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Purpose: Dysphagia is thought to be prevalent and a leading cause of morbidity and mortality in people with Parkinson disease (PwPD). The aim of this study was to compare the frequencies of atypical and extreme values for measures of swallowing physiology in PwPD and in an age- and sex-matched cohort of healthy adults. Atypical and extreme values were defined, respectively, as values falling in the 25% and 5% tails of the reference distribution for healthy adults under age 60 years. Method: A standard videofluoroscopy (VF) protocol was performed in 17 adults with mild PD and 17 age- and sex-matched healthy adults using 20% w/v liquid barium ranging from thin to extremely thick consistency. Blinded VF analysis was performed according to the Analysis of Swallowing Physiology: Events, Kinematics and Timing Method. Frequencies for atypical and extreme values were tabulated by cohort and compared using odds ratios. Results: Increased frequencies of atypical values (> 25%) were seen in the PwPD for prolonged swallow reaction time, prolonged time-to-laryngeal-vestibule-closure (LVC), and poor pharyngeal constriction. However, these findings were also observed in the healthy controls. The PwPD showed significantly higher odds of atypical values for narrow upper esophageal sphincter (UES) diameter on thin liquids, a short hyoid-burst-to-UES-opening interval on extremely thick liquids, and prolonged time-to-LVC, LVC duration, and UES opening duration on multiple consistencies. The frequencies of extreme values failed to show any significant cohort differences for any parameter. Conclusions: In this study, a group of people with mild PD did not show clear evidence of swallowing impairments distinct from the changes seen in a healthy age-matched control group when odds ratios were used to compare the frequencies of atypical values between PwPD and the control group; only a few parameters showed significant differences. These were findings of significantly higher frequencies in PwPD of prolonged LVC and UES opening duration. Supplemental Material: https://doi.org/10.23641/asha. 15032241, Parkinson disease (PD) is one of the most common neurological disorders internationally (Pringsheim et al., 2014). In the context of increasing life expectancies globally, a steady increase in PD is [...]

Purpose: The purpose of this study was to examine the aging effects on the categorical perception (CP) of Mandarin lexical Tones 1-4 and Tones 1-2 in noise. It also investigated whether listeners' categorical tone perception in noise correlated with their general tone identification of 20 natural vowel-plus-tone signals in noise. Method: Twelve younger and 12 older listeners with normal hearing were recruited in both tone identification and discrimination tasks in a CP paradigm where fundamental frequency contours of target stimuli varied systematically from the flat tone (Tone 1) to the rising/falling tones (Tones 2/4). Both tasks were conducted in quiet and noise with signal-to-noise ratios set at -5 and -10 dB, respectively, and general tone identification of natural speech signals was also tested in noise conditions. Results: Compared with younger listeners, older listeners had shallower identification slopes and smaller discrimination peakedness in Tones 1-2/4 perception in all listening conditions, except for Tones 1-4 perception in quiet where no group differences were found. Meanwhile, noise affected Tones 1-2/4 perception: The signal-to-noise ratio condition at -10 dB brought shallower slope in Tones 1-2/4 identification and less peakedness in Tones 1-4 discrimination for both listener groups. Older listeners' CP in noise, the identification slopes in particular, positively correlated with their general tone identification in noise, but such correlations were partially missing for younger listeners. Conclusions: Both aging and the presence of speech-shaped noise significantly reduced the CP of Mandarin Tones 1-2/4. Listeners' Mandarin tone recognition may be related to their CP of Mandarin tones., Categorical perception, a well-documented phenomenon in speech perception, is a fundamental mechanism to explain how human listeners can perceive speech signals with infinite variability as finite linguistic representations (Liberman et [...]

In blood vessels, vascular smooth muscle cells (VSMCs) generally exist in two major phenotypes: contractile and non-contractile (synthetic). The contractile phenotype is predominant and includes quiescent or differentiated VSMCs, which function as the regulators of blood vessel diameter and blood flow. According to some literature in the field, contractile VSMCs do not switch to the non-contractile phenotype due to the activation of specific transcription factors that are considered as guardians of the contractile phenotype. However, a vast amount of the literature uses the terms remodeling and phenotype switching of contractile VSMCs interchangeably based mainly on studies dealing with atherosclerosis. The use of the terms remodeling and switching to describe changes in phenotype based on morphological criteria can be confusing. The term remodeling was first used to describe morphological changes in the heart and was soon used to describe phenotype changes of contractile VSMCs based on morphological criteria. The latter were introduced in early studies, and new molecular criteria were later added, including changes in gene expression, which could be irreversible. In this review, we will discuss the different views concerning remodeling and possible switching of contractile VSMCs to a non-contractile phenotype. We conclude that only remodeling of contractile VSMCs may take place upon vascular injury and disease. Key words: vascular smooth muscle cells, remodeling, contractile phenotype, synthetic phenotype, aging. Dans les vaisseaux sanguins, les cellules musculaires lisses vasculaires (CMLV) se presentent generalement selon deux principaux phenotypes: contractile et non contractile (synthetique). Le phenotype contractile est predominant et comprend des CMLV quiescentes ou differentiees, qui fonctionnent comme des regulateurs du diametre des vaisseaux et du flux sanguin. Selon certains articles dans le domaine, les CMLV contractiles ne passent pas au phenotype non contractile a la suite de l'activation de facteurs de transcription specifiques, qui sont consideres comme etant des gardiens du phenotype contractile. Cependant, tout un pan de la litterature utilise les termes remodelage et commutation phenotypique des CMLV contractiles de maniere interchangeable, avant tout sur la base d'etudes traitant de l'atherosclerose. L'utilisation des termes remodelage et commutation phenotypique pour decrire les variations du phenotype fondees sur des criteres morphologiques peut porter a confusion. Le terme remodelage a tout d'abord ete utilise pour decrire les variations morphologiques dans le creur et a tres tot ete utilise pour decrire les variations des CMLV contractiles sur la base de criteres morphologiques. Ces derniers ont ete introduits dans le cadre d'etudes precoces, et de nouveaux criteres moleculaires ont plus tard ete ajoutes, y compris des variations de l'expression genique, qui peuvent etre irreversibles. Dans cet article de synthese, nous discuterons de differents points de vue sur le remodelage et la commutation eventuelle des CMLV contractiles vers un phenotype non contractile. Nous en concluons qu'uniquement le remodelage des CMLV contractiles peut se produire dans le cadre de lesions et de maladies vasculaires. [Traduit par la Redaction] Mots-cles: cellules musculaires lisses vasculaires, remodelage, phenotype contractile, phenotype synthetique, vieillissement., Introduction The literature dealing with contractile and non-contractile VSMCs in health and disease makes it difficult to distinguish between fact and assumption concerning whether contractile VSMCs remodel or switch phenotype. [...]

Research demonstrates that senescence is associated with tissue and organ dysfunction, and the eye is no exception. Sequelae arising from aging have been well defined as distinct clinical entities and vision impairment has significant psychosocial consequences. Retina and adjacent tissues like retinal pigmented epithelium and choroid are the key structures that are required for visual perception. Any structural and functional changes in retinal layers and blood retinal barrier could lead to age-related macular degeneration, diabetic retinopathy, and glaucoma. Further, there are significant oxygen gradients in the eye that can lead to excessive reactive oxygen species, resulting in endoplasmic reticulum and mitochondrial stress response. These radicals are source of functional and morphological impairment in retinal pigmented epithelium and retinal ganglion cells. Therefore, ocular diseases could be summarized as disturbance in the redox homeostasis. Hyperhomocysteinemia is a risk factor and causes vascular occlusive disease of the retina. Interestingly, hydrogen sulfide ([H.sub.2]S) has been proven to be an effective antioxidant agent, and it can help treat diseases by alleviating stress and inflammation. Concurrent glutamate excitotoxicity, endoplasmic reticulum stress, and microglia activation are also linked to stress; thus, [H.sub.2]S may offer additional interventional strategy. A refined understanding of the aging eye along with [H.sub.2]S biology and pharmacology may help guide newer therapies for the eye. Key words: hyperhomocysteinemia, inflammation, redox homeostasis, senescence, vision impairment. Les recherches montrent que la senescence est associee a des dysfonctionnements tissulaires et organiques et que l'oeil ne fait pas exception a la regle. Les sequelles decoulant du vieillissement ont ete bien caracterisees comme etant des entites cliniques distinctes et les troubles de la vue ont des consequences psychosociales importantes. La retine et les tissus adjacents comme l'epithelium retinien pigmente (ERP) et la choroide constituent des structures cles qui sont necessaires pour la perception visuelle. Toute modification structurelle ou fonctionnelle des couches retiniennes et des barrieres hemoretiniennes (BHR) peuvent mener a la degenerescence maculaire liee a l'age (DMLA), a la retinopathie diabetique (RD) et au glaucome. En outre, il existe dans l'reil des gradients d'oxygene importants, qui peuvent mener a un exces de derives reactifs de l'oxygene (DRO) entrainant une reaction de stress dans le reticulum endoplasmique (RE) et les mitochondries. Ces radicaux sont a la base de troubles fonctionnels et morphologiques dans l'ERP et les cellules ganglionnaires retiniennes (CGR). Par consequent, les maladies oculaires pourraient se resumer a des perturbations de l'homeostasie du systeme redox. L'hyperhomocysteinemie (HHcy) constitue un facteur de risque et entraine une maladie vasculaire occlusive de la retine. Il est interessant de noter que le sulfure d'hydrogene ([H.sub.2]S) s'est revele etre un agent antioxydant efficace, et qu'il peut contribuer au traitement de maladies en entrainant une attenuation du stress et de l'inflammation. En concomitance, l'excitotoxicite du glutamate, le stress du RE et l'activation de la microglie sont aussi lies au stress, et le [H.sub.2]S pourrait donc permettre d'obtenir des strategies interventionnelles supplementaires. Une comprehension affinee du vieillissement de l'oeil, ainsi que de la biologie et de la pharmacologie du [H.sub.2]S pourrait contribuer a guider de nouveaux traitements pour les yeux. [Traduit par la Redaction] Mots-cles: hyperhomocysteinemie, inflammation, homeostasie du systeme redox, senescence, trouble de la vue., Introduction Advances in medicine and technology have contributed to a marked increase in average life expectancy during the past few decades. As a result, age-related health issues are rising and [...]

Liver cancer remains difficult to treat, owing to a paucity of drugs that target critical dependencies.sup.1,2; broad-spectrum kinase inhibitors such as sorafenib provide only a modest benefit to patients with hepatocellular carcinoma.sup.3. The induction of senescence may represent a strategy for the treatment of cancer, especially when combined with a second drug that selectively eliminates senescent cancer cells (senolysis).sup.4,5. Here, using a kinome-focused genetic screen, we show that pharmacological inhibition of the DNA-replication kinase CDC7 induces senescence selectively in liver cancer cells with mutations in TP53. A follow-up chemical screen identified the antidepressant sertraline as an agent that kills hepatocellular carcinoma cells that have been rendered senescent by inhibition of CDC7. Sertraline suppressed mTOR signalling, and selective drugs that target this pathway were highly effective in causing the apoptotic cell death of hepatocellular carcinoma cells treated with a CDC7 inhibitor. The feedback reactivation of mTOR signalling after its inhibition.sup.6 is blocked in cells that have been treated with a CDC7 inhibitor, which leads to the sustained inhibition of mTOR and cell death. Using multiple in vivo mouse models of liver cancer, we show that treatment with combined inhibition of of CDC7 and mTOR results in a marked reduction of tumour growth. Our data indicate that exploiting an induced vulnerability could be an effective treatment for liver cancer. CDC7 inhibition selectively induces senescence in hepatocellular carcinoma cells with TP53 mutations, which enables the selective apoptotic cell death of these senescent cells using inhibitors of mTOR signalling., Author(s): Cun Wang [sup.1] [sup.2] , Serena Vegna [sup.3] , Haojie Jin [sup.1] [sup.2] , Bente Benedict [sup.3] , Cor Lieftink [sup.2] , Christel Ramirez [sup.3] , Rodrigo Leite de [...]

Abstract: Glycation of apolipoproteins is a major feature of the production of dysfunctional high-density lipoprotein (HDL), which is associated with the incidence of several metabolic diseases such as coronary artery [...]

In animal mitochondria, the four electron reduction of molecular oxygen to produce water at respiratory complex IV is the terminal step in substrate oxidation. However, respiratory complexes I, II, and III can participate in the single electron reduction of oxygen to produce the radical species superoxide. This progenitor reactive oxygen species (ROS) participates in a number of reactions that generate other ROS. These molecules may react with, and damage, intracellular macromolecules, leading to cellular dysfunction. Mitochondrial ROS production is often considered from this perspective of macromolecular damage and is central to the 'oxidative damage theory of aging', which suggests the accumulation of oxidative damage in animal cells underlies the aging phenotype and limits lifespan. In this review, we discuss some experimental results accumulated over the past decade that are inconsistent with this theory. A limitation of the theory is that it presupposes mitochondrial ROS are inherently harmful. However, it is increasingly apparent that some basic cellular functions are physiologically regulated by normal levels of mitochondrial ROS. For example, cell growth and division, the apoptotic pathway, and mitochondrial fusion-fission dynamics all appear to be redox-regulated by mitochondrial ROS and perhaps the matrix manganese superoxide dismutase (MnSOD). Therefore, it is less clear how the balance between ROS regulation of normal cellular activities and ROS-mediated macromolecular damage is maintained and how this relates to aging and longevity in animals. Key words: superoxide, hydrogen peroxide, aging, longevity, signaling, oxidative damage, antioxidant enzymes. Dans les mitochondries animales, la reduction a quatre electrons de l'oxygene moleculaire pour produire de l'eau au complexe respiratoire IV est l'etape terminale de l'oxydation du substrat. Toutefois, les complexes respiratoires I, II et III peuvent participer a la reduction a un seul electron de l'oxygene pour produire le superoxyde radicalaire. Cette forme reactive de l'oxygene (FRO) precurseur intervient dans diverses reactions qui generent d'autres FRO. Ces molecules peuvent reagir avec des macromolecules intracellulaires et les endommager, menant ainsi a un dysfonctionnement cellulaire. La production de FRO mitochondriales est souvent consideree du point de vue des dommages macromoleculaires et occupe une place centrale dans la theorie du vieillissement decoulant des dommages oxydatifs, qui postule que l'accumulation de dommages oxydatifs dans les cellules animales sous-tend le phenotype du vieillissement et limite la duree de vie. Dans la presente synthese, nous abordons certains resultats experimentaux accumules au cours de la derniere decennie qui sont incompatibles avec cette theorie. Une des limites de la theorie est qu'elle presume que les FRO mitochondriales sont necessairement nefastes. Il appert toutefois de plus en plus que des concentrations normales de FRO mitochondriales assurent une regulation physiologique de certaines fonctions cellulaires de base. Par exemple, la croissance et la division cellulaires, le mecanisme apoptotique et la dynamique de la fusion-fission mitochondriale semblent tous faire l'objet d'une regulation redox par les FRO mitochondriales et, possiblement, la superoxyde dismutase de la matrice MnSOD. Le mecanisme qui permet de maintenir un equilibre entre la regulation par les FRO des activites cellulaires normales et les dommages macromoleculaires dans lesquels interviennent les FRO reste donc a elucider, ainsi que son lien avec le vieillissement et la longevite chez les animaux. [Traduit par la Redaction] Mots-cles : superoxyde, peroxyde d'hydrogene, vieillissement, longevite, signalisation, dommage oxydatif, enzymes antioxydants., Introduction Although mitochondria are often referred to as the primary endogenous source of reactive oxygen species (ROS) in animal cells, it may be more accurate to state that they contribute [...]

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 [beta]-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 [beta]-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. REST, a developmental regulator, is markedly induced in human neurons during ageing but is lost in Alzheimer's disease; REST represses genes that promote neurodegeneration, is neuroprotective in animal models, and is associated with cognitive preservation and longevity in humans. REST protein counters neurodegeneration Age is the biggest risk factor for neurodegenerative disease. But why do some age with cognitive function intact, yet others decline and develop Alzheimer's disease? Here Bruce Yankner and colleagues show that during ageing, a protein known as REST (repressor element 1-silencing transcription factor, also called NRSF) is increasingly expressed in human cortical and hippocampal neurons. REST levels are strongly correlated with cognitive preservation and longevity. REST represses genes that promote cell death and Alzheimer's disease pathology and induces those that mediate the stress response. Moreover, REST protects neurons from oxidative stress and amyloid [beta]-protein toxicity. Deleting REST from the mouse brain results in age-related neuronal cell death. And, in humans with mild cognitive impairment or Alzheimer's disease, REST is excluded from the nucleus in neurons, and this exclusion is associated with autophagy and misfolded proteins. This work suggests that the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain., Author(s): Tao Lu [sup.1] , Liviu Aron [sup.1] , Joseph Zullo [sup.1] , Ying Pan [sup.1] , Haeyoung Kim [sup.1] , Yiwen Chen [sup.2] , Tun-Hsiang Yang [sup.1] , Hyun-Min [...]

Regeneration of skeletal muscle depends on a population of adult stem cells (satellite cells) that remain quiescent throughout life. Satellite cell regenerative functions decline with ageing. Here we report that geriatric satellite cells are incapable of maintaining their normal quiescent state in muscle homeostatic conditions, and that this irreversibly affects their intrinsic regenerative and self-renewal capacities. In geriatric mice, resting satellite cells lose reversible quiescence by switching to an irreversible pre-senescence state, caused by derepression of [p16.sup.INK4a] (also called Cdkn2a). On injury, these cells fail to activate and expand, undergoing accelerated entry into a full senescence state (geroconversion), even in a youthful environment. [p16.sup.INK4a] silencing in geriatric satellite cells restores quiescence and muscle regenerative functions. Our results demonstrate that maintenance of quiescence in adult life depends on the active repression of senescence pathways. As [p1.sup.6INK4a] is dysregulated in human geriatric satellite cells, these findings provide the basis for stem-cell rejuvenation in sarcopenic muscles., A hallmark of advanced ageing in humans is sarcopenia, an age-related loss of skeletal muscle mass and function, which is maximal in geriatric individuals and in patients with progeria syndromes [...]

Oxidative stress is considered to be critically involved in the normal aging process but also in the development and progression of various human pathologies like cardiovascular and neurodegenerative diseases, as well as of infections and malignant tumors. These pathological conditions involve an overwhelming production of reactive oxygen species (ROS), which are released as part of an anti-proliferative strategy during pro-inflammatory immune responses. Moreover, ROS themselves are autocrine forward regulators of the immune response. Most of the beneficial effects of antioxidants are considered to derive from their influence on the immune system. Due to their antioxidant and/or radical scavenging nature, phytochemicals, botanicals and herbal preparations can be of great importance to prevent oxidation processes and to counteract the activation of redox-regulated signaling pathways. Antioxidants can antagonize the activation of T-cells and macrophages during the immune response and this anti-inflammatory activity could be of utmost importance for the treatment of above-mentioned disorders and for the development of immunotolerance. Herein, we provide an overview of in vitro assays for the measurement of antioxidant and antiinflammatory activities of plant-derived substances and extracts, by discussing possibilities and limitations of these methods. To determine the capacity of antioxidants, the oxygen radical absorbance capacity (ORAC) assay and the cell-based antioxidant activity (CAA) assay are widely applied. To examine the influence of compounds on the human immune response more closely, the model of mitogen stimulated human peripheral blood mononuclear (PBMC) cells can be applied, and the production of the inflammatory marker neopterin as well as the breakdown of the amino acid tryptophan in culture supernatants can be used as readout to indicate an immunomodulatory potential of the tested compound. These two biomarkers of immune system activation are robust and correlate with the course of cardiovascular, neurodegenerative and malignant tumor diseases, but also with the normal aging process, and they are strongly predictive. Thus, while the simpler ORAC and CAA assays provide insight into one peculiar chemical aspect, namely the neutralization of peroxyl radicals, the more complex PBMC assay is closer to the in vivo conditions as the assay comprehensively enlights several properties of immunomodulatory test compounds. Keywords: Cell-based antioxidant activity (CAA) Immunomodulation Inflammation In vitro test systems Oxidative stress Oxygen radical absorbance capacity (ORAC) assay Peripheral blood mononuclear cells Reactive oxygen species, Introduction Antioxidants are reducing chemicals that are able to inhibit or prevent oxidation processes and/or to interrupt radical chain reactions. Such compounds may be produced within the human body or [...]

Purpose: The study was aimed at characterizing age-related changes in speech motor performance on a nonword repetition task as a function of practice and nonword length and complexity. Method: Nonword repetition accuracy, lip aperture coordination, and nonword production durations were assessed on 2 consecutive days for 16 young and 16 elderly participants for the production of 6 novel nonwords increasing in length and complexity. Results: The effect of age on the ability to accurately and rapidly repeat long, complex nonwords was significant. However, the authors found no differences between the speech motor coordinative patterns of young and elderly adults. Further, the authors demonstrated age- and nonword-specific within- and between-session gains in speech motor performance. Conclusions: The authors speculate that cognitive, sensory, and motor factors interact in complex ways in elderly individuals to produce individual differences in nonword repetition ability at the levels of both behavioral and speech motor performance. Key Words: aging, nonword repetition, practice, speech motor performance, kinematics, speech motor control, Aging is associated with changes in the structural and functional integrity of the brain (Hof, 1997; Liu, Erikson, & Brun, 1996; Raz et al., 1997; Raz, Gunning-Dixon, Head, Williamson, & [...]

Purpose: Previously, Gygi and Shafiro (2011) found that when environmental sounds are semantically incongruent with the background scene (e.g., horse galloping in a restaurant), they can be identified more accurately by young normal-hearing listeners (YNH) than sounds congruent with the scene (e.g., horse galloping at a racetrack). This study investigated how age and high-frequency audibility affect this Incongruency Advantage (IA) effect. Method: In Experiments 1a and 1b, elderly listeners (N = 18 for 1a; N = 10 for 1b) with age-appropriate hearing (EAH) were tested on target sounds and auditory scenes in 5 sound-to-scene ratios (So/Sc) between -3 and -18 dB. Experiment 2 tested 11 YNH on the same sound-scene pairings lowpass-filtered at 4 kHz (YNH-4k). Results: The EAH and YNH-4k groups exhibited an almost identical pattern of significant IA effects, but both were at approximately 3.9 dB higher So/Sc than the previously tested YNH listeners. However, the psychometric functions revealed a shallower slope for EAH listeners compared with YNH listeners for the congruent stimuli only, suggesting a greater difficulty for the EAH listeners in attending to sounds expected to occur in a scene. Conclusions: These findings indicate that semantic relationships between environmental sounds in soundscapes are mediated by both audibility and cognitive factors and suggest a method for dissociating these factors. Key Words: aging, cognition, psychoacoustics, development, hearing loss, gerontology, auditory rehabilitation, Older listeners face ever-increasing challenges operating in the modern world of dense acoustic environments such as streets, restaurants, offices, and hospitals, all of which contain a multitude of objects and [...]

Ageing is due to an accumulation of various types of damage (1,2), and mitochondrial dysfunction has long been considered to be important in this process (3-8). There is substantial sequence variation in mammalian mitochondrial DNA (mtDNA) (9), and the high mutation rate is counteracted by different mechanisms that decrease maternal transmission of mutated mtDNA (10-13). Despite these protective mechanisms (14), it is becoming increasingly clear that low-level mtDNA heteroplasmy is quite common and often inherited in humans (15,16). We designed a series of mouse mutants to investigate the extent to which inherited mtDNA mutations can contribute to ageing. Here we report that maternally transmitted mtDNA mutations can induce mild ageing phenotypes in mice with a wild-type nuclear genome. Furthermore, maternally transmitted mtDNA mutations lead to anticipation of reduced fertility in mice that are heterozygous for the mtDNA mutator allele ([PolgA.sup.wt/mut]) and aggravate premature ageing phenotypes in mtDNA mutator mice ([PolgA.sup.mut/mut]). Unexpectedly, a combination of maternally transmitted and somatic mtDNA mutations also leads to stochastic brain malformations. Our findings show that a pre-existing mutation load will not only allow somatic mutagenesis to create a critically high total mtDNA mutation load sooner but will also increase clonal expansion of mtDNA mutations (17) to enhance the normally occurring mosaic respiratory chain deficiency in ageing tissues (18,19). Our findings suggest that maternally transmitted mtDNA mutations may have a similar role in aggravating aspects of normal human ageing., We generated a series of inbred mutant mice (Fig. 1a-c) to study the role of mtDNA mutations in ageing, taking into account that [PolgA.sup.wt/mut] mice transmit low levels of mtDNA [...]

ABSTRACT Specimens of Illex argentinus from trawl catches along southern Brazil were sampled between March 2007 and January 2008 to study aspects of their life cycle and the connectivity with [...]

ABSTRACT We describe some growth aspects of Octopus vulgaris located along the eastern coast of Tunisia. Age and growth parameters of this species were studied from August 2004 to July [...]

Different strategies of petal senescence and some important events associated with it have been discussed. On the basis of sensitivity to ethylene and associated symptoms of senescence, petal senescence has been classified into five different classes; besides changes in membrane permeability, autophagy and involvement of VPEs (Vacuolar processing enzymes), degradation of nucleic acids, protein turn over and remobilization of essential nutrients during petal senescence have been discussed. Nucleus appears to play a central role in administrating the execution of the events associated with petal senescence. Protein turn over appears to be an important factor governing petal senescence in both ethylene-sensitive and ethylene-insensitive flower systems and that the loss of membrane integrity, vacuolar autophagy and remobilization of essential nutrients being its important consequences. Autophagy seems to be a main process responsible for cell dismantling and remobilization of macromolecules besides final disintegration of nucleus. A large number of senescence-associated genes have been found to be differentially expressed during petal senescence. On the basis of the available literature, a schematic model representing some important events associated with petal senescence has been constructed. The review recommends that more elaborate work is required at cellular and organelle level to understand the ethylene-independent pathway and its execution in both ethylene-sensitive and ethylene-insensitive flower systems. It also recommends that ethylene sensitivity should not be generally assigned to plants at the family level on the basis of response of a few species in a family. Resumes des strategies differentes de petale senescence et certains evenements importants associes ont ete discutes. Sur la base d'une sensibilite d'ethylene et les symptomes associes de senescence, petale senescence ont ete classe en cinq differentes classes ; outre les modifications dans la permeabilite de la membrane, Autophagie et l'implication des VPEs (Vacuolar traitement des enzymes), la degradation des acides nucleiques, proteines tour sur re de nutriments essentiels au cours de la senescence petale ont ete discutes. Noyau semble jouer un role central dans l'administration de l'execution des evenements associes petale senescence. Tour de proteines sur semble etre un facteur important regissant petale senescence dans les systemes de fleur d'ethylene sensibles et ethylene-insensible et que la perte d'integrite de la membrane, Autophagie vacuolar et re de nutriments essentiels a ses consequences importantes. Autophagie semble etre un processus principal responsable du demante1ement de la cellule et re de macromolecules outre finale desintegration du noyau. Un grand hombre de genes associes senescence a ete trouve pour etre exprime differemment au cours de la senescence petale. Sur la base de la documentation disponible, un mode1e schematic representant certains evenements importants associes petale senescence a ete construit. L'examen recommande qu'un travail plus elabore est necessaire au niveau cellulaire et Organite pour comprendre la voie de l'ethylene-independante et son execution dans les deux systemes de fleur d'ethylene sensibles et ethylene-insensible. Elle recommande egalement que ethylene sensibilite ne doit pas etre generalement affectee aux plantes au niveau familial sur la base de la reponse de quelques especes dans une famille. Keywords Autophagy * Membrane integrity * Proteases * Proteasomes * Remobilization * Senescence Motscles autophagie * integrite de membrane * proteases * proteasomes * resenescence, Introduction Senescence comprises those processes that follow physiological maturity which lead to the event of death of a whole plant, organ or tissue at macroscopic level. At microscopic level the [...]

Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response. attrition | frontal lobe | multimodal | reorganization doi/ 10.1073/pnas.1012651108

In the conventional view, aging of the brain is associated with atrophy vascular abnormalities and loss of volume in hippocampus and amygdala. Cognitively, aging is associated with slowing of processing and memory loss. However, many studies of aging do not examine the cases to exclude demented people. The nutrition and memory in the homebound elderly study (NAME) excluded cases clinically diagnosed as having dementia. Cortical atrophy based on MRI ratings was significantly correlated with vascular disease, white matter hyperintensities, processing speed, and memory but not hippocampus and amygdala volume. Renal function and homocysteine were also associated with cortical atrophy but not with the cognitive variables. In conclusion, brain atrophy of aging in the absence of dementia is related to vascular disease but not hippocampal atrophy. Studies of nutritional interventions should consider using MRI atrophy rather than cognition as outcome. [c] 2010 International Life Sciences Institute doi: 10.1111/j.1753-4887.2010.00351.x

Objectives. To propose and test a conceptual two-factor model of successful aging that includes objective and subjective components. Methods. Data were derived from 5,688 persons aged 50-74 years living in New Jersey who participated in the ORANJ BOWL panel. Participants were recruited using random digit dial procedures and interviewed by telephone. A measurement model was developed and tested using data from two independent samples (each n = 1,000); a structural model examining the effects of age and gender was tested using data from another 3,688 people. Results. Confirmatory factor analyses provided support for a multidimensional model incorporating objective criteria and subjective perceptions. Age and gender were associated with objective but not subjective success. Discussion. Results add rigor to the measurement of a construct that has intrigued philosophers and scientists for hundreds of years, providing the empirical foundation on which to build research about successful aging. Key Words: Confirmatory factor analysis--Measurement model--Structural modeling--Successful aging. doi: 10.1093/geronb/gbq051.

The beneficial effects of caloric restriction in increasing longevity and forestalling age-related diseases are well known. Dietary restriction of methionine also renders similar benefits. We recently showed in a renal epithelial cell culture system that reduction of culture medium methionine by 80% resulted in altered tight junctional (TJ) claudin composition and also improved epithelial barrier function (51). In the current study, we examined the effect of dietary restriction of methionine on TJ barrier function in rat gastrointestinal tissue to see whether this phenomenon also holds true in a tissue model and for a different epithelial cell type. After 28 days on methionine-restricted (MR) diet, rats showed small but significant reductions in the plasma and (intracellular) colonocyte levels of methionine. Colon mucosal sheets from rats on the MR diet showed increased transepithelial electrical resistance with concomitant decrease in paracellular diffusion of [sup.14]C-D-mannitol, suggesting improved barrier function relative to rats on control diet. This improved barrier function could not be explained by changes in colon crypt length or frequency. Neither was the colonocyte mitotic index nor the apoptotic frequency altered significantly. However, TJ composition/structure was being altered by the MR diet. RT-PCR and Western blot analysis showed an increase in the abundance of claudin-3 and an apparent change in the posttranslational modification of occludin, data reinforcing a paracellular barrier alteration. Overall, our data suggest that reduction in dietary intake of methionine results in improved epithelial barrier function by inducing altered TJ protein composition. claudin-3; occludin; mannitol flux; paracellular doi: 10.1152/ajpcell.00482.2009.

Life expectancies have increased dramatically over the last 100 years, affording greater opportunities to study the impact of age on adult craniofacial morphology. This article employs a novel application of established geometric morphometric methods to examine shape differences in adult regional facial bone curvature with age. Three-dimensional semiland-marks representing the curvature of the orbits, zygomatic arches, nasal aperture, and maxillary alveolar process were collected from a cross-sectional cranial sample of mixed sex and ancestry (male and female; African- and European-American), partitioned into three age groups (young adult = 18-39; middle-aged = 40-59 years; and elderly = 60+ years). Each facial region's semilandmarks were aligned into a common coordinate system via generalized Procrustes superim-position. Regional variation in shape was then explored via a battery of multivariate statistical techniques. Age-related shape differences were detected in the orbits, zygomatic arches, and maxillary alveolar process. Interactions between age, sex, and ancestry were also identified. Vector plots revealed patterns of superoinferior compression, lateral expansion, and posterior recession depending on the population/subpopulation, location, and age groups examined. These findings indicate that adult craniofacial curvature shape is not static throughout human life. Instead, age-related spatial modifications occur in various regions of the craniofacial skeleton. Moreover, these regional alterations vary not only through time, but across human populations and the sexes. Am J Phys Anthropol 143:437-447, 2010. [c] 2010 Wiley-Liss, Inc. KEY WORDS semilandmarks; aging; geometric morphometrics; crania; morphology DOI 10.1002/ajpa.21332