‘Molecular habituation’ as a potential mechanism of gradual homeostatic loss with age
We report that constitutive signals can give rise to a ‘molecular habituation’ effect that can prime for a gradual loss of biological function. This is because a constitutive signal in the environment has the potential to reduce the responsiveness of a signalling pathway through the prolonged activation of negative regulators. Additionally, we demonstrate how this phenomenon is likely to occur in different signalling pathways exposed to persistent signals and furthermore at different levels of biological organisation (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - November 15, 2017 Category: Geriatrics Source Type: research

Autoamplificatory singlet oxygen generation sensitizes tumor cells for intercellular apoptosis-inducing signaling
Publication date: Available online 11 November 2017 Source:Mechanisms of Ageing and Development Author(s): Georg Bauer Tumor cells express NADPH oxidase-1 (NOX1) in their membrane and control NOX1-based intercellular reactive oxygen and nitrogen species (ROS/RNS)-dependent apoptosis-inducing signaling through membrane-associated catalase and superoxide dismutase. Treatment: of tumor cells with high concentrations of H2O2, peroxnitrite, HOCl, or increasing the concentration of cell-derived NO causes initial generation of singlet oxygen and local inactivation of membrane-associated catalase. As a result, free peroxynitrite ...
Source: Mechanisms of Ageing and Development - November 13, 2017 Category: Geriatrics Source Type: research

The role of TGF β in wound healing pathologies
Publication date: Available online 11 November 2017 Source:Mechanisms of Ageing and Development Author(s): Dimitra Kiritsi, Alexander Nyström Wound healing is one of the most complex processes in multicellular organisms, involving numerous intra- and intercellular signalling pathways in various cell types. It involves extensive communication between the cellular constituents of diverse skin compartments and its extracellular matrix. Miscommunication during healing may have two distinct damaging consequences: the development of a chronic wound or the formation of a hypertrophic scar/keloid. Chronic wounds are defined ...
Source: Mechanisms of Ageing and Development - November 11, 2017 Category: Geriatrics Source Type: research

Phagocyte NADPH oxidase, oxidative stress and lipids: Anti- or pro ageing?
Publication date: Available online 2 November 2017 Source:Mechanisms of Ageing and Development Author(s): Laura Baciou, Rawand Masoud, Hager Souabni, Xavier Serfaty, Gilda Karimi, Tania Bizouarn, Chantal Houée Levin The role of NADPH oxidase in ageing is debated because of the dual roles of free radicals, toxic though necessary. In this paper we summarize some results about two aspects linked to the regulation of the activity of phagocyte NADPH oxidase (Nox2), encountered frequently in elderly people: inflammation and hypercholesterolemia. In the presence of a high amount of reactive oxygen species (ROS) created by...
Source: Mechanisms of Ageing and Development - November 10, 2017 Category: Geriatrics Source Type: research

Keratinocytes oxidative damage mechanisms related to airbone particle matter exposure
Publication date: Available online 2 November 2017 Source:Mechanisms of Ageing and Development Author(s): Arianna Romani, Carlo Cervellati, Ximena M Muresan, Giuseppe Belmonte, Alessandra Pecorelli, Franco Cervellati, Mascia Benedusi, Pablo Evelson, Giuseppe Valacchi Epidemiological evidences have correlated airbone particulate matter (PM) to adverse health effects, mainly linking to pulmonary and cardiovascular disease. Nevertheless, only recently, some studies reported detrimental effects of PM on other organs such as skin. In a recent work, we have reported increased oxidative and inflammatory responses in Reconstitute...
Source: Mechanisms of Ageing and Development - November 9, 2017 Category: Geriatrics Source Type: research

Oxidative stress in ageing and disease development studied by FT-IR spectroscopy
Publication date: Available online 4 November 2017 Source:Mechanisms of Ageing and Development Author(s): Jane Anastassopoulou, Maria Kyriakidou, Stylianos Kyriazis, Andreas F. Mavrogenis, Vasiliki Mamareli, Ioannis Mamarelis, Marianna Petra, Efthymia Malesiou, Christoforos Kotoulas, Panagiota Kolovou, Emmanouil Koutoulakis, Athina Markouizou, Theophile Theophanides FT-IR spectroscopy was used to investigate the effect of oxidative stress and to approach the mechanism on cancer bone demineralization, aortic valve mineralization and heterotopic ossification on disease development. The FT-IR spectra obtained from paediatric...
Source: Mechanisms of Ageing and Development - November 5, 2017 Category: Geriatrics Source Type: research

Modulation of cutaneous Scavenger Receptor B1 levels by exogenous stressors impairs “in vitro” wound closure
Publication date: Available online 1 November 2017 Source:Mechanisms of Ageing and Development Author(s): Ximena Maria Muresan, Claudia Sticozzi, Giuseppe Belmonte, Vinno Savelli, Pablo Evelson, Giuseppe Valacchi Scavenger receptor B1 (SR-B1) is a trans-membrane protein, involved in tissue reverse cholesterol transport. Several studies have demonstrated that SR-B1 is also implicated in other physiological processes, such as bacteria and apoptotic cells recognition and regulation of intracellular tocopherol and carotenoids levels. Among the tissues where it is localized, SR-B1 has been shown to be significantly expressed i...
Source: Mechanisms of Ageing and Development - November 2, 2017 Category: Geriatrics Source Type: research

Centenarians as a model to discover genetic and epigenetic signatures of healthy ageing
Publication date: Available online 31 October 2017 Source:Mechanisms of Ageing and Development Author(s): Annibale Alessandro Puca, Chiara Spinelli, Giulia Accardi, Francesco Villa, Calogero Caruso Centenarians are a model of successful ageing. The data favours the theory that, in order to live to 100, it is mandatory to inherit the right genetic variants from parents or acquire epigenetic variants through the environment. Therefore, the study of epigenetic signatures of healthy ageing is becoming an important aspect to identify the role of chromatin modification in ageing and understand how manage this fine-tuning system...
Source: Mechanisms of Ageing and Development - November 1, 2017 Category: Geriatrics Source Type: research

Alzheimer ’s disease pathogenesis: Is there a role for folate?
Publication date: Available online 13 October 2017 Source:Mechanisms of Ageing and Development Author(s): Natassia Robinson, Peter Grabowski, Ishtiaq Rehman Epigenetic modifications, including changes in DNA methylation, have been implicated in a wide range of diseases including neurological diseases such as Alzheimer’s. The role of dietary folate in providing methyl groups required for maintenance and modulation of DNA methylation makes it a nutrient of interest in Alzheimer’s. Late onset Alzheimer’s disease is the most common form of dementia and at present its aetiology is largely undetermined. From e...
Source: Mechanisms of Ageing and Development - October 14, 2017 Category: Geriatrics Source Type: research

Increased age-adjusted hazard of death associated with a common single nucleotide polymorphism of the human RAD52 gene in a cardiovascular cohort
This study indicates that the SNP affecting efficiency of DSB repair may influence aging in humans. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - October 10, 2017 Category: Geriatrics Source Type: research

Telomere length, sibling competition and development of antioxidant defense in wild house mice
Publication date: Available online 7 October 2017 Source:Mechanisms of Ageing and Development Author(s): Janina Stauffer, Bineet Panda, Petteri Ilmonen Antioxidants and telomere length are potential biomarkers for individuals’ exposure and ability to cope with environmental stressors. However, intraspecific variations in antioxidant alterations due to natural, life cycle related stress, have been rarely estimated. We investigated those changes in wild-derived house mice in a longitudinal study with natural sibling competition as a stressor. Blood was used for telomere length measurements at 8-weeks age and for sever...
Source: Mechanisms of Ageing and Development - October 7, 2017 Category: Geriatrics Source Type: research

DNA methylation age and perceived age in elderly Danish twins
Publication date: Available online 28 September 2017 Source:Mechanisms of Ageing and Development Author(s): Birgit Debrabant, Mette Soerensen, Lene Christiansen, Qihua Tan, Matt McGue, Kaare Christensen, Jacob Hjelmborg Perceived age is an easily accessible biomarker of aging. Here, we studied its relation to DNA methylation age (DNAm age) as introduced in (Horvath, 2013) in 180 elderly Danish twins. We found perceived age and DNAm age to be associated with chronological age (P=0.04 resp. P=2.2e-10) when correcting for gender, but did not see an association between perceived age and DNAm age (P=0.44). Intrapair-analysis s...
Source: Mechanisms of Ageing and Development - September 29, 2017 Category: Geriatrics Source Type: research

A preliminary attempt to establish multiple stress response profiles of human skin fibroblasts exposed to mild or severe stress during ageing in vitro
Publication date: Available online 22 September 2017 Source:Mechanisms of Ageing and Development Author(s): Suresh I.S. Rattan, Dino Demirovic, Carine Nizard Optimal stress response (SR) is an essential aspect of the property of dynamic homeostasis of all biological systems, including cells in culture. Whereas severe stress can induce the so-called stress-induced premature senescence (SIPS), a model developed by Olivier Toussaint, mild stress can strengthen homeodynamics and can postpone senescence through the phenomenon of hormesis. We have attempted to establish multiple stress response profiles (SRP) of early passage y...
Source: Mechanisms of Ageing and Development - September 23, 2017 Category: Geriatrics Source Type: research

Mitochondrial depletion in CD4+ and CD19+ peripheral lymphocytes in early stage Alzheimer ’s disease
Publication date: October 2017 Source:Mechanisms of Ageing and Development, Volume 167 Author(s): Gökhan Terzioğlu, Burcu Örmeci, Özlem Türksoy, Ceyhun Sayman, Nilgün Çınar, Gökçen Akar Öztürk, Gülderen Yanıkkaya Demirel Alzheimer's disease (AD) may be associated with mitochondrial defects. The aim of the present study was to investigate changes in mitochondrial abundance in peripheral lymphocytes of early and late stage AD patients. We analysed levels of mitochondrial DNA (mtDNA) and mean fluorescence intensity (MFI) of the mitochondria-specific antibody 113-1...
Source: Mechanisms of Ageing and Development - September 21, 2017 Category: Geriatrics Source Type: research

Mitochondrial depletion in CD4+ and CD19+ peripheral lymphocytes in early stage Alzheimer's disease
Publication date: Available online 18 September 2017 Source:Mechanisms of Ageing and Development Author(s): Gökhan Terzioğlu, Burcu Örmeci, Özlem Türksoy, Ceyhun Sayman, Nilgün Çınar, Gökçen Akar Öztürk, Gülderen Yanıkkaya Demirel Alzheimer's disease (AD) may be associated with mitochondrial defects. The aim of the present study was to investigate changes in mitochondrial abundance in peripheral lymphocytes of early and late stage AD patients. We analysed levels of mitochondrial DNA (mtDNA) and mean fluorescence intensity (MFI) of the mitochondria-specific anti...
Source: Mechanisms of Ageing and Development - September 19, 2017 Category: Geriatrics Source Type: research

AGE-DEPENDENT ATRIAL ARRHYTHMIC PHENOTYPE SECONDARY TO MITOCHONDRIAL DYSFUNCTION IN Pgc-1 β DEFICIENT MURINE HEARTS
Publication date: Available online 14 September 2017 Source:Mechanisms of Ageing and Development Author(s): Haseeb Valli, Shiraz Ahmad, Karan Chadda, Ali Al-Hadithi, Andrew A. Grace, Kamalan Jeevaratnam, Christopher L-H Huang Introduction Ageing and several age-related chronic conditions including obesity, insulin resistance and hypertension are associated with mitochondrial dysfunction and represent independent risk factors for atrial fibrillation (AF). Materials and methods Atrial arrhythmogenesis was investigated in Langendorff-perfused young (3–4 month) and aged (>12 month), wild type (WT) and peroxisome ...
Source: Mechanisms of Ageing and Development - September 14, 2017 Category: Geriatrics Source Type: research

Regulated expression of the lncRNA TERRA and its impact on telomere biology
Publication date: Available online 6 September 2017 Source:Mechanisms of Ageing and Development Author(s): Diego Oliva-Rico, Luis A. Herrera The telomere protects against genomic instability by minimizing the accelerated end resection of the genetic material, a phenomenon that results in severe chromosome instability that could favor the transformation of a cell by enabling the emergence of tumor-promoting mutations. Some mechanisms that avoid this fate, such as capping and loop formation, have been very well characterized; however, telomeric non-coding transcripts, such as long non-coding RNAs (lncRNAs), should also be c...
Source: Mechanisms of Ageing and Development - September 7, 2017 Category: Geriatrics Source Type: research

Age-associated alterations in the levels of cytotoxic lipid molecular species and oxidative stress in the murine thymus are reduced by growth hormone treatment
In conclusion, GH treatment attenuated inflammation and age-related increases in oxidative stress and lipotoxicity in the thymus. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - September 1, 2017 Category: Geriatrics Source Type: research

The role of nitric oxide in diabetic skin (patho)physiology
Publication date: Available online 1 September 2017 Source:Mechanisms of Ageing and Development Author(s): Ana Stancic, Aleksandra Jankovic, Aleksandra Korac, Biljana Buzadzic, Vesna Otasevic, Bato Korac The role of nitric oxide (NO) in cutaneous physiology/pathology became a growing research field since the discovery that almost all types of skin cells can synthetize this redox signaling molecule about 20 years ago. Now, it is evident that NO is an important player in skin physiological processes and in responses of cutaneous cells to external insults, while the impaired NO signaling has an important consequence in skin ...
Source: Mechanisms of Ageing and Development - September 1, 2017 Category: Geriatrics Source Type: research

Circadian clock as possible protective mechanism to pollution induced keratinocytes damage
Publication date: Available online 30 August 2017 Source:Mechanisms of Ageing and Development Author(s): Mascia Benedusi, Elena Frigato, Mattia Beltramello, Cristiano Bertolucci, Giuseppe Valacchi Ozone is among the most toxic environmental stressors to which we are continuously exposed. Due to its critical location, skin is one of the most susceptible tissues to oxidative stress damaging effect of ozone. An increasing collection of data suggests a significant role of circadian system in regulation of cellular response to oxidative stress. However, the molecular mechanism linking circadian clock and antioxidant pathway it...
Source: Mechanisms of Ageing and Development - August 31, 2017 Category: Geriatrics Source Type: research

Plasma melatonin levels in hip fracture patients with and without delirium: A confirmation study
Conclusion Undergoing surgery and aging in general may induce changes in melatonin metabolism. Future research should focus on daily multiple melatonin measurements to determine whether melatonin supplementation might be beneficial for delirium treatment or prevention. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - August 30, 2017 Category: Geriatrics Source Type: research

Genetically driven antioxidant capacity in a Caucasian Southeastern European population
In conclusion, observed distributions of the polymorphisms studied in the Southeastern population demonstrate a positive impact (rs4880, rs1799895, rs660339, rs28665122) and a negative impact (rs1050450, rs1138272, rs109179, rs1695) against oxidative stress when compared to other population groups. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - August 27, 2017 Category: Geriatrics Source Type: research

Mechanisms of fetal epigenetics that determine telomere dynamics and health span in adulthood
Publication date: Available online 26 August 2017 Source:Mechanisms of Ageing and Development Author(s): Sanda Ravlić, Nikolina Škrobot Vidaček, Lucia Nanić, Mario Laganović, Neda Slade, Bojan Jelaković, Ivica Rubelj Advances in epigenetics now enable us to better understand environmental influences on the genetic background of human diseases. This refers especially to fetal development where an adverse intrauterine environment impacts oxygen and nutrient supply to the fetus. Recently, differences in telomere length and telomere loss dynamics among individuals born with intrauterine growth restriction compared...
Source: Mechanisms of Ageing and Development - August 27, 2017 Category: Geriatrics Source Type: research

The senescent bystander effect is caused by ROS-activated NF- κB signalling
Publication date: Available online 25 August 2017 Source:Mechanisms of Ageing and Development Author(s): Glyn Nelson, Olena Kucheryavenko, James Wordsworth, Thomas von Zglinicki Cell senescence is an important driver of the ageing process. The accumulation of senescent cells in tissues is accelerated by stress signals from senescent cells that induce DNA damage and ultimately senescence in bystander cells. We examine here the interplay of senescence-associated mitochondrial dysfunction (SAMD)—driven production of reactive oxygen species (ROS) and senescence-associated secretory phenotype (SASP) in causing the bystan...
Source: Mechanisms of Ageing and Development - August 26, 2017 Category: Geriatrics Source Type: research

miRNAs in stem cell aging and age-related disease
Publication date: Available online 25 August 2017 Source:Mechanisms of Ageing and Development Author(s): Soon Won Choi, Jin Young Lee, Kyung-Sun Kang MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the expression of mRNA targets and play a part in the post-transcriptional silencing. To date, the prominent roles of miRNAs in stem cells have been investigated in a wide range of biological processes, including self-renewal, differentiation and proliferation. In this commentary, we first demonstrate the causes and mechanisms of somatic stem cell aging in a new aspect of miRNAs. The functions of stem cells decline ...
Source: Mechanisms of Ageing and Development - August 26, 2017 Category: Geriatrics Source Type: research

The physiopathologic role of oxidative stress in skeletal muscle
Publication date: Available online 26 August 2017 Source:Mechanisms of Ageing and Development Author(s): Bianca Maria Scicchitano, Laura Pelosi, Gigliola Sica, Antonio Musarò Muscle senescence is a complex mechanism that is usually associated with a decrease in mass, strength and velocity of contraction. This state, known as sarcopenia, is a multifactorial process and it may be the consequence of several events, including accumulation of oxidative stress. The role of oxidative stress in the physiopathology of skeletal muscle is quite complex. Transiently increased levels of oxidative stress might reflect a potentia...
Source: Mechanisms of Ageing and Development - August 26, 2017 Category: Geriatrics Source Type: research

Aging and immortality in unicellular species
Publication date: Available online 24 August 2017 Source:Mechanisms of Ageing and Development Author(s): Michael Florea It has been historically thought that in conditions that permit growth, most unicellular species do not to age. This was particularly thought to be the case for symmetrically dividing species, as such species lack a clear distinction between the soma and the germline. Despite this, studies of the symmetrically dividing model species Escherichia coli and Schizosaccharomyces pombe have recently started to challenge this notion. They indicate that E. coli and S. pombe do age, but only when subjected to envi...
Source: Mechanisms of Ageing and Development - August 25, 2017 Category: Geriatrics Source Type: research

Age related depth profiles of human Stratum Corneum barrier-related molecular parameters by confocal Raman microscopy in vivo
This study also reveals, that the hydrogen bonding state of water highly correlates with NMF and the lateral structure of ICL but not with keratin’s folding/unfolding properties. The presented results let suggest, that the decreased trans-epidermal water loss (TEWL) with increasing age cannot be sufficiently explained by only the increased SC thickness, but additionally by the increase of ICL ordering, higher NMF concentration and thus larger amount of hydrogen bound water molecules at the depth 20–40% of the SC thickness. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - August 25, 2017 Category: Geriatrics Source Type: research

Role of DNA Methylation in Human Age Prediction
Publication date: Available online 24 August 2017 Source:Mechanisms of Ageing and Development Author(s): Neelam Goel, Priya Karir, Vivek Kumar Garg DNA methylation (DNAm) is a fundamental biochemical modification which occurs over the lifespan of an individual and it is a significant component in the aging process. Methylation level of CpG sites plays an important role in finding the age of a person. Different approaches were used to extract age-related CpG (AR-CpG) sites for developing age-prediction models because the level of methylation is directly related to age for some CpG sites. Several age prediction models have ...
Source: Mechanisms of Ageing and Development - August 25, 2017 Category: Geriatrics Source Type: research

HDAC Inhibitors: A New Promising Drug Class in Anti-Aging Research
Publication date: Available online 24 August 2017 Source:Mechanisms of Ageing and Development Author(s): Elena G. Pasyukova, Alexander M. Vaiserman In the last years, epigenetic regulation of gene expression is regarded as an important factor involved in a broad spectrum of aging-associated processes including loss of physical activity, frailty and genomic instability, and in development of various pathological conditions such as atherosclerosis, type 2 diabetes, cancer, immune deficits and neurodegenerative diseases. Accordingly, inhibitors of the members of superfamilies of histone deacetylases (HDACs) have been propose...
Source: Mechanisms of Ageing and Development - August 24, 2017 Category: Geriatrics Source Type: research

Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype
Publication date: Available online 19 August 2017 Source:Mechanisms of Ageing and Development Author(s): Kevin Ngo, Prashanti Patil, Sara J. McGowan, Laura J. Niedernhofer, Paul D. Robbins, James Kang, Gwendolyn Sowa, Nam Vo Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular...
Source: Mechanisms of Ageing and Development - August 19, 2017 Category: Geriatrics Source Type: research

Is DNA damage indispensable for stress-induced senescence?
Publication date: Available online 16 August 2017 Source:Mechanisms of Ageing and Development Author(s): Anna Bielak-Zmijewska, Grazyna Mosieniak, Ewa Sikora Cellular senescence is a fundamental trait of many eukaryotic organisms. Senescent cells participate both in the developmental program and in normal ageing and age-related diseases. Senescence of proliferation-prone cells is a state of permanent cell cycle arrest accompanied by metabolic activity manifested by high secretion levels of numerous factors, including pro-inflammatory ones. It seems that cell senescence is a stress response. There are many intrinsic and ex...
Source: Mechanisms of Ageing and Development - August 17, 2017 Category: Geriatrics Source Type: research

The ATF6 α arm of the Unfolded Protein Response mediates replicative senescence in human fibroblasts through a COX2/prostaglandin E2 intracrine pathway
Publication date: Available online 10 August 2017 Source:Mechanisms of Ageing and Development Author(s): Johanna Cormenier, Nathalie Martin, Julie Deslé, Clara Salazar-Cardozo, Albin Pourtier, Corinne Abbadie, Olivier Pluquet Senescence is recognized as a cellular state acquired in response to various stresses. It occurs in correlation with the activation of the Unfolded Protein Response (UPR) pathway. However, the UPR targets which might relay the establishment of the senescent phenotype are not known. Herein, we investigated whether the up-regulation of the COX2 (PTGS2) limiting enzyme in the prostaglandin biosyn...
Source: Mechanisms of Ageing and Development - August 11, 2017 Category: Geriatrics Source Type: research

Role of Prion protein in premature senescence of human fibroblasts
Publication date: Available online 8 August 2017 Source:Mechanisms of Ageing and Development Author(s): Emmanuelle Boilan, Virginie Winant, Elise Dumortier, Benaissa ElMoualij, Pascale Quatresooz, Heinz D. Osiewacz, Florence Debacq-Chainiaux, Olivier Toussaint Prion protein (PrP) is essentially known for its capacity to induce neurodegenerative prion diseases in mammals caused by a conformational change in its normal cellular isoform (PrPC) into an infectious and disease-associated misfolded form, called scrapie isoform (PrPSc). Although its sequence is highly conserved, less information is available on its physiological ...
Source: Mechanisms of Ageing and Development - August 9, 2017 Category: Geriatrics Source Type: research

Involvement of tRNAs in replication of human mitochondrial DNA and modifying effects of telomerase
Publication date: Available online 29 July 2017 Source:Mechanisms of Ageing and Development Author(s): Meenakshisundaram Balasubramaniam, Robert J. Shmookler Reis, Srinivas Ayyadevara, Xianwei Wang, Akshatha Ganne, Magomed Khaidakov Overexpression of telomerase has been shown to significantly increase the lifespan of mice. When mechanistically attributed to repair of critically short telomeres, the lifespan extending action of telomerase cannot be reconciled with the observation that telomerase-null mice do not exhibit shortening of lifespan for at least two generations. We hypothesized that telomerase may interfere with ...
Source: Mechanisms of Ageing and Development - August 6, 2017 Category: Geriatrics Source Type: research

Investigating the amyloid-beta enhancing effect of cGMP in neuro2a cells
Publication date: Available online 5 August 2017 Source:Mechanisms of Ageing and Development Author(s): Elisa Calcagno, Francesca Caudano, Mario Passalacqua, Maria A. Pronzato, Ernesto Fedele, Roberta Ricciarelli Long-term potentiation (LTP) and the process of memory formation require activation of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) pathways. Notably, recent evidence indicated that both cyclic nucleotides boost the production of amyloid-beta (Aβ) peptides. In particular, cAMP was shown to favor hippocampal LTP by stimulating the synthesis of the amyloid precursor protein A...
Source: Mechanisms of Ageing and Development - August 6, 2017 Category: Geriatrics Source Type: research

Dicarbonyls induce senescence of human vascular endothelial cells
Conclusion Our data are relevant as they suggest that in diseases with elevated dicarbonyl concentrations, deleterious effects on the endothelium and the development of vascular dysfunction have to be expected. On the other hand, treatment of patients with dicarbonyl scavenger could prevent this. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - August 3, 2017 Category: Geriatrics Source Type: research

Involvement of tRNAs in replication of human mitochondrial DNA and modifying effects of telomerase.
Publication date: Available online 29 July 2017 Source:Mechanisms of Ageing and Development Author(s): Meenakshisundaram Balasubramaniam, Robert J. Shmookler Reis, D. Phil, Srinivas Ayyadevara, Xianwei Wang, Akshatha Ganne, Magomed Khaidakov Overexpression of telomerase has been shown to significantly increase the lifespan of mice. When mechanistically attributed to repair of critically short telomeres, the lifespan extending action of telomerase cannot be reconciled with the observation that telomerase-null mice do not exhibit shortening of lifespan for at least two generations. We hypothesized that telomerase may interf...
Source: Mechanisms of Ageing and Development - July 30, 2017 Category: Geriatrics Source Type: research

Proteome oxidative carbonylation during oxidative stress-induced premature senescence of WI-38 human fibroblasts
Publication date: Available online 27 July 2017 Source:Mechanisms of Ageing and Development Author(s): Marine Le Boulch, Emad K. Ahmed, Adelina Rogowska-Wrzesinska, Martín A. Baraibar, Bertrand Friguet Accumulation of oxidatively damaged proteins is a hallmark of cellular and organismal ageing, and is also a phenotypic feature shared by both replicative senescence and stress-induced premature senescence of human fibroblasts. Moreover, proteins that are building up as oxidized (i.e. the “Oxi-proteome”) during ageing and age-related diseases represent a restricted set of cellular proteins, indicating that...
Source: Mechanisms of Ageing and Development - July 28, 2017 Category: Geriatrics Source Type: research

SIPS as a model to study age-related changes in proteolysis and aggregate formation
Publication date: Available online 27 July 2017 Source:Mechanisms of Ageing and Development Author(s): Christiane Ott, Tobias Jung, Tilman Grune, Annika Höhn Aging is accompanied by the accumulation of cellular damage over time in response to stress, lifestyle and environmental factors ultimately leading to age-related diseases and death. Additionally, the number of senescent cells increases with age. Senescence is most likely not a static endpoint, it represents a series of hallmarks including morphological changes, alterations in protein turnover and accumulation of protein aggregates. The importance of protein oxi...
Source: Mechanisms of Ageing and Development - July 27, 2017 Category: Geriatrics Source Type: research

Centenarians maintain miRNA biogenesis pathway while it is impaired in octogenarians
Publication date: Available online 25 July 2017 Source:Mechanisms of Ageing and Development Author(s): C. Borrás, E. Serna, J. Gambini, M. Inglés, J. Vina Centenarians but not octogenarians up regulate the expression of miRNAs, as we previously reported. We have looked into miRNA biogenesis. We show that RNA POL II, DROSHA, EXPORTIN 5 and DICER, are up-regulated in centenarians compared with octogenarians. Furthermore, factors involved in the control of these miRNAs biogenesis genes are also up-regulated in centenarians. Therefore, the up-regulation of miRNA expression in centenarians can be explained in par...
Source: Mechanisms of Ageing and Development - July 26, 2017 Category: Geriatrics Source Type: research

CARF is a multi-module regulator of cell proliferation and a molecular bridge between cellular senescence and carcinogenesis
Publication date: Available online 25 July 2017 Source:Mechanisms of Ageing and Development Author(s): Renu Wadhwa, Rajkumar Singh Kalra, Sunil C. Kaul CARF (Collaborator of ARF) was first identified as an ARF (Alternative Reading Frame, p14ARF)-interacting protein in a yeast two-hybrid interactive screening. Subsequently, it was shown to stabilize the p53-tumor suppressor protein in an ARF-dependent or −independent manner. It acts as a transcriptional repressor of HDM2 that exerts a negative feedback on p53 by its proteasomal-mediated degradation. CARF-driven control over p53-HDM2-p21WAF1 axis was shown to regulate...
Source: Mechanisms of Ageing and Development - July 26, 2017 Category: Geriatrics Source Type: research

Oxidative stress and inhibition of nitric oxide generation underlie methotrexate-induced senescence in human colon cancer cells
Publication date: Available online 21 July 2017 Source:Mechanisms of Ageing and Development Author(s): Magdalena Dabrowska, Lukasz Uram, Zbigniew Zielinski, Wojciech Rode, Ewa Sikora The response of human colon cancer C85 cells to methotrexate takes the form of reversible growth arrest of the type of stress-induced senescence. In the present study it is shown that during C85 cell progression into methotrexate-induced senescence, dihydrofolate reductase, the primary intracellular target for the drug, is stabilized at the protein level and its enzymatic activity, assayed in crude cellular extracts, decreases by 2-fold. Dihy...
Source: Mechanisms of Ageing and Development - July 22, 2017 Category: Geriatrics Source Type: research

Age-dependent ventricular arrhythmias risk, structural and molecular remodeling in systemic arterial hypertension
This study confirms the presence of higher ventricular ectopy in SHRs than in age-matched WKYs. LVH appeared to be an adaptive, antiarrhythmic process. Myocardial energetic changes with advancing age, as reflected by Kcnj11 expression changes, could underlie this age-dependency of ventricular arrhythmias. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - July 11, 2017 Category: Geriatrics Source Type: research

Stress, cell senescence and organismal ageing
Publication date: Available online 5 July 2017 Source:Mechanisms of Ageing and Development Author(s): João Pedro de Magalhães, João F. Passos Cellular senescence was first described by Hayflick and Moorhead in the 1960s as the irreversible arrest of cells following prolonged cultivation. Telomere shortening is the key mechanism driving replicative senescence in human fibroblasts. Later, pioneering work by Olivier Toussaint and others showed that stress plays a major role in the induction of senescence in vitro, a phenomenon known as stress-induced premature senescence or SIPS. It is also now widely ac...
Source: Mechanisms of Ageing and Development - July 6, 2017 Category: Geriatrics Source Type: research

In memoriam Olivier Toussaint – Stress-induced premature senescence and the role of DNA damage
Publication date: Available online 3 July 2017 Source:Mechanisms of Ageing and Development Author(s): Alexander Bürkle In the present paper, a concise review on the major contribution of our recently deceased colleague, Dr Olivier Toussaint, to the topic of stress-induced premature senescence (SIPS) of cells is presented together with a hypothesis on a mechanistic role of DNA damage, based on accumulating evidence for an important role of DNA damage as a driving factor in ageing. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - July 4, 2017 Category: Geriatrics Source Type: research

A novel role of the mitochondrial permeability transition pore in ( −)-gossypol-induced mitochondrial dysfunction
Publication date: Available online 3 July 2017 Source:Mechanisms of Ageing and Development Author(s): Verena Warnsmann, Nina Meyer, Andrea Hamann, Donat Kögel, Heinz D. Osiewacz Gossypol, a natural polyphenolic compound from cotton seeds, is known to trigger different forms of cell death in various types of cancer. Gossypol acts as a Bcl-2 inhibitor that induces apoptosis in apoptosis-competent cells. In apoptosis-resistant cancers such as glioblastoma, it triggers a non-apoptotic type of cell death associated with increased oxidative stress, mitochondrial depolarisation and fragmentation. In order to investigate the...
Source: Mechanisms of Ageing and Development - July 4, 2017 Category: Geriatrics Source Type: research

CENTENARIANS AS A 21st CENTURY HEALTHY AGING MODEL: A LEGACY OF HUMANITY AND THE NEED FOR A WORLD-WIDE CONSORTIUM (WWCC100+)
Publication date: Available online 23 June 2017 Source:Mechanisms of Ageing and Development Author(s): Claudio Franceschi, Giuseppe Passarino, Daniela Mari, Daniela Monti (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - June 24, 2017 Category: Geriatrics Source Type: research

The effect of CD34+ cell telomere length and hTERT expression on the outcome of autologous CD34+ cell transplantation in patients with chronic heart failure
Publication date: Available online 19 June 2017 Source:Mechanisms of Ageing and Development Author(s): Jasmina-Ziva Rozman, Maja Pohar Perme, Mojca Jez, Elvira Malicev, Metka Krasna, Srdjan Novakovic, Bojan Vrtovec, Primoz Rozman Age-related telomere attrition in stem/progenitor cells may diminish their functional capacity and thereby impair the outcome of cell-based therapies. The aim of the present study was to investigate the effect of CD34+ cell telomere length and hTERT expression on the clinical outcome of autologous CD34+ cell transplantation. We studied 43 patients with cardiomyopathy. Their peripheral blood CD34+...
Source: Mechanisms of Ageing and Development - June 20, 2017 Category: Geriatrics Source Type: research

Cancer —Incidence, prevalence and mortality in the oldest-old. A comprehensive review
Publication date: June 2017 Source:Mechanisms of Ageing and Development, Volume 164 Author(s): Shantell C. Nolen, Marcella A. Evans, Avital Fischer, Maria M. Corrada, Claudia H. Kawas, Daniela A. Bota Chronic health conditions are commonplace in older populations. The process of aging impacts many of the world’s top health concerns. With the average life expectancy continuing to climb, understanding patterns of morbidity in aging populations has become progressively more important. Cancer is an age-related disease, whose risk has been proven to increase with age. Limited information is published about the epidemiolo...
Source: Mechanisms of Ageing and Development - May 21, 2017 Category: Geriatrics Source Type: research