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O121 HIV and ageing E Negredo Germans Trias i Pujol Hospital, HIV Unit, and University of Vic, Barcelona, Spain In the last decades, HIV-infected population has significantly aged in high-income [...]

Keywords: ageing; HIV; PWH; WHO model of healthy ageing; interventions; life course, 1 | INTRODUCTION At the end of 2019, there were an estimated 38 million people living with HIV (PLWH) globally and approximately 7.5 million were 50 years and older [1]. [...]

N-acetyl-L-cysteine (NAC) is a precursor of cysteine, which is known to increase the level of glutathione (GSH) in the brain. Several neurodegenerative changes linked to oxidative stress take place in the aging brain. This study aimed to assess the neuroprotective effect of NAC supplementation on age-dependent neurodegeneration in the rat brain. Young (4 months) and old (24 months) Wistar rats (n = 6 rats/group) were supplemented with NAC (100 mg/kg b.w. orally) for 14 days. Enzymatic and nonenzymatic antioxidants such as superoxide dismutase and catalase, and GSH and total thiol respectively, prooxidants such as protein carbonyl, advanced oxidation protein products, reactive oxygen species, and malondialdehyde were assessed in the brain homogenates. Furthermore, nitric oxide level, acetylcholinesterase activity, and [Na.sup.+]/[K.sup.+]-ATPase activity were measured and gene expression studies were also performed. The results indicated that NAC augmented the level of enzymatic and nonenzymatic antioxidants with a significant reduction in prooxidant levels in old rats. NAC supplementation also downregulated the expression of inflammatory markers (TNF-[alpha], IL-1[beta], IL-6) and upregulated the expression of marker genes associated with aging (sirtuin-1) and neurodegeneration (neuron-specific enolase, neuroglobin, synapsin-I, myelin basic protein 2) in old rats. The present findings support a neuroprotective role of NAC which has therapeutic implication in controlling age-related neurological disorders.Key words: aging, cytokines, neurodegeneration, N-acetyl-L-cysteine, oxidative stress.La N-acetyl-L-cysteine (NAC) est un precurseur de la cysteine que l'on sait entrainer une augmentation des taux de glutathion dans le cerveau. Plusieurs modifications neurodegeneratives liees au stress oxydatif ont lieu dans le cerveau vieillissant. Cette etude visait a evaluer l'effet neuroprotecteur de la supplementation en NAC dans la neurodegenerescence liee au vieillissement du cerveau chez le rat. Des rats Wistar jeunes (4 mois; n = 6) et ages (24 mois; n = 6) ont recu des supplements de NAC (100 mg/kg de poids corporel) par voie orale pendant 14 jours. Nous avons evalue les antioxydants enzymatiques et non enzymatiques ci-dessous dans des homogenats de cerveau : superoxyde dismutase, glutathion, thiols totaux et prooxydants comme le carbonyle proteinique, les substances proteiques d'oxydation avancee, les derives reactifs de l'oxygene et le malondialdehyde. De plus, nous avons mesure les taux d'oxyde nitrique et procede a des etudes d'activite enzymatique (acetylcholinesterase et [Na.sup.+]/[K.sup.+]-ATPase), ainsi que d'expression genique. Les resultats montraient que la NAC entrainait une augmentation des taux d'antioxydants enzymatiques et non enzymatiques, avec une diminution marquee des taux de prooxydants chez les rats ages. La supplementation en NAC entrainait aussi une regulation a la baisse de l'expression de marqueurs de l'inflammation (TNF-[alpha], IL-1[beta], IL-6), ainsi qu'une regulation a la hausse de l'expression de marqueurs geniques associes au vieillissement (sirtuine-1) et a la neurodegenerescence (enolase specifique des neurones, neuroglobine, synapsine-I, proteines basiques de la myeline 2) chez les rats ages. Les presents resultats viennent appuyer le role neuroprotecteur de la NAC, qui a une incidence therapeutique dans le controle de maladies neurologiques liees a l'age. [Traduit par la Redaction]Mots-cles: vieillissement, cytokines, neurodegenerescence N-acetyl-L-cysteine, stress oxydatif., IntroductionDuring aging, the brain is associated with ultrastructural modifications, biochemical deficits, inflammatory changes, and impairment of memory and cognition, all linked to oxidative stress (Chakrabarti et al. 2011; Pizza et [...]

Author(s): Maja Milanovic [1]; Dorothy N. Y. Fan [1, 2, 3, 4]; Dimitri Belenki [1]; J. Henry M. Dbritz [1]; Zhen Zhao [5]; Yong Yu [6]; Jan R. Drr [1]; [...]

Author(s): Zhixun Dou [1]; Kanad Ghosh [1]; Maria Grazia Vizioli [2, 3]; Jiajun Zhu [1]; Payel Sen [1]; Kirk J. Wangensteen [4]; Johayra Simithy [1, 5]; Yemin Lan [1]; Yanping [...]

In the vascular system, ageing is accompanied by the accrual of senescent cells and is associated with an increased risk of vascular disease. Endothelial cell (EC) dysfunction is a hallmark of vascular disease and is characterized by decreased angiogenic potential, reduced nitric oxide bioavailability, impaired vasodilation, increased production of ROS, and enhanced inflammation. In ECs, the major producer of nitric oxide is the endothelial nitric oxide synthase (eNOS) enzyme that is encoded by the NOS3 gene. NOS3/eNOS function is tightly regulated at both the transcriptional and post-transcriptional levels to maintain normal vascular function. A key transcriptional regulator of eNOS expression is p53, which has been shown to play a central role in mediating cellular senescence and thereby vascular dysfunction. Herein, we show that, in ECs, the MEOX homeodomain transcription factors decrease the expression of genes involved in angiogenesis, repress eNOS expression at the mRNA and protein levels, and increase the expression of p53. These findings support a role for the MEOX proteins in promoting endothelial dysfunction. Key words: endothelial cells, ageing, progeria, senescence, nitric oxide synthase, transcription, p53, MEOX2. Dans le systeme cardiovasculaire, le vieillissement s'accompagne de l'accumulation de cellules senescentes et est associe a une augmentation du risque de maladie vasculaire. Le dysfonctionnement des cellules endotheliales (CE) est au creur de la maladie vasculaire : il est caracterise par une diminution du potentiel angiogenique, une diminution de la biodisponibilite de l'oxyde nitrique, une alteration de la vasodilatation, une augmentation de la production de derives reactifs de l'oxygene et une amplification de l'inflammation. L'oxyde nitrique synthase endotheliale (eNOS), le plus important producteur d'oxyde nitrique, est un enzyme code par le gene NOS3 dans les CE. Le fonctionnement du couple NOS3/eNOS est regule rigoureusement au niveau transcriptionnel comme post-transcriptionnel pour le maintien de la fonction vasculaire normale. La proteine p53 est un regulateur transcriptionnel de l'eNOS cle, que l'on a montre jouer un role central dans la mediation de la senescence des cellules, et donc dans le dysfonctionnement vasculaire. Dans la presente synthese, nous montrons que dans les CE, les facteurs de transcription de l'homeodomaine MEOX entrainent une diminution de l'expression de genes jouant un role dans l'angiogenese, une repression de l'expression d'eNOS au niveau de l'ARNm et des proteines, ainsi qu'une augmentation de l'expression de la proteine p53. Ces resultats appuient l'hypothese selon laquelle les proteines MEOX participent a la promotion du dysfonctionnement endothelial. [Traduit par la Redaction] Mots-cles: cellules endotheliales, vieillissement, progeria, senescence, oxyde nitrique synthase, transcription, p53, MEOX2., Introduction Ageing is accompanied by the progressive loss of tissue homeostasis and gradual organ deterioration. Vascular physiology must be carefully regulated to meet the changing metabolic needs of the body [...]

An increasing number of older people receive organ transplants for various end-stage conditions. Although organ transplantation is an effective therapy for older patients (i.e., older than 65 years of age), such as in end-stage renal disease, this therapy has not been optimized for older patients because of our lack of understanding of the effect of aging and the immune response to organ transplantation. Here, we provide an overview of the impact of aging on both the allograft and the recipient and its effect on the immune response to organ transplantation. We describe what has been determined to date, discuss existing gaps in our knowledge, and make suggestions on necessary future studies to optimize organ transplantation for older people., Introduction The number of people over 65 years of age seeking and receiving organ transplants is growing. Presently, the average age of those receiving kidney transplants is approximately 50 years [...]

Background: Growing evidence indicates that major depressive disorder (MDD) is characterized by accelerated biological aging, including greater age-related changes in physiological functioning. The disorder is also associated with abnormal neural reward circuitry, particularly in the basal ganglia (BG). Here we assessed age-related changes in BG volume in both patients with MDD and healthy control participants. Methods: We obtained whole-brain {T.sub.1]-weighted images from patients with MDD and healthy controls. We estimated grey matter volumes of the BG, including the nucleus accumbens, caudate, pallidum and putamen. Volumes were assessed using multivariate analysis of covariance (MANCOVA) with age as a covariate, followed by appropriate post hoc tests. Results: We included 232 individuals (116 patients with MDD) in our analysis. The MANCOVA yielded a significant group x age interaction (p = 0.043). Analyses for each region yielded a significant group x age interaction in the putamen (univariate test, p = 0.005; permutation test, p = 0.004); this effect was not significant in the other regions. The negative association between age and putamen volume was twice as large in the MDD than in the control group (-35.2 v. -16.7 [mm.sup.3]/yr), indicating greater age-related volumetric decreases in the putamen in individuals with MDD than in controls. Limitations: These findings are cross-sectional; future studies should assess the longitudinal impact of accelerated aging on anhedonia and neural indices of reward processing. Conclusion: Our results indicate that putamen aging is accelerated in patients with MDD. Thus, the putamen may uniquely contribute to the adverse long-term effects of depressive psychopathology and may be a useful target for the treatment of MDD across the lifespan., Introduction Major depressive disorder (MDD) is primarily characterized by depressed mood and a blunted experience of pleasure (i.e., anhedonia). (1) The disorder is prevalent and chronic and represents a substantial [...]

SPEECH RECOGNITION ERRORS: IMPLICATIONS FOR AGING. RACHEL SHORT AND KIMBERLY SMITH, UNIVERSITY OF SOUTH ALABAMA. In natural environments, listeners are faced with having to understand speech in a variety of [...]

Although systemic diseases take the biggest toll on human health and well-being, increasingly, a failing brain is the arbiter of a death preceded by a gradual loss of the essence of being. Ageing, which is fundamental to neurodegeneration and dementia, affects every organ in the body and seems to be encoded partly in a blood-based signature. Indeed, factors in the circulation have been shown to modulate ageing and to rejuvenate numerous organs, including the brain. The discovery of such factors, the identification of their origins and a deeper understanding of their functions is ushering in a new era in ageing and dementia research., Author(s): Tony Wyss-Coray (corresponding author) [1, 2] According to a 2015 United Nations report on world population ageing [1], the number of people aged 60 and older worldwide is projected [...]

Orthopedic surgical care, like all health care today, is in flux owing to an aging population and to chronic medical conditions leading to an increased number of people with illnesses [...]

Idiopathic pulmonary fibrosis (IPF) has been gathering interest in recent years and as such this review will focus on the potential contributions that age plays on its onset and prevalence. Environmental stress over time caused by the inhalation of foreign substances results in subsequent damage and repair of lung tissue. This damage prematurely causes a decrease in stem cell differentiation potential. In conjunction with declining proliferation, the correlation between age and general attenuation of the immune system allows for the introduction of viral components such as the Epstein-Barr virus which has been associated with lung injury, a causation which has not yet been investigated. But, regardless of environmental factors, cellular alterations due to, or in correlation with, age could result in the onset or prolonging of IPF. General genetic mutation and epigenetic methylations accumulate over a person's lifespan while miRNA expression changes from birth to adulthood. This collection of alterations over time may cause dysregulation of expressed genetic material which can result in many age-related diseases including pulmonary fibrosis. Such alterations would be prevented by autophagy or cell-mediated apoptosis, but due to age-related dysregulations, these systems function at a diminished capacity. On the cellular level, the end result is an accumulation of dysfunctional organelles with damaged molecules, such as reactive oxygen species, and general genetic and epigenetic alterations resulting in excess generation of fibrous tissue and overall damage to the pulmonary system., Author(s): Joseph Leung[sup.1] , Young Cho[sup.1] , Richard F. Lockey[sup.1] , Narasaiah Kolliputi[sup.1] Author Affiliations: (1) Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University [...]

Author(s): Manuel Serrano (corresponding author) [1] If cells incur too much damage, they undergo either a self-elimination process known as apoptosis or a self-disabling process called senescence. Senescent cells can [...]

Author(s): Jan Paul Medema If cells encounter certain types of stress, they can enter a state of cell-division arrest termed senescence, which is usually thought to be irreversible. Senescence protects [...]

Author(s): Christina D. Camell [1, 2]; Jil Sander [3]; Olga Spadaro [1, 2]; Aileen Lee [1, 2]; Kim Y. Nguyen [1, 2]; Allison Wing [4]; Emily L. Goldberg [1, 2]; [...]

You might remember when your parents turned 40 and mentioned how their bodies were rapidly changing right before their eyes. You probably gave them a confused but interesting gaze, then [...]

Yoshitake Yokokura has been driving efforts to renew primary health care in Japan to meet the needs of an ageing population. He talks to Fiona Fleck. Q: How did you [...]

Author(s): Erika Check Hayden Doctors and scientists want drug regulators and research funding agencies to consider medicines that delay ageing-related disease as legitimate drugs. Such treatments have a physiological basis, [...]