial in the prevention or delay of age-associated diseases. A central molecule seems to be the peroxisome proliferator-activated receptor γ coactivator α (PGC-1α), which is the key regulator of mitochondrial biogenesis. Besides regulating mitochondrial function, PGC-1α targets several other cellular processes and thereby influences cell fate on multiple levels. This paper discusses how mitochondrial function and PGC-1α are affected in age-associated diseases and how modulation of PGC-1α might offer a therapeutic potential for age-related pathology.

  15. Vaccination against pox diseases under immunosuppressive conditions.

    PubMed

    Mayr, A; Danner, K

    1978-01-01

    Pox diseases, caused either by smallpox virus or zoonotic pox viruses or animals, continue to be of potential danger to a non-vaccinated population. Mass vaccinations will become necessary and will then also be administered to persons with immunological aberrations. The vaccines which are presently used against smallpox cause severe complications in such hosts. In contrast, the attenuated vaccinia virus strain MVA is safe even under the conditions of immunosuppression and is recommended for the production of smallpox vaccines. Because of the special epizootic situations and the numerous immunosuppressive factors present in developing countries, the use of such a safe pox vaccine there is of crucial importance.

  16. Mitochondrial dysfunction underlying outer retinal diseases.

    PubMed

    Lefevere, Evy; Toft-Kehler, Anne Katrine; Vohra, Rupali; Kolko, Miriam; Moons, Lieve; Van Hove, Inge

    2017-03-29

    Dysfunction of photoreceptors, retinal pigment epithelium (RPE) or both contribute to the initiation and progression of several outer retinal disorders. Disrupted Müller glia function might additionally subsidize to these diseases. Mitochondrial malfunctioning is importantly associated with outer retina pathologies, which can be classified as primary and secondary mitochondrial disorders. This review highlights the importance of oxidative stress and mitochondrial DNA damage, underlying outer retinal disorders. Indeed, the metabolically active photoreceptors/RPE are highly prone to these hallmarks of mitochondrial dysfunction, indicating that mitochondria represent a weak link in the antioxidant defenses of outer retinal cells.

  17. Ageing and the border between health and disease.

    PubMed

    MacNee, William; Rabinovich, Roberto A; Choudhury, Gourab

    2014-11-01

    Ageing is associated with a progressive degeneration of the tissues, which has a negative impact on the structure and function of vital organs and is among the most important known risk factors for most chronic diseases. Since the proportion of the world's population aged >60 years will double in the next four decades, this will be accompanied by an increased incidence of chronic age-related diseases that will place a huge burden on healthcare resources. There is increasing evidence that many chronic inflammatory diseases represent an acceleration of the ageing process. Chronic pulmonary diseases represents an important component of the increasingly prevalent multiple chronic debilitating diseases, which are a major cause of morbidity and mortality, particularly in the elderly. The lungs age and it has been suggested that chronic obstructive pulmonary disease (COPD) is a condition of accelerated lung ageing and that ageing may provide a mechanistic link between COPD and many of its extrapulmonary effects and comorbidities. In this article we will describe the physiological changes and mechanisms of ageing, with particular focus on the pulmonary effects of ageing and how these may be relevant to the development of COPD and its major extrapulmonary manifestations.

  18. Applicant Age as a Subjective Employability Factor: A Study of Workers over and under Age Fifty.

    ERIC Educational Resources Information Center

    Forte, Catherine Sabin; Hansvick, Christine L.

    1999-01-01

    Three hundred employers in a suburban area of the Pacific Northwest were surveyed for their perceptions of older (ages 50 and over) and younger (aged 49 and under) workers on 12 attributes. In contrast to previous research, this study found more favorable ratings for older workers overall, including categories such as attendance and salary…

  19. 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.

  20. Between destiny and disease: genetics and molecular pathways of human central nervous system aging

    PubMed Central

    Glorioso, Christin; Sibille, Etienne

    2010-01-01

    Aging of the human brain is associated with “normal” functional, structural, and molecular changes that underlie alterations in cognition, memory, mood and motor function, amongst other processes. Normal aging also imposes a robust constraint on the onset of many neurological diseases, ranging from late onset neurodegenerative diseases, such as Alzheimer’s (AD) and Parkinson’s diseases (PD), to early onset psychiatric disorders, such as bipolar disorder (BPD) and schizophrenia (SCZ). The molecular mechanisms and genetic underpinnings of age-related changes in the brain are understudied, and, while they share some overlap with peripheral mechanisms of aging, many are unique to the largely non-mitotic brain. Hence, understanding mechanisms of brain aging and identifying associated modulators may have profound consequences for the prevention and treatment of age-related impairments and diseases. Here we review current knowledge on age-related functional and structural changes, their molecular and genetic underpinnings, and discuss how these pathways may contribute to the vulnerability to develop age-related neurological diseases. We highlight recent findings from human postmortem brain microarray studies, which we hypothesize, point to a potential genetically-controlled transcriptional program underlying molecular changes and age-gating of neurological diseases. Finally, we discuss the implications of this model for understanding basic mechanisms of brain aging and for the future investigation of therapeutic approaches. PMID:21130140

  1. Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement.

    PubMed

    Candore, G; Caruso, C; Jirillo, E; Magrone, T; Vasto, S

    2010-01-01

    Nowadays, people are living much longer than they used to do, however they are not free from ageing. Ageing, an inexorable intrinsic process that affects all cells, tissues, organs and individuals, is a post-maturational process that, due to a diminished homeostasis and increased organism frailty, causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death. However, the high incidence of death due to infectious, cardiovascular and cancer diseases underlies a common feature in these pathologies that is represented by dysregulation of both instructive and innate immunity. Several studies show that a low-grade systemic inflammation characterizes ageing and that inflammatory markers are significant predictors of mortality in old humans. This pro-inflammatory status of the elderly underlies biological mechanisms responsible for physical function decline and age-related diseases such as Alzheimer's disease and atherosclerosis are initiated or worsened by systemic inflammation. Understanding of the ageing process should have a prominent role in new strategies for extending the health old population. Accordingly, as extensively discussed in the review and in the accompanying related papers, investigating ageing pathophysiology, particularly disentangling age-related low grade inflammation, is likely to provide important clues about how to develop drugs that can slow or delay ageing.

  2. Hearing-Impaired Children under Age 6: 1977 and 1984.

    ERIC Educational Resources Information Center

    Schildroth, Arthur

    1986-01-01

    A review of annual survey data revealed that hearing impaired children under age 6 reported in 1984, when compared to those reported in 1977, tended to be younger; had higher percentages of heredity, meningitis, and prematurity as causes of hearing loss; and were more likely to have additional handicaps. (CL)

  3. [Constrictive pericarditis in children under 2 years of age].

    PubMed

    Silva, Lia; Anjos, Rui; Martins, Fernando Maymone; Telo, Margarida

    2002-01-01

    Two cases of constrictive pericarditis, in children under 2 years of age, of non-tuberculosis aetiology, diagnosed from June 97 to May 98 are reported. This entity is rare in paediatrics and it may progress to severe condition. Surgical treatment has a low risk and is generally associated with good prognosis. Aetiology, clinic presentation, differential diagnosis with restrictive cardiomyopathy and treatment are discussed.

  4. Optimal Dynamic Advertising Strategy Under Age-Specific Market Segmentation

    NASA Astrophysics Data System (ADS)

    Krastev, Vladimir

    2011-12-01

    We consider the model proposed by Faggian and Grosset for determining the advertising efforts and goodwill in the long run of a company under age segmentation of consumers. Reducing this model to optimal control sub problems we find the optimal advertising strategy and goodwill.

  5. Fatty Liver Disease is Associated with Underlying Cardiovascular Disease in HIV-Infected Persons

    PubMed Central

    Crum-Cianflone, Nancy; Krause, David; Wessman, Dylan; Medina, Sheila; Stepenosky, James; Brandt, Carolyn; Boswell, Gilbert

    2010-01-01

    Background Cardiovascular disease is an increasing concern among HIV-infected persons and their providers. We determined if fatty liver disease is a marker for underlying coronary atherosclerosis among HIV-infected persons. Methods We performed a cross-sectional study among HIV-infected adults to evaluate the prevalence of and factors, including fatty liver disease, associated with subclinical coronary atherosclerosis. All participants underwent computed tomography for determination of coronary artery calcium (CAC; positive defined as a score >0) and fatty liver disease (defined as a liver-to-spleen ratio <1.0). Factors associated with CAC were determined using multivariate logistic regression models. Results We studied 223 HIV-infected adults with a median age of 43 years (IQR 36–50), 96% were male, and 49% were Caucasian. Median CD4 count was 586 cells/mm3, and 83% were receiving antiretroviral medications. Seventy-five (34%) had a positive CAC score, and 29 (13%) subjects had fatty liver disease. Among those with CAC scores of 0, 1–100, >100, the percentage with concurrent fatty liver disease was 8%, 18%, and 41%, respectively (p=0.001). In the multivariate model, CAC was associated with increasing age (OR 4.3 per 10 years, p<0.01), hypertension (OR 2.6, p<0.01), and fatty liver disease (OR 3.8, p<0.01). Conclusions Coronary atherosclerosis as detected by CAC is prevalent among young HIV-infected persons. The detection of fatty liver disease among HIV-infected adults should prompt consideration for assessment for underlying cardiovascular disease and risk factor reduction. PMID:21251186

  6. Iron and copper toxicity in diseases of aging, particularly atherosclerosis and Alzheimer's disease.

    PubMed

    Brewer, George J

    2007-02-01

    In this review, we point out that natural selection does not act to lessen human diseases after the reproductive and caregiving period and that normal levels of iron and copper that may be healthy during the reproductive years appear to be contributing to diseases of aging and possibly the aging process itself. It is clear that oxidant damage contributes to many of the diseases of aging, such as atherosclerosis, Alzheimer's disease, Parkinson's diseases, diabetes, diseases of inflammation, diseases of fibrosis, diseases of autoimmunity, and so on. It is equally clear that both iron and copper can contribute to excess production of damaging reactive oxygen species through Fenton chemistry. Here, we examine the evidence that "normal" levels of iron and copper contribute to various diseases of aging.

  7. Aging and age-related diseases--from endocrine therapy to target therapy.

    PubMed

    Bao, Qi; Pan, Jie; Qi, Hangfei; Wang, Lu; Qian, Huan; Jiang, Fangzhen; Shao, Zheren; Xu, Fengzhi; Tao, Zhiping; Ma, Qi; Nelson, Peter; Hu, Xueqing

    2014-08-25

    Aging represents an important health issue not only for the individual, but also for society in general. Burdens associated with aging are expanding as longevity increases. This has led to an enhanced focus on issues related to aging and age-related diseases. Until recently, anti-aging endocrine-therapy has been largely limited to hormone-replacement therapy (HRT) that is associated with multiple side effects, including an increased risk of cancer. This has greatly limited the application of HRT in anti-aging therapy. Recently, the focus of anti-aging research has expanded from endocrine signaling pathways to effects on regulatory gene networks. In this regard, the GHRH-GH-IGF-1/Insulin, TOR-S6K1,NAD(+)-Sirtuin, P53, Klotho and APOE pathways have been linked to processes associated with age-related diseases, including cancer, cardiovascular disease, diabetes, osteoporosis, and neurodegenerative diseases, all of which directly influence health in aging, and represent key targets in anti-aging therapy.

  8. Health- and Disease-Related Biomarkers in Aging Research

    PubMed Central

    Thompson, Hilaire J.; Voss, Joachim G.

    2011-01-01

    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

  9. Aging Is Not a Disease: Implications for Intervention

    PubMed Central

    Rattan, Suresh I. S.

    2014-01-01

    Aging of biological systems occurs in spite of numerous complex pathways of maintenance, repair and defense. There are no gerontogenes which have the specific evolutionary function to cause aging. Although aging is the common cause of all age-related diseases, aging in itself cannot be considered a disease. This understanding of aging as a process should transform our approach towards interventions from developing illusory anti-aging treatments to developing realistic and practical methods for maintaining health throughout the lifespan. The concept of homeodynamic space can be a useful one in order to identify a set of measurable, evidence-based and demonstratable parameters of health, robustness and resilience. Age-induced health problems, for which there are no other clear-cut causative agents, may be better tackled by focusing on health mechanisms and their maintenance, rather than only disease management and treatment. Continuing the disease-oriented research and treatment approaches, as opposed to health-oriented and preventive strategies, are economically, socially and psychologically unsustainable. PMID:24900942

  10. Colorectal cancer in patients under 50 years of age: A retrospective analysis of two institutions' experience

    PubMed Central

    Myers, Elizabeth A; Feingold, Daniel L; Forde, Kenneth A; Arnell, Tracey; Jang, Joon Ho; Whelan, Richard L

    2013-01-01

    AIM: To investigate the epidemiological characteristics of colorectal cancer (CRC) in patients under 50 years of age across two institutions. METHODS: Records of patients under age 50 years of age who had CRC surgery over a 16 year period were assessed at two institutions. The following documents where reviewed: admission notes, operative notes, and discharge summaries. The main study variables included: age, presenting symptoms, family history, tumor location, operation, stage/differentiation of disease, and post operative complications. Stage of disease was classified according to the American Joint Committee on Cancer TNM staging system: tumor depth; node status; and metastases. RESULTS: CRC was found in 180 patients under age 50 years (87 females, 93 males; mean age 41.4 ± 6.2 years). Young patients accounted for 11.2% of cases during a 6 year period for which the full data set was available. Eight percent had a 1st degree and 12% a 2nd degree family CRC history. Almost all patients (94%) were symptomatic at diagnosis; common symptoms included: bleeding (59%), obstruction (9%), and abdominal/rectal pain (35%). Evaluation was often delayed and bleeding frequently attributed to hemorrhoids. Advanced stage CRC (Stage 3 or 4) was noted in 53% of patients. Most tumors were distal to the splenic flexure (77%) and 39% involved the rectum. Most patients (95%) had segmental resections; 6 patients had subtotal/total colectomy. Poorly differentiated tumors were noted in 12% and mucinous lesions in 19% of patients of which most had Stage 3 or 4 disease. Twenty-two patients (13%) developed recurrence and/or progression of disease to date. Three patients (ages 42, 42 and 49 years) went on to develop metachronous primary colon cancers within 3 to 4 years of their initial resection. CONCLUSION: CRC was common in young patients with no family history. Young patients with symptoms merit a timely evaluation to avoid presentation with late stage CRC. PMID:24039357

  11. Increased brain-predicted aging in treated HIV disease

    PubMed Central

    Underwood, Jonathan; Caan, Matthan W.A.; De Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W.N.M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B.L.M.; Winston, Alan; Reiss, Peter; Sharp, David J.

    2017-01-01

    Objective: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. Methods: A large sample of virologically suppressed HIV-positive adults (n = 162, age 45–82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18–90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age − chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. Results: HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (−0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Conclusion: Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. PMID:28258081

  12. Production of Complex Syntax in Normal Aging and Alzheimer's Disease.

    ERIC Educational Resources Information Center

    Bates, Elizabeth; And Others

    1995-01-01

    This study compared the production of complex syntax by 16 older adults diagnosed with probable Alzheimer's disease and 25 age-matched control subjects. It found that although individuals diagnosed with Alzheimer's disease did not produce frank lexical or grammatical errors, they did find it difficult to access the "best fit" between meaning and…

  13. 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

  14. Nutritional Considerations for Healthy Aging and Reduction in Age-Related Chronic Disease.

    PubMed

    Shlisky, Julie; Bloom, David E; Beaudreault, Amy R; Tucker, Katherine L; Keller, Heather H; Freund-Levi, Yvonne; Fielding, Roger A; Cheng, Feon W; Jensen, Gordon L; Wu, Dayong; Meydani, Simin N

    2017-01-01

    A projected doubling in the global population of people aged ≥60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifestyle modification, including diet. However, as adults age they become at risk of "nutritional frailty," which can compromise their ability to meet nutritional requirements at a time when specific nutrient needs may be high. This review highlights the role of nutrition science in promoting healthy aging and in improving the prognosis in cases of age-related diseases. It serves to identify key knowledge gaps and implementation challenges to support adequate nutrition for healthy aging, including applicability of metrics used in body-composition and diet adequacy for older adults and mechanisms to reduce nutritional frailty and to promote diet resilience. This review also discusses management recommendations for several leading chronic conditions common in aging populations, including cognitive decline and dementia, sarcopenia, and compromised immunity to infectious disease. The role of health systems in incorporating nutrition care routinely for those aged ≥60 y and living independently and current actions to address nutritional status before hospitalization and the development of disease are discussed.

  15. NADPH oxidase deficiency underlies dysfunction of aged CD8+ Tregs

    PubMed Central

    Wen, Zhenke; Shimojima, Yasuhiro; Shirai, Tsuyoshi; Li, Yinyin; Ju, Jihang; Yang, Zhen; Tian, Lu; Goronzy, Jörg J.

    2016-01-01

    Immune aging results in progressive loss of both protective immunity and T cell–mediated suppression, thereby conferring susceptibility to a combination of immunodeficiency and chronic inflammatory disease. Here, we determined that older individuals fail to generate immunosuppressive CD8+CCR7+ Tregs, a defect that is even more pronounced in the age-related vasculitic syndrome giant cell arteritis. In young, healthy individuals, CD8+CCR7+ Tregs are localized in T cell zones of secondary lymphoid organs, suppress activation and expansion of CD4 T cells by inhibiting the phosphorylation of membrane-proximal signaling molecules, and effectively inhibit proliferative expansion of CD4 T cells in vitro and in vivo. We identified deficiency of NADPH oxidase 2 (NOX2) as the molecular underpinning of CD8 Treg failure in the older individuals and in patients with giant cell arteritis. CD8 Tregs suppress by releasing exosomes that carry preassembled NOX2 membrane clusters and are taken up by CD4 T cells. Overexpression of NOX2 in aged CD8 Tregs promptly restored suppressive function. Together, our data support NOX2 as a critical component of the suppressive machinery of CD8 Tregs and suggest that repairing NOX2 deficiency in these cells may protect older individuals from tissue-destructive inflammatory disease, such as large-vessel vasculitis. PMID:27088800

  16. 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

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

    PubMed

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

    2015-12-01

    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.

  18. 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.

  19. Performance of bolted closure joint elastomers under cask aging conditions

    SciTech Connect

    Verst, C.; Sindelar, R.; Skidmore, E.; Daugherty, W.

    2015-07-23

    The bolted closure joint of a bare spent fuel cask is susceptible to age-related degradation and potential loss of confinement function under long-term storage conditions. Elastomeric seals, a component of the joint typically used to facilitate leak testing of the primary seal that includes the metallic seal and bolting, is susceptible to degradation over time by several mechanisms, principally via thermo-oxidation, stress-relaxation, and radiolytic degradation under time and temperature condition. Irradiation and thermal exposure testing and evaluation of an ethylene-propylene diene monomer (EPDM) elastomeric seal material similar to that used in the CASTOR® V/21 cask for a matrix of temperature and radiation exposure conditions relevant to the cask extended storage conditions, and development of semiempirical predictive models for loss of sealing force is in progress. A special insert was developed to allow Compressive Stress Relaxation (CSR) measurements before and after the irradiation and/or thermal exposure without unloading the elastomer. A condition of the loss of sealing force for the onset of leakage was suggested. The experimentation and modeling being performed could enable acquisition of extensive coupled aging data as well as an estimation of the timeframe when loss of sealing function under aging (temperature/radiation) conditions may occur.

  20. Review: quantifying mitochondrial dysfunction in complex diseases of aging.

    PubMed

    Horan, Martin P; Pichaud, Nicolas; Ballard, J William O

    2012-10-01

    There is accumulating evidence that mitochondrial respiratory malfunction is associated with aging-associated complex diseases. However, progress in our understanding of these diseases has been hampered by the sensitivity and throughput of systems employed to quantify dysfunction and inherent limitations of the biological systems studied. In this review, we describe and contrast two methodologies that have been developed for measuring mitochondrial function to address the need for improved sensitivity and increased throughput. We then consider the utility of each methodology in studying three biological systems: isolated mitochondria, cultured cells, and cell fibers and tissues. Finally, we discuss the application of each methodology in the study of mitochondrial dysfunction in Alzheimer's disease, type 2 diabetes mellitus, and aging-associated autophagy impairment and mitochondrial malfunction. We conclude that the methodologies are complementary, and researchers may need to examine multiple biological systems to unravel complex diseases of aging.

  1. Neural correlates underlying micrographia in Parkinson's disease.

    PubMed

    Wu, Tao; Zhang, Jiarong; Hallett, Mark; Feng, Tao; Hou, Yanan; Chan, Piu

    2016-01-01

    Micrographia is a common symptom in Parkinson's disease, which manifests as either a consistent or progressive reduction in the size of handwriting or both. Neural correlates underlying micrographia remain unclear. We used functional magnetic resonance imaging to investigate micrographia-related neural activity and connectivity modulations. In addition, the effect of attention and dopaminergic administration on micrographia was examined. We found that consistent micrographia was associated with decreased activity and connectivity in the basal ganglia motor circuit; while progressive micrographia was related to the dysfunction of basal ganglia motor circuit together with disconnections between the rostral supplementary motor area, rostral cingulate motor area and cerebellum. Attention significantly improved both consistent and progressive micrographia, accompanied by recruitment of anterior putamen and dorsolateral prefrontal cortex. Levodopa improved consistent micrographia accompanied by increased activity and connectivity in the basal ganglia motor circuit, but had no effect on progressive micrographia. Our findings suggest that consistent micrographia is related to dysfunction of the basal ganglia motor circuit; while dysfunction of the basal ganglia motor circuit and disconnection between the rostral supplementary motor area, rostral cingulate motor area and cerebellum likely contributes to progressive micrographia. Attention improves both types of micrographia by recruiting additional brain networks. Levodopa improves consistent micrographia by restoring the function of the basal ganglia motor circuit, but does not improve progressive micrographia, probably because of failure to repair the disconnected networks.

  2. 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

  3. 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...

  4. Mitochondrial function and dysfunction in the cell: its relevance to aging and aging-related disease.

    PubMed

    Nicholls, David G

    2002-11-01

    Mitochondria plays a complex multi-factorial role in the cell. In addition to their primary role in ATP generation, the organelles sequester calcium and both generate and detoxify reactive oxygen species. All these functions are intimately inter-linked through the central bioenergetic parameter of the proton electrochemical gradient across the inner mitochondrial membrane. Subtle changes in respiratory chain capacity, substrate supply, glutathione levels, cytoplasmic calcium and membrane potential occur in aging and in conditions predisposing towards neurodegenerative disease. These interactions are incompletely understood and in this review I present an overview of some of the current research in this area, and its possible relevance to aging and aging-related disease.

  5. Neuroimaging of Cerebrovascular Disease in the Aging Brain

    PubMed Central

    Gupta, Ajay; Nair, Sreejit; Schweitzer, Andrew D.; Kishore, Sirish; Johnson, Carl E.; Comunale, Joseph P.; Tsiouris, Apostolos J.; Sanelli, Pina C.

    2012-01-01

    Cerebrovascular disease remains a significant public health burden with its greatest impact on the elderly population. Advances in neuroimaging techniques allow detailed and sophisticated evaluation of many manifestations of cerebrovascular disease in the brain parenchyma as well as in the intracranial and extracranial vasculature. These tools continue to contribute to our understanding of the multifactorial processes that occur in the age-dependent development of cerebrovascular disease. Structural abnormalities related to vascular disease in the brain and vessels have been well characterized with CT and MRI based techniques. We review some of the pathophysiologic mechanisms in the aging brain and cerebral vasculature and the related structural abnormalities detectable on neuroimaging, including evaluation of age-related white matter changes, atherosclerosis of the cerebral vasculature, and cerebral infarction. In addition, newer neuroimaging techniques, such as diffusion tensor imaging, perfusion techniques, and assessment of cerebrovascular reserve, are also reviewed, as these techniques can detect physiologic alterations which complement the morphologic changes that cause cerebrovascular disease in the aging brain.Further investigation of these advanced imaging techniques has potential application to the understanding and diagnosis of cerebrovascular disease in the elderly. PMID:23185721

  6. Temporal evolution of age data under transient pumping conditions

    NASA Astrophysics Data System (ADS)

    Leray, S.; de Dreuzy, J.-R.; Aquilina, L.; Vergnaud-Ayraud, V.; Labasque, T.; Bour, O.; Le Borgne, T.

    2014-04-01

    While most age data derived from tracers have been analyzed in steady-state flow conditions, we determine their temporal evolution when starting a pumping. Our study is based on a model made up of a shallowly dipping aquifer overlain by a less permeable aquitard characteristic of the crystalline aquifer of Plœmeur (Brittany, France). Under a pseudo transient flow assumption (instantaneous shift between two steady-state flow fields), we solve the transport equation with a backward particle-tracking method and determine the temporal evolution of the concentrations at the pumping well of CFC-11, CFC-12, CFC-113 and SF6. Apparent ages evolve because of the modifications of the flow pattern and because of the non-linear evolution of the tracer atmospheric concentrations. To identify the respective role of these two causes, we propose two successive analyses. We first convolute residence time distributions initially arising at different times at the same sampling time. We secondly convolute one residence time distribution at various sampling times. We show that flow pattern modifications control the apparent ages evolution in the first pumping year when the residence time distribution is modified from a piston-like distribution to a much broader distribution. In the first pumping year, the apparent age evolution contains transient information that can be used to better constrain hydrogeological systems and slightly compensate for the small number of tracers. Later, the residence time distribution hardly evolves and apparent ages only evolve because of the tracer atmospheric concentrations. In this phase, apparent age time-series do not reflect any evolution in the flow pattern.

  7. Temporal evolution of age data under transient pumping conditions

    NASA Astrophysics Data System (ADS)

    Leray, S.; De Dreuzy, J.; Aquilina, L.; Vergnaud, V.; Labasque, T.; Bour, O.; Le Borgne, T.

    2013-12-01

    While most age data derived from tracers have been analyzed in steady-state flow conditions, we determine their temporal evolution under transient pumping conditions. Starting pumping in a well modifies the natural flow patterns induced by the topographical gradient to a mainly convergent flow to the well. Our study is based on a set of models made up of a shallowly dipping aquifer overlain by a less permeable aquitard. These settings are characteristic of the crystalline aquifer of Plœmeur (Brittany, France) located in a highly fractured zone at the contact between a granite and micaschists. Under a pseudo steady-state flow assumption (instantaneous shift between two steady-state flow fields), we solve the transport equation with a backward particle-tracking method and determine the temporal evolution of the concentrations at the pumping well of the four atmospheric tracers CFC 11, CFC 12, CFC 113 and SF6. We show that apparent ages deduced from these concentrations evolve both because of the flow patterns modifications and because of the non-linear evolution of the atmospheric tracer concentrations. Flow patterns modifications only intervene just after the start of pumping, when the initially piston-like residence time distribution is transformed to a broader distribution mixing residence times from a wide variety of flow lines. Later, while flow patterns and the supplying volume of the pumping well still evolve, the residence time distributions are hardly modified and apparent ages are solely altered by the non-linear atmospheric tracer concentrations that progressively modifies the weighting of the residence time distribution. These results are confirmed by the observations at the site of Plœmeur in the pumping area. First, long term chloride observations confirm the quick evolution of the flow patterns after the start of pumping. Second, posterior and more recent evolutions of apparent ages derived from CFCs are consistent with the modeling results revealing

  8. Oxidative stress and epigenetic regulation in ageing and age-related diseases.

    PubMed

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

    2013-08-28

    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.

  9. 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

  10. 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

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

    PubMed

    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.

  12. 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.

  13. 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.

  14. 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

  15. Parental Age of Onset of Cardiovascular Disease as a Predictor for Offspring Age of Onset of Cardiovascular Disease

    PubMed Central

    Kikah, Ngum; Ekokobe, Fonkem; Atem, Folefac D.

    2016-01-01

    Objective The risk for cardiovascular disease (CVD) is higher for individuals with a first-degree relative who developed premature CVD (with a threshold at age 55 years for a male or 65 years for a female). However, little is known about the effect that each unit increase or decrease of maternal or paternal age of onset of CVD has on offspring age of onset of CVD. We hypothesized that there is an association between maternal and paternal age of onset of CVD and offspring age of onset of CVD. Methods We used the Framingham Heart Study database and performed conditional imputation for CVD-censored parental age (i.e. parents that didn’t experience onset of CVD) and Cox proportional regression analysis, with offspring’s age of onset of CVD as the dependent variable and parental age of onset of CVD as the primary predictor. Modifiable risk factors in offspring, such as cigarette smoking, body mass index (BMI), diabetes mellitus, systolic blood pressure (SBP), high-density lipoprotein (HDL) level, and low-density lipoprotein (LDL) level, were controlled for. Separate analyses were performed for the association between maternal age of onset of CVD and offspring age of onset of CVD and the association between paternal age of onset of CVD and offspring age of onset of CVD. Results Parental age of onset of CVD was predictive of offspring age of onset of CVD for maternal age of onset of CVD (P < .0001; N = 1401) and for paternal age of onset of CVD (P = 0.0134; N = 1221). A negative estimate of the coefficient of interest signifies that late onset of cardiovascular events in parents is protective of onset of CVD in offspring. Cigarette smoking and HDL level were important associated confounders. Conclusions Offspring age of onset of cardiovascular disease is significantly associated with both maternal and paternal age of onset CVD. The incorporation of the parameters, maternal or paternal age of onset of CVD, into risk estimate calculators may improve accuracy of

  16. Fractal dynamics in physiology: alterations with disease and aging.

    PubMed

    Goldberger, Ary L; Amaral, Luis A N; Hausdorff, Jeffrey M; Ivanov, Plamen Ch; Peng, C-K; Stanley, H Eugene

    2002-02-19

    According to classical concepts of physiologic control, healthy systems are self-regulated to reduce variability and maintain physiologic constancy. Contrary to the predictions of homeostasis, however, the output of a wide variety of systems, such as the normal human heartbeat, fluctuates in a complex manner, even under resting conditions. Scaling techniques adapted from statistical physics reveal the presence of long-range, power-law correlations, as part of multifractal cascades operating over a wide range of time scales. These scaling properties suggest that the nonlinear regulatory systems are operating far from equilibrium, and that maintaining constancy is not the goal of physiologic control. In contrast, for subjects at high risk of sudden death (including those with heart failure), fractal organization, along with certain nonlinear interactions, breaks down. Application of fractal analysis may provide new approaches to assessing cardiac risk and forecasting sudden cardiac death, as well as to monitoring the aging process. Similar approaches show promise in assessing other regulatory systems, such as human gait control in health and disease. Elucidating the fractal and nonlinear mechanisms involved in physiologic control and complex signaling networks is emerging as a major challenge in the postgenomic era.

  17. Epigenetic Determinants of Healthy and Diseased Brain Aging and Cognition

    PubMed Central

    S., Akbarian; S., Beeri M.; V., Haroutunian

    2014-01-01

    A better understanding of normal and diseased brain aging and cognition will have a significant public health impact, given that the oldest-old persons over 85 years of age represent the fastest growing segment in the population in developed countries, with over 30 million new cases of dementia predicted to occur world-wide each year by 2040. Dysregulation of gene expression, and more generally, genome organization and function, is thought to contribute to age-related declines in cognition. Remarkably, nearly all neuronal nuclei that reside in an aged brain had permanently exited from the cell cycle during prenatal development, and DNA methylation and histone modifications and other molecular constituents of the epigenome are likely to play a critical role in the maintenance of neuronal health and function throughout the entire lifespan. Here, we provide an overview on age-related changes in the brain’s chromatin structures, highlight potential epigenetic drug targets for cognitive decline and age-related neurodegenerative disease and discuss opportunities and challenges when studying ‘epigenetic biomarkers’ in aging research. PMID:23571692

  18. Deciphering the mechanism underlying late-onset Alzheimer disease.

    PubMed

    Krstic, Dimitrije; Knuesel, Irene

    2013-01-01

    Despite tremendous investments in understanding the complex molecular mechanisms underlying Alzheimer disease (AD), recent clinical trials have failed to show efficacy. A potential problem underlying these failures is the assumption that the molecular mechanism mediating the genetically determined form of the disease is identical to the one resulting in late-onset AD. Here, we integrate experimental evidence outside the 'spotlight' of the genetic drivers of amyloid-β (Aβ) generation published during the past two decades, and present a mechanistic explanation for the pathophysiological changes that characterize late-onset AD. We propose that chronic inflammatory conditions cause dysregulation of mechanisms to clear misfolded or damaged neuronal proteins that accumulate with age, and concomitantly lead to tau-associated impairments of axonal integrity and transport. Such changes have several neuropathological consequences: focal accumulation of mitochondria, resulting in metabolic impairments; induction of axonal swelling and leakage, followed by destabilization of synaptic contacts; deposition of amyloid precursor protein in swollen neurites, and generation of aggregation-prone peptides; further tau hyperphosphorylation, ultimately resulting in neurofibrillary tangle formation and neuronal death. The proposed sequence of events provides a link between Aβ and tau-related neuropathology, and underscores the concept that degenerating neurites represent a cause rather than a consequence of Aβ accumulation in late-onset AD.

  19. 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

  20. Dietary restriction delays aging, but not neuronal dysfunction, in Drosophila models of Alzheimer's disease

    PubMed Central

    Kerr, F.; Augustin, H.; Piper, M.D.W.; Gandy, C.; Allen, M.J.; Lovestone, S.; Partridge, L.

    2011-01-01

    Dietary restriction (DR) extends lifespan in diverse organisms and, in animal and cellular models, can delay a range of aging-related diseases including Alzheimer's disease (AD). A better understanding of the mechanisms mediating these interactions, however, may reveal novel pathways involved in AD pathogenesis, and potential targets for disease-modifying treatments and biomarkers for disease progression. Drosophila models of AD have recently been developed and, due to their short lifespan and susceptibility to genetic manipulation, we have used the fly to investigate the molecular connections among diet, aging and AD pathology. DR extended lifespan in both Arctic mutant Aβ42 and WT 4R tau over-expressing flies, but the underlying molecular pathology was not altered and neuronal dysfunction was not prevented by dietary manipulation. Our data suggest that DR may alter aging through generalised mechanisms independent of the specific pathways underlying AD pathogenesis in the fly, and hence that lifespan-extending manipulations may have varying effects on aging and functional declines in aging-related diseases. Alternatively, our analysis of the specific effects of DR on neuronal toxicity downstream of Aβ and tau pathologies with negative results may simply confirm that the neuro-protective effects of DR are upstream of the initiating events involved in the pathogenesis of AD. PMID:19969390

  1. Small molecule SIRT1 activators for the treatment of aging and age-related diseases

    PubMed Central

    Hubbard, Basil P.; Sinclair, David A.

    2014-01-01

    Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, significantly extending healthy years of life. In this review we discuss recent advances, controversies, opportunities, and challenges surrounding the development of SIRT1 activators, molecules with the potential to delay aging and age-related diseases. Sirtuins comprise a family of NAD+-dependent deacylases that are central to the body’s response to diet and exercise. New studies indicate that both natural and synthetic sirtuin activating compounds (STACs) work via a common allosteric mechanism to stimulate sirtuin activity, thereby conferring broad health benefits in rodents, primates, and possibly humans. The fact that the two-thirds of people in the USA who consume multiple dietary supplements consume resveratrol, a SIRT1 activator, underscores the importance of understanding the biochemical mechanism, physiological effects, and safety of STACs. PMID:24439680

  2. 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

  3. 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…

  4. Tacrolimus ointment: utilization patterns in children under age 2 years.

    PubMed

    Housman, Tamara Salam; Norton, Amy B; Feldman, Steven R; Fleischer, Alan B; Simpson, Eric L; Hanifin, Jon M; Antaya, Richard J

    2004-07-15

    Atopic dermatitis (AD) is a common eczematous skin condition; as many as 10-17 percent of all children are affected, and 35-60 percent of affected patients manifest symptoms manifest during the first year of life. Treatment principles for AD in young children involve conservative measures such as avoidance of hot water and environmental irritants, combined with liberal use of emollients after bathing. Low potency topical corticosteroids (TCS) are the current standard of therapy for AD in young children, reserving mid- and high-potency TCS for severe disease. However, complications of long-term use of TCS include skin atrophy, stria formation, telangiectasia, hypopigmentation, secondary infections, steroid acne, allergic contact dermatitis, and miliaria. The pediatric population is also at increased risk for systemic absorption because of their high ratio of skin surface to body mass. Systemic absorption may result in hypothalamic-pituitary-adrenal axis suppression and ultimately growth retardation. Although most topical and systemic corticosteroids are not approved by the Food and Drug Administration for use in children less than 2 years of age, conservative treatment often fails in this age group and frequently patients are treated with TCS, antibiotics, and antihistamines.

  5. The endoplasmic reticulum stress response in aging and age-related diseases

    PubMed Central

    Brown, Marishka K.; Naidoo, Nirinjini

    2012-01-01

    The endoplasmic reticulum(ER) is a multifunctional organelle within which protein folding, lipid biosynthesis, and calcium storage occurs. Perturbations such as energy or nutrient depletion, disturbances in calcium or redox status that disrupt ER homeostasis lead to the misfolding of proteins, ER stress and up-regulation of several signaling pathways coordinately called the unfolded protein response (UPR). The UPR is characterized by the induction of chaperones, degradation of misfolded proteins and attenuation of protein translation. The UPR plays a fundamental role in the maintenance of cellular homeostasis and thus is central to normal physiology. However, sustained unresolved ER stress leads to apoptosis. Aging linked declines in expression and activity of key ER molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the UPR. One mechanism to explain age associated declines in cellular functions and age-related diseases is a progressive failure of chaperoning systems. In many of these diseases, proteins or fragments of proteins convert from their normally soluble forms to insoluble fibrils or plaques that accumulate in a variety of organs including the liver, brain or spleen. This group of diseases, which typically occur late in life includes Alzheimer's, Parkinson's, type II diabetes and a host of less well known but often equally serious conditions such as fatal familial insomnia. The UPR is implicated in many of these neurodegenerative and familial protein folding diseases as well as several cancers and a host of inflammatory diseases including diabetes, atherosclerosis, inflammatory bowel disease and arthritis. This review will discuss age-related changes in the ER stress response and the role of the UPR in age-related diseases. PMID:22934019

  6. Optic nerve head biomechanics in aging and disease.

    PubMed

    Downs, J Crawford

    2015-04-01

    This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression.

  7. Systemic DNA damage responses in aging and diseases

    PubMed Central

    Ribezzo, Flavia; Shiloh, Yosef; Schumacher, Björn

    2016-01-01

    The genome is constantly attacked by a variety of genotoxic insults. The causal role for DNA damage in aging and cancer is exemplified by genetic defects in DNA repair that underlie a broad spectrum of acute and chronic human disorders that are characterized by developmental abnormalities, premature aging, and cancer predisposition. The disease symptoms are typically tissue-specific with uncertain genotype-phenotype correlation. The cellular DNA damage response (DDR) has been extensively investigated ever since yeast geneticists discovered DNA damage checkpoint mechanisms, several decades ago. In recent years, it has become apparent that not only cell-autonomous but also systemic DNA damage responses determine the outcome of genome instability in organisms. Understanding the mechanisms of non-cell-autonomous DNA damage responses will provide important new insights into the role of genome instability in human aging and a host of diseases including cancer and might better explain the complex phenotypes caused by genome instability. PMID:26773346

  8. 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.

  9. Amniotic Epithelial Cells: A New Tool to Combat Aging and Age-Related Diseases?

    PubMed Central

    Di Germanio, Clara; Bernier, Michel; de Cabo, Rafael; Barboni, Barbara

    2016-01-01

    The number of elderly people is growing at an unprecedented rate and this increase of the aging population is expected to have a direct impact on the incidence of age-related diseases and healthcare-associated costs. Thus, it is imperative that new tools are developed to fight and slow age-related diseases. Regenerative medicine is a promising strategy for the maintenance of health and function late in life; however, stem cell-based therapies face several challenges including rejection and tumor transformation. As an alternative, the placenta offers an extraordinary source of fetal stem cells, including the amniotic epithelial cells (AECs), which retain some of the characteristics of embryonic stem cells, but show low immunogenicity, together with immunomodulatory and anti-inflammatory activities. Because of these characteristics, AECs have been widely utilized in regenerative medicine. This perspective highlights different mechanisms triggered by transplanted AECs that could be potentially useful for anti-aging therapies, which include: Graft and differentiation for tissue regeneration in age-related settings, anti-inflammatory behavior to combat “inflammaging,” anti-tumor activity, direct lifespan and healthspan extension properties, and possibly rejuvenation in a manner reminiscent of heterochronic parabiosis. Here, we critically discuss benefits and limitation of AECs-based therapies in age-related diseases. PMID:27921031

  10. Compromised respiratory adaptation and thermoregulation in aging and age-related diseases.

    PubMed

    Chan, Sic L; Wei, Zelan; Chigurupati, Srinivasulu; Tu, Weihong

    2010-01-01

    Mitochondrial dysfunction and reactive oxygen species (ROS) production are at the heart of the aging process and are thought to underpin age-related diseases. Mitochondria are not only the primary energy-generating system but also the dominant cellular source of metabolically derived ROS. Recent studies unravel the existence of mechanisms that serve to modulate the balance between energy metabolism and ROS production. Among these is the regulation of proton conductance across the inner mitochondrial membrane that affects the efficiency of respiration and heat production. The field of mitochondrial respiration research has provided important insight into the role of altered energy balance in obesity and diabetes. The notion that respiration and oxidative capacity are mechanistically linked is making significant headway into the field of aging and age-related diseases. Here we review the regulation of cellular energy and ROS balance in biological systems and survey some of the recent relevant studies that suggest that respiratory adaptation and thermodynamics are important in aging and age-related diseases.

  11. Maine Department of Education Regulation 180: Early Intervention and Special Education for Children Age Birth to under Age Six.

    ERIC Educational Resources Information Center

    Maine State Dept. of Education, Augusta.

    This document contains regulations governing the administration of the Childfind system for children age birth to under age 6, the provision of early intervention services to eligible children birth through two with disabilities and their families, and the provision of special education and related services to eligible children age 3 to under 6…

  12. Age estimation from dental cementum incremental lines and periodontal disease.

    PubMed

    Dias, P E M; Beaini, T L; Melani, R F H

    2010-12-01

    Age estimation by counting incremental lines in cementum added to the average age of tooth eruption is considered an accurate method by some authors, while others reject it stating weak correlation between estimated and actual age. The aim of this study was to evaluate this technique and check the influence of periodontal disease on age estimates by analyzing both the number of cementum lines and the correlation between cementum thickness and actual age on freshly extracted teeth. Thirty one undecalcified ground cross sections of approximately 30 µm, from 25 teeth were prepared, observed, photographed and measured. Images were enhanced by software and counts were made by one observer, and the results compared with two control-observers. There was moderate correlation ((r)=0.58) for the entire sample, with mean error of 9.7 years. For teeth with periodontal pathologies, correlation was 0.03 with a mean error of 22.6 years. For teeth without periodontal pathologies, correlation was 0.74 with mean error of 1.6 years. There was correlation of 0.69 between cementum thickness and known age for the entire sample, 0.25 for teeth with periodontal problems and 0.75 for teeth without periodontal pathologies. The technique was reliable for periodontally sound teeth, but not for periodontally diseased teeth.

  13. Managing nut genetic resources under disease threat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The USDA ARS, National Clonal Germplasm Repository (NCGR) Corvallis, Oregon, is assigned to preserve genetic resources of hazelnuts (Corylus L.) and butternuts (Juglans cinerea L.). Both crops are threatened by fungal diseases. Hazelnuts are challenged by Eastern filbert blight (EFB) [caused by Anis...

  14. Screening for Future Cardiovascular Disease Using Age Alone Compared with Multiple Risk Factors and Age

    PubMed Central

    Wald, Nicholas J.; Simmonds, Mark; Morris, Joan K.

    2011-01-01

    Background Risk factors such as blood pressure and serum cholesterol are used, with age, in screening for future cardiovascular disease (CVD) events. The value of using these risk factors with age compared with using age alone is not known. We compared screening for future CVD events using age alone with screening using age and multiple risk factors based on regular Framingham risk assessments. Methods Ten-year CVD risk was estimated using Framingham risk equations in a hypothetical sample population of 500,000 people aged 0–89 years. Risk estimates were used to identify individuals who did and did not have a CVD event over a ten-year period. For screening using age alone (age screening) and screening using multiple risk factors and age (Framingham screening) we estimated the (i) detection rate (sensitivity); (ii) false–positive rate; (iii) proportion of CVD-free years of life lost in affected individuals with positive results (person-years detection rate); and (iv) cost per CVD-free life year gained from preventive treatment. Results Age screening using a cut-off of 55 years detected 86% of all first CVD events arising in the population every year and 72% of CVD-free years of life lost for a 24% false-positive rate; for five yearly Framingham screening the false-positive rate was 21% for the same 86% detection rate. The estimated cost per CVD-free year of life gained was £2,000 for age screening and £2,200 for Framingham screening if a Framingham screen costs £150 and the annual cost of preventive treatment is £200. Conclusion Age screening for future CVD events is simpler than Framingham screening with a similar screening performance and cost-effectiveness. It avoids blood tests and medical examinations. The advantages of age screening in the prevention of heart attack and stroke warrant considering its use in preference to multiple risk factor screening. PMID:21573224

  15. [The relationship between the polymorphism of immunity genes and both aging and age-related diseases].

    PubMed

    Ruan, Qing-Wei; Yu, Zhuo-Wei; Bao, Zhi-Jun; Ma, Yong-Xing

    2013-07-01

    Aging is acommon, progressive and irreversible state of multi-cell dysfunction. Immune aging mainly includes the declines of regenerative capacity and lymphoid lineage differentiation potential, the hyporesponsive to infection and vaccination, the hyperresponsive in the context of inflammatory pathology, and the increased risk of autoimmunity. The dysfunction of aged immune system accelerates the occurrence of aging and age-related diseases. The mutation of immunity genes that affect immune responses accelerates or slows aging process and age-related diseases. The frequencies of acquired immunity genes, such as immune protective HLA II DRB1*11 and DRB*16-associated haplotype, are increased in the longevity populations. The increased susceptibility of immune inflammatory response, morbidity and mortality in the elderly is often associated with decreased frequencies of anti-inflammatory factor IL-10 -1082G allele, TNF-β1 haplotype cnd10T/C, cnd25G/G, -988C/C, -800G/A, low proinflammatory fator TNFa level related extended TNF-A genotype -1031C/C, -863C/A, -857C/C, IL-6-174 CC and IFN-γ+874 T allele as well. The innate immunity genes, such as highly expressed anti-inflammatory +896 G KIR4 allele, CCR5Δ32 variant, -765 C Cox-2 allele, -1708 G and 21 C 5-Lox alleles are detected in centenarians. In age-related diseases, a higher CMV-specific IgG antibody level in elderly individuals is associated with a decreased frequency of KIR haplotypes KIR2DS5 and A1B10 and an increased frequency of MBL2 haplotypes LYPB, LYQC and HYPD that result in the absence of MBL2 protein. The increased frequencies of CRP ATG haplotypes and CFH 402 His allele indicate high mortality in the elderly. In the present study, we review the advances in the polymorphism and haplotype of innate and adoptive immunity genes, and their association with both aging and age-related diseases. To strengthen the analysis of extended haplotypes, epigenetic studies of immunity genes and genetic study of

  16. 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

  17. Factors related to onset age of Huntington disease.

    PubMed Central

    Myers, R H; Madden, J J; Teague, J L; Falek, A

    1982-01-01

    One prominent feature of Huntington disease (HD) is the variable age at which the characteristic neurological or psychiatric symptoms appear. Ages of manifestation varying from 4 to 65 years are found in a sample of 95 HD pedigrees compiled since 1968 from the Southeastern United States. Significant parent-child correlations of age of onset indicate consistency of onset age within nuclear families. However, an average intrafamily range of 9 years and an average intrapedigree range of 12 years reveal substantial variability of onset age within these groups. Of the nine cases of juvenile-onset HD identified in this sample, seven were of paternal descent. The preponderance of juvenile patients inheriting the HD gene from a father confirms similar findings from other studies. In addition, a trend toward earlier onset in all offspring of paternal transmission suggests that the juvenile-onset phenomenon is only the tail of a shift in the curve of onset ages for this group. A trend toward earlier onset in successive generations was noted. This "anticipation" may reflect the finding that persons of early onset in prior generations are selectively nonreproductive as a result of manifestation of the disorder. By identifying familial factors influencing onset age of HD, it may be possible to more effectively evaluate environmental factors that influence the onset of the disorder. PMID:6211092

  18. Genetic mouse models of brain ageing and Alzheimer's disease.

    PubMed

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed.

  19. Striatal function in normal aging: Implications for Parkinson's disease

    SciTech Connect

    Sawle, G.V.; Colebatch, J.G.; Shah, A.; Brooks, D.J.; Marsden, C.D.; Frackowiak, R.S. )

    1990-12-01

    Central to several current theories of the etiology of Parkinson's disease is the premise that the nigrostriatal dopaminergic system degenerates with normal aging. Much of the evidence for this assertion has come from postmortem neurochemical studies. We have used L-6-({sup 18}F) fluoro-Dopa and positron emission tomography in 26 healthy volunteers (age range, 27-76 years) to examine striatal and frontal cortical tracer uptake. Data have been analyzed by using a graphical approach to calculate an influx constant (Ki) for L-6-({sup 18}F)fluoro-Dopa uptake into the caudate, putamen, and medial frontal cortex of each subject. In the population studied, there was no decline in Ki with age for any of these structures. A series of physiological measurements made on the older subjects also showed few significant changes with age. The positron emission tomographic findings demonstrate preservation of nigrostriatal dopaminergic function in normal aging. The pathological process causing Parkinson's disease may operate closer to the time of presentation than has been suggested.

  20. A-type lamins and cardiovascular disease in premature aging syndromes.

    PubMed

    Dorado, Beatriz; Andrés, Vicente

    2017-01-10

    Lamin A is a nuclear intermediate filament protein with important structural and regulatory roles in most differentiated mammalian cells. Excessive accumulation of its precursor prelamin A or the mutant form called 'progerin' causes premature aging syndromes. Progeroid 'laminopathies' are characterized by severe cardiovascular problems (cardiac electrical defects, vascular calcification and stiffening, atherosclerosis, myocardial infarction, and stroke) and premature death. Here, we review studies in cell and mouse models and patients that are unraveling how abnormal prelamin A and progerin accumulation accelerates cardiovascular disease and aging. This knowledge is essential for developing effective therapies to treat progeria and may help identify new mechanisms underlying normal aging.

  1. The microbiota and microbiome in aging: potential implications in health and age-related diseases.

    PubMed

    Zapata, Heidi J; Quagliarello, Vincent J

    2015-04-01

    Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome). Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina). A myriad of clinical changes, including a basal proinflammatory state (inflamm-aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging. Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long-term care settings), and basal level of inflammation. Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease. Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging.

  2. 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

  3. Independent Role of Underlying Kidney Disease on Renal Prognosis of Patients with Chronic Kidney Disease under Nephrology Care.

    PubMed

    De Nicola, Luca; Provenzano, Michele; Chiodini, Paolo; Borrelli, Silvio; Garofalo, Carlo; Pacilio, Mario; Liberti, Maria Elena; Sagliocca, Adelia; Conte, Giuseppe; Minutolo, Roberto

    2015-01-01

    Primary kidney disease is suggested to affect renal prognosis of CKD patients; however, whether nephrology care modifies this association is unknown. We studied patients with CKD stage I-IV treated in a renal clinic and with established diagnosis of CKD cause to evaluate whether the risk of renal event (composite of end-stage renal disease and eGFR decline ≥ 40%) linked to the specific diagnosis is modified by the achievement or maintenance in the first year of nephrology care of therapeutic goals for hypertension (BP ≤ 130/80 mmHg in patients with proteinuria ≥ 1 50 mg/24h and/or diabetes and ≤ 140/90 in those with proteinuria <150 mg/24h and without diabetes) anemia (hemoglobin, Hb ≥ 11 g/dL), and proteinuria (≤ 0.5 g/24h). Survival analysis started after first year of nephrology care. We studied 729 patients (age 64 ± 15 y; males 59.1%; diabetes 34.7%; cardiovascular disease (CVD) 44.9%; hypertensive nephropathy, HTN 53.8%; glomerulonephritis, GN 17.3%; diabetic nephropathy, DN 15.9%; tubule-interstitial nephropathy, TIN 9.5%; polycystic kidney disease, PKD 3.6%). During first year of Nephrology care, therapy was overall intensified in most patients and prevalence of main therapeutic goals generally improved. During subsequent follow up (median 3.3 years, IQR 1.9-5.1), 163 renal events occurred. Cox analysis disclosed a higher risk for PKD (Hazard Ratio 5.46, 95% Confidence Intervals 2.28-10.6) and DN (1.28,2.99-3.05), versus HTN (reference), independently of age, gender, CVD, BMI, eGFR or CKD stage, use of RAS inhibitors and achievement or maintenance in the first year of nephrology care of each of the three main therapeutic goals. No interaction was found on the risk of CKD progression between diagnostic categories and month-12 eGFR (P=0.737), as with control of BP (P=0.374), Hb (P=0.248) or proteinuria (P=0.590). Therefore, in CKD patients under nephrology care, diagnosis of kidney disease should be considered in conjunction with the main risk

  4. Aging and the Kidneys: Anatomy, Physiology and Consequences for Defining Chronic Kidney Disease.

    PubMed

    Glassock, Richard J; Rule, Andrew D

    2016-01-01

    The varied functions of the kidneys are influenced by the complex process of aging. The glomerular filtration rate (GFR) steadily declines with normal aging, and the progress of this process can be influenced by superimposed diseases. Microscopically, nephron numbers decrease as global glomerulosclerosis becomes more evident. The precise mechanisms underlying nephron loss with aging are not well understood, but derangements in podocyte biology appear to be involved. Classifications of chronic kidney disease (CKD) incorporate GFR values and attendant risk of adverse events. Arbitrary and fixed thresholds of GFR for defining CKD have led to an overdiagnosis of CKD in the elderly. An age-sensitive definition of CKD could offer a solution to this problem and more meaningfully capture the prognostic implications of CKD.

  5. 42 CFR 435.118 - Infants and children under age 19.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Coverage of Pregnant Women, Children Under 8, and Newborn Children § 435.118 Infants and children under age... 42 Public Health 4 2012-10-01 2012-10-01 false Infants and children under age 19. 435.118 Section... infants under age 1, such higher income standard up to 185 percent FPL, if any, as the State...

  6. Accelerated Aging Influences Cardiovascular Disease Risk in Rheumatoid Arthritis

    PubMed Central

    Crowson, Cynthia S.; Therneau, Terry M.; Davis, John M.; Roger, Véronique L.; Matteson, Eric L.; Gabriel, Sherine E.

    2014-01-01

    OBJECTIVE To determine whether the impact of aging on cardiovascular disease (CVD) risk in the general population (as estimated by the Framingham risk score [FRS]) differs in patients with rheumatoid arthritis (RA). METHODS A population-based inception cohort of Olmsted County, Minnesota residents aged ≥30 years who fulfilled 1987 ACR criteria for RA in 1988–2008 was assembled and followed until death, migration, or 7-1-2012. Data on CVD events were collected by medical record review. The 10-year FRS for CVD was calculated. Cox models adjusted for FRS were used to examine the influence of age on CVD risk. RESULTS The study included 563 patients with RA without prior CVD (mean age: 55 years, 72% women; 69% seropositive [i.e., rheumatoid factor and/or anti-citrullinated protein antibody positive]). During a mean follow-up of 8.2 years, 98 patients developed CVD (74 seropositive and 24 seronegative), but FRS predicted only 59.7 events (35.4 seropositive and 24.3 seronegative). The gap between observed and predicted CVD risk increased exponentially across age, and the age effect on CVD risk in seropositive RA was nearly double its effect in the general population with additional log(age) coefficients of 2.91 for women (p=0.002) and 2.06 for men (p=0.027). CONCLUSION Age exerts an exponentially increasing effect on CVD risk in seropositive RA, but no increased effect among seronegative patients. The causes of accelerated aging in patients with seropositive RA deserve further investigation. PMID:23818136

  7. 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

  8. Benefits from dietary polyphenols for brain aging and Alzheimer's disease.

    PubMed

    Rossi, L; Mazzitelli, S; Arciello, M; Capo, C R; Rotilio, G

    2008-12-01

    Brain aging and the most diffused neurodegenerative diseases of the elderly are characterized by oxidative damage, redox metals homeostasis impairment and inflammation. Food polyphenols can counteract these alterations in vitro and are therefore suggested to have potential anti-aging and brain-protective activities, as also indicated by the results of some epidemiological studies. Despite the huge and increasing amount of the in vitro studies trying to unravel the mechanisms of action of dietary polyphenols, the research in this field is still incomplete, and questions about bioavailability, biotransformation, synergism with other dietary factors, mechanisms of the antioxidant activity, risks inherent to their possible pro-oxidant activities are still unanswered. Most of all, the capacity of the majority of these compounds to cross the blood-brain barrier and reach brain is still unknown. This commentary discusses recent data on these aspects, particularly focusing on effects of curcumin, resveratrol and catechins on Alzheimer's disease.

  9. Mitochondrial DNA mutations in ageing and disease: implications for HIV?

    PubMed

    Payne, Brendan A I; Gardner, Kristian; Chinnery, Patrick F

    2015-01-01

    Mitochondrial DNA (mtDNA) mutations cause neurological and multisystem disease. Somatic (acquired) mtDNA mutations are also associated with degenerative diseases and with normal human ageing. It is well established that certain nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral drugs cause inhibition of the mtDNA polymerase, pol γ, leading to a reduction in mtDNA content (depletion). Given this effect of NRTI therapy on mtDNA replication, it is plausible that NRTI treatment may also lead to increased mtDNA mutations. Here we review recent evidence for an effect of HIV infection or NRTI therapy on mtDNA mutations, as well as discussing the methodological challenges in addressing this question. Finally, we discuss the possible implications for HIV-infected persons, with particular reference to ageing.

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

    PubMed

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

    2015-06-01

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

  11. Versatile Functions of Caveolin-1 in Aging-related Diseases

    PubMed Central

    Nguyen, Kim Cuc Thi

    2017-01-01

    Caveolin-1 (Cav-1) is a trans-membrane protein that is a major component of the caveolae structure on the plasma membrane. Cav-1 is involved in the regulation of various cellular processes, including cell growth, differentiation, endocytosis, and in particular it has been implied in cellular senescence. Here we review current knowledge about Cav-1 in cellular signaling and discuss the role of Cav-1 in aging-related diseases. PMID:28184336

  12. 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

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

    PubMed

    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.

  14. The Role of Vitamin K in Chronic Aging Diseases: Inflammation, Cardiovascular Disease, and Osteoarthritis.

    PubMed

    Harshman, Stephanie G; Shea, M Kyla

    2016-06-01

    Vitamin K is an enzyme cofactor required for the carboxylation of vitamin K dependent proteins, several of which have been implicated in diseases of aging. Inflammation is recognized as a crucial component of many chronic aging diseases and evidence suggests vitamin K has an anti-inflammatory action that is independent of its role as an enzyme co-factor. Vitamin K-dependent proteins and inflammation have been implicated in cardiovascular disease and osteoarthritis, which are leading causes of disability and mortality in older adults. The purpose of this review is to summarize observational studies and randomized trials focused on vitamin K status and inflammation, cardiovascular disease, and osteoarthritis. Although mechanistic evidence suggests a protective role for vitamin K in these age-related conditions, the benefit of vitamin K supplementation is controversial because observational data are equivocal and the number of randomized trials is few.

  15. 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.

  16. Metabolomics of human brain aging and age-related neurodegenerative diseases.

    PubMed

    Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

    2014-07-01

    Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

  17. Of sound mind and body: depression, disease, and accelerated aging

    PubMed Central

    M. Wolkowitz, Owen; I. Reus, Victor; H. Mellon, Synthia

    2011-01-01

    Major depressive disorder (MDD) is associated with a high rate of developing serious medical comorbidities such as cardiovascular disease, stroke, dementia, osteoporosis, diabetes, and the metabolic syndrome. These are conditions that typically occur late in life, and it has been suggested that MDD may be associated with “accelerated aging.” We review several moderators and mediators that may accompany MDD and that may give rise to these comorbid medical conditions. We first review the moderating effects of psychological styles of coping, genetic predisposition, and epigenetic modifications (eg, secondary to childhood adversity). We then focus on several interlinked mediators occurring in MDD (or at least in subtypes of MDD) that may contribute to the medical comorbidity burden and to accelerated aging: limbic-hypothalamic-pituitary-adrenal axis alterations, diminution in glucocorticoid receptor function, altered glucose tolerance and insulin sensitivity, excitotoxicity, increases in intracellular calcium, oxidative stress, a proinflammatory milieu, lowered levels of “counter-regulatory” neurosteroids (such as allopregnanolone and dehydroepiandrosterone), diminished neurotrophic activity, and accelerated cell aging, manifest as alterations in telomerase activity and as shortening of telomeres, which can lead to apoptosis and cell death. In this model, MDD is characterized by a surfeit of potentially destructive mediators and an insufficiency of protective or restorative ones. These factors interact in increasing the likelihood of physical disease and of accelerated aging at the cellular level. We conclude with suggestions for novel mechanism-based therapeutics based on these mediators. PMID:21485744

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. OTC Cough and Cold Products: Not for Infants and Children Under 2 Years of Age

    MedlinePlus

    ... Cold Products: Not For Infants and Children Under 2 Years of Age Share Tweet Linkedin Pin it ... and cold products for infants and children under 2 years of age? A. FDA strongly recommends that ...

  3. The Effects of Aerobic Exercise on Cognitive and Neural Decline in Aging and Cardiovascular Disease

    PubMed Central

    Alosco, Michael L.; Forman, Daniel E.

    2015-01-01

    Aging is characterized by a decline in cognitive functions, particularly in the domains of executive function, processing speed and episodic memory. These age-related declines are exacerbated by cardiovascular disease (CVD) and cardiovascular risk factors (hypertension, diabetes, obesity, elevated total cholesterol). Structural and functional alterations in brain regions, including the fronto-parietal and medial temporal lobes, have been linked to age- and CVD-related cognitive decline. Multiple recent studies indicate that aerobic exercise programs may slow the progression of age-related neural changes and reduce the risk for mild cognitive impairment as well as dementia. We review age- and CVD-related decline in cognition and the underlying changes in brain morphology and function, and then clarify the impact of aerobic exercise on moderating these patterns. PMID:25750853

  4. The Effects of Aerobic Exercise on Cognitive and Neural Decline in Aging and Cardiovascular Disease.

    PubMed

    Hayes, Scott M; Alosco, Michael L; Forman, Daniel E

    2014-12-01

    Aging is characterized by a decline in cognitive functions, particularly in the domains of executive function, processing speed and episodic memory. These age-related declines are exacerbated by cardiovascular disease (CVD) and cardiovascular risk factors (hypertension, diabetes, obesity, elevated total cholesterol). Structural and functional alterations in brain regions, including the fronto-parietal and medial temporal lobes, have been linked to age- and CVD-related cognitive decline. Multiple recent studies indicate that aerobic exercise programs may slow the progression of age-related neural changes and reduce the risk for mild cognitive impairment as well as dementia. We review age- and CVD-related decline in cognition and the underlying changes in brain morphology and function, and then clarify the impact of aerobic exercise on moderating these patterns.

  5. Cortical cathepsin D activity and immunolocalization in Alzheimer disease, critical coronary artery disease, and aging.

    PubMed

    Haas, U; Sparks, D L

    1996-09-01

    The activity and immunocytochemical localization of cathepsin D in the frontal cortex were investigated in patients with Alzheimer disease (AD) and two groups of nondemented subjects; individuals with critical coronary artery disease (cCAD; > 75% stenosis) and non-heart disease controls (non-HD). The cathepsin D activity significantly increased with age in the non-HD population. No such age-related increase was observed in either AD or cCAD. Enzymatic activity was significantly increased in only the midaged, but not the older AD and cCAD subjects compared to controls. Immunocytochemical reactivity paralleled cathepsin D enzymatic activity. Frontal cortex neurons displayed an increased accumulation of cathepsin D immunoreactivity in aging (non-HD controls) with a further increase in cCAD, especially in the midaged group. Such immunoreactivity was markedly increased in AD. There was also an apparent age-related increase in the number of cathepsin D immunoreactive neurons in the non-HD population and a disease-related increase in only the mid-aged AD and cCAD subjects compared to controls. Senile plaques (SP) occurred in all AD patients, many cCAD, and a few of the oldest non-HD subjects, and they were immunoreactive to cathepsin D in each group. The data suggest a possible relationship between activation of cathepsin D and SP formation in AD, cCAD, and aging.

  6. Circulating Heat Shock Protein 70 in Health, Aging and Disease

    PubMed Central

    2011-01-01

    Background Heat shock proteins (Hsp) are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects. Recent studies have identified circulating Hsp as an important mediator in inflammation - the effects of low-grade inflammation in the aging process are overwhelming. While much is known about intracellular Hsp70, scant data exist on circulating Hsp70 in the aging context. Therefore, the objectives of this study were to investigate the effect of age and disease on circulating Hsp70 and, in particular, to evaluate the association between circulating Hsp70 and inflammatory parameters. Results Serum Hsp70, Interleukin (IL) -10, IL-6 and Tumor Necrosis Factor (TNF) alpha concentrations were determined in 90 hospitalised geriatric patients (aged 83 ± 6 years) and in 200 community-dwelling control subjects (100 elderly, aged 74 ± 5 years, and 100 young, aged 23 ± 3 years). In the community-dwelling elderly, serum Hsp70 and IL-10 concentrations were significantly lower and IL-6 was significantly higher when compared to healthy young control subjects. Elderly patients presenting inflammation (CRP serum levels ≥5 mg/L) showed significantly (p = 0.007) higher Hsp70 values; and Hsp70 correlated positively (p < 0.001) with IL-6 and CRP, but not with TNF-alpha or IL-10. A significant association was also noted between Hsp70 levels and the degree of dependency and cognitive decline in geriatric patients. Conclusions The present data provide new evidence that serum concentration of Hsp70 decreases with age in a normal population. Our study also shows that higher levels of Hsp70 are associated with inflammation and frailty in elderly patients. PMID:21443787

  7. 78 FR 9765 - Assigning New Social Security Numbers (SSN) for Children Age 13 and Under

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-11

    ... ADMINISTRATION Assigning New Social Security Numbers (SSN) for Children Age 13 and Under AGENCY: Social Security... assigning new SSNs to children age 13 and under. We are requesting information from the public to ensure... an SSN for a child age 13 and under. DATES: To ensure that your comments are considered, we...

  8. 36 CFR 1280.6 - Can children under the age of 14 use NARA facilities?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Conduct on NARA Property? General Information on Using Nara Facilities § 1280.6 Can children under the age of 14 use NARA facilities? Children under the age of 14 will be admitted to NARA facilities only if... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Can children under the age...

  9. 26 CFR 1.7702-2 - Attained age of the insured under a life insurance contract.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Attained age of the insured under a life...-2 Attained age of the insured under a life insurance contract. (a) In general. This section provides guidance on determining the attained age of an insured under a contract that is a life insurance...

  10. 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.

  11. 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

  12. Ages of celiac disease: from changing environment to improved diagnostics.

    PubMed

    Tommasini, Alberto; Not, Tarcisio; Ventura, Alessandro

    2011-08-28

    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.

  13. 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.

  14. Aging and infectious diseases in the developing world.

    PubMed

    Gavazzi, Gaëtan; Herrmann, Francois; Krause, Karl-Heinz

    2004-07-01

    Although demographic aging does not remain restricted to industrialized countries, the medical challenge arising from the aging population will be distinct in the developing world. This is particularly true with respect to infectious diseases, which have a distinct spectrum in the elderly population, as well as a greater overall relevance in the developing world. Tropical diseases have a specific presentation and epidemiology in elderly patients. Infectious diseases with a worldwide distribution impact elderly patients in the developing world in a specific manner, which is most obvious with respect to human immunodeficiency virus and tuberculosis but is also true with respect to "trivial" manifestations of infection, such as diarrhea and pneumonia. Malnutrition contributes in a major way to the immunodeficiency of elderly patients in the developing world. Poorly controlled use of antimicrobial drugs leads to multidrug-resistant microorganisms, which, together with the limited resources available for drug treatment, makes appropriate treatment of infections in elderly patients in developing countries very difficult. Infections in elderly patients will have an increasing impact on the public health and economy of developing countries.

  15. 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.

  16. Developmental origin of age-related coronary artery disease

    PubMed Central

    Wei, Ke; Díaz-Trelles, Ramon; Liu, Qiaozhen; Diez-Cuñado, Marta; Scimia, Maria-Cecilia; Cai, Wenqing; Sawada, Junko; Komatsu, Masanobu; Boyle, Joseph J.; Zhou, Bin; Ruiz-Lozano, Pilar; Mercola, Mark

    2015-01-01

    Aim Age and injury cause structural and functional changes in coronary artery smooth muscle cells (caSMCs) that influence the pathogenesis of coronary artery disease. Although paracrine signalling is widely believed to drive phenotypic changes in caSMCs, here we show that developmental origin within the fetal epicardium can have a profound effect as well. Methods and results Fluorescent dye and transgene pulse-labelling techniques in mice revealed that the majority of caSMCs are derived from Wt1+, Gata5-Cre+ cells that migrate before E12.5, whereas a minority of cells are derived from a later-emigrating, Wt1+, Gata5-Cre− population. We functionally evaluated the influence of early emigrating cells on coronary artery development and disease by Gata5-Cre excision of Rbpj, which prevents their contribution to coronary artery smooth muscle cells. Ablation of the Gata5-Cre+ population resulted in coronary arteries consisting solely of Gata5-Cre− caSMCs. These coronary arteries appeared normal into early adulthood; however, by 5–8 months of age, they became progressively fibrotic, lost the adventitial outer elastin layer, were dysfunctional and leaky, and animals showed early mortality. Conclusion Taken together, these data reveal heterogeneity in the fetal epicardium that is linked to coronary artery integrity, and that distortion of the coronaries epicardial origin predisposes to adult onset disease. PMID:26054850

  17. Management of the aging risk factor for Parkinson's disease.

    PubMed

    Phillipson, Oliver T

    2014-04-01

    The aging risk factor for Parkinson's disease is described in terms of specific disease markers including mitochondrial and gene dysfunctions relevant to energy metabolism. This review details evidence for the ability of nutritional agents to manage these aging risk factors. The combination of alpha lipoic acid, acetyl-l-carnitine, coenzyme Q10, and melatonin supports energy metabolism via carbohydrate and fatty acid utilization, assists electron transport and adenosine triphosphate synthesis, counters oxidative and nitrosative stress, and raises defenses against protein misfolding, inflammatory stimuli, iron, and other endogenous or xenobiotic toxins. These effects are supported by gene expression via the antioxidant response element (ARE; Keap/Nrf2 pathway), and by peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha), a transcription coactivator, which regulates gene expression for energy metabolism and mitochondrial biogenesis, and maintains the structural integrity of mitochondria. The effectiveness and synergies of the combination against disease risks are discussed in relation to gene action, dopamine cell loss, and the accumulation and spread of pathology via misfolded alpha-synuclein. In addition there are potential synergies to support a neurorestorative role via glial derived neurotrophic factor expression.

  18. Aging of distribution composite insulators under environmental and electrical stresses

    SciTech Connect

    de Oliveira, S.M. ); de Tourreil, C.H

    1990-04-01

    Seven types of commercially available distribution composite insulators with sheds made of EPR or epoxy resin have been subjected to various functional aging tests recommended by the IEC or the IEEE. The influence of UV radiation on the aging of the shed materials was also evaluated. The usefulness of the various aging and diagnostic tests is discussed and a modification of the recommended test procedures is proposed in order to improve the evaluation of the long term performance of these insulators.

  19. 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.

  20. Genomewide association study for onset age in Parkinson disease

    PubMed Central

    Latourelle, Jeanne C; Pankratz, Nathan; Dumitriu, Alexandra; Wilk, Jemma B; Goldwurm, Stefano; Pezzoli, Gianni; Mariani, Claudio B; DeStefano, Anita L; Halter, Cheryl; Gusella, James F; Nichols, William C; Myers, Richard H; Foroud, Tatiana

    2009-01-01

    Background Age at onset in Parkinson disease (PD) is a highly heritable quantitative trait for which a significant genetic influence is supported by multiple segregation analyses. Because genes associated with onset age may represent invaluable therapeutic targets to delay the disease, we sought to identify such genetic modifiers using a genomewide association study in familial PD. There have been previous genomewide association studies (GWAS) to identify genes influencing PD susceptibility, but this is the first to identify genes contributing to the variation in onset age. Methods Initial analyses were performed using genotypes generated with the Illumina HumanCNV370Duo array in a sample of 857 unrelated, familial PD cases. Subsequently, a meta-analysis of imputed SNPs was performed combining the familial PD data with that from a previous GWAS of 440 idiopathic PD cases. The SNPs from the meta-analysis with the lowest p-values and consistency in the direction of effect for onset age were then genotyped in a replication sample of 747 idiopathic PD cases from the Parkinson Institute Biobank of Milan, Italy. Results Meta-analysis across the three studies detected consistent association (p < 1 × 10-5) with five SNPs, none of which reached genomewide significance. On chromosome 11, the SNP with the lowest p-value (rs10767971; p = 5.4 × 10-7) lies between the genes QSER1 and PRRG4. Near the PARK3 linkage region on chromosome 2p13, association was observed with a SNP (rs7577851; p = 8.7 × 10-6) which lies in an intron of the AAK1 gene. This gene is closely related to GAK, identified as a possible PD susceptibility gene in the GWAS of the familial PD cases. Conclusion Taken together, these results suggest an influence of genes involved in endocytosis and lysosomal sorting in PD pathogenesis. PMID:19772629

  1. Complex and differential glial responses in Alzheimer's disease and ageing.

    PubMed

    Rodríguez, José J; Butt, Arthur M; Gardenal, Emanuela; Parpura, Vladimir; Verkhratsky, Alexei

    2016-01-01

    Glial cells and their association with neurones are fundamental for brain function. The emergence of complex neurone-glial networks assures rapid information transfer, creating a sophisticated circuitry where both types of neural cells work in concert, serving different activities. All glial cells, represented by astrocytes, oligodendrocytes, microglia and NG2-glia, are essential for brain homeostasis and defence. Thus, glia are key not only for normal central nervous system (CNS) function, but also to its dysfunction, being directly associated with all forms of neuropathological processes. Therefore, the progression and outcome of neurological and neurodegenerative diseases depend on glial reactions. In this review, we provide a concise account of recent data obtained from both human material and animal models demonstrating the pathological involvement of glia in neurodegenerative processes, including Alzheimer's disease (AD), as well as physiological ageing.

  2. Dynamics of DNA methylation in aging and Alzheimer's disease.

    PubMed

    Irier, Hasan A; Jin, Peng

    2012-10-01

    Gene expression is modulated by epigenetic factors that come in varying forms, such as DNA methylation, histone modifications, microRNAs, and long noncoding RNAs. Recent studies reveal that these epigenetic marks are important regulatory factors in brain function. In particular, DNA methylation dynamics are found to be essential components of epigenetic regulation in the mammalian central nervous system. In this review, we provide an overview of the literature on DNA methylation in neurodegenerative diseases, with a special focus on methylation of 5-position of cytosine base (5mC) and hydroxymethylation of 5-position of cytosine base (5hmC) in the context of neurodegeneration associated with aging and Alzheimer's disease.

  3. 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.

  4. 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.

  5. [Dementia and lifestyle-related diseases in Japanese aging society].

    PubMed

    Iwamoto, Toshihiko

    2011-05-01

    Recently, the number of elderly patients with dementia has been increasing in Japan because of both the extension of average life expectancy and a considerable rise in the incidence of dementia with age. For these reasons, dementia in Japan has become common, and more than half of all cases are Alzheimer disease. This disease has typically been considered to be a degenerative disorder due to genetic abnormalities, but recent epidemiological studies have indicated that lifestyle-related diseases such as hypertension, diabetes, dyslipidemia, and obesity in midlife could accelerate the dementing process, via either vascular changes in cerebral infarction or Alzheimer-related pathological changes with plaque and tangle formations which result in dementia in later life. Furthermore, several studies have suggested that a high intake of vegetables and fish, an active daily life, and lifelong education might positively influence cognitive function as neuroprotective factors. Therefore, we should try to prevent dementia based on the clinical and hygienic management of the lifestyles and lifestyle-related diseases, even in the youth.

  6. Impairments of Synaptic Plasticity in Aged Animals and in Animal Models of Alzheimer's Disease

    PubMed Central

    Balietti, Marta; Tamagnini, Francesco; Fattoretti, Patrizia; Burattini, Costanza; Casoli, Tiziana; Platano, Daniela; Lattanzio, Fabrizia

    2012-01-01

    Abstract Aging is associated with a gradual decline in cognitive functions, and more dramatic cognitive impairments occur in patients affected by Alzheimer's disease (AD). Electrophysiological and molecular studies performed in aged animals and in animal models of AD have shown that cognitive decline is associated with significant modifications in synaptic plasticity (i.e., activity-dependent changes in synaptic strength) and have elucidated some of the cellular mechanisms underlying this process. Morphological studies have revealed a correlation between the quality of memory performance and the extent of structural changes of synaptic contacts occurring during memory consolidation. We briefly review recent experimental evidence here. PMID:22533439

  7. Hutchinson-Gilford Progeria Syndrome: A premature aging disease caused by LMNA gene mutations.

    PubMed

    Gonzalo, Susana; Kreienkamp, Ray; Askjaer, Peter

    2017-01-01

    Products of the LMNA gene, primarily lamin A and C, are key components of the nuclear lamina, a proteinaceous meshwork that underlies the inner nuclear membrane and is essential for proper nuclear architecture. Alterations in lamin A and C that disrupt the integrity of the nuclear lamina affect a whole repertoire of nuclear functions, causing cellular decline. In humans, hundreds of mutations in the LMNA gene have been identified and correlated with over a dozen degenerative disorders, referred to as laminopathies. These diseases include neuropathies, muscular dystrophies, lipodystrophies, and premature aging diseases. This review focuses on one of the most severe laminopathies, Hutchinson-Gilford Progeria Syndrome (HGPS), which is caused by aberrant splicing of the LMNA gene and expression of a mutant product called progerin. Here, we discuss current views about the molecular mechanisms that contribute to the pathophysiology of this devastating disease, as well as the strategies being tested in vitro and in vivo to counteract progerin toxicity. In particular, progerin accumulation elicits nuclear morphological abnormalities, misregulated gene expression, defects in DNA repair, telomere shortening, and genomic instability, all of which limit cellular proliferative capacity. In patients harboring this mutation, a severe premature aging disease develops during childhood. Interestingly, progerin is also produced in senescent cells and cells from old individuals, suggesting that progerin accumulation might be a factor in physiological aging. Deciphering the molecular mechanisms whereby progerin expression leads to HGPS is an emergent area of research, which could bring us closer to understanding the pathology of aging.

  8. 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

  9. 42 CFR 436.308 - Medically needy coverage of individuals under age 21.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) Individuals in foster homes or private institutions for whom a public agency is assuming a full or partial... nursing facility services are provided under the plan to individuals within the age group selected under... are provided under the plan....

  10. A survey of the causes of sudden cardiac death in the under 35-year-age group.

    PubMed

    Quigley, F; Greene, M; O'Connor, D; Kelly, F

    2005-09-01

    CRY (Cardiac Risk in the Young) is a registered Irish charity established by parents who are bereaved as a result of sudden cardiac death. The aim of this study is to establish the incidence and causes of sudden cardiac death in Dublin city in the 10-year period from 1st January 1993 to 31st December 2002. All sudden cardiac deaths in the under 35-year age group which were reported to the city coroner in the study period were examined. Details regarding age, sex, previous symptoms, investigations, circumstances of death and main pathological finding were recorded in each case. A total of 72 cases of sudden cardiac death in the under-35 year age group were reported. 52 were men. The median age was 26.5 years (range 12-34 years). The cause of death in 20 cases was reported as atherosclerotic Coronary Artery Disease. The second commonest cause of death (24% cases) was Hypertrophic Cardiomyopathy. Hypertrophic Cardiomyopathy was the commonest cause of death under the age of 25 years. Overall atherosclerotic coronary artery disease was the commonest cause of death in this group. The importance of Hypertrophic Cardiomyopathy is highlighted by the fact it was the commonest cause of death in the under 25-year age group. Screening those at high risk of sudden cardiac death especially the relatives of those affected by Hypertrophic Cardiomyopathy need to be discussed and implemented.

  11. 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

  12. Lipidomics of human brain aging and Alzheimer's disease pathology.

    PubMed

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context.

  13. Taste bud homeostasis in health, disease, and aging.

    PubMed

    Feng, Pu; Huang, Liquan; Wang, Hong

    2014-01-01

    The mammalian taste bud is an onion-shaped epithelial structure with 50-100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8-12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging.

  14. Disease onset and aging in the world of circular RNAs.

    PubMed

    Maiese, Kenneth

    Circular ribonucleic acids (circRNAs) are non-coding RNAs of approximately 100 nucleotides in length with thousands of members in mammalian cells. The presence of circRNAs is believed to be even greater than that of messenger RNAs. Identification of circRNAs occurred approximately 37 years ago with the subsequent demonstration that covalent bonds are necessary for the unique circular structure of these ribonucleic acids. However, present understanding of the complex biological role of circRNAs remains limited and requires further elucidation. CircRNAs may impact aging, multiple disorders, function as biomarkers, and are able to regulate gene expression by acting as effective microRNA (miRNA) sponges. New work suggests that circRNAs are vital for the modulation of cellular senescence and programmed cell death pathways such as apoptosis. These non-coding RNAs can control cell cycle progression, cellular proliferation, and cellular survival impacting disorders linked to aging, cardiovascular disease, and atherosclerosis through pathways that involve cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase inhibitor 1 (p21), and mammalian forkhead transcription factors. In addition, circRNAs can oversee cellular metabolism and disorders such as diabetes mellitus through the regulation of insulin signaling as well as limit tumor progression through Wnt signaling and β-catenin pathways. Further understanding of the biology of circRNAs offers great promise for the targeting of novel strategies against a wide spectrum of disease entities.

  15. Taste Bud Homeostasis in Health, Disease, and Aging

    PubMed Central

    2014-01-01

    The mammalian taste bud is an onion-shaped epithelial structure with 50–100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8–12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging. PMID:24287552

  16. Empyema and bacteremic pneumococcal pneumonia in children under five years of age*, **

    PubMed Central

    Cardoso, Maria Regina Alves; Nascimento-Carvalho, Cristiana Maria Costa; Ferrero, Fernando; Berezin, Eitan Naaman; Ruvinsky, Raul; Sant'Anna, Clemax Couto; Brandileone, Maria Cristina de Cunto; March, Maria de Fátima Bazhuni Pombo; Maggi, Ruben; Feris-Iglesias, Jesus; Benguigui, Yehuda; Camargos, Paulo Augusto Moreira

    2014-01-01

    We compared bacteremic pneumococcal pneumonia (BPP) and pneumococcal empyema (PE), in terms of clinical, radiological, and laboratory findings, in under-fives. A cross-sectional nested cohort study, involving under-fives (102 with PE and 128 with BPP), was conducted at 12 centers in Argentina, Brazil, and the Dominican Republic. Among those with PE, mean age was higher; disease duration was longer; and tachypnea, dyspnea, and high leukocyte counts were more common. Among those with BPP, fever and lethargy were more common. It seems that children with PE can be distinguished from those with BPP on the basis of clinical and laboratory findings. Because both conditions are associated with high rates of morbidity and mortality, prompt diagnosis is crucial. PMID:24626272

  17. Aging syndrome genes and premature coronary artery disease

    PubMed Central

    Low, Adrian F; O'Donnell, Christopher J; Kathiresan, Sekar; Everett, Brendan; Chae, Claudia U; Shaw, Stanley Y; Ellinor, Patrick T; MacRae, Calum A

    2005-01-01

    Background Vascular disease is a feature of aging, and coronary vascular events are a major source of morbidity and mortality in rare premature aging syndromes. One such syndrome is caused by mutations in the lamin A/C (LMNA) gene, which also has been implicated in familial insulin resistance. A second gene related to premature aging in man and in murine models is the KLOTHO gene, a hypomorphic variant of which (KL-VS) is significantly more common in the first-degree relatives of patients with premature coronary artery disease (CAD). We evaluated whether common variants at the LMNA or KLOTHO genes are associated with rigorously defined premature CAD. Methods We identified 295 patients presenting with premature acute coronary syndromes confirmed by angiography. A control group of 145 patients with no evidence of CAD was recruited from outpatient referral clinics. Comprehensive haplotyping of the entire LMNA gene, including the promoter and untranslated regions, was performed using a combination of TaqMan® probes and direct sequencing of 14 haplotype-tagging single nucleotide polymorphisms (SNPs). The KL-VS variant of the KLOTHO gene was typed using restriction digest of a PCR amplicon. Results Two SNPs that were not in Hardy Weinberg equilibrium were excluded from analysis. We observed no significant differences in allele, genotype or haplotype frequencies at the LMNA or KLOTHO loci between the two groups. In addition, there was no evidence of excess homozygosity at the LMNA locus. Conclusion Our data do not support the hypothesis that premature CAD is associated with common variants in the progeroid syndrome genes LMNA and KLOTHO. PMID:16262891

  18. The important role of lipid peroxidation processes in aging and age dependent diseases.

    PubMed

    Spiteller, Gerhard

    2007-09-01

    Any change in the cell membrane structure activates lipoxygenases (LOX). LOX transform polyunsaturated fatty acids (PUFAs) to lipidhydroperoxide molecules (LOOHs). When cells are severely wounded, this physiological process switches to a non-enzymatic lipid peroxidation (LPO) process producing LOO* radicals. These oxidize nearly all-biological molecules such as lipids, sugars, and proteins. The LOO* induced degradations proceed by transfer of the radicals from cell to cell like an infection. The chemical reactions induced by LO* and LOO* radicals seem to be responsible for aging and induction of age dependent diseases.Alternatively, LO* and LOO* radicals are generated by frying of fats and involve cholesterol-PUFA esters and thus induce atherogenesis. Plants and algae are exposed to LOO* radicals generating radiation. In order to remove LOO* radicals, plants and algae transform PUFAs to furan fatty acids, which are incorporated after consumption of vegetables into mammalian tissues where they act as excellent scavengers of LOO* and LO* radicals.

  19. 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

  20. 76 FR 73986 - Redelegation of Authority Under the Age Discrimination Act of 1975

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... URBAN DEVELOPMENT Redelegation of Authority Under the Age Discrimination Act of 1975 AGENCY: Office of... Age Discrimination Act of 1975, and retains and redelegates this authority, with noted exceptions, to... statutes. Included in that consolidated delegation is the authority to act under the Age Discrimination...

  1. Brain amyloid-β oligomers in ageing and Alzheimer's disease.

    PubMed

    Lesné, Sylvain E; Sherman, Mathew A; Grant, Marianne; Kuskowski, Michael; Schneider, Julie A; Bennett, David A; Ashe, Karen H

    2013-05-01

    Alzheimer's disease begins about two decades before the onset of symptoms or neuron death, and is believed to be caused by pathogenic amyloid-β aggregates that initiate a cascade of molecular events culminating in widespread neurodegeneration. The microtubule binding protein tau may mediate the effects of amyloid-β in this cascade. Amyloid plaques comprised of insoluble, fibrillar amyloid-β aggregates are the most characteristic feature of Alzheimer's disease. However, the correspondence between the distribution of plaques and the pattern of neurodegeneration is tenuous. This discrepancy has stimulated the investigation of other amyloid-β aggregates, including soluble amyloid-β oligomers. Different soluble amyloid-β oligomers have been studied in several mouse models, but not systematically in humans. Here, we measured three amyloid-β oligomers previously described in mouse models-amyloid-β trimers, Aβ*56 and amyloid-β dimers-in brain tissue from 75 cognitively intact individuals, ranging from young children to the elderly, and 58 impaired subjects with mild cognitive impairment or probable Alzheimer's disease. As in mouse models, where amyloid-β trimers appear to be the fundamental amyloid-β assembly unit of Aβ*56 and are present in young mice prior to memory decline, amyloid-β trimers in humans were present in children and adolescents; their levels rose gradually with age and were significantly above baseline in subjects in their 70s. Aβ*56 levels were negligible in children and young adults, rose significantly above baseline in subjects in their 40s and increased steadily thereafter. Amyloid-β dimers were undetectable until subjects were in their 60s; their levels then increased sharply and correlated with plaque load. Remarkably, in cognitively intact individuals we found strong positive correlations between Aβ*56 and two pathological forms of soluble tau (tau-CP13 and tau-Alz50), and negative correlations between Aβ*56 and two postsynaptic

  2. Systemic oxidative stress associated with the neurological diseases of aging.

    PubMed

    Serra, Jorge A; Domínguez, Raúl O; Marschoff, Enrique R; Guareschi, Eduardo M; Famulari, Arturo L; Boveris, Alberto

    2009-12-01

    Markers of oxidative stress were measured in blood samples of 338 subjects (965 observations): Alzheimer's, vascular dementia, diabetes (type II) superimposed to dementias, Parkinson's disease and controls. Patients showed increased thiobarbituric acid reactive substances (+21%; P < 0.05), copper-zinc superoxide dismutase (+64%; P < 0.001) and decreased antioxidant capacity (-28%; P < 0.001); pairs of variables resulted linearly related across groups (P < 0.001). Catalase and glutathione peroxidase, involved in discrimination between diseases, resulted non-significant. When diabetes is superimposed with dementias, changes resulted less marked but significant. Also, superoxide dismutase resulted not linearly correlated with any other variable or age-related (pure Alzheimer's peaks at 70 years, P < 0.001). Systemic oxidative stress was significantly associated (P < 0.001) with all diseases indicating a disbalance in peripheral/adaptive responses to oxidative disorders through different free radical metabolic pathways. While other changes - methionine cycle, insulin correlation - are also associated with dementias, the responses presented here show a simple linear relation between prooxidants and antioxidant defenses.

  3. Network-Based Analysis for Uncovering Mechanisms Underlying Alzheimer's Disease.

    PubMed

    Kikuchi, Masataka; Ogishima, Soichi; Mizuno, Satoshi; Miyashita, Akinori; Kuwano, Ryozo; Nakaya, Jun; Tanaka, Hiroshi

    2016-01-01

    Alzheimer's disease (AD) is known to be a multifactorial neurodegenerative disorder, and is one of the main causes of dementia in the elderly. Many studies have demonstrated molecules involved in the pathogenesis of AD, however its underlying mechanisms remain obscure. It may be simplistic to try to explain the disease based on the role of a few genes only. Accumulating new, huge amount of information from e.g. genome, proteome and interactome datasets and new knowledge, we are now able to clarify and characterize diseases essentially as a result of dysfunction of molecular networks. Recent studies have indicated that relevant genes affected in human diseases concentrate in a part of the network, often called as "disease module." In the case of AD, some disease-associated pathways seem different, but some of them are clearly disease-related and coherent. This suggests the existence of a common pathway that negatively drives from healthy state to disease state (i.e., the disease module(s)). Additionally, such disease modules should dynamically change through AD progression. Thus, network-level approaches are indispensable to address unknown mechanisms of AD. In this chapter, we introduce network strategies using gene co-expression and protein interaction networks.

  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. Mitochondrial dysfunction: the missing link between aging and sporadic Alzheimer's disease.

    PubMed

    Grimm, Amandine; Friedland, Kristina; Eckert, Anne

    2016-04-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease that represents the most common form of dementia among the elderly. Despite the fact that AD was studied for decades, the underlying mechanisms that trigger this neuropathology remain unresolved. Since the onset of cognitive deficits occurs generally within the 6th decade of life, except in rare familial case, advancing age is the greatest known risk factor for AD. To unravel the pathogenesis of the disease, numerous studies use cellular and animal models based on genetic mutations found in rare early onset familial AD (FAD) cases that represent less than 1 % of AD patients. However, the underlying process that leads to FAD appears to be distinct from that which results in late-onset AD. As a genetic disorder, FAD clearly is a consequence of malfunctioning/mutated genes, while late-onset AD is more likely due to a gradual accumulation of age-related malfunction. Normal aging and AD are both marked by defects in brain metabolism and increased oxidative stress, albeit to varying degrees. Mitochondria are involved in these two phenomena by controlling cellular bioenergetics and redox homeostasis. In the present review, we compare the common features observed in both brain aging and AD, placing mitochondrial in the center of pathological events that separate normal and pathological aging. We emphasize a bioenergetic model for AD including the inverse Warburg hypothesis which postulates that AD is a consequence of mitochondrial deregulation leading to metabolic reprogramming as an initial attempt to maintain neuronal integrity. After the failure of this compensatory mechanism, bioenergetic deficits may lead to neuronal death and dementia. Thus, mitochondrial dysfunction may represent the missing link between aging and sporadic AD, and represent attractive targets against neurodegeneration.

  6. Spatial statistical analysis of basal stem root disease under natural field epidemic of oil palm

    NASA Astrophysics Data System (ADS)

    Kamu, Assis; Phin, Chong Khim; Seman, Idris Abu; Wan, Hoong Hak; Mun, Ho Chong

    2015-02-01

    Oil palm or scientifically known as Elaeis guineensis Jacq. is the most important commodity crop in Malaysia and has greatly contributed to the economy growth of the country. As far as disease is concerned in the industry, Basal Stem Rot (BSR) caused by Ganoderma boninence remains the most important disease. BSR disease is the most widely studied with information available for oil palm disease in Malaysia. However, there is still limited study on the spatial as well as temporal pattern or distribution of the disease especially under natural field epidemic condition in oil palm plantation. The objective of this study is to spatially identify the pattern of BSR disease under natural field epidemic using two geospatial analytical techniques, which are quadrat analysis for the first order properties of partial pattern analysis and nearest-neighbor analysis (NNA) for the second order properties of partial pattern analysis. Two study sites were selected with different age of tree. Both sites are located in Tawau, Sabah and managed by the same company. The results showed that at least one of the point pattern analysis used which is NNA (i.e. the second order properties of partial pattern analysis) has confirmed the disease is complete spatial randomness. This suggests the spread of the disease is not from tree to tree and the age of palm does not play a significance role in determining the spatial pattern of the disease. From the spatial pattern of the disease, it would help in the disease management program and for the industry in the future. The statistical modelling is expected to help in identifying the right model to estimate the yield loss of oil palm due to BSR disease in the future.

  7. Epigenetic mechanisms underlying lifespan and age-related effects of dietary restriction and the ketogenic diet.

    PubMed

    Moreno, Cesar L; Mobbs, Charles V

    2016-11-22

    Aging constitutes the central risk factor for major diseases including many forms of cancer, neurodegeneration, and cardiovascular diseases. The aging process is characterized by both global and tissue-specific changes in gene expression across taxonomically diverse species. While aging has historically been thought to entail cell-autonomous, even stochastic changes, recent evidence suggests that modulation of this process can be hierarchal, wherein manipulations of nutrient-sensing neurons (e.g., in the hypothalamus) produce peripheral effects that may modulate the aging process itself. The most robust intervention extending lifespan, plausibly impinging on the aging process, involves different modalities of dietary restriction (DR). Lifespan extension by DR is associated with broad protection against diseases (natural and engineered). Here we review potential epigenetic processes that may link lifespan to age-related diseases, particularly in the context of DR and (other) ketogenic diets, focusing on brain and hypothalamic mechanisms.

  8. 34 CFR 403.92 - Under what circumstances may the age limit under the Sex Equity Program be waived?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Sex Equity Program be waived? 403.92 Section 403.92 Education Regulations of the Offices of the... the Basic Programs? Sex Equity Program § 403.92 Under what circumstances may the age limit under the Sex Equity Program be waived? The individual appointed under § 403.13(a) may waive the requirement...

  9. 34 CFR 403.92 - Under what circumstances may the age limit under the Sex Equity Program be waived?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Sex Equity Program be waived? 403.92 Section 403.92 Education Regulations of the Offices of the... the Basic Programs? Sex Equity Program § 403.92 Under what circumstances may the age limit under the Sex Equity Program be waived? The individual appointed under § 403.13(a) may waive the requirement...

  10. 34 CFR 403.92 - Under what circumstances may the age limit under the Sex Equity Program be waived?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Sex Equity Program be waived? 403.92 Section 403.92 Education Regulations of the Offices of the... the Basic Programs? Sex Equity Program § 403.92 Under what circumstances may the age limit under the Sex Equity Program be waived? The individual appointed under § 403.13(a) may waive the requirement...

  11. 34 CFR 403.92 - Under what circumstances may the age limit under the Sex Equity Program be waived?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Sex Equity Program be waived? 403.92 Section 403.92 Education Regulations of the Offices of the... the Basic Programs? Sex Equity Program § 403.92 Under what circumstances may the age limit under the Sex Equity Program be waived? The individual appointed under § 403.13(a) may waive the requirement...

  12. 34 CFR 403.92 - Under what circumstances may the age limit under the Sex Equity Program be waived?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Sex Equity Program be waived? 403.92 Section 403.92 Education Regulations of the Offices of the... the Basic Programs? Sex Equity Program § 403.92 Under what circumstances may the age limit under the Sex Equity Program be waived? The individual appointed under § 403.13(a) may waive the requirement...

  13. Resveratrol: a multitargeted agent for age-associated chronic diseases.

    PubMed

    Harikumar, Kuzhuvelil B; Aggarwal, Bharat B

    2008-04-15

    Extensive research within the last decade has revealed that most chronic illnesses such as cancer, cardiovascular and pulmonary diseases, neurological diseases, diabetes, and autoimmune diseases exhibit dysregulation of multiple cell signaling pathways that have been linked to inflammation. Thus mono-targeted therapies developed for the last two decades for these diseases have proven to be unsafe, ineffective and expensive. Although fruits and vegetables are regarded to have therapeutic potential against chronic illnesses, neither their active component nor the mechanism of action is well understood. Resveratrol (trans-3, 5, 4'-trihydroxystilbene), a component of grapes, berries, peanuts and other traditional medicines, is one such polyphenol that has been shown to mediate its effects through modulation of many different pathways. This stilbene has been shown to bind to numerous cell-signaling molecules such as multi drug resistance protein, topoisomerase II, aromatase, DNA polymerase, estrogen receptors, tubulin and F1-ATPase. Resveratrol has also been shown to activate various transcription factor (e.g; NFkappaB, STAT3, HIF-1alpha, beta-catenin and PPAR-gamma), suppress the expression of antiapoptotic gene products (e.g; Bcl-2, Bcl-X(L), XIAP and survivin), inhibit protein kinases (e.g; src, PI3K, JNK, and AKT), induce antioxidant enzymes (e,g; catalase, superoxide dismutase and hemoxygenase-1), suppress the expression of inflammatory biomarkers (e.g., TNF, COX-2, iNOS, and CRP), inhibit the expression of angiogenic and metastatic gene products (e.g., MMPs, VEGF, cathepsin D, and ICAM-1), and modulate cell cycle regulatory genes (e.g., p53, Rb, PTEN, cyclins and CDKs). Numerous animal studies have demonstrated that this polyphenol holds promise against numerous age-associated diseases including cancer, diabetes, Alzheimer, cardiovascular and pulmonary diseases. In view of these studies, resveratrol's prospects for use in the clinics are rapidly accelerating

  14. 42 CFR 435.118 - Infants and children under age 19.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., Children Under 19, and Newborn Children § 435.118 Infants and children under age 19. (a) Basis. This... 42 Public Health 4 2014-10-01 2014-10-01 false Infants and children under age 19. 435.118 Section... standard is the higher of— (i) 133 percent FPL for the applicable family size; or (ii) For infants...

  15. 42 CFR 435.118 - Infants and children under age 19.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., Children Under 19, and Newborn Children § 435.118 Infants and children under age 19. (a) Basis. This... 42 Public Health 4 2013-10-01 2013-10-01 false Infants and children under age 19. 435.118 Section... standard is the higher of— (i) 133 percent FPL for the applicable family size; or (ii) For infants...

  16. Molecular mechanisms underlying the fetal programming of adult disease.

    PubMed

    Vo, Thin; Hardy, Daniel B

    2012-08-01

    Adverse events in utero can be critical in determining quality of life and overall health. It is estimated that up to 50 % of metabolic syndrome diseases can be linked to an adverse fetal environment. However, the mechanisms linking impaired fetal development to these adult diseases remain elusive. This review uncovers some of the molecular mechanisms underlying how normal physiology may be impaired in fetal and postnatal life due to maternal insults in pregnancy. By understanding the mechanisms, which include epigenetic, transcriptional, endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS), we also highlight how intervention in fetal and neonatal life may be able to prevent these diseases long-term.

  17. In vivo imaging of axonal transport of mitochondria in the diseased and aged mammalian CNS.

    PubMed

    Takihara, Yuji; Inatani, Masaru; Eto, Kei; Inoue, Toshihiro; Kreymerman, Alexander; Miyake, Seiji; Ueno, Shinji; Nagaya, Masatoshi; Nakanishi, Ayami; Iwao, Keiichiro; Takamura, Yoshihiro; Sakamoto, Hirotaka; Satoh, Keita; Kondo, Mineo; Sakamoto, Tatsuya; Goldberg, Jeffrey L; Nabekura, Junichi; Tanihara, Hidenobu

    2015-08-18

    The lack of intravital imaging of axonal transport of mitochondria in the mammalian CNS precludes characterization of the dynamics of axonal transport of mitochondria in the diseased and aged mammalian CNS. Glaucoma, the most common neurodegenerative eye disease, is characterized by axon degeneration and the death of retinal ganglion cells (RGCs) and by an age-related increase in incidence. RGC death is hypothesized to result from disturbances in axonal transport and in mitochondrial function. Here we report minimally invasive intravital multiphoton imaging of anesthetized mouse RGCs through the sclera that provides sequential time-lapse images of mitochondria transported in a single axon with submicrometer resolution. Unlike findings from explants, we show that the axonal transport of mitochondria is highly dynamic in the mammalian CNS in vivo under physiological conditions. Furthermore, in the early stage of glaucoma modeled in adult (4-mo-old) mice, the number of transported mitochondria decreases before RGC death, although transport does not shorten. However, with increasing age up to 23-25 mo, mitochondrial transport (duration, distance, and duty cycle) shortens. In axons, mitochondria-free regions increase and lengths of transported mitochondria decrease with aging, although totally organized transport patterns are preserved in old (23- to 25-mo-old) mice. Moreover, axonal transport of mitochondria is more vulnerable to glaucomatous insults in old mice than in adult mice. These mitochondrial changes with aging may underlie the age-related increase in glaucoma incidence. Our method is useful for characterizing the dynamics of axonal transport of mitochondria and may be applied to other submicrometer structures in the diseased and aged mammalian CNS in vivo.

  18. Declining Prevalence of Disease Vectors Under Climate Change.

    PubMed

    Escobar, Luis E; Romero-Alvarez, Daniel; Leon, Renato; Lepe-Lopez, Manuel A; Craft, Meggan E; Borbor-Cordova, Mercy J; Svenning, Jens-Christian

    2016-12-16

    More than half of the world population is at risk of vector-borne diseases including dengue fever, chikungunya, zika, yellow fever, leishmaniasis, chagas disease, and malaria, with highest incidences in tropical regions. In Ecuador, vector-borne diseases are present from coastal and Amazonian regions to the Andes Mountains; however, a detailed characterization of the distribution of their vectors has never been carried out. We estimate the distribution of 14 vectors of the above vector-borne diseases under present-day and future climates. Our results consistently suggest that climate warming is likely threatening some vector species with extinction, locally or completely. These results suggest that climate change could reduce the burden of specific vector species. Other vector species are likely to shift and constrain their geographic range to the highlands in Ecuador potentially affecting novel areas and populations. These forecasts show the need for development of early prevention strategies for vector species currently absent in areas projected as suitable under future climate conditions. Informed interventions could reduce the risk of human exposure to vector species with distributional shifts, in response to current and future climate changes. Based on the mixed effects of future climate on human exposure to disease vectors, we argue that research on vector-borne diseases should be cross-scale and include climatic, demographic, and landscape factors, as well as forces facilitating disease transmission at fine scales.

  19. Declining Prevalence of Disease Vectors Under Climate Change

    PubMed Central

    Escobar, Luis E.; Romero-Alvarez, Daniel; Leon, Renato; Lepe-Lopez, Manuel A.; Craft, Meggan E.; Borbor-Cordova, Mercy J.; Svenning, Jens-Christian

    2016-01-01

    More than half of the world population is at risk of vector-borne diseases including dengue fever, chikungunya, zika, yellow fever, leishmaniasis, chagas disease, and malaria, with highest incidences in tropical regions. In Ecuador, vector-borne diseases are present from coastal and Amazonian regions to the Andes Mountains; however, a detailed characterization of the distribution of their vectors has never been carried out. We estimate the distribution of 14 vectors of the above vector-borne diseases under present-day and future climates. Our results consistently suggest that climate warming is likely threatening some vector species with extinction, locally or completely. These results suggest that climate change could reduce the burden of specific vector species. Other vector species are likely to shift and constrain their geographic range to the highlands in Ecuador potentially affecting novel areas and populations. These forecasts show the need for development of early prevention strategies for vector species currently absent in areas projected as suitable under future climate conditions. Informed interventions could reduce the risk of human exposure to vector species with distributional shifts, in response to current and future climate changes. Based on the mixed effects of future climate on human exposure to disease vectors, we argue that research on vector-borne diseases should be cross-scale and include climatic, demographic, and landscape factors, as well as forces facilitating disease transmission at fine scales. PMID:27982119

  20. Declining Prevalence of Disease Vectors Under Climate Change

    NASA Astrophysics Data System (ADS)

    Escobar, Luis E.; Romero-Alvarez, Daniel; Leon, Renato; Lepe-Lopez, Manuel A.; Craft, Meggan E.; Borbor-Cordova, Mercy J.; Svenning, Jens-Christian

    2016-12-01

    More than half of the world population is at risk of vector-borne diseases including dengue fever, chikungunya, zika, yellow fever, leishmaniasis, chagas disease, and malaria, with highest incidences in tropical regions. In Ecuador, vector-borne diseases are present from coastal and Amazonian regions to the Andes Mountains; however, a detailed characterization of the distribution of their vectors has never been carried out. We estimate the distribution of 14 vectors of the above vector-borne diseases under present-day and future climates. Our results consistently suggest that climate warming is likely threatening some vector species with extinction, locally or completely. These results suggest that climate change could reduce the burden of specific vector species. Other vector species are likely to shift and constrain their geographic range to the highlands in Ecuador potentially affecting novel areas and populations. These forecasts show the need for development of early prevention strategies for vector species currently absent in areas projected as suitable under future climate conditions. Informed interventions could reduce the risk of human exposure to vector species with distributional shifts, in response to current and future climate changes. Based on the mixed effects of future climate on human exposure to disease vectors, we argue that research on vector-borne diseases should be cross-scale and include climatic, demographic, and landscape factors, as well as forces facilitating disease transmission at fine scales.

  1. Mitochondrial Lon protease in human disease and aging: Including an etiologic classification of Lon-related diseases and disorders

    PubMed Central

    Bota, Daniela A.; Davies, Kelvin J.A.

    2016-01-01

    The Mitochondrial Lon protease, also called LonP1 is a product of the nuclear gene LONP1. Lon is a major regulator of mitochondrial metabolism and response to free radical damage, as well as an essential factor for the maintenance and repair of mitochondrial DNA. Lon is an ATP-stimulated protease that cycles between being bound (at the inner surface of the inner mitochondrial membrane) to the mitochondrial genome, and being released into the mitochondrial matrix where it can degrade matrix proteins. At least three different roles or functions have been ascribed to Lon: 1) Proteolytic digestion of oxidized proteins and the turnover of specific essential mitochondrial enzymes such as aconitase, TFAM, and StAR; 2) Mitochondrial (mt)DNA-binding protein, involved in mtDNA replication and mitogenesis; and 3) Protein chaperone, interacting with the Hsp60–mtHsp70 complex. LONP1 orthologs have been studied in bacteria, yeast, flies, worms, and mammals, evincing the widespread importance of the gene, as well as its remarkable evolutionary conservation. In recent years, we have witnessed a significant increase in knowledge regarding Lon's involvement in physiological functions, as well as in an expanding array of human disorders, including cancer, neurodegeneration, heart disease, and stroke. In addition, Lon appears to have a significant role in the aging process. A number of mitochondrial diseases have now been identified whose mechanisms involve various degrees of Lon dysfunction. In this paper we review current knowledge of Lon's function, under normal conditions, and we propose a new classification of human diseases characterized by a either over-expression or decline or loss of function of Lon. Lon has also been implicated in human aging, and we review the data currently available as well as speculating about possible interactions of aging and disease. Finally, we also discuss Lon as potential therapeutic target in human disease. PMID:27387767

  2. Interleukin-6 in Aging and Chronic Disease: A Magnificent Pathway

    PubMed Central

    Maggio, Marcello; Guralnik, Jack M.; Longo, Dan L.; Ferrucci, Luigi

    2009-01-01

    The human interleukin IL-6 was originally cloned in 1986. In 1993, William Ershler, in his article “IL-6: A Cytokine for Gerontologists,” indicated IL-6 as one of the main signaling pathways modulating the complex relationship between aging and chronic morbidity. Over the last 12 years, our understanding of the role of IL-6 in human physiology and pathology has substantially grown, although some of the questions originally posed by Ershler are still debated. In this review, we will focus on IL-6 structure, IL-6 signaling, and trans signaling pathways, and the role of IL-6 in geriatric syndromes and chronic disease. In the final section of this review, we dissect the critical elements of the IL-6 signaling pathway and point out targets for intervention that are targeted by emerging drugs, some still on the horizon and others already being tested in clinical trials. PMID:16799139

  3. [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.

  4. Parkinson's disease accelerates age-related decline in haptic perception by altering somatosensory integration.

    PubMed

    Konczak, Jürgen; Sciutti, Alessandra; Avanzino, Laura; Squeri, Valentina; Gori, Monica; Masia, Lorenzo; Abbruzzese, Giovanni; Sandini, Giulio

    2012-11-01

    This study investigated how Parkinson's disease alters haptic perception and the underlying mechanisms of somatosensory and sensorimotor integration. Changes in haptic sensitivity and acuity (the abilities to detect and to discriminate between haptic stimuli) due to Parkinson's disease were systematically quantified and contrasted to the performance of healthy older and young adults. Using a robotic force environment, virtual contours of various curvatures were presented. Participants explored these contours with their hands and indicated verbally whether they could detect or discriminate between two contours. To understand what aspects of sensory or sensorimotor integration are altered by ageing and disease, we manipulated the sensorimotor aspect of the task: the robot either guided the hand along the contour or the participant actively moved the hand. Active exploration relies on multimodal sensory and sensorimotor integration, while passive guidance only requires sensory integration of proprioceptive and tactile information. The main findings of the study are as follows: first, a decline in haptic precision can already be observed in adults before the age of 70 years. Parkinson's disease may lead to an additional decrease in haptic sensitivity well beyond the levels typically seen in middle-aged and older adults. Second, the haptic deficit in Parkinson's disease is general in nature. It becomes manifest as a decrease in sensitivity and acuity (i.e. a smaller perceivable range and a diminished ability to discriminate between two perceivable haptic stimuli). Third, thresholds during both active and passive exploration are elevated, but not significantly different from each other. That is, active exploration did not enhance the haptic deficit when compared to passive hand motion. This implies that Parkinson's disease affects early stages of somatosensory integration that ultimately have an impact on processes of sensorimotor integration. Our results suggest that

  5. Age- and bite-structured models for vector-borne diseases.

    PubMed

    Rock, K S; Wood, D A; Keeling, M J

    2015-09-01

    The biology and behaviour of biting insects is a vitally important aspect in the spread of vector-borne diseases. This paper aims to determine, through the use of mathematical models, what effect incorporating vector senescence and realistic feeding patterns has on disease. A novel model is developed to enable the effects of age- and bite-structure to be examined in detail. This original PDE framework extends previous age-structured models into a further dimension to give a new insight into the role of vector biting and its interaction with vector mortality and spread of disease. Through the PDE model, the roles of the vector death and bite rates are examined in a way which is impossible under the traditional ODE formulation. It is demonstrated that incorporating more realistic functions for vector biting and mortality in a model may give rise to different dynamics than those seen under a more simple ODE formulation. The numerical results indicate that the efficacy of control methods that increase vector mortality may not be as great as predicted under a standard host-vector model, whereas other controls including treatment of humans may be more effective than previously thought.

  6. 29 CFR 780.321 - Minors 16 years of age or under.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Minors 16 years of age or under. 780.321 Section 780.321... 13(a)(6) Statutory Provisions § 780.321 Minors 16 years of age or under. Section 13(a)(6)(D) by its very terms is available only to employees 16 years of age or under. Accordingly, even though all...

  7. 29 CFR 780.321 - Minors 16 years of age or under.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Minors 16 years of age or under. 780.321 Section 780.321... 13(a)(6) Statutory Provisions § 780.321 Minors 16 years of age or under. Section 13(a)(6)(D) by its very terms is available only to employees 16 years of age or under. Accordingly, even though all...

  8. 29 CFR 780.321 - Minors 16 years of age or under.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Minors 16 years of age or under. 780.321 Section 780.321... 13(a)(6) Statutory Provisions § 780.321 Minors 16 years of age or under. Section 13(a)(6)(D) by its very terms is available only to employees 16 years of age or under. Accordingly, even though all...

  9. 29 CFR 780.321 - Minors 16 years of age or under.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Minors 16 years of age or under. 780.321 Section 780.321... 13(a)(6) Statutory Provisions § 780.321 Minors 16 years of age or under. Section 13(a)(6)(D) by its very terms is available only to employees 16 years of age or under. Accordingly, even though all...

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

    PubMed Central

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

    2015-01-01

    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

  11. BRAIN FUEL METABOLISM, AGING AND ALZHEIMER’S DISEASE

    PubMed Central

    Cunnane, SC; Nugent, S; Roy, M; Courchesne-Loyer, A; Croteau, E; Tremblay, S; Castellano, A; Pifferi, F; Bocti, C; Paquet, N; Begdouri, H; Bentourkia, M; Turcotte, E; Allard, M; Barberger-Gateau, P; Fulop, T; Rapoport, S

    2012-01-01

    Lower brain glucose metabolism is present before the onset of clinically-measurable cognitive decline in two groups of people at risk of Alzheimer’s disease (AD) - carriers of apoE4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and contribute to the neuropathological cascade leading cognitive decline in AD. The reason for brain hypometabolism is unclear but may include defects in glucose transport at the blood-brain barrier, glycolysis, and/or mitochondrial function. Methodological issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization which, in turn, may increase the risk of declining brain glucose uptake, at least in some regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e. that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and, hence, reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to – (i) improve insulin sensitivity by improving systemic glucose utilization, or (ii) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia. PMID:21035308

  12. 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

  13. Leukocyte telomere length and prevalence of age-related diseases in semisupercentenarians, centenarians and centenarians' offspring.

    PubMed

    Tedone, Enzo; Arosio, Beatrice; Gussago, Cristina; Casati, Martina; Ferri, Evelyn; Ogliari, Giulia; Ronchetti, Francesco; Porta, Alessandra; Massariello, Francesca; Nicolini, Paola; Mari, Daniela

    2014-10-01

    Centenarians and their offspring are increasingly considered a useful model to study and characterize the mechanisms underlying healthy aging and longevity. The aim of this project is to compare the prevalence of age-related diseases and telomere length (TL), a marker of biological age and mortality, across five groups of subjects: semisupercentenarians (SSCENT) (105-109years old), centenarians (CENT) (100-104years old), centenarians' offspring (CO), age- and gender-matched offspring of parents who both died at an age in line with life expectancy (CT) and age- and gender-matched offspring of both non-long-lived parents (NLO). Information was collected on lifestyle, past and current diseases, medical history and medication use. SSCENT displayed a lower prevalence of acute myocardial infarction (p=0.027), angina (p=0.016) and depression (p=0.021) relative to CENT. CO appeared to be healthier compared to CT who, in turn, displayed a lower prevalence of both arrhythmia (p=0.034) and hypertension (p=0.046) than NLO, characterized by the lowest parental longevity. Interestingly, CO and SSCENT exhibited the longest (p<0.001) and the shortest (p<0.001) telomeres respectively while CENT showed no difference in TL compared to the younger CT and NLO. Our results strengthen the hypothesis that the longevity of parents may influence the health status of their offspring. Moreover, our data also suggest that both CENT and their offspring may be characterized by a better TL maintenance which, in turn, may contribute to their longevity and healthy aging. The observation that SSCENT showed considerable shorter telomeres compared to CENT may suggest a progressive impairment of TL maintenance mechanisms over the transition from centenarian to semisupercentenarian age.

  14. Multiple skin neoplasms in subjects under 40 years of age in Goiania, Brazil.

    PubMed

    Pereira, Samir; Curado, Maria Paula; Ribeiro, Ana Maria Quinteiro

    2015-01-01

    OBJECTIVE To describe the trend for malignant skin neoplasms in subjects under 40 years of age in a region with high ultraviolet radiation indices.METHODS A descriptive epidemiological study on melanoma and nonmelanoma skin cancers that was conducted in Goiania, Midwest Brazil, with 1,688 people under 40 years of age, between 1988 and 2009. Cases were obtained fromRegistro de Câncer de Base Populacional de Goiânia(Goiania's Population-Based Cancer File). Frequency, trends, and incidence of cases with single and multiple lesions were analyzed; transplants and genetic skin diseases were found in cases with multiple lesions.RESULTS Over the period, 1,995 skin cancer cases were observed to found, of which 1,524 (90.3%) cases had single lesions and 164 (9.7%) had multiple lesions. Regarding single lesions, incidence on men was observed to have risen from 2.4 to 3.1/100,000 inhabitants; it differed significantly for women, shifting from 2.3 to 5.3/100,000 (Annual percentage change - [APC] 3.0%, p = 0.006). Regarding multiple lesions, incidence on men was observed to have risen from 0.30 to 0.98/100,000 inhabitants; for women, it rose from 0.43 to 1.16/100,000 (APC 8.6%, p = 0.003). Genetic skin diseases or transplants were found to have been correlated with 10.0% of cases with multiple lesions - an average of 5.1 lesions per patient. The average was 2.5 in cases without that correlation.CONCLUSIONS Skin cancer on women under 40 years of age has been observed to be increasing for both cases with single and multiple lesions. It is not unusual to find multiple tumors in young people - in most cases, they are not associated with genetic skin diseases or transplants. It is necessary to avoid excessive exposure to ultraviolet radiation from childhood.

  15. Multiple skin neoplasms in subjects under 40 years of age in Goiania, Brazil

    PubMed Central

    Pereira, Samir; Curado, Maria Paula; Ribeiro, Ana Maria Quinteiro

    2015-01-01

    OBJECTIVE To describe the trend for malignant skin neoplasms in subjects under 40 years of age in a region with high ultraviolet radiation indices. METHODS A descriptive epidemiological study on melanoma and nonmelanoma skin cancers that was conducted in Goiania, Midwest Brazil, with 1,688 people under 40 years of age, between 1988 and 2009. Cases were obtained from Registro de Câncer de Base Populacional de Goiânia (Goiania’s Population-Based Cancer File). Frequency, trends, and incidence of cases with single and multiple lesions were analyzed; transplants and genetic skin diseases were found in cases with multiple lesions. RESULTS Over the period, 1,995 skin cancer cases were observed to found, of which 1,524 (90.3%) cases had single lesions and 164 (9.7%) had multiple lesions. Regarding single lesions, incidence on men was observed to have risen from 2.4 to 3.1/100,000 inhabitants; it differed significantly for women, shifting from 2.3 to 5.3/100,000 (Annual percentage change – [APC] 3.0%, p = 0.006). Regarding multiple lesions, incidence on men was observed to have risen from 0.30 to 0.98/100,000 inhabitants; for women, it rose from 0.43 to 1.16/100,000 (APC 8.6%, p = 0.003). Genetic skin diseases or transplants were found to have been correlated with 10.0% of cases with multiple lesions – an average of 5.1 lesions per patient. The average was 2.5 in cases without that correlation. CONCLUSIONS Skin cancer on women under 40 years of age has been observed to be increasing for both cases with single and multiple lesions. It is not unusual to find multiple tumors in young people – in most cases, they are not associated with genetic skin diseases or transplants. It is necessary to avoid excessive exposure to ultraviolet radiation from childhood. PMID:26465667

  16. Ageing, lifestyle modifications, and cardiovascular disease in developing countries.

    PubMed

    Dominguez, L J; Galioto, A; Ferlisi, A; Pineo, A; Putignano, E; Belvedere, M; Costanza, G; Barbagallo, M

    2006-01-01

    Developing countries face the double menace of still prevalent infectious diseases and increasing cardiovascular disease (CVD) with epidemic proportions in the near future, linked to demographic changes (expansion and ageing), and to urbanisation and lifestyle modifications. It is estimated that the elderly population will increase globally (over 80% during the next 25 years), with a large share of this rise in the developing world because of expanding populations. Increasing longevity prolongs the time exposure to risk factors, resulting in a greater probability of CVD. As a paradox, increased longevity due to improved social and economical conditions associated with lifestyle changes in the direction of a rich diet and sedentary habits in the last century, is one of the main contributors to the incremental trend in CVD. The variable increase rate of CVD in different nations may reflect different stages of "epidemiological transition" and it is probable that the relatively slow changes seen in developing populations through the epidemiological transition may occur at an accelerated pace in individuals migrating from nations in need to affluent societies (i.e. Hispanics to the USA, Africans to Europe). Because of restrained economic conditions in the developing world, the greatest gains in controlling the CVD epidemic lies in its prevention. Healthy foods should be widely available and affordable, and healthy dietary practices such as increased consumption of fresh fruits and vegetables, reduced consumption of saturated fat, salt, and simple sugars, may be promoted in all populations. Specific strategies for smoking and overweight control may be regulation of marketed tobacco and unhealthy fast food and promotion of an active lifestyle. Greater longevity and economic progress are accompanied by an increasing burden of CVD and other chronic diseases with an important decrease in quality of life, which should question the benefit of these additional years without

  17. 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

  18. Age Related Patterns of Disease and Mortality in Hospitalised Adults in Malawi

    PubMed Central

    Allain, Theresa J.; Aston, Stephen; Mapurisa, Gugulethu; Ganiza, Thokozani N.; Banda, Ndaziona P.; Sakala, Servace; Gonani, Andrew; Heyderman, Robert S.; Peterson, Ingrid

    2017-01-01

    Background The epidemic of non-communicable diseases (NCDs) in low and middle income countries (LMICs) is widely recognised as the next major challenge to global health. However, in many LMICs, infectious diseases are still prevalent resulting in a “double burden” of disease. With increased life expectancy and longevity with HIV, older adults may particularly be at risk of this double burden. Here we describe the relative contributions of infections and NCDs to hospital admissions and mortality, according to age, in Malawi’s largest hospital. Methods Primary diagnosis on discharge/death, mortality rates, and HIV status were recorded prospectively on consecutive adult medical in-patients over 2 years using an electronic medical records system. Diagnoses were classified as infections or NCDs and analysed according to age and gender. Findings 10,191 records were analysed. Overall, infectious diseases, particularly those associated with HIV, were the leading cause of admission. However, in adults ≥55 years, NCDs were the commonest diagnoses. In adults <55 years 71% of deaths were due to infections whereas in adults ≥55 years 56% of deaths were due to NCDs. Interpretation Infectious diseases are still the leading cause of adult admission to a central hospital in Malawi but in adults aged ≥55 years NCDs are the most frequent diagnoses. HIV was an underlying factor in the majority of adults with infections and was also present in 53% of those with NCDs. These findings highlight the need for further health sector shifts to address the double burden of infectious and NCDs, particularly in the ageing population. PMID:28099438

  19. Effect of age on left ventricular function during exercise in patients with coronary artery disease

    SciTech Connect

    Hakki, A.H.; DePace, N.L.; Iskandrian, A.S.

    1983-10-01

    The purpose of this study was to assess the effect of age on left ventricular performance during exercise in 79 patients with coronary artery disease (greater than or equal to 50% narrowing of one or more major coronary arteries). Fifty patients under the age of 60 years (group I) and 29 patients 60 years or older (group II) were studied. Radionuclide angiograms were obtained at rest and during symptom-limited upright bicycle exercise. The history of hypertension, angina or Q wave myocardial infarction was similar in both groups. Multivessel coronary artery disease was present in 30 patients (60%) in group I and in 19 patients (66%) in group II (p . not significant). There were no significant differences between the two groups in the hemodynamic variables (at rest or during exercise) of left ventricular ejection fraction, end-diastolic volume, end-systolic volume and cardiac index. Exercise tolerance was higher in group I than in group II (7.8 +/- 0.4 versus 5.7 +/- 0.4 minutes, p . 0.009), although the exercise heart rate and rate-pressure product were not significantly different between the groups. There was poor correlation between age and ejection fraction, end-diastolic volume and end-systolic volume at rest and during exercise. Abnormal left ventricular function at rest or an abnormal response to exercise was noted in 42 patients (84%) in group I and in 25 patients (86%) in group II (p . not significant). Thus, in patients with coronary artery disease, age does not influence left ventricular function at rest or response to exercise. Older patients with coronary artery disease show changes in left ventricular function similar to those in younger patients with corresponding severity of coronary artery disease.

  20. Effect of age on left ventricular function during exercise in patients with coronary artery disease.

    PubMed

    Hakki, A H; DePace, N L; Iskandrian, A S

    1983-10-01

    The purpose of this study was to assess the effect of age on left ventricular performance during exercise in 79 patients with coronary artery disease (greater than or equal to 50% narrowing of one or more major coronary arteries). Fifty patients under the age of 60 years (group I) and 29 patients 60 years or older (group II) were studied. Radionuclide angiograms were obtained at rest and during symptom-limited upright bicycle exercise. The history of hypertension, angina or Q wave myocardial infarction was similar in both groups. Multivessel coronary artery disease was present in 30 patients (60%) in group I and in 19 patients (66%) in group II (p = not significant). There were no significant differences between the two groups in the hemodynamic variables (at rest or during exercise) of left ventricular ejection fraction, end-diastolic volume, end-systolic volume and cardiac index. Exercise tolerance was higher in group I than in group II (7.8 +/- 0.4 versus 5.7 +/- 0.4 minutes, p = 0.009), although the exercise heart rate and rate-pressure product were not significantly different between the groups. There was poor correlation between age and ejection fraction, end-diastolic volume and end-systolic volume at rest and during exercise. Abnormal left ventricular function at rest or an abnormal response to exercise was noted in 42 patients (84%) in group I and in 25 patients (86%) in group II (p = not significant). Thus, in patients with coronary artery disease, age does not influence left ventricular function at rest or response to exercise. Older patients with coronary artery disease show changes in left ventricular function similar to those in younger patients with corresponding severity of coronary artery disease.

  1. Levodopa, vitamins, ageing and the neuropathy of Parkinson's disease.

    PubMed

    Rajabally, Yusuf A; Martey, Jean

    2013-11-01

    Higher prevalence of neuropathy has been described in patients with Parkinson's disease (PD) in comparison with age and gender-matched controls. The cause of neuropathy may be levodopa-induced impairment of vitamin B12 metabolism, suggesting levodopa-naïve subjects should be unaffected. There may, however, be other yet unidentified determinants of neuropathy in PD. We screened 33 consecutive levodopa-naïve PD patients for neuropathy. Demographics, vitamin B12 and folate levels were studied. Findings were analyzed in the light of our previous available data on levodopa-treated PD patients. Four of 33 (12.1 %) levodopa-naïve PD patients were diagnosed with neuropathy. This compared to 13/36 (36.1 %) previously evaluated levodopa-treated patients (p = 0.027) and 3/37 controls (p = 0.7). Analysis of our whole PD cohort consisting of a total of 70 subjects, including levodopa-naïve and levodopa-treated patients, revealed that neuropathy correlated with use of levodopa (p = 0.041), cumulative levodopa exposure (p = 0.046), age at time of study (p = 0.005) and serum folate levels <10 μg/L (p = 0.003). There was no association of neuropathy with PD duration. Multivariate regression analysis showed that neuropathy was only independently associated with age (p = 0.016) and serum folate levels <10 μg/L (p = 0.012). We conclude that this study confirms the roles of levodopa usage and cumulative levodopa exposure in the neuropathy of PD. However, the effects of levodopa only appear contributory and are surpassed by age and lower folate levels. In view of the independent implication of lower folate levels, the need for preventative/protective supplementation including folate in addition to vitamin B12, probably irrespective of levodopa use, may deserve consideration in patients with PD.

  2. Enzyme Replacement Therapy in Mucopolysaccharidosis II Patients Under 1 Year of Age.

    PubMed

    Lampe, Christina; Atherton, Andrea; Burton, Barbara K; Descartes, Maria; Giugliani, Roberto; Horovitz, Dafne D G; Kyosen, Sandra O; Magalhães, Tatiana S P C; Martins, Ana Maria; Mendelsohn, Nancy J; Muenzer, Joseph; Smith, Laurie D

    2014-01-01

    Mucopolysaccharidosis (MPS) II, or Hunter syndrome, is a lysosomal storage disease characterized by multi-systemic involvement and a progressive clinical course. Enzyme replacement therapy with idursulfase has been approved in more than 50 countries worldwide; however, safety and efficacy data from clinical studies are currently only available for patients 1.4 years of age and older. Sibling case studies of infants with MPS I, II, and VI who initiated ERT in the first weeks or months of life have reported no new safety concerns and a more favorable clinical course for the sibling treated in infancy than for the later-treated sibling. Here we describe our experiences with a case series of eight MPS II patients for whom idursulfase treatment was initiated at under 1 year of age. The majority of the patients were diagnosed because of a family history of disease. All of the infants displayed abnormalities consistent with MPS II at diagnosis. The youngest age at treatment start was 10 days and the oldest was 6.5 months, with duration of treatment varying between 6 weeks and 5.5 years. No new safety concerns were observed, and none of the patients experienced an infusion-related reaction. All of the patients treated for more than 6 weeks showed improvements and/or stabilization of some somatic manifestations while on treatment. In some cases, caregivers made comparisons with other affected family members and reported that the early-treated patients experienced a less severe clinical course, although a lack of medical records for many family members precluded a rigorous comparison.

  3. 42 CFR 440.160 - Inpatient psychiatric services for individuals under age 21.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Definitions § 440.160 Inpatient psychiatric services for individuals under age 21. “Inpatient psychiatric... 42 Public Health 4 2010-10-01 2010-10-01 false Inpatient psychiatric services for individuals under age 21. 440.160 Section 440.160 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES,...

  4. 25 CFR 117.3 - Payment of taxes of Indians under 21 years of age.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Payment of taxes of Indians under 21 years of age. 117.3... CERTIFICATES OF COMPETENCY § 117.3 Payment of taxes of Indians under 21 years of age. All taxes assessed... direct to the collector from the rents and income derived from such lands, and the balance, if any,...

  5. 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…

  6. 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…

  7. Onset of mortality increase with age and age trajectories of mortality from all diseases in the four Nordic countries

    PubMed Central

    Dolejs, Josef; Marešová, Petra

    2017-01-01

    Background The answer to the question “At what age does aging begin?” is tightly related to the question “Where is the onset of mortality increase with age?” Age affects mortality rates from all diseases differently than it affects mortality rates from nonbiological causes. Mortality increase with age in adult populations has been modeled by many authors, and little attention has been given to mortality decrease with age after birth. Materials and methods Nonbiological causes are excluded, and the category “all diseases” is studied. It is analyzed in Denmark, Finland, Norway, and Sweden during the period 1994–2011, and all possible models are screened. Age trajectories of mortality are analyzed separately: before the age category where mortality reaches its minimal value and after the age category. Results Resulting age trajectories from all diseases showed a strong minimum, which was hidden in total mortality. The inverse proportion between mortality and age fitted in 54 of 58 cases before mortality minimum. The Gompertz model with two parameters fitted as mortality increased with age in 17 of 58 cases after mortality minimum, and the Gompertz model with a small positive quadratic term fitted data in the remaining 41 cases. The mean age where mortality reached minimal value was 8 (95% confidence interval 7.05–8.95) years. The figures depict an age where the human population has a minimal risk of death from biological causes. Conclusion Inverse proportion and the Gompertz model fitted data on both sides of the mortality minimum, and three parameters determined the shape of the age–mortality trajectory. Life expectancy should be determined by the two standard Gompertz parameters and also by the single parameter in the model c/x. All-disease mortality represents an alternative tool to study the impact of age. All results are based on published data. PMID:28176929

  8. Basic and Clinical Research Against Advanced Glycation End Products (AGEs): New Compounds to Tackle Cardiovascular Disease and Diabetic Complications.

    PubMed

    Nenna, Antonio; Spadaccio, Cristiano; Lusini, Mario; Ulianich, Luca; Chello, Massimo; Nappi, Francesco

    2015-01-01

    Diabetes is a major risk factor for cardiovascular disease, and recent advances in research indicate that a detailed understanding of the pathophysiology of its effects is mandatory to reduce diabetes-related mortality and morbidity. Advanced Glycation End Products (AGEs) play a central role in the genesis and progression of complications of both type 1 and type 2 diabetes mellitus, and have been found to be important even in non-diabetic patients as a marker of cardiovascular disease. AGEs have a profound impact on patient's prognosis regardless of the glycemic control, and therefore pharmacologic approaches against AGEs accumulation have been proposed over the years to treat cardiovascular diseases, parallel to a more detailed understanding of AGEs pathophysiology. Compounds with anti-AGEs effects are currently under investigation in both pre-clinical and clinical scenarios, and many of the drugs previously used to treat specific diseases have been found to have AGE-inhibitory effects. Some products are still in "bench evaluation", whereas others have been already investigated in clinical trials with conflicting evidences. This review aims at summarizing the mechanisms of AGEs formation and accumulation, and the most relevant issues in pre-clinical and clinical experiences in anti-AGEs treatment in cardiovascular research.

  9. Cerebrovascular disease, beta-amyloid and cognition in aging

    PubMed Central

    Marchant, Natalie L.; Reed, Bruce R.; DeCarli, Charles S.; Madison, Cindee M.; Weiner, Michael W.; Chui, Helena C.; Jagust, William J.

    2011-01-01

    The present study evaluated cerebrovascular disease (CVD), β-amyloid (Aβ), and cognition in clinically normal elderly adults. Fifty-four participants underwent MRI, PIB-PET imaging, and neuropsychological evaluation. High white matter hyperintensity burden and/or presence of infarct defined CVD status (CVD−: N = 27; CVD+: N = 27). PIB-PET ratios of Aβ deposition were extracted using Logan plotting (cerebellar reference). Presence of high levels of Aβ in prespecified regions determined PIB status (PIB−: N = 33; PIB+: N = 21). Executive functioning and episodic memory were measured using composite scales. CVD and Aβ, defined as dichotomous or continuous variables, were unrelated to one another. CVD+ participants showed lower executive functioning (P = 0.001) when compared to CVD− individuals. Neither PIB status nor amount of Aβ affected cognition (Ps ≥ .45), and there was no statistical interaction between CVD and PIB on either cognitive measure. Within this spectrum of normal aging CVD and Aβ aggregation appear to be independent processes with CVD primarily affecting cognition. PMID:22048124

  10. [Discussions on acute pharyngo - laryngeal diseases treated with acupuncture by physicians of successive ages].

    PubMed

    Zhang, Y; Li, Z

    1999-07-01

    Originated from Neijing, the acupuncture treatment for acute pharyngo-laryngeal diseases was applied by Zhang Zhongjing under the guidance of Neijing and many acupuncture treatments for the disorders were mentioned by Huangfu Mi in his first monograph on acupuncture- moxibustion. Sun Simiao of the Tang dynasty further developed this technique and different therapeutic styles were developed by the Four Schools of Jinyuan dynasties. It was further supplemented by Yang Jizhou and Xue Ji of the Ming dynasty, and the scope of acupuncture treatment was further expanded by Zheng Meijian with disciplinary features and therapeutic mechanism. All the above descriptions from successive ages further pushed forward the development in this field.

  11. NOX4 NADPH Oxidase-Dependent Mitochondrial Oxidative Stress in Aging-Associated Cardiovascular Disease

    PubMed Central

    Vendrov, Aleksandr E.; Vendrov, Kimberly C.; Smith, Alberto; Yuan, Jinling; Sumida, Arihiro; Robidoux, Jacques; Madamanchi, Nageswara R.

    2015-01-01

    Abstract Aims: Increased oxidative stress and vascular inflammation are implicated in increased cardiovascular disease (CVD) incidence with age. We and others demonstrated that NOX1/2 NADPH oxidase inhibition, by genetic deletion of p47phox, in Apoe−/− mice decreases vascular reactive oxygen species (ROS) generation and atherosclerosis in young age. The present study examined whether NOX1/2 NADPH oxidases are also pivotal to aging-associated CVD. Results: Both aged (16 months) Apoe−/− and Apoe−/−/p47phox−/− mice had increased atherosclerotic lesion area, aortic stiffness, and systolic dysfunction compared with young (4 months) cohorts. Cellular and mitochondrial ROS (mtROS) levels were significantly higher in aortic wall and vascular smooth muscle cells (VSMCs) from aged wild-type and p47phox−/− mice. VSMCs from aged mice had increased mitochondrial protein oxidation and dysfunction and increased vascular cell adhesion molecule 1 expression, which was abrogated with (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (MitoTEMPO) treatment. NOX4 expression was increased in the vasculature and mitochondria of aged mice and its suppression with shRNA in VSMCs from aged mice decreased mtROS levels and improved function. Increased mtROS levels were associated with enhanced mitochondrial NOX4 expression in aortic VSMCs from aged subjects, and NOX4 expression levels in arterial wall correlated with age and atherosclerotic severity. Aged Apoe−/− mice treated with MitoTEMPO and 2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione had decreased vascular ROS levels and atherosclerosis and preserved vascular and cardiac function. Innovation and Conclusion: These data suggest that NOX4, but not NOX1/2, and mitochondrial oxidative stress are mediators of CVD in aging under hyperlipidemic conditions. Regulating NOX4 activity/expression and using mitochondrial antioxidants are

  12. 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

  13. 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

  14. The microbiome and disease: reviewing the links between the oral microbiome, aging, and Alzheimer's disease.

    PubMed

    Shoemark, Deborah K; Allen, Shelley J

    2015-01-01

    This review, gathered from diverse sources, shows how our microbiome influences health and ultimately how well we age. Evidence linking oral bacteria to Alzheimer's disease (AD) is discussed in the context of aging, drawing together data from epidemiological, experimental, genetic, and environmental studies. Immunosenescence results in increased bacterial load as cell-mediated and humoral immune responses wane. The innate immune system gradually takes over; contributing to the rise in circulating proinflammatory cytokines such as TNFα. Maintaining the integrity of the blood-brain barrier (BBB) against a backdrop of increasing bacterial load is important. Aging may favor the proliferation of anaerobes in the mouth eliciting a robust TNFα response from the oral epithelium. Prolonged exposure to high levels of circulating TNFα compromises the integrity of the BBB. Sensitive techniques now detect the "asymptomatic" presence of bacteria in areas previously thought to be sterile, providing new insights into the wider distribution of components of the microbiome. These "immune-tolerated" bacteria may slowly multiply elsewhere until they elicit a chronic inflammatory response; some are now considered causal in instances of atherosclerosis and back pain. Inflammatory processes have long been associated with AD. We propose for a subset of AD patients, aging favors the overgrowth of oral anaerobes established earlier in life provoking a pro-inflammatory innate response that weakens the BBB allowing bacteria to spread and quietly influence the pathogenesis of AD. Finally, we suggest that human polymorphisms considered alongside components of the microbiome may provide new avenues of research for the prevention and treatment of disease.

  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. Characterization of Finnish Building materials under salt frost artificial ageing

    NASA Astrophysics Data System (ADS)

    Luodes, Nike M.; Torppa, Akseli; Pirinen, Heikki; Bellopede, Rossana; Marini, Paola

    2016-04-01

    Under a national project co financed by the Confederation of Finnish Construction Industries RT (CFCI), the Finnish Natural Stone Association and the Geological Survey of Finland (GTK), and thanks to the cooperation with the Polytechnic of Turin a comprehensive number of Finnish natural stones has been tested according to SFS EN standards for national CE marking and according to non standardized methods for research purposes. The aim was to evaluate the effects of combined salt and frost weathering caused by de-icing salts and to research a possible correlation between laboratory's accelerated decay and site weathering. The materials tested (60 stones in total) are mainly silicate rocks showing good resistance to the weathering. Results have been affected in some cases by uncertainties connected to the variation of material quality. Some materials have been from new quarries and variation of their properties has been higher than the effects of artificial weathering. Material sampled from crop presented higher weathering level and the additional artificial weathering has induced small variations. Results have shown that material weathering has been better represented by variation of flexural strength compared to uniaxial compressive strength. The most probable reason has been that small changes of planarity and perpendicularity had greater effects on the compressive strength than variations by weathering. Fifteen representative typologies of natural stones have been tested with non standardized methodologies to study the changes of the material and finding a possible correlation with methods used on site. Schmidt rebound test and Ultra Pulse Velocity (UPV) have been used on site to assess the durability of stone on construction. Materials tested in laboratory have shown less variation between rebounds compared to site tests, this can be because of a more controlled environment and saw cut surface instead of rocky or chiselled ones. Laboratory tests showed an average

  17. Measures of Chronic Conditions and Diseases Associated With Aging in the National Social Life, Health, and Aging Project

    PubMed Central

    Pham-Kanter, Genevieve; Leitsch, Sara A.

    2009-01-01

    Objectives This paper presents a description of the methods used in the National Social Life, Health, and Aging Project to detect the presence of chronic conditions and diseases associated with aging. It also discusses the validity and distribution of these measures. Methods Markers associated with common chronic diseases and conditions of aging were collected from 3,005 community-dwelling older adults living in the United States, aged 57–85 years, during 2006. Dried blood spots, physical function tests, anthropometric measurements, self-reported history, and self-rated assessments were used to detect the presence of chronic conditions associated with aging or of risk factors associated with the development of chronic diseases. Results The distribution of each measure, disaggregated by age group and gender, is presented. Conclusions This paper describes the methodology used as well as the distribution of each of these measures. In addition, we discuss how the measures used in the study relate to specific chronic diseases and conditions associated with aging and how these measures might be used in social science analyses. PMID:19204070

  18. [Functional, involutional and pathological oral changes with age. 6. Systemic disease].

    PubMed

    Castellanos, J L; Díaz Guzman, L

    1990-01-01

    The present study was realized to determine the frequency variety and concentration of old and new health disease in patients attending a school of Dentistry, classification to an age variable. This paper ends a series of articles about estomatological changes associated to an aging process. The main findings indicate that when patients grow older an increment in variety and number of pathological personal background. The results suggest a very well defined difference in the prevalence and concentration among subjects over and under 50 years. The risk factor was 1:1 in patients older than that. The importance of considering the Clinical history in patients as a determining factor in the global dental evaluation, for the decision. making in treatment planning.

  19. Systems biological approach on neurological disorders: a novel molecular connectivity to aging and psychiatric diseases

    PubMed Central

    2011-01-01

    Background Systems biological approach of molecular connectivity map has reached to a great interest to understand the gene functional similarities between the diseases. In this study, we developed a computational framework to build molecular connectivity maps by integrating mutated and differentially expressed genes of neurological and psychiatric diseases to determine its relationship with aging. Results The systematic large-scale analyses of 124 human diseases create three classes of molecular connectivity maps. First, molecular interaction of disease protein network generates 3632 proteins with 6172 interactions, which determines the common genes/proteins between diseases. Second, Disease-disease network includes 4845 positively scored disease-disease relationships. The comparison of these disease-disease pairs with Medical Subject Headings (MeSH) classification tree suggests 25% of the disease-disease pairs were in same disease area. The remaining can be a novel disease-disease relationship based on gene/protein similarity. Inclusion of aging genes set showed 79 neurological and 20 psychiatric diseases have the strong association with aging. Third and lastly, a curated disease biomarker network was created by relating the proteins/genes in specific disease contexts, such analysis showed 73 markers for 24 diseases. Further, the overall quality of the results was achieved by a series of statistical methods, to avoid insignificant data in biological networks. Conclusions This study improves the understanding of the complex interactions that occur between neurological and psychiatric diseases with aging, which lead to determine the diagnostic markers. Also, the disease-disease association results could be helpful to determine the symptom relationships between neurological and psychiatric diseases. Together, our study presents many research opportunities in post-genomic biomarkers development. PMID:21226925

  20. Scientific truth or false hope? Understanding Alzheimer's disease from an aging perspective.

    PubMed

    Chen, Ming; Maleski, Jerome J; Sawmiller, Darrell R

    2011-01-01

    In this paper, we argue that the current official definition for Alzheimer's disease is misleading, since it defines senile dementia (SD), a long-known incurable senile/geriatric condition, as a discrete/curable disease. This overly optimistic definition was incepted in the 1970s amid the public's fear of the upcoming SD crisis and desperate hope for a cure. Scientifically, however, it has overturned Alois Alzheimer's age-based concept for disease classification-the essence of modern Geriatric Medicine and the National Institute of Aging. Thus, the current definition for SD, though socially and politically appealing, would be scientifically flawed. As an authoritative study guideline, it has caused profound and far-reaching confusions in research by misleading attention to the presumptive pathogenic/erroneous factors as drug targets for "silver bullets". Such well-intentioned studies would generate numerous data, but render SD a scientific and logical enigma. In this context we discuss: 1) why and how senile conditions including SD differ from discrete diseases by origin, thus also by study paradigm and intervention strategy; 2) why senile conditions may not be explained by abnormal/pathogenic factors, but logically should be explained by "normal" elements in life, perhaps advanced aging plus risk factors; and 3) why the "amyloid-β toxicity" controversy, a simple scientific issue, has lasted for so long. Finally, we ask: can scientific inquiry preserve its integrity and objectivity under social pressure? It appears that these fundamental questions warrant serious attention if the scientific nature of SD is to be eventually understood.

  1. Association between MAPT haplotype and memory function in patients with Parkinson's disease and healthy aging individuals.

    PubMed

    Winder-Rhodes, Sophie E; Hampshire, Adam; Rowe, James B; Peelle, Jonathan E; Robbins, Trevor W; Owen, Adrian M; Barker, Roger A

    2015-03-01

    Genetic variation is associated with differences in the function of the brain as well as its susceptibility to disease. The common H1 haplotypic variant of the microtubule-associated protein tau gene (MAPT) has been related to an increased risk for Parkinson's disease (PD). Furthermore, among PD patients, H1 homozygotes have an accelerated progression to dementia. We investigated the neurocognitive correlates of MAPT haplotypes using functional magnetic resonance imaging. Thirty-seven nondemented patients with PD (19 H1/H1, 18 H2 carriers) and 40 age-matched controls (21 H1/H1, 19 H2 carriers) were scanned during performance of a picture memory encoding task. Behaviorally, H1 homozygosity was associated with impaired picture recognition memory in PD patients and control subjects. These impairments in the H1 homozygotes were accompanied by an altered blood-oxygen level-dependent response in the medial temporal lobe during successful memory encoding. Additional age-related differences in blood-oxygen level-dependent response were observed in the medial temporal lobes of H1 homozygotes with PD. These results suggest that common variation in MAPT is not only associated with the dementia of PD but also differences in the neural circuitry underlying aspects of cognition in normal aging.

  2. Implementation of an active aging model in Mexico for prevention and control of chronic diseases in the elderly

    PubMed Central

    Mendoza-Núñez, Víctor Manuel; Martínez-Maldonado, María de la Luz; Correa-Muñoz, Elsa

    2009-01-01

    Background World Health Organization cites among the main challenges of populational aging the dual disease burden: the greater risk of disability, and the need for care. In this sense, the most frequent chronic diseases during old age worldwide are high blood pressure, type 2 diabetes mellitus, cancer, arthritis, osteoporosis, depression, and dementia. Chronic disease-associated dependency represents an onerous sanitary and financial burden for the older adult, the family, and the health care system. Thus, it is necessary to propose community-level models for chronic disease prevention and control in old age. The aim of the present work is to show our experience in the development and implementation of a model for chronic disease prevention and control in old age at the community level under the active aging paradigm. Methods/Design A longitudinal study will be carried out in a sample of 400 elderly urban and rural-dwelling individuals residing in Hidalgo State, Mexico during five years. All participants will be enrolled in the model active aging. This establishes the formation of 40 gerontological promoters (GPs) from among the older adults themselves. The GPs function as mutual-help group coordinators (gerontological nuclei) and establish self-care and self-promotion actions for elderly well-being and social development. It will be conformed a big-net of social network of 40 mutual-help groups of ten elderly adults each one, in which self-care is a daily practice for chronic disease prevention and control, as well as for achieving maximal well-being and life quality in old age. Indicators of the model's impact will be (i) therapeutic adherence; (ii) the incidence of the main chronic diseases in old age; (iii) life expectancy without chronic diseases at 60 years of age; (iv) disability adjusted life years lost; (v) years of life lost due to premature mortality, and (vi) years lived with disability. Discussion We propose that the implementation of the model active

  3. What is the impact of age on adult patients with inflammatory bowel disease?

    PubMed Central

    PRELIPCEAN, CRISTINA CIJEVSCHI; MIHAI, CĂTĂLINA; GOGALNICEANU, PETRUŢ; MIHAI, BOGDAN

    2013-01-01

    Inflammatory bowel disease (IBD) is a chronic disease that affects both young adults and also the elderly. This article emphasises the particularities related to age in the epidemiology, diagnosis, natural course of the disease, prognosis and therapy of adult patients with IBD. Even though the main characteristics in geriatric populations with IBD may not differ much from those in younger patients, distinct problems exist. The majority of IBD studies were performed on young subjects, younger than 40 years of age. The optimal therapeutic choice in young individuals with IBD is a challenge for the physician who needs to take in account the risk of untreated or suboptimally treated chronic intestinal inflammation, long term prognosis, quality of life, the impact of side-effects of aggressive therapeutic approaches, the impact on pregnancy, as well as personal and healthcare costs. The diagnosis in elderly patients can be challenging due to the large number of conditions that mimic IBD. 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 in account. The risks associated with the use of some IBD medications may be increased in older patients, but so is the risk of under-treated IBD and surgery. PMID:26527906

  4. Roles of O-GlcNAc in chronic diseases of aging.

    PubMed

    Banerjee, Partha S; Lagerlöf, Olof; Hart, Gerald W

    2016-10-01

    O-GlcNAcylation, a dynamic nutrient and stress sensitive post-translational modification, occurs on myriad proteins in the cell nucleus, cytoplasm and mitochondria. O-GlcNAcylation serves as a nutrient sensor to regulate signaling, transcription, translation, cell division, metabolism, and stress sensitivity in all cells. Aberrant protein O-GlcNAcylation plays a critical role both in the development, as well as in the progression of a variety of age related diseases. O-GlcNAcylation underlies the etiology of diabetes, and changes in specific protein O-GlcNAc levels and sites are responsible for insulin expression and sensitivity and glucose toxicity. Abnormal O-GlcNAcylation contributes directly to diabetes related dysfunction of the heart, kidney and eyes and affects progression of cardiomyopathy, nephropathy and retinopathy. O-GlcNAcylation is a critical modification in the brain and plays a role in both plaque and tangle formation, thus making its study important in neurodegenerative disorders. O-GlcNAcylation also affects cellular growth and metabolism during the development and metastasis of cancer. Finally, alterations in O-GlcNAcylation of transcription factors in macrophages and lymphocytes affect inflammation and cytokine production. Thus, O-GlcNAcylation plays key roles in many of the major diseases associated with aging. Elucidation of its specific functions in both normal and diseased tissues is likely to uncover totally novel avenues for therapeutic intervention.

  5. Cerebral hemodynamics of the aging brain: risk of Alzheimer disease and benefit of aerobic exercise.

    PubMed

    Tarumi, Takashi; Zhang, Rong

    2014-01-01

    Alzheimer disease (AD) and cerebrovascular disease often coexist with advanced age. Mounting evidence indicates that the presence of vascular disease and its risk factors increase the risk of AD, suggesting a potential overlap of the underlying pathophysiological mechanisms. In particular, atherosclerosis, endothelial dysfunction, and stiffening of central elastic arteries have been shown to associate with AD. Currently, there are no effective treatments for the cure and prevention of AD. Vascular risk factors are modifiable via either pharmacological or lifestyle intervention. In this regard, habitual aerobic exercise is increasingly recognized for its benefits on brain structure and cognitive function. Considering the well-established benefits of regular aerobic exercise on vascular health, exercise-related improvements in brain structure and cognitive function may be mediated by vascular adaptations. In this review, we will present the current evidence for the physiological mechanisms by which vascular health alters the structural and functional integrity of the aging brain and how improvements in vascular health, via regular aerobic exercise, potentially benefits cognitive function.

  6. Under pressure: pulmonary hypertension associated with left heart disease.

    PubMed

    Farber, Harrison W; Gibbs, Simon

    2015-12-01

    Pulmonary hypertension (PH) associated with left heart disease (PH-LHD) is the most common type of PH, but its natural history is not well understood. PH-LHD is diagnosed by right heart catheterisation with a mean pulmonary arterial pressure ≥25 mmHg and a pulmonary capillary wedge pressure >15 mmHg. The primary causes of PH-LHD are left ventricular dysfunction of systolic and diastolic origin, and valvular disease. Prognosis is poor and survival rates are low. Limited progress has been made towards specific therapies for PH-LHD, and management focuses on addressing the underlying cause of the disease with supportive therapies, surgery and pharmacological treatments. Clinical trials of therapies for pulmonary arterial hypertension in patients with PH-LHD have thus far been limited and have provided disappointing or conflicting results. Robust, long-term clinical studies in appropriate target populations have the potential to improve the outlook for patients with PH-LHD. Herein, we discuss the knowledge gaps in our understanding of PH-LHD, and describe the current unmet needs and challenges that are faced by clinicians when identifying and managing patients with this disease.

  7. Ewing Sarcoma of the Bone in Children under 6 Years of Age

    PubMed Central

    De Ioris, Maria Antonietta; Prete, Arcangelo; Cozza, Raffaele; Podda, Marta; Manzitti, Carla; Pession, Andrea; Schiavello, Elisabetta; Contoli, Benedetta; Balter, Rita; Fagioli, Franca; Bisogno, Gianni; Amoroso, Loredana

    2013-01-01

    Background Ewing Sarcoma Family Tumours (ESFT) are rare in early childhood. The aim of this study was to report the clinical characteristics and outcome of children under 6 years of age affected by ESFT of the bone in Italy. Methods The records of all the children diagnosed with osseous ESFT in centres members of the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) from 1990 to 2008 were reviewed. The Kaplan–Meier method was used for estimating overall and progression-free survival (OS, PFS) curves; multivariate analyses were performed using Cox proportional hazards regression model. Results This study includes 62 patients. An axial primary localization was present in 66% of patients, with the primary site in the chest wall in 34%. Fourteen (23%) patients presented metastatic disease. The 5-year OS and PFS were 73% (95% confidence interval, CI, 58–83%) and 72% (95% CI 57–83%) for patients with localized disease and 38% (95% CI 17–60%) and 21% (95% CI 5–45%) for patients with metastatic disease. Metastatic spread, skull/pelvis/spine primary localization, progression during treatment and no surgery predicted worse survival (P<0.01), while patients treated in the last decade had better survival (P  = 0.002). In fact, the 5-year OS and PFS for patients diagnosed in the period 2000–2008 were 89% (95% CI 71–96%) and 86% (95% CI 66–94%), respectively. Conclusion The axial localization is the most common site of ESFT in pre-scholar children. Patients treated in the most recent period have an excellent outcome. PMID:23382839

  8. [Consensus document on pneumococcal vaccination in adults at risk by age and underlying clinical conditions. 2017 Update].

    PubMed

    González-Romo, F; Picazo, J J; García Rojas, A; Labrador Horrillo, M; Barrios, V; Magro, M C; Gil Gregorio, P; de la Cámara, R; Rodríguez, A; Barberán, J; Botía Martínez, F; Linares Rufo, M; Jimeno Sanz, I; Portolés, J M; Sanz Herrero, F; Espinosa Arranz, J; García-Sánchez, V; Galindo Izquierdo, M; Mascarós, E

    2017-04-01

    Invasive pneumococcal disease (IPD) and pneumococcal pneumonia (PP) represent an important health problem among aging adults and those with certain underlying pathologies and some diseases, especially immunosuppressed and some immunocompetent subjects, who are more susceptible to infections and present greater severity and worse evolution. Among the strategies to prevent IPD and PP, vaccination has its place, although vaccination coverage in this group is lower than desirable. Nowadays, there are 2 vaccines available for adults. Polysacharide vaccine (PPV23), used in patients aged 2 and older since decades ago, includes a greater number of serotypes (23), but it does not generate immune memory, antibody levels decrease with time, causes an immune tolerance phenomenon, and have no effect on nasopharyngeal colonization. PCV13 can be used from children 6 weeks of age to elderly and generates an immune response more powerful than PPV23 against most of the 13 serotypes included in it. In the year 2013 the 16 most directly related to groups of risk of presenting IPD publised a series of vaccine recommendations based on scientific evidence regarding anti-pneumococcal vaccination in adults with underlying pathologies and special conditions. A commitment was made about updating it if new scientific evidence became available. We present an exhaustive revised document focusing mainly in recommendation by age in which some more Scientific Societies have been involved.

  9. 29 CFR 570.38 - Effect of a certificate of age under this subpart.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Employment of Minors Between 14 and 16 Years of Age (Child Labor Reg. 3) § 570.38 Effect of a certificate of age under this subpart... to the periods specified in § 570.35, shall not be deemed to constitute oppressive child labor...

  10. 29 CFR 570.38 - Effect of a certificate of age under this subpart.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Employment of Minors Between 14 and 16 Years of Age (Child Labor Reg. 3) § 570.38 Effect of a certificate of age under this subpart... to the periods specified in § 570.35, shall not be deemed to constitute oppressive child labor...

  11. 29 CFR 570.38 - Effect of a certificate of age under this subpart.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Employment of Minors Between 14 and 16 Years of Age (Child Labor Reg. 3) § 570.38 Effect of a certificate of age under this subpart... to the periods specified in § 570.35, shall not be deemed to constitute oppressive child labor...

  12. 29 CFR 570.38 - Effect of a certificate of age under this subpart.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Employment of Minors Between 14 and 16 Years of Age (Child Labor Reg. 3) § 570.38 Effect of a certificate of age under this subpart... to the periods specified in § 570.35, shall not be deemed to constitute oppressive child labor...

  13. 29 CFR 570.36 - Effect of a certificate of age under this subpart.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Employment of Minors Between 14 and 16 Years of Age (Child Labor Reg. 3) § 570.36 Effect of a certificate of age under this subpart... be deemed to constitute oppressive child labor within the meaning of the act if the employer...

  14. 29 CFR 780.321 - Minors 16 years of age or under.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Employment in Agriculture That Is Exempted From the Minimum Wage and Overtime Pay Requirements Under Section... years of age and the employer must pay to such an employee the applicable statutory minimum wage unless..., although section 13(a)(6)(D) provides a minimum wage and overtime exemption for minors 16 years of age...

  15. 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...

  16. DNA damage response at telomeres contributes to lung aging and chronic obstructive pulmonary disease.

    PubMed

    Birch, Jodie; Anderson, Rhys K; Correia-Melo, Clara; Jurk, Diana; Hewitt, Graeme; Marques, Francisco Madeira; Green, Nicola J; Moisey, Elizabeth; Birrell, Mark A; Belvisi, Maria G; Black, Fiona; Taylor, John J; Fisher, Andrew J; De Soyza, Anthony; Passos, João F

    2015-11-15

    Cellular senescence has been associated with the structural and functional decline observed during physiological lung aging and in chronic obstructive pulmonary disease (COPD). Airway epithelial cells are the first line of defense in the lungs and are important to COPD pathogenesis. However, the mechanisms underlying airway epithelial cell senescence, and particularly the role of telomere dysfunction in this process, are poorly understood. We aimed to investigate telomere dysfunction in airway epithelial cells from patients with COPD, in the aging murine lung and following cigarette smoke exposure. We evaluated colocalization of γ-histone protein 2A.X and telomeres and telomere length in small airway epithelial cells from patients with COPD, during murine lung aging, and following cigarette smoke exposure in vivo and in vitro. We found that telomere-associated DNA damage foci increase in small airway epithelial cells from patients with COPD, without significant telomere shortening detected. With age, telomere-associated foci increase in small airway epithelial cells of the murine lung, which is accelerated by cigarette smoke exposure. Moreover, telomere-associated foci predict age-dependent emphysema, and late-generation Terc null mice, which harbor dysfunctional telomeres, show early-onset emphysema. We found that cigarette smoke accelerates telomere dysfunction via reactive oxygen species in vitro and may be associated with ataxia telangiectasia mutated-dependent secretion of inflammatory cytokines interleukin-6 and -8. We propose that telomeres are highly sensitive to cigarette smoke-induced damage, and telomere dysfunction may underlie decline of lung function observed during aging and in COPD.

  17. Why AMD is a disease of ageing and not of development: mechanisms and insights

    PubMed Central

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

    2014-01-01

    Ageing disorders can be defined as the progressive and cumulative outcome of several defective cellular mechanisms as well as metabolic pathways, consequently resulting in degeneration. Environment plays an important role in its pathogenesis. In contrast, developmental disorders arise from inherited mutations and usually the role of environmental factors in development of disease is minimal. Age related macular degeneration (AMD) is one such retinal degenerative disorder which starts with the progression of age. Metabolism plays an important role in initiation of such diseases of ageing. Cholesterol metabolism and their oxidized products like 7-ketocholesterol have been shown to adversely impact retinal pigment epithelium (RPE) cells. These molecules can initiate mitochondrial apoptotic processes and also influence the complements factors and expression of angiogenic proteins like VEGF etc. In this review we highlight why and how AMD is an ageing disorder and not a developmental disease substantiated by disrupted cholesterol metabolism common to several age related diseases. PMID:25071560

  18. Detection of Epstein-Barr virus genomes in Hodgkin's disease: relation to age.

    PubMed Central

    Jarrett, R F; Gallagher, A; Jones, D B; Alexander, F E; Krajewski, A S; Kelsey, A; Adams, J; Angus, B; Gledhill, S; Wright, D H

    1991-01-01

    An investigation as to whether any particular subgroup of patients with Hodgkin's disease was particularly likely to be Epstein-Barr virus (EBV) genome positive was made on samples from 95 patients. These were grouped according to age and Hodgkin's disease subtype, and analysed using Southern blot analysis. Most samples from children or adults aged 50 years or over contained detectable EBV genomes; samples from young adults were only rarely positive. The differences in EBV positivity by age were highly significant, but there was no significant association between EBV and histological subtype after allowing for the effect of age. The results support the hypothesis that Hodgkin's disease in different age groups may have different aetiologies, and suggest that EBV does have a pathogenetic role in Hodgkin's disease in children and older age groups. Images PMID:1660054

  19. The interrelationship between disease and ageing and the implications for longevity.

    PubMed

    Potter, Paul K

    2015-01-01

    Ageing is generally viewed as a detrimental phenotype; with age comes increasing susceptibility to disease and frailty. Recent data also suggests that disease can result in an increase in ageing phenotypes suggesting a positive feedback loop. It is clear that lifespan can be modified genetically and by interventions in certain organisms but the mechanisms by which this is achieved have not yet been fully elucidated, as indeed is the case for the ageing process itself. Because of the intimate relationship between disease, ageing and ultimately lifespan it is difficult to dissect the effects of individual changes. As we learn more about individual pathways and allelic variants influencing ageing and disease we can begin to unravel the influence of natural selection on these processes.

  20. The Interrelationship between Disease and Ageing and the Implications for Longevity.

    PubMed

    Potter, Paul K

    2015-04-22

    Ageing is generally viewed as a detrimental phenotype; with age comes increasing susceptibility to disease and frailty. Recent data also suggests that disease can result in an increase in ageing phenotypes suggesting a positive feedback loop. It is clear that lifespan can be modified genetically and by interventions in certain organisms but the mechanisms by which this is achieved have not yet been fully elucidated, as indeed is the case for the ageing process itself. Because of the intimate relationship between disease, ageing and ultimately lifespan it is difficult to dissect the effects of individual changes. As we learn more about individual pathways and allelic variants influencing ageing and disease we can begin to unravel the influence of natural selection on these processes.

  1. [Underlying Mechanisms and Management of Refractory Gastroesophageal Reflux Disease].

    PubMed

    Lee, Kwang Jae

    2015-08-01

    The prevalence of gastroesophageal reflux disease (GERD) in South Korea has increased over the past 10 years. Patients with erosive reflux disease (ERD) shows better response to proton pump inhibitors (PPIs) than those with non-erosive reflux disease (NERD). NERD is a heterogeneous condition, showing pathological gastroesophageal reflux or esophageal hypersensitivity to reflux contents. NERD patients with pathological gastroesophageal reflux or hypersensitivity to acid may respond to PPIs. However, many patients with esophageal hypersensitivity to nonacid or functional heartburn do not respond to PPIs. Therefore, careful history and investigations are required when managing patients with refractory GERD who show poor response to conventional dose PPIs. Combined pH-impedance studies and a PPI diagnostic trial are recommended to reveal underlying mechanisms of refractory symptoms. For those with ongoing reflux-related symptoms, split dose administration, change to long-acting PPIs or PPIs less influenced by CYP2C19 genotypes, increasing dose of PPIs, and the addition of alginate preparations, prokinetics, selective serotonin reuptake inhibitors, or tricyclic antidepressants can be considered. Pain modulators, selective serotonin reuptake inhibitors, or tricyclic antidepressants are more likely to be effective for those with reflux-unrelated symptoms. Surgery or endoscopic per oral fundoplication may be effective in selected patients.

  2. Puzzles in modern biology. III.Two kinds of causality in age-related disease.

    PubMed

    Frank, Steven A

    2016-01-01

    The two primary causal dimensions of age-related disease are rate and function. Change in rate of disease development shifts the age of onset. Change in physiological function provides necessary steps in disease progression. A causal factor may alter the rate of physiological change, but that causal factor itself may have no direct physiological role. Alternatively, a causal factor may provide a necessary physiological function, but that causal factor itself may not alter the rate of disease onset. The rate-function duality provides the basis for solving puzzles of age-related disease. Causal factors of cancer illustrate the duality between rate processes of discovery, such as somatic mutation, and necessary physiological functions, such as invasive penetration across tissue barriers. Examples from cancer suggest general principles of age-related disease.

  3. Puzzles in modern biology. III.Two kinds of causality in age-related disease

    PubMed Central

    Frank, Steven A.

    2017-01-01

    The two primary causal dimensions of age-related disease are rate and function. Change in rate of disease development shifts the age of onset. Change in physiological function provides necessary steps in disease progression. A causal factor may alter the rate of physiological change, but that causal factor itself may have no direct physiological role. Alternatively, a causal factor may provide a necessary physiological function, but that causal factor itself may not alter the rate of disease onset. The rate-function duality provides the basis for solving puzzles of age-related disease. Causal factors of cancer illustrate the duality between rate processes of discovery, such as somatic mutation, and necessary physiological functions, such as invasive penetration across tissue barriers. Examples from cancer suggest general principles of age-related disease. PMID:28184283

  4. 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.…

  5. Primary care supply moderates the impact of diseases on self-perceptions of aging.

    PubMed

    Wurm, Susanne; Wolff, Julia K; Schüz, Benjamin

    2014-06-01

    Self-perceptions of aging, important indicators of successful aging, are closely linked to health. Previous research has mainly examined the role of individual factors on self-perceptions of aging, but health is partly dependent on contextual factors such as primary care supply. This study therefore examined whether the impact of diseases on self-perceptions of aging is buffered by primary care supply in the district, as it ensures sustained health care continuity. Nationally representative German survey data on health and self-perceptions of aging (N = 4,442, 40-85 years) were linked to primary care supply (general practitioner density in regional districts). Multilevel modeling shows that the impact of disease burden (multiple illnesses) was buffered by primary care supply: Disease burden was less strongly associated with negative self-perceptions of aging in districts with good primary health care supply. This underlines the importance of health care resources for successful aging.

  6. Disrupting the key circadian regulator CLOCK leads to age-dependent cardiovascular disease.

    PubMed

    Alibhai, Faisal J; LaMarre, Jonathan; Reitz, Cristine J; Tsimakouridze, Elena V; Kroetsch, Jeffrey T; Bolz, Steffen-Sebastian; Shulman, Alex; Steinberg, Samantha; Burris, Thomas P; Oudit, Gavin Y; Martino, Tami A

    2017-04-01

    The circadian mechanism underlies daily rhythms in cardiovascular physiology and rhythm disruption is a major risk factor for heart disease and worse outcomes. However, the role of circadian rhythms is generally clinically unappreciated. Clock is a core component of the circadian mechanism and here we examine the role of Clock as a vital determinant of cardiac physiology and pathophysiology in aging. Clock(Δ19/Δ19) mice develop age-dependent increases in heart weight, hypertrophy, dilation, impaired contractility, and reduced myogenic responsiveness. Young Clock(Δ19/Δ19) hearts express dysregulated mRNAs and miRNAs in the PTEN-AKT signal pathways important for cardiac hypertrophy. We found a rhythm in the Pten gene and PTEN protein in WT hearts; rhythmic oscillations are lost in Clock(Δ19/Δ19) hearts. Changes in PTEN are associated with reduced AKT activation and changes in downstream mediators GSK-3β, PRAS40, and S6K1. Cardiomyocyte cultures confirm that Clock regulates the AKT signalling pathways crucial for cardiac hypertrophy. In old Clock(Δ19/Δ19) mice cardiac AKT, GSK3β, S6K1 phosphorylation are increased, consistent with the development of age-dependent cardiac hypertrophy. Lastly, we show that pharmacological modulation of the circadian mechanism with the REV-ERB agonist SR9009 reduces AKT activation and heart weight in old WT mice. Furthermore, SR9009 attenuates cardiac hypertrophy in mice subjected to transverse aortic constriction (TAC), supporting that the circadian mechanism plays an important role in regulating cardiac growth. These findings demonstrate a crucial role for Clock in growth and renewal; disrupting Clock leads to age-dependent cardiomyopathy. Pharmacological targeting of the circadian mechanism provides a new opportunity for treating heart disease.

  7. Urban groundwater age modeling under unconfined condition - Impact of underground structures on groundwater age: Evidence of a piston effect

    NASA Astrophysics Data System (ADS)

    Attard, Guillaume; Rossier, Yvan; Eisenlohr, Laurent

    2016-04-01

    In this paper, underground structures are shown to have a major influence on the groundwater mean age distribution described as a dispersive piston effect. Urban underground development does not occur without impacts on subsoil resources. In particular, groundwater resources can be vulnerable and generate disturbances when this space is exploited. Groundwater age spatial distribution data are fundamental for resource management as it can provide operational sustainability indicators. However, the application of groundwater age modeling is neglected regarding the potential effect of underground structures in urban areas. A three dimensional modeling approach was conducted to quantify the impact of two underground structures: (1) an impervious structure and (2) a draining structure. Both structures are shown to cause significant mixing processes occurring between shallow and deeper aquifers. The design technique used for draining structures is shown to have the greatest impact, generating a decrease in mean age of more than 80% under the structure. Groundwater age modeling is shown to be relevant for highlighting the role played by underground structures in advective-dispersive flows in urban areas.

  8. A proposed strategy for international collaborative research in brain aging and Alzheimer's disease.

    PubMed

    Khachaturian, Z S; Radebaugh, T S

    1990-01-01

    A description and discussion are given of several of the programmes initiated by the United States' National Institute on Aging that could be expanded to facilitate multicentre collaboration studies. It includes: the Alzheimer's Disease Research Centers; the Alzheimer's Disease Patient Registry Program; the World Health Organization Special Programme for Research on Aging; and how collaborative links with scientists working on this disease in other countries may be established.

  9. Adoption of Gene Expression Profiling for Breast Cancer in US Oncology Practice for Women Under Age 65

    PubMed Central

    O’Neill, Suzanne C.; Isaacs, Claudine; Chao, Calvin; Tsai, Huei-Ting; Liu, Chunfu; Ekezue, Bola F.; Selvam, Nandini; Kessler, Larry G.; Schwartz, Marc D.; Lobo, Tania; Potosky, Arnold L.

    2016-01-01

    Background Four practice guidelines incorporate the use of gene expression profiling (GEP) tests for early-stage, hormone-receptor positive, HER2 negative breast tumors. Few studies describe factors associated with GEP testing in US oncology practice. We assessed the relationship between clinical, demographic, and group-level socioeconomic variables and test use in women under age 65. Patients and Methods Data from five state cancer registries were linked with insurance claims data and GEP test results. We assessed rates of testing and variables associated with test use in an incident cohort of 9444 commercially-insured women under age 65, newly-diagnosed with Stage I or II hormone-receptor positive breast cancer from 2006–2012. Results Rates of testing for women with N0 disease increased from 20.4% in 2006 to 35.2% in 2011. Variables associated with higher rates of testing, beyond clinical factors such as nodal status (P < .001), included being diagnosed from 2008–2012 vs. 2006–2007 (adjusted odds ratio, 1.67; 95% CI, 1.47 to 1.90), having preexisting comorbidities (adjusted odds ratio, 1.35; 95% CI, 1.14 to 1.59), and higher out-of-pocket pharmacy costs (adjusted odds ratio, 1.66; 95% CI, 1.40 to 1.97). Women under age 50 were more likely to be tested if they had Stage I vs. Stage II disease (P < .0001). Conclusions In an insured population of women under age 65, GEP testing increased following its inclusion in guidelines and mounting evidence. Additional research is needed to better understand oncologists’ decision not to order GEP testing for their patients who are otherwise eligible. PMID:26483061

  10. Interventions for increasing fruit and vegetable consumption in children aged 5 years and under

    PubMed Central

    Wolfenden, Luke; Wyse, Rebecca J; Britton, Ben I; Campbell, Karen J; Hodder, Rebecca K; Stacey, Fiona G; McElduff, Patrick; James, Erica L

    2014-01-01

    Background Insufficient consumption of fruits and vegetables in childhood increases the risk of future chronic diseases including cardiovascular disease. Objectives To assess the effectiveness, cost-effectiveness and associated adverse events of interventions designed to increase the consumption of fruit and/or vegetables amongst children aged five years and under. Search methods The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 2, 2010, MEDLINE (1950 to 2010 April week 4), EMBASE (1947 to 2010 week 18), CINAHL (up to 12 May 2010), PsycINFO (up to 12 May 2010) and Proquest Dissertations and Theses (up to February 2011) were searched to identify eligible trials, as well as electronic trial registers (also up to February 2011). The reference lists of included trials were reviewed and handsearches of three international nutrition journals were also performed. Authors of all included trials were contacted in order to identify further potentially relevant trials. Selection criteria We included randomised controlled trials (RCTs), including cluster-randomised controlled trials, of any intervention primarily targeting fruit and/or vegetable consumption among children aged five years and under and incorporating a biochemical or dietary assessment of fruit and/or vegetable consumption. Two review authors independently screened the titles and abstracts of identified papers. A third review author with expertise in review methodology resolved any disagreements regarding study eligibility. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias of the included studies. A third reviewer resolved disagreements between review authors. Fixed-effect models were used to perform meta-analysis for the primary review outcomes where a sufficient number of trials with suitable data and homogeneity were identified. Main results Five trials, with 13 trial arms and 3967 participants were included in

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

    PubMed Central

    2016-01-01

    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

  12. Advanced glycation end-products (AGEs): involvement in aging and in neurodegenerative diseases.

    PubMed

    Grillo, M A; Colombatto, S

    2008-06-01

    Advanced glycation end-products (AGEs) are formed from the so-called Amadori products by rearrangement followed by other reactions giving rise to compounds bound irreversibly. The structure of some of them is shown and the mechanism of formation is described. Several AGE binding molecules (Receptors for AGE, RAGE) are known and it is thought that many of the effects caused by AGEs are mediated by RAGE. Some of these were shown to be toxic, and called TAGE. The mechanism of detoxification of glyoxal and methylglyoxal by the glyoxalase system is described and also the possibility to eliminate glycated proteins by deglycation enzymes. Compounds able to inhibit AGEs formation are also taken into consideration.

  13. Aging promotes neoplastic disease through effects on the tissue microenvironment

    PubMed Central

    Doratiotto, Silvia; Sini, Marcella; Fanti, Maura; Cadoni, Erika; Serra, Monica; Laconi, Ezio

    2016-01-01

    A better understanding of the complex relationship between aging and cancer will provide important tools for the prevention and treatment of neoplasia. In these studies, the hypothesis was tested that aging may fuel carcinogenesis via alterations imposed in the tissue microenvironment. Preneoplastic hepatocytes isolated from liver nodules were orthotopically injected into either young or old syngeneic rats and their fate was followed over time using the dipeptidyl-peptidase type IV (DPPIV) system to track donor-derived-cells. At 3 months post-Tx, the mean size of donor-derived clusters was 11±3 cells in young vs. 42±8 in old recipients. At 8 months post-Tx, no visible lesion were detected in any of 21 young recipients, while 17/18 animals transplanted at old age displayed hepatic nodules, including 7 large tumors. All tumors expressed the DPPIV marker enzyme, indicating that they originated from transplanted cells. Expression of senescence-associated β-galactosidase was common in liver of 18-month old animals, while it was a rare finding in young controls. Finally, both mRNA and IL6 protein were found to be increased in the liver of aged rats compared to young controls. These results are interpreted to indicate that the microenvironment of the aged liver promotes the growth of pre-neoplastic hepatocytes. PMID:27929382

  14. Mother-daughter asymmetry of pH underlies aging and rejuvenation in yeast.

    PubMed

    Henderson, Kiersten A; Hughes, Adam L; Gottschling, Daniel E

    2014-09-04

    Replicative aging in yeast is asymmetric-mother cells age but their daughter cells are rejuvenated. Here we identify an asymmetry in pH between mother and daughter cells that underlies aging and rejuvenation. Cytosolic pH increases in aging mother cells, but is more acidic in daughter cells. This is due to the asymmetric distribution of the major regulator of cytosolic pH, the plasma membrane proton ATPase (Pma1). Pma1 accumulates in aging mother cells, but is largely absent from nascent daughter cells. We previously found that acidity of the vacuole declines in aging mother cells and limits lifespan, but that daughter cell vacuoles re-acidify. We find that Pma1 activity antagonizes mother cell vacuole acidity by reducing cytosolic protons. However, the inherent asymmetry of Pma1 increases cytosolic proton availability in daughter cells and facilitates vacuole re-acidification and rejuvenation.

  15. What's on TV? Detecting age-related neurodegenerative eye disease using eye movement scanpaths

    PubMed Central

    Crabb, David P.; Smith, Nicholas D.; Zhu, Haogang

    2014-01-01

    Purpose: We test the hypothesis that age-related neurodegenerative eye disease can be detected by examining patterns of eye movement recorded whilst a person naturally watches a movie. Methods: Thirty-two elderly people with healthy vision (median age: 70, interquartile range [IQR] 64–75 years) and 44 patients with a clinical diagnosis of glaucoma (median age: 69, IQR 63–77 years) had standard vision examinations including automated perimetry. Disease severity was measured using a standard clinical measure (visual field mean deviation; MD). All study participants viewed three unmodified TV and film clips on a computer set up incorporating the Eyelink 1000 eyetracker (SR Research, Ontario, Canada). Eye movement scanpaths were plotted using novel methods that first filtered the data and then generated saccade density maps. Maps were then subjected to a feature extraction analysis using kernel principal component analysis (KPCA). Features from the KPCA were then classified using a standard machine based classifier trained and tested by a 10-fold cross validation which was repeated 100 times to estimate the confidence interval (CI) of classification sensitivity and specificity. Results: Patients had a range of disease severity from early to advanced (median [IQR] right eye and left eye MD was −7 [−13 to −5] dB and −9 [−15 to −4] dB, respectively). Average sensitivity for correctly identifying a glaucoma patient at a fixed specificity of 90% was 79% (95% CI: 58–86%). The area under the Receiver Operating Characteristic curve was 0.84 (95% CI: 0.82–0.87). Conclusions: Huge data from scanpaths of eye movements recorded whilst people freely watch TV type films can be processed into maps that contain a signature of vision loss. In this proof of principle study we have demonstrated that a group of patients with age-related neurodegenerative eye disease can be reasonably well separated from a group of healthy peers by considering these eye movement

  16. 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...

  17. 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.

  18. A clinical correlation of anti-DNA-AGE autoantibodies in type 2 diabetes mellitus with disease duration.

    PubMed

    Ashraf, Jalaluddin M; Arfat, Mir Yasir; Arif, Zarina; Ahmad, Jamal; Moinuddin; Alam, Khursheed

    2015-02-01

    Nonenzymatic glycation of amino groups of DNA bases by reducing sugars can generate advanced glycation end products (AGEs). Cellular formation of AGEs under normal physiology is continuously scanned and removed by efficient system in the cells. However, excess formation and accumulation of AGEs may be cause or consequence of some human diseases. Mammalian DNA incubated with d-glucose for 28 days at 37°C showed structural changes in DNA as confirmed by UV, fluorescence, CD, melting temperature, S1 nuclease sensitivity and gel electrophoresis. Formation of DNA-AGE was confirmed by HPLC and LC-MS. Enzyme immunoassay and electrophoretic mobility shift assay of autoantibodies in type 2 diabetes patients' sera with disease duration of 5-15 years exhibited significantly high binding with DNA-AGE as compared to patients with 1-5 years of disease duration. Autoantibodies against aberrant DNA-AGE may be important in the assessment of initiation/progression of secondary complications in type 2 diabetes mellitus patients.

  19. Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat

    PubMed Central

    Khojah, Sohair M.; Payne, Anthony P.; McGuinness, Dagmara; Shiels, Paul G.

    2016-01-01

    There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16Ink4a, Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16INK4a expression was significantly higher in AS/AGU animals compared to age-matched AS controls (p < 0.001) and displayed segmental expression across various brain regions. The age-related expression of sirtuins similarly showed differences between strains and between brain regions. Our data clearly show segmental aging processes within the rat brain, and that these are accelerated in the AS/AGU mutant. The accelerated aging, Parkinsonian phenotype, and disruption to dopamine signalling in the basal ganglia in AS/AGU rats, suggests that this rat strain represents a useful model for studies of development and progression of Parkinson’s disease in the context of biological aging and may offer unique mechanistic insights into the biology of aging. PMID:27763519

  20. Measuring underreporting and under-ascertainment in infectious disease datasets: a comparison of methods

    PubMed Central

    2014-01-01

    Background Efficient and reliable surveillance and notification systems are vital for monitoring public health and disease outbreaks. However, most surveillance and notification systems are affected by a degree of underestimation (UE) and therefore uncertainty surrounds the 'true’ incidence of disease affecting morbidity and mortality rates. Surveillance systems fail to capture cases at two distinct levels of the surveillance pyramid: from the community since not all cases seek healthcare (under-ascertainment), and at the healthcare-level, representing a failure to adequately report symptomatic cases that have sought medical advice (underreporting). There are several methods to estimate the extent of under-ascertainment and underreporting. Methods Within the context of the ECDC-funded Burden of Communicable Diseases in Europe (BCoDE)-project, an extensive literature review was conducted to identify studies that estimate ascertainment or reporting rates for salmonellosis and campylobacteriosis in European Union Member States (MS) plus European Free Trade Area (EFTA) countries Iceland, Norway and Switzerland and four other OECD countries (USA, Canada, Australia and Japan). Multiplication factors (MFs), a measure of the magnitude of underestimation, were taken directly from the literature or derived (where the proportion of underestimated, under-ascertained, or underreported cases was known) and compared for the two pathogens. Results MFs varied between and within diseases and countries, representing a need to carefully select the most appropriate MFs and methods for calculating them. The most appropriate MFs are often disease-, country-, age-, and sex-specific. Conclusions When routine data are used to make decisions on resource allocation or to estimate epidemiological parameters in populations, it becomes important to understand when, where and to what extent these data represent the true picture of disease, and in some instances (such as priority setting) it is

  1. Effects of aging and idiopathic Parkinson's disease on tactile temporal order judgment.

    PubMed

    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.

  2. [Bolsa Família: food and nutrition insecurity of children under five years of age].

    PubMed

    Monteiro, Flávia; Schmidt, Suely Teresinha; da Costa, Islandia Bezerra; Almeida, Claudia Choma Bettega; Matuda, Nívea da Silva

    2014-05-01

    This is a descriptive cross-sectional study of the population base conducted in the town of Colombo in the state of Paraná. The objectives were to identify the prevalence of food insecurity in families that are beneficiaries of the Bolsa Família Program and the factors related to this condition, and describe the nutritional status of children under five years of age. Analyses of association were performed using Fisher's exact test. The sample included 442 families, of which 168 have children under five years of age. The Brazilian Food Insecurity Scale was applied to evaluate food insecurity and the nutritional status of the 199 children evaluated was determined by the height-for-age, weight-for-age and body mass-for-age indices in accordance with the WHO reference values for 2006. The prevalence of food insecurity was 81.6%. Overweight and stunting among children coexisted. Food insecurity was found to be associated with the height-for-age index among children under two years of age. The per capita income and food deficits influenced the situation of food insecurity significantly.

  3. 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

  4. Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

    PubMed Central

    He, Liang; Kernogitski, Yelena; Kulminskaya, Irina; Loika, Yury; Arbeev, Konstantin G.; Loiko, Elena; Bagley, Olivia; Duan, Matt; Yashkin, Arseniy; Ukraintseva, Svetlana V.; Kovtun, Mikhail; Yashin, Anatoliy I.; Kulminski, Alexander M.

    2016-01-01

    the expression of nearby genes. Our mediation analyses suggest that the effects of some SNPs are mediated by specific endophenotypes. In conclusion, these findings indicate that loci with pleiotropic effects on age-related disorders tend to be enriched in genes involved in underlying mechanisms potentially related to nervous, cardiovascular and immune system functions, stress resistance, inflammation, ion channels and hematopoiesis, supporting the hypothesis of shared pathological role of infection, and inflammation in chronic age-related diseases. PMID:27790247

  5. Sexually transmitted diseases in the age of AIDS.

    PubMed

    Wimalawansa, S J

    1993-03-01

    Sexually transmitted diseases (STD) are common illnesses in the world. There is at least one new sexually transmitted disease consultation for every 100 persons a year in industrialised countries. Today the World Health Organisation estimates that there are 250 million new cases of STD every year world-wide, and over 20 distinct pathogens are currently recognised. While the overall incidence of STD have remained high in industrialised countries, the rates of increase of many bacterial STD such as syphilis and gonorrhoea were beginning to stabilise; but currently there is again a trend for these bacterial STD to rise in urban populations.

  6. Aging in Sickle Cell Disease: Co-morbidities and New Issues in Management.

    PubMed

    Sandhu, Manpreet K; Cohen, Alice

    2015-01-01

    Availability of hydroxyurea (HU) coupled with early therapeutic interventions has increased the life expectancy of patients with sickle cell disease. Hence, the sickle cell community needs to be aware of common diseases of aging that survivors are predisposed to. We chose to investigate the sickle cell disease-related complications as well as non sickle cell disease-related medical problems of aging in 45 sickle cell patients over the age of 40 years. The most frequent chronic complications of sickle cell disease were elevated tricuspid regurgitant jet velocity on echocardiogram, chronic renal disease, iron overload and leg ulcers. Medical co-morbidities in this patient group included hypertension, diabetes mellitus (DM), hypercholesterolemia and symptomatic coronary artery disease (CAD). In our cohort, only 38.0% had a primary care doctor. Only 11.0% over age 50 had a screening colonoscopy, and of the women, 42.0% had a screening mammography. Medical co-morbidities and lack of health maintenance in older sickle cell patients are likely to impact overall health and mortality. Aging patients with sickle cell disease may benefit from a primary medical home for age appropriate comprehensive health care.

  7. 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…

  8. 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…

  9. Thyroid functional disease: an under-recognized cardiovascular risk factor in kidney disease patients

    PubMed Central

    Rhee, Connie M.; Brent, Gregory A.; Kovesdy, Csaba P.; Soldin, Offie P.; Nguyen, Danh; Budoff, Matthew J.; Brunelli, Steven M.; Kalantar-Zadeh, Kamyar

    2015-01-01

    Thyroid functional disease, and in particular hypothyroidism, is highly prevalent among chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In the general population, hypothyroidism is associated with impaired cardiac contractility, endothelial dysfunction, atherosclerosis and possibly higher cardiovascular mortality. It has been hypothesized that hypothyroidism is an under-recognized, modifiable risk factor for the enormous burden of cardiovascular disease and death in CKD and ESRD, but this has been difficult to test due to the challenge of accurate thyroid functional assessment in uremia. Low thyroid hormone levels (i.e. triiodothyronine) have been associated with adverse cardiovascular sequelae in CKD and ESRD patients, but these metrics are confounded by malnutrition, inflammation and comorbid states, and hence may signify nonthyroidal illness (i.e. thyroid functional test derangements associated with underlying ill health in the absence of thyroid pathology). Thyrotropin is considered a sensitive and specific thyroid function measure that may more accurately classify hypothyroidism, but few studies have examined the clinical significance of thyrotropin-defined hypothyroidism in CKD and ESRD. Of even greater uncertainty are the risks and benefits of thyroid hormone replacement, which bear a narrow therapeutic-to-toxic window and are frequently prescribed to CKD and ESRD patients. In this review, we discuss mechanisms by which hypothyroidism adversely affects cardiovascular health; examine the prognostic implications of hypothyroidism, thyroid hormone alterations and exogenous thyroid hormone replacement in CKD and ESRD; and identify areas of uncertainty related to the interplay between hypothyroidism, cardiovascular disease and kidney disease requiring further investigation. PMID:24574542

  10. Metabolic Syndrome As an Underlying Disease Entity and Its Relationship to Subclinical Atherosclerosis in Andean Hispanics

    PubMed Central

    Medina-Lezama, Josefina; Arguelles, William; Goldberg, Ronald; Schneiderman, Neil; Khan, Zubair; Morey, Oscar O.; Raja, Muhammad Waheed; Paz, Roberto; Chirinos, Julio A.; Llabre, Maria M.

    2014-01-01

    Abstract Background: The question of whether the metabolic syndrome truly reflects a single disease entity with a common underlying pathology remains unclear. In this study, we assess whether metabolic syndrome represents an underlying disease construct in a large population-based sample of Andean Hispanic adults and examine its relationship to subclinical atherosclerosis. Methods: The study sample was comprised of 2513 participants. Confirmatory factor analysis (CFA) was used to identify a metabolic syndrome latent factor using waist circumference, systolic and diastolic blood pressure, high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), and glucose levels as indicators. The relationship with subclinical atherosclerosis, measured by carotid intima media thickness (cIMT), was assessed using structural equation modeling. Results: Results supported the proposed structure of the metabolic syndrome latent factor evidenced by adequate fit indexes. HDL-C did not significantly load on the metabolic syndrome latent factor (standardized factor loading=0.01, P=0.88). The metabolic syndrome latent factor was significantly associated with cIMT in women (B=0.007, P<0.001) and men (B=0.008, P<0.001) after controlling for age, low-density lipoprotein cholesterol and smoking. Conclusions: Our findings suggest that metabolic syndrome components, such as waist circumference, blood pressure, TGs, and glucose levels, but not HDL-C, share a common underlying pathophysiology that may contribute to the progression of atherosclerosis in Andean Hispanics. Its longitudinal association with cardiovascular disease should be the focus of future research. PMID:24206171

  11. Pregnancy and labor in Tanzanian primigravidae aged 15 years and under.

    PubMed

    Arkutu, A A

    The outcome of pregnancy and labor in 259 Tanzanian primigravidae 15 years and under is compared with that of 377 primigravidae between the ages of 21 and 25. The risk of antenatal complications, such as anemia, and premature labor and low birth weight babies was much higher in the younger age group. There was no difference in the incidence of preeclampsia or complications during labor between the two groups. The younger women had a lower perinatal mortality rate than the controls.

  12. Toward a Radical Praxis for Over-Age, Under-Credited African American Students

    ERIC Educational Resources Information Center

    Jackson, Iesha

    2016-01-01

    The "over-age, under-credited" (OA/UC) student population is defined as high school students who are at least two years behind their peers in terms of age and credits earned toward a high school diploma. To date, few studies have examined the schooling of OA/UC students. The purpose of this study is to use the insights of six African…

  13. Telomere length in epidemiology: a biomarker of aging, age-related disease, both, or neither?

    PubMed

    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.

  14. Age-dependent impairment of auditory processing under spatially focused and divided attention: an electrophysiological study.

    PubMed

    Wild-Wall, Nele; Falkenstein, Michael

    2010-01-01

    By using event-related potentials (ERPs) the present study examines if age-related differences in preparation and processing especially emerge during divided attention. Binaurally presented auditory cues called for focused (valid and invalid) or divided attention to one or both ears. Responses were required to subsequent monaurally presented valid targets (vowels), but had to be suppressed to non-target vowels or invalidly cued vowels. Middle-aged participants were more impaired under divided attention than young ones, likely due to an age-related decline in preparatory attention following cues as was reflected in a decreased CNV. Under divided attention, target processing was increased in the middle-aged, likely reflecting compensatory effort to fulfill task requirements in the difficult condition. Additionally, middle-aged participants processed invalidly cued stimuli more intensely as was reflected by stimulus ERPs. The results suggest an age-related impairment in attentional preparation after auditory cues especially under divided attention and latent difficulties to suppress irrelevant information.

  15. Attention! Cardiac tamponade may be caused by underlying Castleman's disease.

    PubMed

    Atay, Hilmi; Kelkitli, Engin; Okuyucu, Muhammed; Yildiz, Levent; Turgut, Mehmet

    2015-05-01

    Castleman's disease is a rarely observed lymphoproliferative disease. In the literature, various signs and symptoms of the disease have been reported; one of these is secondary cardiac tamponade. We describe the case of a 41-year-old man who developed cardiac tamponade during examination, and who was later diagnosed with Castleman's disease, based on his lymph node biopsies.

  16. Influence of age on androgen deprivation therapy-associated Alzheimer’s disease

    NASA Astrophysics Data System (ADS)

    Nead, Kevin T.; Gaskin, Greg; Chester, Cariad; Swisher-McClure, Samuel; Dudley, Joel T.; Leeper, Nicholas J.; Shah, Nigam H.

    2016-10-01

    We recently found an association between androgen deprivation therapy (ADT) and Alzheimer’s disease. As Alzheimer’s disease is a disease of advanced age, we hypothesize that older individuals on ADT may be at greatest risk. We conducted a retrospective multi-institutional analysis among 16,888 individuals with prostate cancer using an informatics approach. We tested the effect of ADT on Alzheimer’s disease using Kaplan–Meier age stratified analyses in a propensity score matched cohort. We found a lower cumulative probability of remaining Alzheimer’s disease-free between non-ADT users age ≥70 versus those age <70 years (p < 0.001) and between ADT versus non-ADT users ≥70 years (p = 0.034). The 5-year probability of developing Alzheimer’s disease was 2.9%, 1.9% and 0.5% among ADT users ≥70, non-ADT users ≥70 and individuals <70 years, respectively. Compared to younger individuals older men on ADT may have the greatest absolute Alzheimer’s disease risk. Future work should investigate the ADT Alzheimer’s disease association in advanced age populations given the greater potential clinical impact.

  17. Influence of age on androgen deprivation therapy-associated Alzheimer's disease.

    PubMed

    Nead, Kevin T; Gaskin, Greg; Chester, Cariad; Swisher-McClure, Samuel; Dudley, Joel T; Leeper, Nicholas J; Shah, Nigam H

    2016-10-18

    We recently found an association between androgen deprivation therapy (ADT) and Alzheimer's disease. As Alzheimer's disease is a disease of advanced age, we hypothesize that older individuals on ADT may be at greatest risk. We conducted a retrospective multi-institutional analysis among 16,888 individuals with prostate cancer using an informatics approach. We tested the effect of ADT on Alzheimer's disease using Kaplan-Meier age stratified analyses in a propensity score matched cohort. We found a lower cumulative probability of remaining Alzheimer's disease-free between non-ADT users age ≥70 versus those age <70 years (p < 0.001) and between ADT versus non-ADT users ≥70 years (p = 0.034). The 5-year probability of developing Alzheimer's disease was 2.9%, 1.9% and 0.5% among ADT users ≥70, non-ADT users ≥70 and individuals <70 years, respectively. Compared to younger individuals older men on ADT may have the greatest absolute Alzheimer's disease risk. Future work should investigate the ADT Alzheimer's disease association in advanced age populations given the greater potential clinical impact.

  18. Trends in age-adjusted coronary heart disease mortality rates in Slovakia between 1993 and 2009.

    PubMed

    Psota, Marek; Pekarciková, Jarmila; O'Mullane, Monica; Rusnák, Martin

    2013-06-01

    Cardiovascular diseases (CVD) and especially coronary heart disease (CHD) are the main causes of death in the Slovak Republic (SR). The aim of this study is to explore trends in age-adjusted coronary heart disease mortality rates in the whole Slovak population and in the population of working age between the years 1993 and 2009. A related indicator - potential years of life lost (PYLL) due to CHD--was calculated in the same period for males and females. Crude CHD mortality rates were age-adjusted using European standard population. The joinpoint Poisson regression was performed in order to find out the annual percentage change in trends. The age-adjusted CHD mortality rates decreased in the Slovak population and also in the population of working age. The change was significant only within the working-age sub-group. We found that partial diagnoses (myocardial infarction and chronic ischaemic heart disease) developed in the mirror-like manner. PYLL per 100,000 decreased during the observed period and the decline was more prominent in males. For further research we recommend to focus on several other issues, namely, to examine the validity of cause of death codes, to examine the development of mortality rates in selected age groups, to find out the cause of differential development of mortality rates in the Slovak Republic in comparison with the Czech Republic and Poland, and to explain the causes of decrease of the age-adjusted CHD mortality rates in younger age groups in Slovakia.

  19. Mitotic epitopes are incorporated into age-dependent neurofibrillary tangles in Niemann-Pick disease type C.

    PubMed

    Zhang, Min; Wang, Xuezhen; Jiang, Feng; Wang, Wei; Vincent, Inez; Bu, Bitao

    2010-03-01

    The mechanism underlying neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) and other neurodegenerative disorders remains elusive. Niemann-Pick disease type C (NPC) is a kind of genetic neurovisceral disorder in which the intracellular sequestration of cholesterol and other lipids in neurons, NFT formation and neuronal degeneration in brain are the neuropathology hallmarks. The age of onset and progression of the disease vary dramatically. We have analyzed the hippocampus from 17 NPC cases, aged from 7 months to 55 years, to depict the temporal characteristics of NFT formation. Unexpectedly, classic NFT was observed in about 4-year-old NPC brain, suggesting that NFT is not aging dependent, and that juvenile brain neurons satisfy the requirements for NFT formation. NFT in the hippocampus of NPC was significantly increased in number with the advance of age. More importantly, multiple mitotic phase markers, which are not usually found in normal mature neurons, were abundant in the affected neurons and incorporated into NFT. The unusual activation of cdc2/cyclin B kinase and downstream mitotic indices are closely associated with the age-dependent NFT formation, signifying the contribution of abortive cell cycle to neurodegeneration. The cdc2 inhibitors may be therapeutically used for early intervention of neurodegeneration and NFT formation in NPC.

  20. Aging in the circadian system: considerations for health, disease prevention and longevity.

    PubMed

    Gibson, Erin M; Williams, Wilbur P; Kriegsfeld, Lance J

    2009-01-01

    The circadian system orchestrates internal physiology on a daily schedule to promote optimal health and maximize disease prevention. Chronic disruptions in circadian function are associated with an increase in a variety of disease states including, heart disease, ulcers and diabetes. With advanced age, the genes regulating circadian function at the cellular level become disorganized and the ability of the brain clock to entrain to local time diminishes. As a result, aged individuals exhibit a loss of temporal coordination among bodily systems, leading to deficits in homeostasis and sub-optimal functioning. Such disruptions in the circadian system appear to accelerate the aging process and contribute to senescence, with some systems being more vulnerable than others. This review explores aging-associated changes in circadian function and examines evidence linking such alterations to adverse health consequences in late life and promotion of the aging process.

  1. Chemo- and ergoreflexes in health, disease and ageing.

    PubMed

    Schmidt, Hendrik; Francis, Darrel P; Rauchhaus, Mathias; Werdan, Karl; Piepoli, Massimo F

    2005-02-28

    The chemo- and ergoreflexes (muscle receptors) are among the major reflex arches, which adapt the respiratory and the cardiovascular system to the needs of the body and contribute to its homeostasis. The present paper reviews the interplay of these reflexes with other major cardiovascular reflex arches; the methods used for their calculation and their normal range data. The clinical implications of chemoreflex sensitivities and ergoreflexes in chronic heart failure (CHF) as well as the application of chemoreflexes in coronary artery disease, sudden cardiac death and multiple organ dysfunction syndrome are discussed.

  2. Varicella vaccination coverage of children under two years of age in Germany

    PubMed Central

    2010-01-01

    Background Since July 2004, routine varicella vaccination is recommended by the German Standing Vaccination Committee in Germany. Health Insurance Funds started to cover vaccination costs at different time points between 2004 and 2006 in the Federal States. Nationwide representative data on vaccination coverage against varicella of children under two years of age are not available. We aimed to determine varicella vaccination coverage in statutory health insured children under two years of age in twelve German Federal States using data from associations of statutory health insurance physicians (ASHIPs), in order to investigate the acceptance of the recommended routine varicella vaccination programme. Methods We analysed data on varicella vaccination from 13 of 17 ASHIPs of the years 2004 to 2007. The study population consisted of all statutory health insured children under two years of age born in 2004 (cohort 2004) or 2005 (cohort 2005) in one of the studied regions. Vaccination coverage was determined by the number of children vaccinated under 2 years of age within the study population. Results Varicella vaccination coverage of children under two years of age with either one dose of the monovalent varicella vaccine or two doses of the measles, mumps, rubella, and varicella vaccine increased from 34% (cohort 2004) to 51% (cohort 2005) in the studied regions (p < 0.001). More than half of the vaccinated children of cohort 2004 and two third of cohort 2005 were immunised at the recommended age 11 to 14 months. The level of vaccination coverage of cohort 2004 was significantly associated with the delay in introduction of cost coverage since the recommendation of varicella vaccination (p < 0.001). Conclusions Our study shows increasing varicella vaccination coverage of young children, indicating a growing acceptance of the routine varicella vaccination programme by the parents and physicians. We recommend further monitoring of vaccination coverage using data from

  3. Interest of active posturography to detect age-related and early Parkinson's disease-related impairments in mediolateral postural control.

    PubMed

    Bonnet, Cédrick T; Delval, Arnaud; Defebvre, Luc

    2014-11-15

    Patients with Parkinson's disease display impairments of postural control most particularly in active, challenging conditions. The objective of the present study was to analyze early signs of disease-related and also age-related impairments in mediolateral body extension and postural control. Fifty-five participants (18 Hoehn and Yahr stage 2 patients in the off-drug condition, 18 healthy elderly control subjects, and 19 young adults) were included in the study. The participants performed a quiet stance task and two active tasks that analyzed the performance in mediolateral body motion: a limit of stability and a rhythmic weight shift task. As expected, the patients displayed significantly lower and slower body displacement (head, neck, lower back, center of pressure) than elderly control subjects when performing the two body excursion tasks. However, the behavioral variability in both tasks was similar between the groups. Under these active conditions, the patients showed significantly lower contribution of the hip postural control mechanisms compared with the elderly control subjects. Overall, the patients seemed to lower their performance in order to prevent a mediolateral postural instability. However, these patients, at an early stage of their disease, were not unstable in quiet stance. Complementarily, elderly control subjects displayed slower body performance than young adults, which therefore showed an additional age-related impairment in mediolateral postural control. Overall, the study illustrated markers of age-related and Parkinson's disease impairments in mediolateral postural control that may constrain everyday activities in elderly adults and even more in patients with Parkinson's disease.

  4. 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

  5. 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

  6. Endothelin receptor antagonists and cardiovascular diseases of aging.

    PubMed

    Love, M P; McMurray, J J

    2001-01-01

    Our understanding of the role of the endothelin system in human cardiovascular physiology and pathophysiology has evolved very rapidly since the initial description of its constituent parts in 1988. Endothelin-1 (ET-1) is the predominant endothelin isoform in the human cardiovascular system and has potent vasoconstrictor, mitogenic and antinatriuretic properties which have implicated it in the pathophysiology of a number of cardiovascular diseases. The effects of ET-1 have been shown to be mediated by 2 principal endothelin receptor subtypes: ET(A) and ET(B). The development of a range of peptidic and nonpeptidic endothelin receptor antagonists represents an exciting breakthrough in human cardiovascular therapeutics. Two main classes of endothelin receptor antagonist have been developed for possible human therapeutic use: ET(A)-selective and nonselective antagonists. Extensive laboratory and clinical research with these agents has highlighted their promise in various cardiovascular diseases. Randomised, placebo-controlled clinical trials have yielded very encouraging results in patients with hypertension and chronic heart failure with more preliminary data suggesting a possible role in the treatment and prevention of atherosclerosis and stroke. Much more research is needed, however, before endothelin receptor antagonists can be considered for clinical use.

  7. 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.

  8. Music and Memory in Alzheimer's Disease and The Potential Underlying Mechanisms.

    PubMed

    Peck, Katlyn J; Girard, Todd A; Russo, Frank A; Fiocco, Alexandra J

    2016-01-01

    With population aging and a projected exponential expansion of persons diagnosed with Alzheimer's disease (AD), the development of treatment and prevention programs has become a fervent area of research and discovery. A growing body of evidence suggests that music exposure can enhance memory and emotional function in persons with AD. However, there is a paucity of research that aims to identify specific underlying neural mechanisms associated with music's beneficial effects in this particular population. As such, this paper reviews existing anecdotal and empirical evidence related to the enhancing effects of music exposure on cognitive function and further provides a discussion on the potential underlying mechanisms that may explain music's beneficial effect. Specifically, this paper will outline the potential role of the dopaminergic system, the autonomic nervous system, and the default network in explaining how music may enhance memory function in persons with AD.

  9. 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

  10. Notch signaling deficiency underlies age-dependent depletion of satellite cells in muscular dystrophy.

    PubMed

    Jiang, Chunhui; Wen, Yefei; Kuroda, Kazuki; Hannon, Kevin; Rudnicki, Michael A; Kuang, Shihuan

    2014-08-01

    Duchenne muscular dystrophy (DMD) is a devastating disease characterized by muscle wasting, loss of mobility and death in early adulthood. Satellite cells are muscle-resident stem cells responsible for the repair and regeneration of damaged muscles. One pathological feature of DMD is the progressive depletion of satellite cells, leading to the failure of muscle repair. Here, we attempted to explore the molecular mechanisms underlying satellite cell ablation in the dystrophin mutant mdx mouse, a well-established model for DMD. Initial muscle degeneration activates satellite cells, resulting in increased satellite cell number in young mdx mice. This is followed by rapid loss of satellite cells with age due to the reduced self-renewal ability of mdx satellite cells. In addition, satellite cell composition is altered even in young mdx mice, with significant reductions in the abundance of non-committed (Pax7+ and Myf5-) satellite cells. Using a Notch-reporter mouse, we found that the mdx satellite cells have reduced activation of Notch signaling, which has been shown to be necessary to maintain satellite cell quiescence and self-renewal. Concomitantly, the expression of Notch1, Notch3, Jag1, Hey1 and HeyL are reduced in the mdx primary myoblast. Finally, we established a mouse model to constitutively activate Notch signaling in satellite cells, and show that Notch activation is sufficient to rescue the self-renewal deficiencies of mdx satellite cells. These results demonstrate that Notch signaling is essential for maintaining the satellite cell pool and that its deficiency leads to depletion of satellite cells in DMD.

  11. 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…

  12. Glial hemichannels and their involvement in aging and neurodegenerative diseases.

    PubMed

    Orellana, Juan A; von Bernhardi, Rommy; Giaume, Christian; Sáez, Juan C

    2012-01-26

    During the last two decades, it became increasingly evident that glial cells accomplish a more important role in brain function than previously thought. Glial cells express pannexins and connexins, which are member subunits of two protein families that form membrane channels termed hemichannels. These channels communicate intra- and extracellular compartments and allow the release of autocrine/paracrine signaling molecules [e.g., adenosine triphosphate (ATP), glutamate, nicotinamide adenine dinucleotide, and prostaglandin E2] to the extracellular milieu, as well as the uptake of small molecules (e.g., glucose). An increasing body of evidence has situated glial hemichannels as potential regulators of the beginning and maintenance of homeostatic imbalances observed in diverse brain diseases. Here, we review and discuss the current evidence about the possible role of glial hemichannels on neurodegenerative diseases. A subthreshold pathological threatening condition leads to microglial activation, which keeps active defense and restores the normal function of the central nervous system. However, if the stimulus is deleterious, microglial cells and the endothelium become overactivated, both releasing bioactive molecules (e.g., glutamate, cytokines, prostaglandins, and ATP), which increase the activity of glial hemichannels, reducing the astroglial neuroprotective functions, and further reducing neuronal viability. Because ATP and glutamate are released via glial hemichannels in neurodegenerative conditions, it is expected that they contribute to neurotoxicity. More importantly, toxic molecules released via glial hemichannels could increase the Ca2+ entry in neurons also via neuronal hemichannels, leading to neuronal death. Therefore, blockade of hemichannels expressed by glial cells and/or neurons during neuroinflammation might prevent neurodegeneration.

  13. Age-related dysfunctions of the autophagy lysosomal pathway in hippocampal pyramidal neurons under proteasome stress.

    PubMed

    Gavilán, Elena; Pintado, Cristina; Gavilan, Maria P; Daza, Paula; Sánchez-Aguayo, Inmaculada; Castaño, Angélica; Ruano, Diego

    2015-05-01

    Autophagy plays a key role in the maintenance of cellular homeostasis, and autophagy deregulation gives rise to severe disorders. Many of the signaling pathways regulating autophagy under stress conditions are still poorly understood. Using a model of proteasome stress in rat hippocampus, we have characterized the functional crosstalk between the ubiquitin proteasome system and the autophagy-lysosome pathway, identifying also age-related modifications in the crosstalk between both proteolytic systems. Under proteasome inhibition, both autophagy activation and resolution were efficiently induced in young but not in aged rats, leading to restoration of protein homeostasis only in young pyramidal neurons. Importantly, proteasome stress inhibited glycogen synthase kinase-3β in young but activated in aged rats. This age-related difference could be because of a dysfunction in the signaling pathway of the insulin growth factor-1 under stress situations. Present data highlight the potential role of glycogen synthase kinase-3β in the coordination of both proteolytic systems under stress situation, representing a key molecular target to sort out this deleterious effect.

  14. An Evaluation of the Aberrant Behavior Checklist for Children under Age 5

    ERIC Educational Resources Information Center

    Schmidt, Jonathan D.; Huete, John M.; Fodstad, Jill C.; Chin, Michelle D.; Kurtz, Patricia F.

    2013-01-01

    Severe problem behaviors such as self-injury and aggression are frequently observed in young children under age 5 with intellectual and developmental disabilities (IDD). Although early identification of problem behavior is critical to effective intervention, there are few standardized measures available that identify severe problem behavior in…

  15. Neurofunctional (Re)Organization Underlying Narrative Discourse Processing in Aging: Evidence from fNIRS

    ERIC Educational Resources Information Center

    Scherer, Lilian Cristine; Fonseca, Rochele Paz; Giroux, Francine; Senhadji, Noureddine; Marcotte, Karine; Tomitch, Leda Maria Braga; Benali, Habib; Lesage, Frederic; Ska, Bernadette; Joanette, Yves

    2012-01-01

    Relatively few studies have analyzed the mechanisms underlying the cognitive changes that affect language in the elderly, and fewer have done so for narrative discourse. The goal of this study was to explore the neurofunctional changes associated with aging for different components of narrative discourse. Functional near-infrared spectroscopy…

  16. Shared genetic etiology underlying Alzheimer's disease and type 2 diabetes.

    PubMed

    Hao, Ke; Di Narzo, Antonio Fabio; Ho, Lap; Luo, Wei; Li, Shuyu; Chen, Rong; Li, Tongbin; Dubner, Lauren; Pasinetti, Giulio Maria

    2015-01-01

    Epidemiological evidence supports the observation that subjects with type 2 diabetes (T2D) are at higher risk to develop Alzheimer's disease (AD). However, whether and how these two conditions are causally linked is unknown. Possible mechanisms include shared genetic risk factors, which were investigated in this study based on recent genome wide association study (GWAS) findings. In order to achieve our goal, we retrieved single nucleotide polymorphisms (SNPs) associated with T2D and AD from large-scale GWAS meta-analysis consortia and tested for overlap among the T2D- and AD-associated SNPs at various p-value thresholds. We then explored the function of the shared T2D/AD GWAS SNPs by leveraging expressional quantitative trait loci, pathways, gene ontology data, and co-expression networks. We found 927 SNPs associated with both AD and T2D with p-value ≤0.01, an overlap significantly larger than random chance (overlapping p-value of 6.93E-28). Among these, 395 of the shared GWAS SNPs have the same risk allele for AD and T2D, suggesting common pathogenic mechanisms underlying the development of both AD and T2D. Genes influenced by shared T2D/AD SNPs with the same risk allele were first identified using a SNP annotation variation (ANNOVAR) software, followed by using Association Protein-Protein Link Evaluator (DAPPLE) software to identify additional proteins that are known to physically interact with the ANNOVAR gene annotations. We found that gene annotations from ANNOVAR and DAPPLE significantly enriched specific KEGG pathways pertaining to immune responses, cell signaling and neuronal plasticity, cellular processes in which abnormalities are known to contribute to both T2D and AD pathogenesis. Thus, our observation suggests that among T2D subjects with common genetic predispositions (e.g., SNPs with consistent risk alleles for T2D and AD), dysregulation of these pathogenic pathways could contribute to the elevated risks for AD in subjects. Interestingly, we

  17. "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…

  18. Radiographic evaluation of destructive periodontal disease in blue mink in relation to age and blood morphology

    PubMed Central

    2005-01-01

    Abstract In this study, blood samples and jaws were collected from 2 genotypes of blue mink (n = 289) in order to examine phenotypic expression of specific characteristics of Chediak-Higashi Syndrome (C-HS). Blood samples were subjected to differential counts to assess the proportion of abnormal polymorphonuclear leukocytes characteristic for CH-S (C-HS-leukocytes). Abnormal leukocytes with characteristic signs of C-HS were found in blood smears from all mink included in this study. Four teeth in one half of the mandible (P3, P4, M1, M2) were subjected to quantitative radiographic evaluation of alveolar bone loss and tooth loss. There was a high prevalence of destructive periodontal disease among blue mink included in this study. Mild to moderate periodontal disease (defined by less than 50% alveolar bone loss related to 1 or more teeth) affected 73.7% of young mink (age = 7 mo) and 67.9% of older animals (age ≥ 19 mo). Severe periodontal disease (defined by more than 50% bone loss related to one or more teeth) was not detected in mink aged 7 mo, but affected 15.3% of mink aged 19 mo and 39.6% of mink aged 31 mo. The positive relationship between age and periodontal disease was statistically significant (P < 0.01). The prevalence of tooth loss was found to be high among blue mink aged >19 mo (21.6%) and was also significantly related to age (P < 0.01). A significant positive interaction between alveolar bone loss and tooth loss (P < 0.01), implies that the highly prevalent tooth loss in the mink was related to and possibly caused by destructive periodontal disease. There was no significant difference in the prevalence of periodontal disease between the 2 genotypes and age was found to be the only statistical predictor of poor production results (P < 0.01) in blue mink. PMID:15971677

  19. Dysregulated TGF-β Production Underlies the Age-Related Vulnerability to Chikungunya Virus

    PubMed Central

    Uhrlaub, Jennifer L.; Pulko, Vesna; DeFilippis, Victor R.; Streblow, Daniel N.; Coleman, Gary D.; Lindo, John F.; Vickers, Ivan; Anzinger, Joshua J.; Nikolich-Žugich, Janko

    2016-01-01

    Chikungunya virus (CHIKV) is a re-emerging global pathogen with pandemic potential, which causes fever, rash and debilitating arthralgia. Older adults over 65 years are particularly susceptible to severe and chronic CHIKV disease (CHIKVD), accounting for >90% of all CHIKV-related deaths. There are currently no approved vaccines or antiviral treatments available to limit chronic CHIKVD. Here we show that in old mice excessive, dysregulated TGFβ production during acute infection leads to a reduced immune response and subsequent chronic disease. Humans suffering from CHIKV infection also exhibited high TGFβ levels and a pronounced age-related defect in neutralizing anti-CHIKV antibody production. In vivo reduction of TGFβ levels minimized acute joint swelling, restored neutralizing antibody production and diminished chronic joint pathology in old mice. This study identifies increased and dysregulated TGFβ secretion as one key mechanism contributing to the age-related loss of protective anti-CHIKV-immunity leading to chronic CHIKVD. PMID:27736984

  20. Neuroanatomical correlates of verbal fluency in early Alzheimer's disease and normal aging.

    PubMed

    Rodríguez-Aranda, Claudia; Waterloo, Knut; Johnsen, Stein Harald; Eldevik, Petter; Sparr, Sigurd; Wikran, Gry C; Herder, Marit; Vangberg, Torgil Riise

    2016-01-01

    Verbal fluency (VF) impairments occur early in Alzheimer's disease (AD) and to a lesser extent also in normal aging. However, the neural underpinnings of these impairments are not fully understood. The present study evaluated whether VF impairments in early AD and normal aging rely upon common or different neuroanatomical correlates. We examined the association between VF performance and brain structure in 18 mild AD patients and 24 healthy elderly. Linear regressions were performed between accuracy and time intervals in VF scores and structural measurements of cerebral gray matter (GM) and white matter (WM) using MRI. Results showed that semantic VF correlated exclusively with GM in cerebellum, left temporal fusiform cortex, and WM in uncinate fasciculus, inferior fronto-occipital fasciculus and corpus callosum. Phonemic VF showed unique associations between intervals and WM in left-hemisphere tracts. The association between GM in hippocampus, subcortical structures and semantic accuracy differentiated patients from controls. Results showed that VF impairments are primarily associated with same structural brain changes in AD as in healthy elderly but at exaggerated levels. However, specific VF deficiencies and their underlying neural correlates exist and these clearly differentiate the initial stages of AD.

  1. Effect of single aging on stress corrosion cracking susceptibility of INCONEL X-750 under PWR conditions

    NASA Astrophysics Data System (ADS)

    Mishra, B.; Moore, J. J.

    1988-05-01

    Unfavorable morphology of precipitates and inclusions has been thought to be the cause of severe intergranular stress corrosion cracking (IGSCC) in double aged INCONEL* X-750 alloy used in reactor water environments. A single step aging treatment of 200 hours at 811 °C followed by furnace cooling after solution treating for 2 hours at 1075 °C has been found to provide an improved combination of strength, ductility, and resistance to SCC under simulated PWR test conditions. In this single aged condition a reprecipitated secondary carbide, together with γ' was produced at the grain boundary which resulted in a mixed fracture mode comprising dimple rupture and microvoid coalescence compared with a predominantly intergranular mode for the fully age hardened specimens. This improvement has been explained in terms of the morphology of the second phase precipitates which are produced in these heat treatment regimes.

  2. 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...

  3. Age and gender as independent predictors of violence under the influence of alcohol in Zurich, Switzerland.

    PubMed

    Mica, Ladislav; Oesterle, Linda; Werner, Clément M L; Simmen, Hans-Peter

    2015-04-08

    Violent behaviour associated with alcohol consumption is frequently reported by different media. Clinical data analysing the correlation between alcohol intoxication, age, gender and violence are scarce. The aim of this study was to evaluate the influence of age, gender and blood alcohol content on violent behaviour under the influence of alcohol under central European conditions. Three hundred patients admitted to the emergency department were included into this study in the time period from January 01. to December 31. 2009. The inclusion criteria were a blood alcohol content (BAC) of ≥10 mmol/l, any traumatic injury and an age ≥16 years. Violence was defined as an evitable act committed by others leading to patient's hospitalisation. The data were compared with Wilcoxon and χ2-test for proportions. The data were considered as significant if p<0,05. Predictive quality was evaluated by using receiver operating characteristic (ROC) curve. Independent predictors were analyzed by logistic regression analysis. The average age was 36,9±16,9 years (range: 16-84 years), 259 (86%) males and 41 (24%) females. There was a significant difference in gender (odds ratio for gender male 2,88; CI 95%: 1,24-6,67; p<0,001) and age dependent (odds ratio for each year of age 0,94; CI 95%: 0,93-0,96; p<0,0001) violence with no correlation to blood alcohol content found. Logistic regression analysis revealed male gender and young age as an independent predictor for violence. These results clarify the relationship between alcohol, age, gender and violence and have important implications for municipal-level alcohol policies.

  4. Physical ageing of polyethylene terephthalate under natural sunlight: correlation study between crystallinity and mechanical properties

    NASA Astrophysics Data System (ADS)

    Aljoumaa, Khaled; Abboudi, Maher

    2016-01-01

    Semi-crystalline polyethylene terephthalate (PET) was aged under the effect of natural UV exposure and outdoor temperature during 670 days. The variation in the mechanical and thermal properties beside to the morphology was tracked by applying different analytical techniques, including scanning electron microscopy, infrared spectroscopy, differential scanning calorimetry and wide angle X-ray diffraction, in addition to tensile strength and hardness measurements. It has been confirmed that the ageing process is the results of physical trend only. The aged PET showed a decrease in both tensile strength and strain with an increase in the degree of crystallinity of aged PET samples during the whole period. These changes in crystallinity were examined by various analysis methods: density, calorimetric and infrared spectroscopy. New peaks in FTIR analysis at 1115 and 1090 cm-1 were characterized and proved that this technique is considered to be an easy tool to track the change in the surface crystallinity of aged PET samples directly. The results of this study showed that an augmentation in the degree of crystallinity of outdoor aged PET samples from 18 to 36 %, accompanied with a decrease in tensile strength from 167.9 to 133.7 MPa. Moreover, a good exponential correlation was found between the degree of crystallinity and the mechanical properties of the aged PET.

  5. 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

  6. Effects of aging on pointing movements under restricted visual feedback conditions.

    PubMed

    Zhang, Liancun; Yang, Jiajia; Inai, Yoshinobu; Huang, Qiang; Wu, Jinglong

    2015-04-01

    The goal of this study was to investigate the effects of aging on pointing movements under restricted visual feedback of hand movement and target location. Fifteen young subjects and fifteen elderly subjects performed pointing movements under four restricted visual feedback conditions that included full visual feedback of hand movement and target location (FV), no visual feedback of hand movement and target location condition (NV), no visual feedback of hand movement (NM) and no visual feedback of target location (NT). This study suggested that Fitts' law applied for pointing movements of the elderly adults under different visual restriction conditions. Moreover, significant main effect of aging on movement times has been found in all four tasks. The peripheral and central changes may be the key factors for these different characteristics. Furthermore, no significant main effects of age on the mean accuracy rate under condition of restricted visual feedback were found. The present study suggested that the elderly subjects made a very similar use of the available sensory information as young subjects under restricted visual feedback conditions. In addition, during the pointing movement, information about the hand's movement was more useful than information about the target location for young and elderly subjects.

  7. The diagnosis and management of age-related veterinary cardiovascular disease.

    PubMed

    Saunders, Ashley B

    2012-07-01

    The American Veterinary Medical Association reported 81.7 million cats and 72.1 million dogs in the United States, with more than 10% over 11 years of age. Disorders of the cardiovascular system are one of the most commonly encountered disease entities in the aging pet population. This article reviews the diseases affecting older cats and dogs including how to make the diagnosis and when to treat while keeping in mind the unique aspects of comorbid conditions and polypharmacy situations encountered while managing pets with cardiovascular disease.

  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).

  9. Neurologic features of chronic minamata disease (organic mercury poisoning) and incidence of complications with aging.

    PubMed

    Uchino, M; Tanaka, Y; Ando, Y; Yonehara, T; Hara, A; Mishima, I; Okajima, T; Ando, M

    1995-09-01

    To elucidate the neurologic features of chronic Minamata disease, and the incidence of complications with aging, we studied 80 patients with documented Minamata disease (organic mercury poisoning) from 1986 to 1994 (mean age: 63 years). Of the cardinal neurologic findings, sensory impairment was seen with highest frequency in 98.8% of patients limited to the extremities in 86.3%. Impairment of lower extremity coordination was observed in 60%, constriction of the visual field in 51.9%, and retrocochlear hearing loss in 41%. To assess age-related complications, patients were separated into three groups by age: Group I (10 to 39 years); Group II (40 to 69 years); Group III (> or = 70 years). The incidences of hypertension and cerebrovascular diseases, organic ophthalmologic disorders (including cataracts), presbyacusis, and cervical spondylosis deformans increased significantly with age. Compared with a preceding survey (1981 to 1985, 171 patients, mean age: 63.5 years), the incidences of complicated hypertension and cataracts had decreased, whereas those of cerebrovascular disease and retinitis pigmentosa remained unchanged. The incidences of abnormal brain computed tomography (CT), presbyacusis, cervical spondylosis deformans, and positive tests for urine sugar also increased. The incidences of these complications other than retinitis pigmentosa were similar to those in the general population. These results accurately reflect the recent epidemiological disease tendencies in Japan toward a decreased incidence of hypertension and an increased incidence of diabetes.

  10. Glutathione and lymphocyte activation: a function of ageing and auto-immune disease.

    PubMed

    Fidelus, R K; Tsan, M F

    1987-08-01

    A decline in tissue and serum of glutathione (GSH) content and GSH-metabolizing enzymes with age has been implicated in the increasing susceptibility to carcinogens, disease and drugs which occurs with advanced age. Immunological senescence has been directly associated with increased incidence of cancer and infection with age. The auto-immune diseases of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) demonstrate depressed T-cell function together with B-cell hyperactivity. In addition, RA and SLE are chronic inflammatory conditions which have been associated with low serum and erythrocyte GSH concentrations when compared to normal. We hypothesized that augmentation of intracellular GSH concentrations in lymphocytes may enhance immune function in depressed immune states. Our data, using murine animal models for ageing (C57BL/6J) and the RA/SLE-like auto-immune diseases of the MRL/lpr mouse, indicate that intracellular glutathione of splenic lymphocytes does not decline with age or with a chronic inflammatory auto-immune disease. In contrast, immune responsiveness in splenic lymphocytes does decline. We can, however, augment both intracellular GSH concentrations and the immune response of splenic lymphocytes from animals of all ages as well as in those animals with the SLE-like auto-immune disease.

  11. 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

  12. Clock-Enhancing Small Molecules and Potential Applications in Chronic Diseases and Aging

    PubMed Central

    Gloston, Gabrielle F.; Yoo, Seung-Hee; Chen, Zheng (Jake)

    2017-01-01

    Normal physiological functions require a robust biological timer called the circadian clock. When clocks are dysregulated, misaligned, or dampened, pathological consequences ensue, leading to chronic diseases and accelerated aging. An emerging research area is the development of clock-targeting compounds that may serve as drug candidates to correct dysregulated rhythms and hence mitigate disease symptoms and age-related decline. In this review, we first present a concise view of the circadian oscillator, physiological networks, and regulatory mechanisms of circadian amplitude. Given a close association of circadian amplitude dampening and disease progression, clock-enhancing small molecules (CEMs) are of particular interest as candidate chronotherapeutics. A recent proof-of-principle study illustrated that the natural polymethoxylated flavonoid nobiletin directly targets the circadian oscillator and elicits robust metabolic improvements in mice. We describe mood disorders and aging as potential therapeutic targets of CEMs. Future studies of CEMs will shed important insight into the regulation and disease relevance of circadian clocks. PMID:28360884

  13. The role of Thyrotropin Releasing Hormone in aging and neurodegenerative diseases

    PubMed Central

    Daimon, Caitlin M.; Chirdon, Patrick; Maudsley, Stuart; Martin, Bronwen

    2013-01-01

    Thyrotropin releasing hormone (TRH) is primarily known as the central regulator of the hypothalamic-pituitary-thyroid (HPT) axis. However, TRH also exerts a variety of central nervous system effects independent from its activity in the HPT axis. With advancing age, decreases in TRH synthesis, expression, and activity have been demonstrated. Associated with this emerging evidence suggests that TRH is implicated in neurodegenerative diseases of aging, including Alzheimer’s disease and Parkinson’s disease. TRH and its synthetic analogs have been recognized as trophic factors in neurons of the diencephalon and spinal cord, and as neuroprotectants against oxidative stress, glutamate toxicity, caspase-induced cell death, DNA fragmentation, and inflammation. In this review, we will provide an overview of some of the roles of TRH, outside of the HPT axis, associated with pathological aging and neurodegeneration and we shall discuss the potential of TRH and TRH analogs for the treatment of neurodegenerative diseases. PMID:24199031

  14. Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection.

    PubMed

    Blackburn, Elizabeth H; Epel, Elissa S; Lin, Jue

    2015-12-04

    Telomeres are the protective end-complexes at the termini of eukaryotic chromosomes. Telomere attrition can lead to potentially maladaptive cellular changes, block cell division, and interfere with tissue replenishment. Recent advances in the understanding of human disease processes have clarified the roles of telomere biology, especially in diseases of human aging and in some aging-related processes. Greater overall telomere attrition predicts mortality and aging-related diseases in inherited telomere syndrome patients, and also in general human cohorts. However, genetically caused variations in telomere maintenance either raise or lower risks and progression of cancers, in a highly cancer type-specific fashion. Telomere maintenance is determined by genetic factors and is also cumulatively shaped by nongenetic influences throughout human life; both can interact. These and other recent findings highlight both causal and potentiating roles for telomere attrition in human diseases.

  15. 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.

  16. 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

  17. Neuronal amyloid-β accumulation within cholinergic basal forebrain in ageing and Alzheimer's disease.

    PubMed

    Baker-Nigh, Alaina; Vahedi, Shahrooz; Davis, Elena Goetz; Weintraub, Sandra; Bigio, Eileen H; Klein, William L; Geula, Changiz

    2015-06-01

    The mechanisms that contribute to selective vulnerability of the magnocellular basal forebrain cholinergic neurons in neurodegenerative diseases, such as Alzheimer's disease, are not fully understood. Because age is the primary risk factor for Alzheimer's disease, mechanisms of interest must include age-related alterations in protein expression, cell type-specific markers and pathology. The present study explored the extent and characteristics of intraneuronal amyloid-β accumulation, particularly of the fibrillogenic 42-amino acid isoform, within basal forebrain cholinergic neurons in normal young, normal aged and Alzheimer's disease brains as a potential contributor to the selective vulnerability of these neurons using immunohistochemistry and western blot analysis. Amyloid-β1-42 immunoreactivity was observed in the entire cholinergic neuronal population regardless of age or Alzheimer's disease diagnosis. The magnitude of this accumulation as revealed by optical density measures was significantly greater than that in cortical pyramidal neurons, and magnocellular neurons in the globus pallidus did not demonstrate a similar extent of amyloid immunoreactivity. Immunoblot analysis with a panel of amyloid-β antibodies confirmed accumulation of high concentration of amyloid-β in basal forebrain early in adult life. There was no age- or Alzheimer-related alteration in total amyloid-β content within this region. In contrast, an increase in the large molecular weight soluble oligomer species was observed with a highly oligomer-specific antibody in aged and Alzheimer brains when compared with the young. Similarly, intermediate molecular weight oligomeric species displayed an increase in aged and Alzheimer brains when compared with the young using two amyloid-β42 antibodies. Compared to cortical homogenates, small molecular weight oligomeric species were lower and intermediate species were enriched in basal forebrain in ageing and Alzheimer's disease. Regional and age

  18. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease.

    PubMed

    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

    2015-09-01

    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.

  19. A Mitochondrial Role of SV2a Protein in Aging and Alzheimer's Disease: Studies with Levetiracetam.

    PubMed

    Stockburger, Carola; Miano, Davide; Baeumlisberger, Marion; Pallas, Thea; Arrey, Tabiwang N; Karas, Michael; Friedland, Kristina; Müller, Walter E

    2016-01-01

    Aberrant neuronal network activity associated with neuronal hyperexcitability seems to be an important cause of cognitive decline in aging and Alzheimer's disease (AD). Out of many antiepileptics, only levetiracetam improved cognitive dysfunction in AD patients and AD animal models by reducing hyperexcitability. As impaired inhibitory interneuronal function, rather than overactive neurons, seems to be the underlying cause, improving impaired neuronal function rather than quieting overactive neurons might be relevant in explaining the lack of activity of the other antiepileptics. Interestingly, improvement of cognitive deficits by levetiracetam caused by small levels of soluble Aβ was accompanied by improvement of synaptic function and plasticity. As the negative effects of Aβ on synaptic plasticity strongly correlate with mitochondrial dysfunction, wehypothesized that the effect of levetiracetam on synaptic activity might be raised by an improved mitochondrial function. Accordingly, we investigated possible effects of levetiracetam on neuronal deficits associated with mitochondrial dysfunction linked to aging and AD. Levetiracetam improved several aspects of mitochondrial dysfunction including alterations of fission and fusion balance in a cell model for aging and early late-onset AD. We demonstrate for the first time, using immunohistochemistry and proteomics, that the synaptic vesicle protein 2A (SV2a), the molecular target of levetiracetam, is expressed in mitochondria. In addition, levetiracetam shows significant effect on the opening of the mitochondrial permeability transition pore. Importantly, the effects of levetiracetam were significantly abolished when SV2a was knockdown using siRNA. In conclusion, interfering with the SV2a protein at the mitochondrial level and thereby improving mitochondrial function might represent an additional therapeutic effect of levetiracetam to improve symptoms of late-onset AD.

  20. Impact of age and cognitive demand on lane choice and changing under actual highway conditions.

    PubMed

    Reimer, Bryan; Donmez, Birsen; Lavallière, Martin; Mehler, Bruce; Coughlin, Joseph F; Teasdale, Normand

    2013-03-01

    Previous research suggests that drivers change lanes less frequently during periods of heightened cognitive load. However, lane changing behavior of different age groups under varying levels of cognitive demand is not well understood. The majority of studies which have evaluated lane changing behavior under cognitive workload have been conducted in driving simulators. Consequently, it is unclear if the patterns observed in these simulation studies carry over to actual driving. This paper evaluates data from an on-road study to determine the effects of age and cognitive demand on lane choice and lane changing behavior. Three age groups (20-29, 40-49, and 60-69) were monitored in an instrumented vehicle. The 40's age group had 147% higher odds of exhibiting a lane change than the 60's group. In addition, drivers in their 60's were less likely to drive on the leftmost lane compared to drivers in their 20's and 40's. These results could be interpreted as evidence that older adults adopt a more conservative driving style as reflected in being less likely to choose the leftmost lane than the younger groups and less likely to change lanes than drivers in their 40's. Regardless of demand level, cognitive workload reduced the frequency of lane changes for all age groups. This suggests that in general drivers of all ages attempt to regulate their behavior in a risk reducing direction when under added cognitive demand. The extent to which such self-regulation fully compensates for the impact of added cognitive demand remains an open question.

  1. Microstructural characterization and thermal cycling reliability of solders under isothermal aging and electrical current

    NASA Astrophysics Data System (ADS)

    Chauhan, Preeti Singh

    Solder joints on printed circuit boards provide electrical and mechanical connections between electronic devices and metallized patterns on boards. These solder joints are often the cause of failure in electronic packages. Solders age under storage and operational life conditions, which can include temperature, mechanical loads, and electrical current. Aging occurring at a constant temperature is called isothermal aging. Isothermal aging leads to coarsening of the bulk microstructure and increased interfacial intermetallic compounds at the solder-pad interface. The coarsening of the solder bulk degrades the creep properties of solders, whereas the voiding and brittleness of interfacial intermetallic compounds leads to mechanical weakness of the solder joint. Industry guidelines on solder interconnect reliability test methods recommend preconditioning the solder assemblies by isothermal aging before conducting reliability tests. The guidelines assume that isothermal aging simulates a "reasonable use period," but do not relate the isothermal aging levels with specific use conditions. Studies on the effect of isothermal aging on the thermal cycling reliability of tin-lead and tin-silver-copper solders are limited in scope, and results have been contradictory. The effect of electrical current on solder joints has been has mostly focused on current densities above 104A/cm2 with high ambient temperature (≥100oC), where electromigration, thermomigration, and Joule heating are the dominant failure mechanisms. The effect of current density below 104A/cm2 on temperature cycling fatigue of solders has not been established. This research provides the relation between isothermal aging and the thermal cycling reliability of select Sn-based solders. The Sn-based solders with 3%, 1%, and 0% silver content that have replaced tin-lead are studied and compared against tin-lead solder. The activation energy and growth exponents of the Arrhenius model for the intermetallic growth in

  2. 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

  3. A common brain network links development, aging, and vulnerability to disease.

    PubMed

    Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

    2014-12-09

    Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

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

    PubMed Central

    Bartzokis, George

    2011-01-01

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

  5. Maremar, prevalence of chronic kidney disease, how to avoid over-diagnosis and under-diagnosis.

    PubMed

    De Broe, Marc E; Gharbi, Mohammed Benghanem; Elseviers, Monique

    2016-04-01

    Chronic kidney disease is considered as a major public health problem. Recent studies mention a prevalence rate between 8%-12%. Several editorials, comments, short reviews described the weaknesses (lack of confirmation of proteinuria, and of chronicity of decreased estimated glomerular filtration rate) of a substantial number of studies and the irrational of using a single arbitrary set point, i.e. diagnosis of chronic kidney disease whenever the estimated glomerular filtration rate is less than 60mL/min/1.73m(2). Maremar (Maladies rénales chroniques au Maroc) is a prevalence study of chronic kidney disease, hypertension, diabetes and obesity in a randomized, representative, high response rate (85%), sample of the adult population of Morocco, strictly applying the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Compared to the vast majority of the available studies, Maremar has a low prevalence of chronic kidney disease (2.9% adjusted to the actual adult population of Morocco). The population pyramid, and particularly the confirmation of proteinuria and "chronicity" of the decreased estimated glomerular filtration rate are the main reasons for this low prevalence of chronic kidney disease. The choice of arbitrary single threshold of estimated glomerular filtration rate for classifying stage 3-5 chronic kidney disease inevitably leads to "over-diagnosis" (false positives) of the disease in the elderly, particularly those without proteinuria, hematuria or hypertension, and to "under-diagnosed" (false negatives) in younger individuals with an estimated glomerular filtration rate above 60mL/min/1.73m(2) and below the 3rd percentile of their age/gender category. There is an urgent need for quality studies using in a correct way the recent KDIGO guidelines when investigating the prevalence of chronic kidney disease, in order to avoid a 50 to 100% overestimation of a disease state with potential dramatic consequences. The combination of the general population

  6. Epigenetic Control of Stem Cell Potential during Homeostasis, Aging, and Disease.

    PubMed

    Beerman, Isabel; Rossi, Derrick J

    2015-06-04

    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.

  7. Stress-Activated Cap’n’collar Transcription Factors in Aging and Human Disease

    PubMed Central

    Sykiotis, Gerasimos P.; Bohmann, Dirk

    2010-01-01

    Cap’n’collar (Cnc) transcription factors are conserved in metazoans and have important developmental and homeostatic functions. The vertebrate Nrf1, Nrf2, and Nrf3, the Caenorhabditis elegans SKN-1, and the Drosophila CncC comprise a subgroup of Cnc factors that mediate adaptive responses to cellular stress. The most studied stress-activated Cnc factor is Nrf2, which orchestrates the transcriptional response of cells to oxidative stressors and electrophilic xenobiotics. In rodent models, signaling by Nrf2 defends against oxidative stress and aging-associated disorders, such as neurodegeneration, respiratory diseases, and cancer. In humans, polymorphisms that decrease Nrf2 abundance have been associated with various pathologies of the skin, respiratory system, and digestive tract. In addition to preventing disease in rodents and humans, Cnc factors have lifespan-extending and anti-aging functions in invertebrates. However, despite the pro-longevity and antioxidant roles of stress-activated Cnc factors, their activity paradoxically declines in aging model organisms and in humans suffering from progressing respiratory disease or neurodegeneration. We review the roles and regulation of stress-activated Cnc factors across species, present all reported instances in which their activity is paradoxically decreased in aging and disease, and discuss the possibility that the pharmacological restoration of Nrf2 signaling may be useful in the prevention and treatment of age-related diseases. PMID:20215646

  8. Does pupil constriction under blue and green monochromatic light exposure change with age?

    PubMed Central

    Daneault, Véronique; Vandewalle, Gilles; Hébert, Marc; Teikari, Petteri; Mure, Ludovic S.; Doyon, Julien; Gronfier, Claude; Cooper, Howard M.; Dumont, Marie; Carrier, Julie

    2017-01-01

    Many non-visual functions are regulated by light through a photoreceptive system involving melanopsin-expressing retinal ganglion cells that are maximally sensitive to blue light. Several studies have suggested that the ability of light to modulate circadian entrainment and to induce acute effects on melatonin secretion, subjective alertness and gene expression, decreases during aging, particularly for blue light. This could contribute to the documented changes in sleep and circadian regulatory processes with aging. However, age-related modification in the impact of light on steady-state pupil constriction, which regulates the amount of light reaching the retina, is not demonstrated. We measured pupil size in 16 young (22.8±4y) and 14 older (61±4.4y) healthy subjects during 45s exposures to blue (480nm) and green (550nm) monochromatic lights at low (7×1012 photons/cm2/s), medium (3×1013 photons/cm2/s), and high (1014 photons/cm2/s) irradiance levels. Results showed that young subjects had consistently larger pupils than older subjects, for dark adaptation and during all light exposures. Steady-state pupil constriction was greater under blue than green light exposure in both age groups and increased with increasing irradiance. Surprisingly, when expressed in relation to baseline pupil size, no significant age-related differences were observed in pupil constriction. The observed reduction in pupil size in older individuals, both in darkness and during light exposure, may reduce retinal illumination and consequently affect non-visual responses to light. The absence of a significant difference between age groups for relative steady-state pupil constriction suggests that other factors such as tonic, sympathetic control of pupil dilation, rather than light sensitivity per se, account for the observed age difference in pupil size regulation. Compared to other nonvisual functions, the light sensitivity of steady-state pupil constriction appears to remain relatively

  9. Recent Developments in Understanding Brain Aging: Implications for Alzheimer’s Disease and Vascular Cognitive Impairment

    PubMed Central

    Deak, Ferenc; Freeman, Willard M.; Ungvari, Zoltan; Csiszar, Anna

    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

  10. 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.

  11. 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

  12. Childhood immunization and atopic disease into middle-age--a prospective cohort study.

    PubMed

    Matheson, Melanie C; Haydn Walters, E; Burgess, John A; Jenkins, Mark A; Giles, Graham G; Hopper, John L; Abramson, Michael J; Dharmage, Shyamali C

    2010-03-01

    The association between childhood immunizations and risk of atopic diseases is unclear. No study has examined possible associations between childhood immunizations and such diseases in middle age. The Tasmanian Longitudinal Health Study (TAHS) is a population based cohort study of respiratory disease. The TAHS participants were followed from 7 to 44 yrs of age. Immunizations during childhood were examined for any association with asthma and atopic disease at age 44 yrs. Multivariable regression models were used to estimate relative risks while adjusting for confounders. Cox regression was used to estimate the association between childhood immunizations and asthma developing after the age of 7 yrs. We found no association between any childhood immunization (Diphtheria, Tetanus, Pertussis, Polio, Smallpox) and asthma (ORs ranged from 0.87 to 1.17 p > 0.05), eczema (ORs ranged from 0.99 to 1.07 p > 0.05), food allergy (ORs ranged from 0.97 to 1.11 p > 0.05), or hay fever (ORs ranged from 1.02 to 1.05 p > 0.05) at age 44. Nor did we find any association between childhood immunizations and an increased risk of incident asthma after the age of 7 yrs (Diphtheria HR = 1.06, 95% CI 0.82, 1.36; Tetanus HR = 1.13, 95% CI 0.88, 1.44; Pertussis HR = 1.03, 95% CI 0.81, 1.30; Polio HR = 1.15, 95% CI 0.86, 1.54; Smallpox HR = 1.21, 95% CI 0.99, 1.48; DTP HR = 1.05, 95% CI 0.85, 1.30). Our analysis does not support any association between common childhood immunizations and risk of asthma and atopic disease in middle-age. Our findings should provide reassurance that in terms of life time risk of asthma and atopic disease, childhood immunization is safe.

  13. Age-related eye diseases: an emerging challenge for public health professionals.

    PubMed

    Gohdes, Dorothy M; Balamurugan, Appathurai; Larsen, Barbara A; Maylahn, Christopher

    2005-07-01

    In April 2004, The Eye Disease Prevalence Research Group published a series of articles that included age-specific estimates for the prevalence of low vision and blindness in whites, African Americans, and Hispanics living in the United States. Also included were age-, sex-, and ethnic-specific incidences of the following age-related eye diseases: diabetic retinopathy, macular degeneration, cataracts, and glaucoma. We reviewed the group's series of articles and highlighted key findings on the overall prevalence of and risk factors for age-related eye diseases, as well as opportunities to preserve and restore vision. We examined publications that show the public health impact of age-related eye diseases and the importance of projected increases in prevalence of low vision and blindness. Approximately 1 in 28 Americans aged older than 40 years is affected by low vision or blindness. Among community-dwelling adults, the prevalence of low vision and blindness increases dramatically with age in all racial and ethnic groups. Whites have higher rates of macular degeneration than African Americans, but glaucoma is more common among older African Americans. Between 2000 and 2020, the prevalence of blindness is expected to double. Age-related eye diseases are costly to treat, threaten the ability of older adults to live independently, and increase the risk for accidents and falls. To prevent vision loss and support rehabilitative services for people with low vision, it is imperative for the public health community to address the issue through surveillance, public education, and coordination of screening, examination, and treatment.

  14. Epidemiology of Kienböck's disease in middle-aged and elderly Japanese women.

    PubMed

    Tsujimoto, Ritsu; Maeda, Junichiro; Abe, Yasuyo; Arima, Kazuhiko; Tomita, Masato; Koseki, Hironobu; Kaida, Eiji; Aoyagi, Kiyoshi; Osaki, Makoto

    2015-01-01

    Little research has been done on the prevalence of Kienböck's disease, and there is no consensus on the relationship between Kienböck's disease and negative ulnar variance. The goal of this cross-sectional study was to determine the prevalence of Kienböck's disease in middle-aged and elderly Japanese women and to clarify the relationship between Kienböck's disease and negative ulnar variance. The authors analyzed plain radiographs of both hands in women 40 years and older residing in the community to investigate the prevalence of Kienböck's disease and the relationship between Kienböck's disease and negative ulnar variance. Kienböck's disease was seen in 7 of the 572 participants. In the group with Kienböck's disease, ulnar variance did not differ significantly between affected (0.3 mm; SD, 1.5) and unaffected (0.3 mm; SD, 1.0; P=.285) sides. No significant difference was seen in ulnar variance values between the affected side in the group with Kienböck's disease and the normal group (P=.118). The number or proportion of participants with negative ulnar variance did not differ significantly between the affected side in the group with Kienböck's disease (3 of 7) and the unaffected side in the group with Kienböck's disease (1 of 7; P=.237) and between the affected side in the group with Kienböck's disease and the normal group (111 of 504; P=.189) by chi-square test. The prevalence of Kienböck's disease was 1.2% in middle-aged and elderly Japanese women. Negative ulnar variance is not a contributing factor to Kienböck's disease.

  15. A novel diagnostic tool reveals mitochondrial pathology in human diseases and aging.

    PubMed

    Scheibye-Knudsen, Morten; Scheibye-Alsing, Karsten; Canugovi, Chandrika; Croteau, Deborah L; Bohr, Vilhelm A

    2013-03-01

    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.

  16. Ménière's disease in children aged 4-7 years.

    PubMed

    Brantberg, Krister; Duan, Maoli; Falahat, Babak

    2012-05-01

    This is a retrospective review of clinical data and audiovestibular test results from four children in whom symptoms suggesting Ménière's disease started at 4-7 years of age. The four patients all had spontaneous recurrent attacks of (spinning) vertigo and fluctuating low frequency sensorineural hearing loss from an early age, suggesting a diagnosis of definite Ménière's disease. Presumably, due to age-related inability to communicate auditory symptoms, the children did not initially meet requirements for a diagnosis of Ménière's disease. However, by 8 years of age, all four children reported tinnitus and/or fullness in the affected ear and, thus, met the AAO criteria for Ménière's disease. Even if information on subjective auditory symptoms is missing, it is reasonable to consider young children with idiopathic spontaneous recurrent attacks of vertigo in whom audiograms reveals fluctuating low frequency hearing loss to have Ménière's disease. This report is a reminder that Ménière's disease may also occur in young children.

  17. Dupuytren disease: an evolving understanding of an age-old disease.

    PubMed

    Black, Eric M; Blazar, Philip E

    2011-12-01

    Dupuytren disease, a clinical entity originally described more than 400 years ago, is a progressive disease of genetic origin. Excessive myofibroblast proliferation and altered collagen matrix composition lead to thickened and contracted palmar fascia; the resultant digital flexion contractures may severely limit function. The pathophysiology is multifactorial and remains a topic of research and debate. Genetic predisposition, trauma, inflammatory response, ischemia, and environment, as well as variable expression of proteins and growth factors within the local tissue, all play a role in the disease process. Common treatments of severe disease include open fasciectomy or fasciotomy. These procedures may be complicated by the complex anatomic relationships between cords (pathologic contracted fascia) and adjacent neurovascular structures. Recent advances in the management of Dupuytren disease involve less invasive treatments, such as percutaneous needle fasciotomy and injectable collagenase Clostridium histolyticum. Postoperative management focuses on minimizing the cellular response of cord disruption and maximizing range of motion through static or dynamic extension splinting.

  18. The research on aging failure rate and optimization estimation of protective relay under haze conditions

    NASA Astrophysics Data System (ADS)

    Wang, Ying-kang; Zhou, Meng-ran; Yang, Jie; Zhou, Pei-qiang; Xie, Ying

    2017-01-01

    In the fog and haze, the air contains large amounts of H2S, SO2, SO3 and other acids, air conductivity is greatly improved, the relative humidity is also greatly increased, Power transmission lines and electrical equipment in such an environment will increase in the long-running failure ratedecrease the sensitivity of the detection equipment, impact protection device reliability. Weibull distribution is widely used in component failure distribution fitting. It proposes a protection device aging failure rate estimation method based on the least squares method and the iterative method,.Combined with a regional power grid statistics, computing protective equipment failure rate function. Binding characteristics of electrical equipment operation status under haze conditions, optimization methods, get more in line with aging protection equipment failure under conditions of haze characteristics.

  19. How old is this bird? The age distribution under some phase sampling schemes.

    PubMed

    Hautphenne, Sophie; Massaro, Melanie; Taylor, Peter

    2017-04-03

    In this paper, we use a finite-state continuous-time Markov chain with one absorbing state to model an individual's lifetime. Under this model, the time of death follows a phase-type distribution, and the transient states of the Markov chain are known as phases. We then attempt to provide an answer to the simple question "What is the conditional age distribution of the individual, given its current phase"? We show that the answer depends on how we interpret the question, and in particular, on the phase observation scheme under consideration. We then apply our results to the computation of the age pyramid for the endangered Chatham Island black robin Petroica traversi during the monitoring period 2007-2014.

  20. Motor and non-motor symptoms in old-age onset Parkinson's disease patients.

    PubMed

    Mendonça, Marcelo D; Lampreia, Tania; Miguel, Rita; Caetano, André; Barbosa, Raquel; Bugalho, Paulo

    2017-03-17

    Advancing age is a well-known risk factor for Parkinson's disease (PD). With population ageing it is expected that the total number of patients with PD onset at oldage increases. Information on the motor but particularly on non-motor phenotype of this late-onset population is lacking. We recruited 24 patients with PD onset at or over 75 years. Each patient was matched with 1 control patient with PD onset between the ages of 40 and 65 and matched for disease duration. Both groups were assessed with the UPDRS, the Non-motor symptoms scale (NMSS) and other scales to assess non-motor symptoms. Groups were compared with conditional logistic regression analysis. Old-age onset PD was, on average, 80 years at the time of PD onset while middle-age onset were 59. Disease duration was approximately 5 years in both groups. While no difference was observed in the total UPDRS-III scores, old-age onset PD was associated with higher axial symptoms (7.42 vs. 4.63, p = 0.011) and a higher frequency of dementia (7/24 vs. 0/24, p = 0.009). While no difference in the total number of non-motor symptoms was observed (6.79 vs. 6.22, p = 0.310), old-age onset patients had a higher prevalence of gastrointestinal symptoms (20/24 vs. 12/24, p = 0.037). For the same disease duration, older age onset is associated with worse axial motor dysfunction and dementia in PD patients. Beside gastrointestinal symptoms, non-motor symptoms are not associated with age.

  1. Underlying chronic granulomatous disease in a patient with bronchocentric granulomatosis

    PubMed Central

    Moltyaner, Y; Geerts, W; Chamberlain, D; Heyworth, P; Noack, D; Rae, J; Doyle, J; Downey, G

    2003-01-01

    We present a case of bronchocentric granulomatosis in a woman with no history of asthma who was colonised with Aspergillusfumigatus. A family history of chronic granulomatous disease prompted further testing that demonstrated severely depressed neutrophil oxidant production and gp91phox deficiency compatible with the X linked carrier state of chronic granulomatous disease. Only one report of the association of these two rare diseases has previously appeared in the literature. We postulate that an ineffective immune response led to the prolonged colonisation of Afumigatus resulting in a hypersensitivity reaction that was manifest clinically as bronchocentric granulomatosis. PMID:14645984

  2. Age-related declines in car following performance under simulated fog conditions

    PubMed Central

    Ni, Rui; Kang, Julie J.; Andersen, George J.

    2010-01-01

    The present study examined age-related differences in car following performance when contrast of the driving scene was reduced by simulated fog. Older (mean age of 72.6) and younger (mean age of 21.1) drivers were presented with a car following scenario in a simulator in which a lead vehicle (LV) varied speed according to a sum of three sine wave functions. Drivers were shown an initial following distance of 18m and were asked to maintain headway distance by controlling speed to match changes in LV speed. Five simulated fog conditions were examined ranging from a no fog condition (contrast of 0.55) to a high fog condition (contrast of 0.03). Average LV speed varied across trials (40, 60, or 80 km/h). The results indicated age-related declines in car following performance for both headway distance and RMS (root mean square) error in matching speed. The greatest decline occurred at moderate speeds under the highest fog density condition, with older drivers maintaining a headway distance that was 21% closer than younger drivers. At higher speeds older drivers maintained a greater headway distance than younger drivers. These results suggest that older drivers may be at greater risk for a collision under high fog density and moderate speeds. PMID:20380908

  3. Mechanical Properties of Anisotropic Conductive Adhesive Film Under Hygrothermal Aging and Thermal Cycling

    NASA Astrophysics Data System (ADS)

    Gao, Li-Lan; Chen, Xu; Gao, Hong

    2012-07-01

    Mechanical properties of anisotropic conductive adhesive film (ACF) were investigated experimentally under various environmental conditions. The temperature sweep test was conducted to investigate the effects of temperature on dynamical mechanical properties of the ACF. The ACF exhibited transitions to the glass state, viscoelastic state, and rubber state with increasing temperature, and its glass-transition temperature ( T g) was determined to be 149°C. The creep-recovery behaviors of the ACF were investigated, and it was found that the initial strains, instantaneous strains, and creep or recovery rates increased with increasing temperature. No obvious creep phenomenon was observed at low temperatures (≤0°C). The creep strain and creep rates at any time decreased with increasing hygrothermal aging time. The uniaxial tensile behaviors of the ACF were also investigated under hygrothermal aging and thermal cycling. The results show that the Young's modulus and tensile strength of the ACF decrease with increasing hygrothermal aging time; however, they increase at first and then decrease with increasing thermal cycling time. T g decreases slightly for the ACF after hygrothermal aging; however, it increases after thermal cycling.

  4. Age-related declines in car following performance under simulated fog conditions.

    PubMed

    Ni, Rui; Kang, Julie J; Andersen, George J

    2010-05-01

    The present study examined age-related differences in car following performance when contrast of the driving scene was reduced by simulated fog. Older (mean age of 72.6) and younger (mean age of 21.1) drivers were presented with a car following scenario in a simulator in which a lead vehicle (LV) varied speed according to a sum of three sine wave functions. Drivers were shown an initial following distance of 18 m and were asked to maintain headway distance by controlling speed to match changes in LV speed. Five simulated fog conditions were examined ranging from a no fog condition (contrast of 0.55) to a high fog condition (contrast of 0.03). Average LV speed varied across trials (40, 60, or 80 km/h). The results indicated age-related declines in car following performance for both headway distance and RMS (root mean square) error in matching speed. The greatest decline occurred at moderate speeds under the highest fog density condition, with older drivers maintaining a headway distance that was 21% closer than younger drivers. At higher speeds older drivers maintained a greater headway distance than younger drivers. These results suggest that older drivers may be at greater risk for a collision under high fog density and moderate speeds.

  5. 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.

  6. How Does Age at Onset Influence the Outcome of Autoimmune Diseases?

    PubMed Central

    Amador-Patarroyo, Manuel J.; Rodriguez-Rodriguez, Alberto; Montoya-Ortiz, Gladis

    2012-01-01

    The age at onset refers to the time period at which an individual experiences the first symptoms of a disease. In autoimmune diseases (ADs), these symptoms can be subtle but are very relevant for diagnosis. They can appear during childhood, adulthood or late in life and may vary depending on the age at onset. Variables like mortality and morbidity and the role of genes will be reviewed with a focus on the major autoimmune disorders, namely, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes mellitus (T1D), Sjögren's syndrome, and autoimmune thyroiditis (AITD). Early age at onset is a worst prognostic factor for some ADs (i.e., SLE and T1D), while for others it does not have a significant influence on the course of disease (i.e., SS) or no unanimous consensus exists (i.e., RA and MS). PMID:22195277

  7. Towards a better monitoring of seed ageing under ex situ seed conservation

    PubMed Central

    Fu, Yong-Bi; Ahmed, Zaheer; Diederichsen, Axel

    2015-01-01

    Long-term conservation of 7.4 million ex situ seed accessions held in agricultural genebanks and botanic gardens worldwide is a challenging mission for human food security and ecosystem services. Recent advances in seed biology and genomics may have opened new opportunities for effective management of seed germplasm under long-term storage. Here, we review the current development of tools for assessing seed ageing and research advances in seed biology and genomics, with a focus on exploring their potential as better tools for monitoring of seed ageing. Seed ageing is found to be associated with the changes reflected in reactive oxygen species and mitochondria-triggered programmed cell deaths, expression of antioxidative genes and DNA and protein repair genes, chromosome telomere lengths, epigenetic regulation of related genes (microRNA and methylation) and altered organelle and nuclear genomes. Among these changes, the signals from mitochondrial and nuclear genomes may show the most promise for use in the development of tools to predict seed ageing. Non-destructive and non-invasive analyses of stored seeds through calorimetry or imaging techniques are also promising. It is clear that research into developing advanced tools for monitoring seed ageing to supplement traditional germination tests will be fruitful for effective conservation of ex situ seed germplasm. PMID:27293711

  8. Mechanical Testing of TR-55 Rubber Thermally Aged Under Tensile Strain

    SciTech Connect

    Small IV, W; Alviso, C T; Wilson, T S; Chinn, S C; Maxwell, R S

    2009-03-10

    TR-55 rubber specimens were previously subjected to an aging process consisting of the application of a tensile strain of approximately 67%, 100%, 133%, or 167% elongation for 4, 8, 12, or 16 h at either 250 C or room temperature. Control specimens at the same temperatures/durations were not subjected to tensile strain. The specimens were allowed to recover at room temperature without external stimuli for over 100 days before tensile testing. A single dog bone was cut from each specimen and a stress-strain curve was obtained. The elastic modulus of each specimen was calculated. Specimens aged under tensile strain exhibited rubber-like behavior dependent on the aging elongation and duration. This behavior was not evident in the unstrained controls. For the unstrained controls, exposure to 250 C resulted in an increase in modulus relative to the unheated material independent of the heating duration. The tensile strain applied during the aging process caused a reduction in modulus relative to the controls; lower moduli were observed for the shorter aging durations. Slippage of the specimens in the grips prevented determination of ultimate strength, as all specimens either slipped completely out of the grip before failure or failed at the original grip edge after slipping.

  9. Surface and interface properties of carbon fiber composites under cyclical aging

    NASA Astrophysics Data System (ADS)

    Lv, Xinying; Wang, Rongguo; Liu, Wenbo; Jiang, Long

    2011-10-01

    Carbon fiber-reinforced BMI composites have been subjected to combination accelerated aging comprising a hygrothermal process, a thermal-oxidative process, and a freezing process in order to simulate their responses under complicated service environments. This cyclical condition, including the freezing process, has not been investigated by other researchers so far. The effects of this combination accelerated aging on the mechanical properties have been characterized by FTIR, SEM/EDXA, XRD, and moisture-uptake determination. The results indicated that combination accelerated aging had great effects on the mechanical properties of the composite, the network structure of the BMI matrix, and the moisture uptake by the composite. After a third cycle of accelerated aging, moisture reached the center layer of the composite and as a result led to an obvious decrease in ILSS due to deterioration of the carbon fiber-BMI interface. Sufficient moisture absorption on the composite surface made the network structure of the BMI matrix more open, which facilitated stress relaxation and the creation of micro-cracks, with a consequent obvious decrease in flexural strength. With increasing number of combined-action accelerated aging cycles, ever more moisture was absorbed during each hygrothermal process due to the plasticizing effect of water, and micro-cracks propagated as a result of internal stresses caused by the hygrothermal process, the thermal-oxidative process, and the freezing process of each cycle. XRD analysis indicated that moisture penetrated through the amorphous region of the BMI matrix.

  10. 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

  11. A culture-brain link: Negative age stereotypes predict Alzheimer's disease biomarkers.

    PubMed

    Levy, Becca R; Ferrucci, Luigi; Zonderman, Alan B; Slade, Martin D; Troncoso, Juan; Resnick, Susan M

    2016-02-01

    Although negative age stereotypes have been found to predict adverse outcomes among older individuals, it was unknown whether the influence of stereotypes extends to brain changes associated with Alzheimer's disease. To consider this possibility, we drew on dementia-free participants, in the Baltimore Longitudinal Study of Aging, whose age stereotypes were assessed decades before yearly magnetic resonance images and brain autopsies were performed. Those holding more-negative age stereotypes earlier in life had significantly steeper hippocampal-volume loss and significantly greater accumulation of neurofibrillary tangles and amyloid plaques, adjusting for relevant covariates. These findings suggest a new pathway to identifying mechanisms and potential interventions related to the pathology of Alzheimer's disease.

  12. Transcranial magnetic stimulation of degenerating brain: a comparison of normal aging, Alzheimer's, Parkinson's and Huntington's disease.

    PubMed

    Ljubisavljevic, M R; Ismail, F Y; Filipovic, S

    2013-07-01

    Although the brain's ability to change constantly in response to external and internal inputs is now well recognized the mechanisms behind it in normal aging and neurodegeneration are less well understood. To gain a better understanding, transcranial magnetic stimulation (TMS) has been used extensively to characterize non-invasively the cortical neurophysiology of the aging and degenerating brain. Furthermore, there has been a surge of studies examining whether repetitive TMS (rTMS) can be used to improve functional deficits in various conditions including normal aging, Alzheimer's and Parkinson's disease. The results of these studies in normal aging and neurodegeneration have emerged reasonably coherent in delineating the main pathology in spite of considerable technical limitations, omnipresent methodological variability, and extraordinary patient heterogeneity. Nevertheless, comparing and integrating what is known about TMS measurements of cortical excitability and plasticity in disorders that predominantly affect cortical brain structures with disorders that predominantly affect subcortical brain structures may provide better understanding of normal and abnormal brain aging fostering new. The present review provides a TMS perspective of changes in cortical neurophysiology and neurochemistry in normal aging and neurodegeneration by integrating what is revealed in individual TMS measurements of cortical excitability and plasticity in physiological aging, Alzheimer's, Parkinson's, and Huntington's, disease. The paper also reflects on current developments in utilizing TMS as a physiologic biomarker to discriminate physiologic aging from neurodegeneration and its potential as a method of therapeutic intervention.

  13. Parasitism in Children Aged Three Years and Under: Relationship between Infection and Growth in Rural Coastal Kenya

    PubMed Central

    McKibben, Maxim; Mungai, Peter; Muchiri, Eric M.; McKibben, Elisabeth; Gildengorin, Ginny; Sutherland, Laura J.; King, Charles H.; King, Christopher L.; Malhotra, Indu

    2015-01-01

    Background Parasitic infections, which are among the most common infections worldwide, disproportionately affect children; however, little is known about the impact of parasitic disease on growth in very early childhood. Our objective was to document the prevalence of parasitic infections and examine their association with growth during the first three years of life among children in coastal Kenya. Methodology/Principal Findings Children enrolled in a maternal-child cohort were tested for soil transmitted helminths (STHs: Ascaris, Trichuris, hookworm, Strongyloides), protozoa (malaria, Entamoeba histolytica and Giardia lamblia), filaria, and Schistosoma infection every six months from birth until age three years. Anthropometrics were measured at each visit. We used generalized estimating equation (GEE) models to examine the relationship between parasitic infections experienced in the first three years of life and growth outcomes (weight, length and head circumference). Of 545 children, STHs were the most common infection with 106 infections (19%) by age three years. Malaria followed in period prevalence with 68 infections (12%) by three years of age. Filaria and Schistosoma infection occurred in 26 (4.8%) and 16 (2.9%) children, respectively. Seven percent were infected with multiple parasites by three years of age. Each infection type (when all STHs were combined) was documented by six months of age. Decreases in growth of weight, length and head circumference during the first 36 months of life were associated with hookworm, Ascaris, E. histolytica, malaria and Schistosoma infection. In a subset analysis of 180 children who followed up at every visit through 24 months, infection with any parasite was associated with decelerations in weight, length and head circumference growth velocity. Multiple infections were associated with greater impairment of linear growth. Conclusions/Significance Our results demonstrate an under-recognized burden of parasitism in the first

  14. Telomere length and cardiovascular risk factors in a middle-aged population free of overt cardiovascular disease.

    PubMed

    Bekaert, Sofie; De Meyer, Tim; Rietzschel, Ernst R; De Buyzere, Marc L; De Bacquer, Dirk; Langlois, Michel; Segers, Patrick; Cooman, Luc; Van Damme, Piet; Cassiman, Peter; Van Criekinge, Wim; Verdonck, Pascal; De Backer, Guy G; Gillebert, Thierry C; Van Oostveldt, Patrick

    2007-10-01

    Evidence assembled over the last decade shows that average telomere length (TL) acts as a biomarker for biological aging and cardiovascular disease (CVD) in particular. Although essential for a more profound understanding of the underlying mechanisms, little reference information is available on TL. We therefore sought to provide baseline TL information and assess the association of prevalent CVD risk factors with TL in subjects free of overt CVD within a small age range. We measured mean telomere restriction fragment length of peripheral blood leukocytes in a large, representative Asklepios study cohort of 2509 community-dwelling, Caucasian female and male volunteers aged approximately 35-55 years and free of overt CVD. We found a manifest age-dependent telomere attrition, at a significantly faster rate in men as compared to women. No significant associations were established with classical CVD risk factors such as cholesterol status and blood pressure, yet shorter TL was associated with increased levels of several inflammation and oxidative stress markers. Importantly, shorter telomere length was associated with an increasingly unhealthy lifestyle, particularly in men. All findings were age and gender adjusted where appropriate. With these cross-sectional results we show that TL of peripheral blood leukocytes primarily reflects the burden of increased oxidative stress and inflammation, whether or not determined by an increasingly unhealthy lifestyle, while the association with classical CVD risk factors is limited. This further clarifies the added value of TL as a biomarker for biological aging and might improve our understanding of how TL is associated with CVD.

  15. 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.

  16. Quantitative proteomic analysis of age-related subventricular zone proteins associated with neurodegenerative disease

    PubMed Central

    Wang, Xianli; Dong, Chuanming; Sun, Lixin; Zhu, Liang; Sun, Chenxi; Ma, Rongjie; Ning, ke; Lu, Bing; Zhang, Jinfu; Xu, Jun

    2016-01-01

    Aging is characterized by a progressive decline in the function of adult tissues which can lead to neurodegenerative disorders. However, little is known about the correlation between protein changes in the subventricular zone (SVZ) and neurodegenerative diseases with age. In the present study, neural stem cells (NSCs) were derived from the SVZ on postnatal 7 d, 1 m, and 12 m-old mice. With age, NSCs exhibited increased SA-β-gal activity and decreased proliferation and pool size in the SVZ zone, and were associated with elevated inflammatory chemokines and cytokines. Furthermore, quantitative proteomics and ingenuity pathway analysis were used to evaluate the significant age-related alterations in proteins and their functions. Some downregulated proteins such as DPYSL2, TPI1, ALDH, and UCHL1 were found to play critical roles in the neurological disease and PSMA1, PSMA3, PSMC2, PSMD11, and UCHL1 in protein homeostasis. Taken together, we have provided valuable insight into the cellular and molecular processes that underlie aging-associated declines in SVZ neurogenesis for the early detection of differences in gene expression and the potential risk of neurological disease, which is beneficial in the prevention of the diseases. PMID:27857231

  17. 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

  18. 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

  19. 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

  20. 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.

  1. BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer's Disease.

    PubMed

    Gaser, Christian; Franke, Katja; 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.

  2. 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

  3. Genetic and Developmental Perspective of Language Abnormality in Autism and Schizophrenia: One Disease Occurring at Different Ages in Humans?

    PubMed

    Wang, Haoran George; Jeffries, Joseph Joel; Wang, Tianren Frank

    2016-04-01

    Language and communication through it are two of the defining features of normally developed human beings. However, both these functions are often impaired in autism and schizophrenia. In the former disorder, the problem usually emerges in early childhood (~2 years old) and typically includes a lack of communication. In the latter condition, the language problems usually occur in adolescence and adulthood and presents as disorganized speech. What are the fundamental mechanisms underlying these two disorders? Is there a shared genetic basis? Are the traditional beliefs about them true? Are there any common strategies for their prevention and management? To answer these questions, we searched PubMed by using autism, schizophrenia, gene, and language abnormality as keywords, and we reconsidered the basic concepts about these two diseases or syndromes. We found many functional genes, for example, FOXP2, COMT, GABRB3, and DISC1, are actually implicated in both of them. After observing the symptoms, genetic correlates, and temporal progression of these two disorders as well as their relationships more carefully, we now infer that the occurrence of these two diseases is likely developmentally regulated via interaction between the genome and the environment. Furthermore, we propose a unified view of autism and schizophrenia: a single age-dependently occurred disease that is newly named as Systemic Integral Disorder: if occurring in children before age 2, it is called autism; if in adolescence or a later age, it is called schizophrenia.

  4. The maternal-age-associated risk of congenital heart disease is modifiable.

    PubMed

    Schulkey, Claire E; Regmi, Suk D; Magnan, Rachel A; Danzo, Megan T; Luther, Herman; Hutchinson, Alayna K; Panzer, Adam A; Grady, Mary M; Wilson, David B; Jay, Patrick Y

    2015-04-09

    Maternal age is a risk factor for congenital heart disease even in the absence of any chromosomal abnormality in the newborn. Whether the basis of this risk resides with the mother or oocyte is unknown. The impact of maternal age on congenital heart disease can be modelled in mouse pups that harbour a mutation of the cardiac transcription factor gene Nkx2-5 (ref. 8). Here, reciprocal ovarian transplants between young and old mothers establish a maternal basis for the age-associated risk in mice. A high-fat diet does not accelerate the effect of maternal ageing, so hyperglycaemia and obesity do not simply explain the mechanism. The age-associated risk varies with the mother's strain background, making it a quantitative genetic trait. Most remarkably, voluntary exercise, whether begun by mothers at a young age or later in life, can mitigate the risk when they are older. Thus, even when the offspring carry a causal mutation, an intervention aimed at the mother can meaningfully reduce their risk of congenital heart disease.

  5. Ageing and inflammation - A central role for mitochondria in brain health and disease.

    PubMed

    Currais, Antonio

    2015-05-01

    To develop successful therapies that prevent or treat neurodegenerative diseases requires an understanding of the upstream events. Ageing is by far the greatest risk factor for most of these diseases, and to clarify their causes will require an understanding of the process of ageing itself. Starting with the question Why do we age as individual organisms, but the line of pluripotent embryonic stem cells and germ cells carried by individuals and transmitted to descendants is immortal? this review discusses how the process of cellular differentiation leads to the accumulation of biological imperfections with ageing, and how these imperfections may be the cause of chronic inflammatory responses to stress that undermine cellular function. Both differentiation and inflammation involve drastic metabolic changes associated with alterations in mitochondrial dynamics that shift the balance between aerobic glycolysis and oxidative phosphorylation. With ageing, mitochondrial dysfunction can be both the cause and consequence of inflammatory processes and elicit metabolic adaptations that might be either protective or become progressively detrimental. It is argued here that an understanding of the relationship between metabolism, differentiation and inflammation is essential to understand the pathological mechanisms governing brain health and disease during ageing.

  6. Induced Accelerated Aging in Induced Pluripotent Stem Cell Lines from Patients with Parkinson’s Disease

    DTIC Science & Technology

    2014-07-01

    Induced Pluripotent Stem Cell Lines from Patients with Parkinson’s Disease PRINCIPAL INVESTIGATOR: Dr. Birgitt Schuele CONTRACTING...contained in this report are those of the author( s ) and should not be construed as an official Department of the Army position, policy or decision...Aging in Induced Pluripotent Stem Cell Lines from Patients with Parkinson’s Disease 5b. GRANT NUMBER W81XWH-12-1-0003 5c. PROGRAM ELEMENT NUMBER

  7. Nuclear membrane diversity: underlying tissue-specific pathologies in disease?

    PubMed Central

    Worman, Howard J.; Schirmer, Eric C.

    2015-01-01

    Human ‘laminopathy’ diseases result from mutations in genes encoding nuclear lamins or nuclear envelope (NE) transmembrane proteins (NETs). These diseases present a seeming paradox: the mutated proteins are widely expressed yet pathology is limited to specific tissues. New findings suggest tissue-specific pathologies arise because these widely expressed proteins act in various complexes that include tissue-specific components. Diverse mechanisms to achieve NE tissue-specificity include tissue-specific regulation of the expression, mRNA splicing, signaling, NE-localization and interactions of potentially hundreds of tissue-specific NETs. New findings suggest these NETs underlie tissue-specific NE roles in cytoskeletal mechanics, cell-cycle regulation, signaling, gene expression and genome organization. This view of the NE as ‘specialized’ in each cell type is important to understand the tissue-specific pathology of NE-linked diseases. PMID:26115475

  8. Nuclear membrane diversity: underlying tissue-specific pathologies in disease?

    PubMed

    Worman, Howard J; Schirmer, Eric C

    2015-06-01

    Human 'laminopathy' diseases result from mutations in genes encoding nuclear lamins or nuclear envelope (NE) transmembrane proteins (NETs). These diseases present a seeming paradox: the mutated proteins are widely expressed yet pathology is limited to specific tissues. New findings suggest tissue-specific pathologies arise because these widely expressed proteins act in various complexes that include tissue-specific components. Diverse mechanisms to achieve NE tissue-specificity include tissue-specific regulation of the expression, mRNA splicing, signaling, NE-localization and interactions of potentially hundreds of tissue-specific NETs. New findings suggest these NETs underlie tissue-specific NE roles in cytoskeletal mechanics, cell-cycle regulation, signaling, gene expression and genome organization. This view of the NE as 'specialized' in each cell type is important to understand the tissue-specific pathology of NE-linked diseases.

  9. Fatigue Crack Growth of Age-Hardened Al Alloy Under Ultrasonic Loading

    NASA Astrophysics Data System (ADS)

    Chen, Q.; Kawagoishi, N.; Kariya, K.; Nu, Y.; Goto, M.

    An age-hardened and extruded Al alloy 7075-T6 was fatigued under both ultrasonic loading (20kHz) and rotating bending (50Hz) in the environments of controlled humidity, distilled water and oxygen gas respectively, to investigate the availability of ultrasonic fatigue test as a time-saving tool for the reliability evaluation of materials subjected to conventional frequency loading. Although fatigue strength decreased slightly at relative humidity below 60-70%, it degraded significantly when the humidity was increased beyond that level, irrespective of the loading frequency. However, the mechanisms of strength degradation involved in high humidity are quite different. Under rotating bending, fatigue strength decreased because crack growth was accelerated due to brittle fracture, whileas the decrease in fatigue strength under ultrasonic loading was caused by crack propagation transition from tensile mode to shear mode cracking.

  10. Epigenetics of Aging and Alzheimer’s Disease: Implications for Pharmacogenomics and Drug Response

    PubMed Central

    Cacabelos, Ramón; Torrellas, Clara

    2015-01-01

    Epigenetic variability (DNA methylation/demethylation, histone modifications, microRNA regulation) is common in physiological and pathological conditions. Epigenetic alterations are present in different tissues along the aging process and in neurodegenerative disorders, such as Alzheimer’s disease (AD). Epigenetics affect life span and longevity. AD-related genes exhibit epigenetic changes, indicating that epigenetics might exert a pathogenic role in dementia. Epigenetic modifications are reversible and can potentially be targeted by pharmacological intervention. Epigenetic drugs may be useful for the treatment of major problems of health (e.g., cancer, cardiovascular disorders, brain disorders). The efficacy and safety of these and other medications depend upon the efficiency of the pharmacogenetic process in which different clusters of genes (pathogenic, mechanistic, metabolic, transporter, pleiotropic) are involved. Most of these genes are also under the influence of the epigenetic machinery. The information available on the pharmacoepigenomics of most drugs is very limited; however, growing evidence indicates that epigenetic changes are determinant in the pathogenesis of many medical conditions and in drug response and drug resistance. Consequently, pharmacoepigenetic studies should be incorporated in drug development and personalized treatments. PMID:26703582

  11. Age-independent seismic anisotropy under oceanic plates explained by strain history in the asthenosphere

    NASA Astrophysics Data System (ADS)

    Hedjazian, Navid; Garel, Fanny; Davies, D. Rhodri; Kaminski, Edouard

    2017-02-01

    The depth of the oceanic lithosphere-asthenosphere boundary (LAB), as inferred from shear wave velocities, increases with lithospheric age, in agreement with models of cooling oceanic lithosphere. On the other hand, the distribution of radial anisotropy under oceanic plates is almost age-independent. In particular, radial anisotropy shows a maximum positive gradient at a depth of ∼70 km, which, if used as a proxy, indicates an age-independent LAB depth. These contrasting observations have fueled a controversy on the seismological signature of the LAB. To better understand the discrepancy between these observations, we model the development of lattice preferred orientation (LPO) in upper mantle crystal aggregates and predict the seismic anisotropy produced by plate-driven mid-ocean ridge flows. The model accounts for the progressive cooling of the lithosphere with age and can incorporate both diffusion and dislocation creep deformation mechanisms. We find that an age-independent distribution of radial anisotropy is the natural consequence of these simple flows. The depth and strength of anisotropy is further controlled by the deformation regime - dislocation or diffusion creep - experienced by crystals during their ascent towards, and subsequent motion away from, the ridge axis. Comparison to surface wave tomography models yield constraints on rheological parameters such as the activation volume. Although not excluded, additional mechanisms proposed to explain some geophysical signatures of the LAB, such as the presence of partial melt or changes in water content, are not required to explain the radial anisotropy proxy. Our prediction, that the age-independent radial anisotropy proxy marks the transition to flow-induced asthenospheric anisotropy, provides a way to reconcile thermal, mechanical and seismological views of the LAB.

  12. The impact of health insurance for children under age 6 in Vietnam: A regression discontinuity approach.

    PubMed

    Palmer, Michael; Mitra, Sophie; Mont, Daniel; Groce, Nora

    2015-11-01

    Accessing health services at an early age is important to future health and life outcomes. Yet, little is currently known on the role of health insurance in facilitating access to care for children. Exploiting a regression discontinuity design made possible through a policy to provide health insurance to pre-school aged children in Vietnam, this paper evaluates the impact of health insurance on the health care utilization outcomes of children at the eligibility threshold of six years. Using three rounds of the Vietnam Household Living Standards Survey, the study finds a positive impact on inpatient and outpatient visits and no significant impact on expenditures per visit at public facilities. We find moderately high use of private outpatient services and no evidence of a switch from private to covered public facilities under insurance. Results suggest that adopting public health insurance programs for children under age 6 may be an important vehicle to improving service utilization in a low- and middle-income country context. Challenges remain in providing adequate protections from the costs and other barriers to care.

  13. Regional differences in incidence and clinical presentation of type 1 diabetes in children aged under 15 years in Croatia

    PubMed Central

    Stipančić, Gordana; La Grasta Sabolić, Lavinia; Požgaj Šepec, Marija; Radica, Ana; Skrabić, Veselin; Severinski, Srećko; Kujundžić Tiljak, Mirjana

    2012-01-01

    Aim To determine regional differences in the incidence, incidence trends, and clinical presentation of type 1 diabetes in children under the age of 15 years in Croatia in a 9-year period (1995-2003). Methods We included the patients who had been diagnosed with the disease and had started the insulin treatment before they were 15 years old. Regional differences between eastern, central, and southern Croatia were observed. The gross incidence was expressed by the number of newly diagnosed type 1 diabetes patients in 100 000 children of the same age and sex per year, ie, for the 0-14 age group, and for the 0-4, 5-9, and 10-14 subgroups. Results The highest incidence was observed in southern Croatia (10.91 per 100 000/y) and the lowest in central Croatia (8.64 per 100 000/y), and in eastern Croatia the incidence was 8.93 per 100 000/y. All three regions showed a growing incidence trend, which was significant only in eastern and southern Croatia. There was 35.9% of patients with diabetic ketoacidosis in eastern Croatia, 41.7% in central Croatia, and 31.3% in southern Croatia. Conclusion Croatian regions show differences in the incidence, incidence trends, and disease presentation of type 1 diabetes. A further follow-up is needed to establish whether the regional differences are a consequence of the population dynamics in the observed period or they will continue to exist, pointing to differences in environmental risk factors. PMID:22522992

  14. Evidence of subclinical prion disease in aged mice following exposure to bovine spongiform encephalopathy.

    PubMed

    Brown, Karen L; Mabbott, Neil A

    2014-01-01

    The occurrence of variant Creutzfeldt-Jakob (vCJD) disease in humans was almost certainly the result of consumption of food contaminated with bovine spongiform encephalopathy (BSE) prions. Despite probable widespread exposure of the UK population to BSE-contaminated food in the 1980s, vCJD has been identified predominantly in young individuals, and there have been fewer cases of clinical disease than anticipated. The reasons for this are uncertain. Following peripheral exposure, many prions replicate within the lymphoid tissues before infecting the central nervous system. We have shown that the effects of host age on the microarchitecture of the spleen significantly impair susceptibility to mouse-adapted prions after peripheral exposure. The transmission of prions between different mammalian species is considered to be limited by the 'species barrier', which is dependent on several factors, including an intact immune system. Thus, cross-species prion transmission may be much less efficient in aged individuals. To test this hypothesis, we compared prion pathogenesis in groups of young (6-8 weeks old) and aged (600 days old) mice injected with primary BSE brain homogenate. We showed that prion pathogenesis was impaired dramatically in aged mice when compared with young animals. Whereas most young mice succumbed to clinical prion disease, all aged mice failed to develop clinical disease during their lifespans. However, the demonstration that prion accumulation was detected in the lymphoid tissues of some aged mice after injection with primary BSE brain homogenate, in the absence of clinical signs of prion disease, has important implications for human health.

  15. Age-related changes and diseases of the ocular surface and cornea.

    PubMed

    Gipson, Ilene K

    2013-12-13

    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.

  16. Duration of illness in Huntington's disease is not related to age at onset.

    PubMed

    Roos, R A; Hermans, J; Vegter-van der Vlis, M; van Ommen, G J; Bruyn, G W

    1993-01-01

    The age at onset and duration of illness were studied in patients with Huntington's disease in the Leiden Roster which at 1 July 1990 contained 2787 patients. Of 1106 patients, 800 deceased and 306 alive, the age at onset was known. The median duration was 16.2 (range 2-45) years. In contrast to the current opinion, the median duration was independent of the age of onset. The median duration in juvenile Huntington's disease was 17.1 years, which is much longer than reported in the literature, and comparable with the categories for the age of onset of 20-34 and 35-49 years. Only in the group where onset was over 50 years of age was the median duration somewhat shorter (15.6 years), which can be ascribed to unrelated causes of death. As age of onset and duration of illness are not related, at least two mechanisms to determine the clinical course have to be postulated: one for age of onset and another for duration of illness. Duration was shorter for males, especially for those with an affected father.

  17. Duration of illness in Huntington's disease is not related to age at onset.

    PubMed Central

    Roos, R A; Hermans, J; Vegter-van der Vlis, M; van Ommen, G J; Bruyn, G W

    1993-01-01

    The age at onset and duration of illness were studied in patients with Huntington's disease in the Leiden Roster which at 1 July 1990 contained 2787 patients. Of 1106 patients, 800 deceased and 306 alive, the age at onset was known. The median duration was 16.2 (range 2-45) years. In contrast to the current opinion, the median duration was independent of the age of onset. The median duration in juvenile Huntington's disease was 17.1 years, which is much longer than reported in the literature, and comparable with the categories for the age of onset of 20-34 and 35-49 years. Only in the group where onset was over 50 years of age was the median duration somewhat shorter (15.6 years), which can be ascribed to unrelated causes of death. As age of onset and duration of illness are not related, at least two mechanisms to determine the clinical course have to be postulated: one for age of onset and another for duration of illness. Duration was shorter for males, especially for those with an affected father. PMID:8429330

  18. Use of anti-aging herbal medicine, Lycium barbarum, against aging-associated diseases. What do we know so far?

    PubMed

    Chang, Raymond Chuen-Chung; So, Kwok-Fai

    2008-08-01

    Lycium barbarum (Gouqizi, Fructus Lycii, Wolfberry) is well known for nourishing the liver, and in turn, improving the eyesight. However, many people have forgotten its anti-aging properties. Valuable components of L. barbarum are not limited to its colored components containing zeaxanthin and carotene, but include the polysaccharides and small molecules such as betaine, cerebroside, beta-sitosterol, p-coumaric, and various vitamins. Despite the fact that L. barbarum has been used for centuries, its beneficial effects to our bodies have not been comprehensively studied with modern technology to unravel its therapeutic effects at the biochemical level. Recently, our laboratory has demonstrated its neuroprotective effects to counter neuronal loss in neurodegenerative diseases. Polysaccharides extracted from L. barbarum can protect neurons against beta-amyloid peptide toxicity in neuronal cell cultures, and retinal ganglion cells in an experimental model of glaucoma. We have even isolated the active component of polysaccharide which can attenuate stress kinases and pro-apoptotic signaling pathways. We have accumulated scientific evidence for its anti-aging effects that should be highlighted for modern preventive medicine. This review is to provide background information and a new direction of study for the anti-aging properties of L. barbarum. We hope that new findings for L. barbarum will pave a new avenue for the use of Chinese medicine in modern evidence-based medicine.

  19. Predictors of peripheral arterial disease in SLE change with patient’s age

    PubMed Central

    Erdozain, Jose-Gabriel; Villar, Irama; Nieto, Javier; Ruiz-Arruza, Ioana

    2017-01-01

    Objective To analyse the differential influence of risk factors of peripheral artery disease (PAD) according to age in patients with SLE. Methods 216 patients from the Lupus-Cruces cohort were divided in three age groups: ≤34 years, 35–49 years and ≥50 years. A low ankle–brachial index defined PAD. Significant variables were identified by univariant and multivariant analysis in each age group. Results Different factors were identified in different age groups: antiphospholipid antibodies/antiphospholipid syndrome and glucocorticoids in patients ≤34 years; in patients 35–49 years old, hypertension was the only statistically significant predictor, although a trend was observed for fibrinogen levels; a trend was observed for hypercholesterolaemia in those ≥50 years. Conclusions Age may modulate the influence of risk factors for PAD in patients with SLE. PMID:28123770

  20. Trends of diarrhoeal diseases in children under five years in the War Memorial Hospital-Navrongo, Ghana: 2010-2013

    PubMed Central

    Anyorikeya, Maria; Ameme, Donne Kofi; Nyarko, Kofi Mensah; Sackey, Samuel Oko; Afari, Edwin

    2016-01-01

    Introduction Diarrhoea is the third leading cause of hospital morbidity in children under five years in the War Memorial Hospital (WMH). With the current changes in climate, little is known about the seasonal and spatial distribution of diarrhoeal diseases in the WMH. We determined trends of diarrhoeal diseases in children under five years in the WMH. Methods We reviewed secondary data of children under five years who attended the WMH and were diagnosed of diarrhoea. Diarrhoea was defined as a clinician's diagnosis of the passage of three or more watery stools a day in a child under five years in the WMH. Descriptive data analysis was done and expressed as frequencies and relative frequencies. Monthly proportions of diarrhoea and rainfall figures were presented to show seasonal distributions of cases. Geographical distribution of cases was determined using Epi Info and Arc GIS. Results A total of 865 diarrhoeal cases in children under five years reported to the hospital. Out of this, 425 (49.13%) were female children with 346 (40%) aged 0-11 months. The highest peak occurred in the rainy season from May to August. However, there was a weak negative relationship between diarrhoeal diseases and rainfall for the whole study period. Cases were clustered in the northeastern part of the Kassena Nankana Municipality (KNM). Conclusion The most affected age group was in 0-11months. Majority of cases were from the North Eastern part of the Municipality. There was seasonal variation of diarrhoeal diseases. Diarrhoeal diseases have the highest occurrence in the rainy season but an increase in rainfall does not necessarily lead to an increase in diarrhoeal cases. Intervention to reduce diarrhoea should be intensified before the rainy season and in the northeastern parts of the municipality. PMID:28210376

  1. AMPA receptor trafficking and the mechanisms underlying synaptic plasticity and cognitive aging.

    PubMed

    Henley, Jeremy M; Wilkinson, Kevin A

    2013-03-01

    Even in healthy individuals there is an inexorable agerelated decline in cognitive function. This is due, in large part, to reduced synaptic plasticity caused by changes in the molecular composition of the postsynaptic membrane. AMPA receptors (AMPARs) are glutamate-gated cation channels that mediate the overwhelming majority of fast excitatory transmission in the brain. Changes in AMPAR number and/or function are a core feature of synaptic plasticity and age-related cognitive decline, AMPARs are highly dynamic proteins that are subject to highly controlled trafficking, recycling, and/or degradation and replacement. This active regulation of AMPAR synthesis, targeting, synaptic dwell time, and degradation is fundamentally important for memory formation and storage. Further, aberrant AMPAR trafficking and consequent detrimental changes in synapses are strongly implicated in many brain diseases, which represent a vast social and economic burden. The purpose of this article is to provide an overview of the molecular and cellular AMPA receptor trafficking events that control synaptic responsiveness and plasticity, and highlight what is known currently known about how these processes change with age and disease.

  2. The Circadian Timing System: A Recent Addition in the Physiological Mechanisms Underlying Pathological and Aging Processes

    PubMed Central

    Arellanes-Licea, Elvira; Caldelas, Ivette; De Ita-Pérez, Dalia; Díaz-Muñoz, Mauricio

    2014-01-01

    Experimental findings and clinical observations have strengthened the association between physio-pathologic aspects of several diseases, as well as aging process, with the occurrence and control of circadian rhythms. The circadian system is composed by a principal pacemaker in the suprachiasmatic nucleus (SNC) which is in coordination with a number of peripheral circadian oscillators. Many pathological entities such as metabolic syndrome, cancer and cardiovascular events are strongly connected with a disruptive condition of the circadian cycle. Inadequate circadian physiology can be elicited by genetic defects (mutations in clock genes or circadian control genes) or physiological deficiencies (desynchronization between SCN and peripheral oscillators). In this review, we focus on the most recent experimental findings regarding molecular defects in the molecular circadian clock and the altered coordination in the circadian system that are related with clinical conditions such as metabolic diseases, cancer predisposition and physiological deficiencies associated to jet-lag and shiftwork schedules. Implications in the aging process will be also reviewed. PMID:25489492

  3. Preservation of Cognitive Performance with Age during Exertional Heat Stress under Low and High Air Velocity

    PubMed Central

    Wright Beatty, Heather E.; Keillor, Jocelyn M.; Hardcastle, Stephen G.; Boulay, Pierre; Kenny, Glen P.

    2015-01-01

    Older adults may be at greater risk for occupational injuries given their reduced capacity to dissipate heat, leading to greater thermal strain and potentially cognitive decrements. Purpose. To examine the effects of age and increased air velocity, during exercise in humid heat, on information processing and attention. Methods. Nine young (24 ± 1 years) and 9 older (59 ± 1 years) males cycled 4 × 15 min (separated by 15 min rest) at a fixed rate of heat production (400 W) in humid heat (35°C, 60% relative humidity) under 0.5 (low) and 3.0 (high) m·s−1 air velocity wearing coveralls. At rest, immediately following exercise (end exercise), and after the final recovery, participants performed an abbreviated paced auditory serial addition task (PASAT, 2 sec pace). Results. PASAT numbers of correct responses at end exercise were similar for young (low = 49 ± 3; high = 51 ± 3) and older (low = 46 ± 5; high = 47 ± 4) males and across air velocity conditions, and when scored relative to age norms. Psychological sweating, or an increased sweat rate with the administration of the PASAT, was observed in both age groups in the high condition. Conclusion. No significant decrements in attention and speeded information processing were observed, with age or altered air velocity, following intermittent exercise in humid heat. PMID:25874223

  4. Risk factors for deaths in under-age-five children attending a diarrhoea treatment centre.

    PubMed

    Teka, T; Faruque, A S; Fuchs, G J

    1996-09-01

    Few case-control studies have examined possible risk factors for diarrhoeal deaths in under-age-five children in the developing countries. We analysed data from the surveillance system of our diarrhoea treatment centre/hospital for the period 1990-94 on 928 children less than 5 years of age. In univariate analysis, 11 factors were significantly associated with death: lack of breastfeeding, severe malnutrition, complicated diarrhoea, pneumonia, xerophthalmia, duration of diarrhoea 7-14 days, moderate or severe dehydration, recent history of measles, Shigella flexneri infection, maternal illiteracy, and very low household income. Rotavirus diarrhoea was negatively associated with fatal outcome. In the assessment of severe malnutrition, weight-for-height measurement discriminated mortality risk better than weight-for-age or height-for-age indices. Only two factors retained their significance, severe malnutrition and non-breastfeeding in the multivariate analysis with adjusted odds ratio (95% confidence interval) of 84.2 (9.1, 775.9) and 4.2 (1.3, 13.2) respectively.

  5. The role of free radicals in the aging brain and Parkinson's Disease: convergence and parallelism.

    PubMed

    Kumar, Hemant; Lim, Hyung-Woo; More, Sandeep Vasant; Kim, Byung-Wook; Koppula, Sushruta; Kim, In Su; Choi, Dong-Kug

    2012-01-01

    Free radical production and their targeted action on biomolecules have roles in aging and age-related disorders such as Parkinson's disease (PD). There is an age-associated increase in oxidative damage to the brain, and aging is considered a risk factor for PD. Dopaminergic neurons show linear fallout of 5-10% per decade with aging; however, the rate and intensity of neuronal loss in patients with PD is more marked than that of aging. Here, we enumerate the common link between aging and PD at the cellular level with special reference to oxidative damage caused by free radicals. Oxidative damage includes mitochondrial dysfunction, dopamine auto-oxidation, α-synuclein aggregation, glial cell activation, alterations in calcium signaling, and excess free iron. Moreover, neurons encounter more oxidative stress as a counteracting mechanism with advancing age does not function properly. Alterations in transcriptional activity of various pathways, including nuclear factor erythroid 2-related factor 2, glycogen synthase kinase 3β, mitogen activated protein kinase, nuclear factor kappa B, and reduced activity of superoxide dismutase, catalase and glutathione with aging might be correlated with the increased incidence of PD.

  6. [Clinical and epidemiological characteristics of ocular trauma in children under 14 years of age].

    PubMed

    Quezada-Del Cid, Nancy C; Zimmermann-Paiz, Martin A; Ordoñez-Rivas, Ana M

    2015-10-01

    Pediatric ocular trauma is common and the leading cause of non congenital unilateral blindness. The information in developing countries is scarce. The objective of this case series is to describe clinical and epidemiological characteristics of ocular trauma in children under 14 years of age who visited Hospital Dr. Rodolfo Robles Valverde in Guatemala City in 2010. In this study 119 patients were included. School-aged (7-9 years) male gender was the most affected. Closed globe injury was the commonest. The most frequent objects causing the lesions were: wooden objects, toys and chemicals. Trauma occurred most frequently at home. Twenty one of the patients were surgically intervened. Education and prevention programs for pediatric ocular trauma are necessary.

  7. 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

  8. 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

  9. Can Neglected Tropical Diseases Compromise Human Wellbeing in Sex-, Age-, and Trait-Specific Ways?

    PubMed

    Geary, David C

    2016-04-01

    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.

  10. 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.

  11. Association between Age at Diagnosis of Graves' Disease and Variants in Genes Involved in Immune Response

    PubMed Central

    Jurecka-Lubieniecka, Beata; Ploski, Rafal; Kula, Dorota; Krol, Aleksandra; Bednarczuk, Tomasz; Kolosza, Zofia; Tukiendorf, Andrzej; Szpak-Ulczok, Sylwia; Stanjek-Cichoracka, Anita; Polanska, Joanna; Jarzab, Barbara

    2013-01-01

    Background Graves' disease (GD) is a complex disease in which genetic predisposition is modified by environmental factors. The aim of the study was to examine the association between genetic variants in genes encoding proteins involved in immune response and the age at diagnosis of GD. Methods 735 GD patients and 1216 healthy controls from Poland were included into the study. Eight genetic variants in the HLA-DRB1, TNF, CTLA4, CD40, NFKb, PTPN22, IL4 and IL10 genes were genotyped. Patients were stratified by the age at diagnosis of GD and the association with genotype was analysed. Results Polymorphism in the HLA-DRB1, TNF and CTLA4 genes were associated with GD. The carriers of the HLA DRB1*03 allele were more frequent in patients with age at GD diagnosis ≤30 years than in patients with older age at GD diagnosis. Conclusions HLADRB1*03 allele is associated with young age at diagnosis of Graves' disease in polish population. PMID:23544060

  12. 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.

  13. Evaluating Health Span in Preclinical Models of Aging and Disease: Guidelines, Challenges, and Opportunities for Geroscience

    PubMed Central

    Huffman, Derek M.; Justice, Jamie N.; Stout, Michael B.; Kirkland, James L.; Barzilai, Nir

    2016-01-01

    Life extension is no longer considered sufficient evidence of delayed aging in research animals. It must also be demonstrated that a broad swathe of health indicators have been extended. During a retreat of the Geroscience Network, a consortium of basic and clinical aging researchers, potential measures of mouse health were considered for their potential as easily standardized, highly informative metrics. Major health domains considered were neuromuscular, cognitive, cardiovascular, metabolic, and inflammatory functions as well as body composition and energetics and a multitude of assays interrogating these domains. A particularly sensitive metric of health is the ability to respond to, and recover, from stress. Therefore, the Network also considered stresses of human relevance that could be implemented in mouse models to assess frailty and resilience. Mouse models already exist for responses to forced immobility, cancer chemotherapy, infectious diseases, dietary challenges, and surgical stress, and it was felt that these could be employed to determine whether putative senescence-retarding interventions increased and extended organismal robustness. The Network discussed challenges in modeling age-related human chronic diseases and concluded that more attention needs to be paid to developing disease models with later age of onset, models of co- and multimorbidity, diversifying the strains and sexes commonly used in aging research, and considering additional species. PMID:27535967

  14. [Cases of atypical pulmonary diseases under influence of industrial aerosols].

    PubMed

    Liubchenko, P N; Stashuk, G A; Terpigorev, S A; Atamanchuk, A A; Massarygin, V V

    2014-01-01

    The article includes discharge epicrises of patients working in contact with quartz-containing dust, welding aerosol, cotton dust, irritant gases emitted in wood burning. Description covers cases of lung fibrosis, idiopathic interstitial pneumonia, systemic vasculitis with lungs involvement, sarcoidosis. The authors suggest that further accumulation of materials, further investigations of lung tissue state, epidemiologic studies will help to widen the list of occupational pulmonary diseases.

  15. Under the lash: Demodex mites in human diseases.

    PubMed

    Lacey, Noreen; Kavanagh, Kevin; Tseng, Scheffer C G

    2009-08-01

    Demodex mites, class Arachnida and subclass Acarina, are elongated mites with clear cephalothorax and abdomens, the former with four pairs of legs. There are more than 100 species of Demodex mite, many of which are obligatory commensals of the pilosebaceous unit of mammals including cats, dogs, sheep, cattle, pigs, goats, deer, bats, hamsters, rats and mice. Among them, Demodex canis, which is found ubiquitously in dogs, is the most documented and investigated. In excessive numbers D. canis causes the inflammatory disease termed demodicosis (demodectic mange, follicular mange or red mange), which is more common in purebred dogs and has a hereditary predisposition in breeding kennels1. Two distinct Demodex species have been confirmed as the most common ectoparasite in man. The larger Demodex folliculorum, about 0.3-0.4 mm long, is primarily found as a cluster in the hair follicle (Figure 1a), while the smaller Demodex brevis, about 0.2-0.3 mm long with a spindle shape and stubby legs, resides solitarily in the sebaceous gland (Figure 1b). These two species are also ubiquitously found in all human races without gender preference. The pathogenic role of Demodex mites in veterinary medicine is not as greatly disputed as in human diseases. In this article, we review the key literature and our joint research experience regarding the pathogenic potential of these two mites in causing inflammatory diseases of human skin and eye. We hope that the evidence summarized herein will invite readers to take a different look at the life of Demodex mites in several common human diseases.

  16. Carboxylate-intercalated layered double hydroxides aged under microwave-hydrothermal treatment

    SciTech Connect

    Benito, P.; Labajos, F.M.; Mafra, L.; Rocha, J.; Rives, V.

    2009-01-15

    Carboxylate-intercalated (terephthalate, TA and oxalate, ox) layered double hydroxides (LDHs) are aged under a microwave-hydrothermal treatment. The influence of the nature of the interlayer anion during the ageing process is studied. Characterization results show that the microwave-hydrothermal method can be extended to synthesize LDHs with anions different than carbonate, like TA. LDH-TA compounds are stable under microwave irradiation for increasing periods of time and the solids show an improved order both in the layers and in the interlayer region as evidenced by powder X-ray diffraction (PXRD), {sup 27}Al MAS NMR and FT-IR spectroscopy. Furthermore, cleaning of the surface through removal of some organic species adsorbed on the surface of the particles also occurs during the microwave-hydrothermal treatment. Conversely, although the expected increase in crystallinity is observed in LDH-ox samples, the side-reaction between Al{sup 3+} and ox is also enhanced under microwave irradiation, and a partial destruction of the structure takes place with an increase in the M{sup 2+}/M{sup 3+} ratio and consequent modification of the cell parameters. - Graphical Abstract: The influence of the nature of the interlayer anion during the ageing process of carboxylate-inte