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Mechanisms of Ageing and Development

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 in CD4(+), CD8(+), CD19(+) and CD56(+) peripheral lymphocytes of early and late stage AD by quantitative real-time PCR and flow cytometry, respectively. In early stage AD, the levels of mtDNA were significantly decreased in CD4(+), CD19(+) and CD56(+) peripheral lymphocytes while the MFI of 113-1 staining was significantly decreased in CD4(+) and CD19(+) cells...
September 18, 2017: Mechanisms of Ageing and Development
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 proliferator activated receptor-γ coactivator-1β deficient (Pgc-1β(-/-)) murine hearts modeling age-dependent chronic mitochondrial dysfunction during regular pacing and programmed electrical stimulation (PES)...
September 14, 2017: Mechanisms of Ageing and Development
Rikie M Scholtens, Barbara C van Munster, Martijn van Faassen, Marijn F van Kempen, Ido P Kema, Sophia E de Rooij
BACKGROUND: Melatonin plays a major role in maintaining circadian rhythm. Changes in melatonin metabolism might lead to circadian rhythm disturbances which are often observed in delirious patients. AIM: To assess if high morning plasma melatonin concentrations were associated with delirium. METHODS: Consecutive hip fracture patients aged ≥65 years were included. Delirium was assessed daily with the Confusion Assessment METHOD: Blood samples were collected at 11...
September 8, 2017: Mechanisms of Ageing and Development
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 considered in this context because they play roles in the organization of telomere dynamics, involving processes such as replication, degradation, extension, and heterochromatin stabilization...
September 6, 2017: Mechanisms of Ageing and Development
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 pathology. Skin disorders are common complications in diabetic conditions. Various metabolic/biochemical and immunological dysregulations in diabetic skin are tightly coupled with the disturbances in the redox state, primarily the ratio between NO and superoxide (О2(-))...
August 30, 2017: Mechanisms of Ageing and Development
Valeria de Mello-Coelho, Roy G Cutler, Allyson Bunbury, Anita Tammara, Mark P Mattson, Dennis D Taub
During age-associated thymic involution, thymocytes decrease and lipid-laden cells accumulate. However, if and how aging affects the thymic lipid profile is not well understood, nor is it known if the hormonal milieu modifies this process. Here we demonstrate a correlation between reduced thymocyte numbers and markers of inflammation and oxidative stress with age. Evaluating the lipidomics profile of the whole thymus, between the ages of 4 (young) and 18 months (old), we found increased amounts of triacylglycerides, free cholesterol, cholesterol ester and 4-hydroxynonenal (4-HNE) with age...
August 30, 2017: Mechanisms of Ageing and Development
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 is not completely understood. Here we investigated a possible protective role of entrained circadian clock to ozone induced damage in keratinocytes, the main cellular component of human epidermis...
August 28, 2017: Mechanisms of Ageing and Development
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 potentially health promoting process, while an uncontrolled accumulation might have pathological implication...
August 26, 2017: Mechanisms of Ageing and Development
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 to normal controls have been described. In this paper we propose possible molecular mechanisms that (pre)program telomere epigenetics during pregnancy...
August 26, 2017: Mechanisms of Ageing and Development
Martha-Spyridoula Katsarou, Maria Giakoumaki, Andriana Papadimitriou, Nikolaos Demertzis, Vasileios Androutsopoulos, Nikolaos Drakoulis
Previous studies have underlined the function of specific xenobiotic metabolizing phase-I or phase-II enzymes and endogenous antioxidant-related enzymes in the reduction and/or progression of oxidative stress and consequently the incidence of several diseases. In the present study, 10 polymorphic variants (rs4880, rs1799895, rs660339, rs1050450, rs1001179, rs28665122, rs1695, rs1138272, rs1051740 and rs2234922) were investigated in 1132 individuals of a Caucasian Southeastern European population. The frequency distribution of alleles and genotypes was compared to data of European (Northern, Central, Northwestern and Southwestern) and Global populations, extracted from the ensembl genome browser...
August 26, 2017: Mechanisms of Ageing and Development
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 with age in diverse tissues due to cellular damages and congenital disorders...
August 25, 2017: Mechanisms of Ageing and Development
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 been developed over the past few years and most of these models were based on regression techniques...
August 24, 2017: Mechanisms of Ageing and Development
ChunSik Choe, Johannes Schleusener, Jürgen Lademann, Maxim E Darvin
In this study, stratum corneum (SC) depth profiles of hydrogen bound water molecule types, intercellular lipid (ICL) ordering, concentration of natural moisturizing factor (NMF) and keratin folding/unfolding properties are investigated in vivo for older (mean 50 years old) and younger (mean 29 years old) human skin using confocal Raman microscopy. The results show that the SC of the older group is modestly thicker (p <0.1), has more hydrogen bound water molecules at the depth 20-30% of the SC thickness (p <0...
August 24, 2017: Mechanisms of Ageing and Development
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 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 environmental stress...
August 24, 2017: Mechanisms of Ageing and Development
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 proposed, among other drugs targeting epigenetic pathways, as a promising type of therapeutics that is able to combat aging and its manifestations...
August 24, 2017: Mechanisms of Ageing and Development
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 bystander effect. We show that in various modes of fibroblast senescence ROS are necessary and sufficient to activate the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), which facilitates a large part of the SASP...
August 21, 2017: Mechanisms of Ageing and Development
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 senescence is dramatically increased in the DNA repair-deficient Ercc1(-/Δ) mouse model of human progeria...
August 19, 2017: Mechanisms of Ageing and Development
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 extrinsic stress inducers which can elicit cell senescence...
August 16, 2017: Mechanisms of Ageing and Development
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 biosynthesis pathway, known to mediate cellular senescence in normal human fibroblasts, could be controlled by the UPR sensors ATF6α, IRE1α and PERK...
August 10, 2017: Mechanisms of Ageing and Development
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 (PrP(C)) into an infectious and disease-associated misfolded form, called scrapie isoform (PrP(Sc)). Although its sequence is highly conserved, less information is available on its physiological role under normal conditions. However, increasing evidence supports a role for PrP(C) in the cellular response to oxidative stress. In the present study, a new link between PrP and senescence is highlighted...
August 8, 2017: Mechanisms of Ageing and Development
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