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Mechanisms of Ageing and Development

Martin S Denzel, Louis R Lapierre, Hildegard I D Mack
Key discoveries in aging research have been made possible with the use of model organisms. Caenorhabditis elegans is a short-lived nematode that has become a well-established system to study aging. The practicality and powerful genetic manipulations associated with this metazoan have revolutionized our ability to understand how organisms age. 25 years after the publication of the discovery of the daf-2 gene as a genetic modifier of lifespan, C. elegans remains as relevant as ever in the quest to understand the process of aging...
August 19, 2018: Mechanisms of Ageing and Development
Christos C Zouboulis, Eugenia Makrantonaki
Intense research during the last few years has elucidated a number of mechanisms of the complex human aging process. Among the body organs, skin has a distinguished role in aging perception both because it constitutes the organ on which the first signs of aging are mostly visible and because skin is recognized as an indicator of human health. Analogous to all other organs, skin undergoes multiple morphological and functional changes with age affected by extrinsic and intrinsic factors. Evaluation of skin morphology as well as of advanced glycation end products, dermal collagen content and alterations of the Wnt signaling pathway may predict - among others - the aging status of the cardiovascular system, the brain and the bones...
August 15, 2018: Mechanisms of Ageing and Development
Solmaz Etemad, Michèle Petit, Alexander K H Weiss, Andre Schrattenholz, Giorgia Baraldo, Pidder Jansen-Dürr
FAHD1, a member of the FAH superfamily of enzymes, was identified in a proteomic screen for mitochondrial proteins with differential expression in young versus senescent human endothelial cells. FAHD1 acts as oxaloacetate decarboxylase, and recent observations suggest that FAHD1 plays an important role in regulating mitochondrial function. Thus, mutation of the nematode homolog, fahd-1, impairs mitochondrial function in Caenorhabditis elegans. When FAHD1 gene expression was silenced in human cells, activity of the mitochondrial electron transport (ETC) system was reduced and the cells entered premature senescence-like growth arrest...
July 25, 2018: Mechanisms of Ageing and Development
Cara L Green, Dudley W Lamming
Although the beneficial effects of calorie restriction (CR) on health and aging were first observed a century ago, the specific macronutrients and molecular processes that mediate the effect of CR have been heavily debated. Recently, it has become clear that dietary protein plays a key role in regulating both metabolic health and longevity, and that both the quantity and quality - the specific amino acid composition - of dietary protein mediates metabolic health. Here, we discuss recent findings in model organisms ranging from yeast to mice and humans regarding the influence of dietary protein as well as specific amino acids on metabolic health, and the physiological and molecular mechanisms which may mediate these effects...
July 22, 2018: Mechanisms of Ageing and Development
George Miloshev, Dessislava Staneva, Katya Uzunova, Bela Vasileva, Milena Draganova-Filipova, Plamen Zagorchev, Milena Georgieva
Linker histones are major players in chromatin organization and per se are essential players in genome homeostasis. As the fifth class of histone proteins the linker histones not only interact with DNA and core histones but also with other chromatin proteins. These interactions prove to be essential for the higher levels of chromatin organization like chromatin loops, transcription factories and chromosome territories. Our recent results have proved that Saccharomyces cerevisiae linker histone - Hho1p, physically interacts with the actin-related protein 4 (Arp4) and that the abrogation of this interaction through the deletion of the gene for the linker histone in arp4 mutant cells leads to global changes in chromatin compaction...
July 17, 2018: Mechanisms of Ageing and Development
Marco Viceconti, Enrico Dall'Ara
Driven by the raising ethical concerns surrounding animal experimentation, there is a growing interest for non-animal methods, in vitro or in silico technologies that can be used to reduce, refine, and replace animal experimentation. In addition, animal experimentation is being critically revised in regard to its ability to predict clinical outcomes. In this manuscript we describe an initial exploration where a set of in vivo imaging based subject-specific technologies originally developed to predict the risk of femoral strength and hip fracture in osteoporotic patients, were adapted to assess the efficacy of bone drugs pre-clinically on mice...
July 10, 2018: Mechanisms of Ageing and Development
Maria Moreno-Villanueva, Alexander Bürkle
Ageing is a multifactorial process that affects most, if not all, of the body's tissues and organs and can be defined as the accumulation of physical and psychological changes in a human being over time. The rate of ageing differs between individuals of the same chronological age, meaning that 'biological age' of a person may be different from 'chronological age'. Furthermore, ageing represents a very potent risk factor for diseases and disability in humans. Therefore, establishment of markers of biological ageing is important for preventing age-associated diseases and extending health span...
June 30, 2018: Mechanisms of Ageing and Development
Angyang Hou, Peng Chen, He Tang, Haoye Meng, Xiaoqing Cheng, Yu Wang, Yuming Zhang, Jiang Peng
In older adults, the prevalence of osteoarthritis (OA) increases directly with age and is the most common cause of chronic disability. It is necessary to recognize that OA is a degenerative disease that strongly correlates with age, and often promotes elevated levels of cartilage injury. Chondrocytes undergo an age-dependent decline in proliferative and synthetic capacity. It is thought that cellular senescence may play a significant role in the pathology of OA, with chondrocytes exhibiting a variety of senescence-associated phenotypes...
October 2018: Mechanisms of Ageing and Development
Justin Cohen, Luca D'Agostino, Ferit Tuzer, Claudio Torres
Developments in medicine have led to a significant increase in the average human lifespan. This increase in aging is most readily apparent in the case of HIV where antiretroviral therapy has shifted infection from a terminal to a chronic but manageable disease. Despite this advance, patients suffer from co-morbidities best described as an accelerated aging phenotype. A potential contributor is cellular senescence, an aging-associated growth arrest, which has already been linked to other HIV co-morbidities such as lipodystrophies and osteoporosis in response to antiretroviral drugs...
October 2018: Mechanisms of Ageing and Development
Anna A Wawer, Amy Jennings, Susan J Fairweather-Tait
A comprehensive literature review of iron status in the elderly was undertaken in order to update a previous review (Fairweather-Tait et al, 2014); 138 summarised papers describe research on the magnitude of the problem, aetiology and age-related physiological changes that may affect iron status, novel strategies for assessing iron status with concurrent health conditions, hepcidin, lifestyle factors, iron supplements, iron status and health outcomes (bone mineral density, frailty, inflammatory bowel disease, kidney failure, cancer, cardiovascular, and neurodegenerative diseases)...
October 2018: Mechanisms of Ageing and Development
Paweł Smykiewicz, Agnieszka Segiet, Michelle Keag, Tymoteusz Żera
Cardiovascular health deteriorates with age, and age is one of the strongest risk factors for cardiovascular complications including myocardial infarction, heart failure, cardiac arrhythmias, and death related to heart diseases. In this review, we show that expression of proinflammatory cytokines (PICs) increases throughout the human lifespan, and this increase is correlated with cardiovascular health, morbidity, and mortality. We argue that increased concentrations of circulating PICs are not only markers of chronic low-grade inflammation, but they also serve as an important pathophysiological link between CV health and ageing...
October 2018: Mechanisms of Ageing and Development
Shanrong Bi, Hanyu Wang, Weihong Kuang
Stem cells being pluripotent in nature can differentiate into a wide array of specific cells and asymmetrically divide to produce new ones but may undergo aging by themselves. Aging has both quantitative and qualitative effects on stem cells, and could eventually restrain them from replenishing into progenitor cells. Reactive oxygen species (ROS) accumulated in the aging cells could not only block the cell cycle but also affect autophagy by damaging the mitochondria. Autophagy could eliminate redundant production of ROS in aging stem cells and helps to maintain the proliferation capacity by restraining the expression of p16INK4a ...
October 2018: Mechanisms of Ageing and Development
Lucas Bet da Rosa Orssatto, Matheus Joner Wiest, Fernando Diefenthaeler
Ageing leads to substantial force production capacity reductions, which is an indicator of frailty and disability, and a mortality predictor in elders. Understanding the age-dependent neuromuscular mechanisms underlying force reductions can optimize healthcare professionals' exercise protocol choices for patients and allows researchers to investigate new interventions to mitigate these reductions. Our primary goal was to provide an updated review about the main neural and musculotendinous mechanisms underpinning age-related reductions in force capacity...
October 2018: Mechanisms of Ageing and Development
Ines Sanchez-Roman, Sofie Lautrup, Maria Diget Aamann, Edward G Neilan, John R Østergaard, Tinna Stevnsner
Cockayne Syndrome (CS) is a rare autosomal recessive disorder, which leads to neurodegeneration, growth failure and premature aging. Most of the cases are due to mutations in the ERCC6 gene, which encodes the protein CSB. CSB is involved in several functions including DNA repair and transcription. Here we describe two Danish brothers with CS. Both patients carried a novel splice site mutation (c.2382+2T>G), and a previously described nonsense mutation (c.3259C>T, p.Arg1087X) in a biallelic state. Both patients presented the cardinal features of the disease including microcephaly, congenital cataract and postnatal growth failure...
October 2018: Mechanisms of Ageing and Development
Mary Revelas, Anbupalam Thalamuthu, Christopher Oldmeadow, Tiffany-Jane Evans, Nicola J Armstrong, John B Kwok, Henry Brodaty, Peter R Schofield, Rodney J Scott, Perminder S Sachdev, John R Attia, Karen A Mather
BACKGROUND: Many factors contribute to exceptional longevity, with genetics playing a significant role. However, to date, genetic studies examining exceptional longevity have been inconclusive. This comprehensive review seeks to determine the genetic variants associated with exceptional longevity by undertaking meta-analyses. METHODS: Meta-analyses of genetic polymorphisms previously associated with exceptional longevity (85+) were undertaken. For each variant, meta-analyses were performed if there were data from at least three independent studies available, including two unpublished additional cohorts...
October 2018: Mechanisms of Ageing and Development
Zaynab El-Gammal, Abdelrahman AlOkda, Nagwa El-Badri
Cellular reprograming paves the way for creating functional patient-specific tissues to eliminate immune rejection responses by applying the same genetic profile. However, the epigenetic memory of a cell remains a challenge facing the current reprograming methods and does not allow transcription factors to bind properly. Because somatic cells can be reprogramed by transferring their nuclear contents into oocytes, introducing specific oocyte factors into differentiated cells is considered a promising approach for mimicking the reprograming process that occurs during fertilization...
October 2018: Mechanisms of Ageing and Development
Sha-Sha Xing, Jian Li, Lin Chen, Ya-Fei Yang, Ping-Lin He, Jun Li, Jin Yang
OBJECTIVE: Endothelial cellular senescence is an important contributor to the endothelial dysfunction and atherosclerosis. Our previous studies suggested that salidroside (SAL) can alleviate atherosclerosis and protect endothelial cells against oxidative stress induced damage. However, the effect and mechanism of SAL on endothelial cellular senescence is still unclear. Here, we investigated the underlying mechanisms of SAL on preventing endothelial cellular premature senescence. METHODS AND RESULTS: We established a hyperhomocysteinemia (HHcy)mouse model via high methionine diet (HMD) to explore the protective effect of SAL...
October 2018: Mechanisms of Ageing and Development
Rosita Gabbianelli, Marco Malavolta
No abstract text is available yet for this article.
September 2018: Mechanisms of Ageing and Development
Carolina J Simoes da Silva, Rocío Simón, Ana Busturia
Over the last decades significant advances have been made in our understanding of the molecular mechanisms controlling organismal development. Among these mechanisms the knowledge gained on the roles played by epigenetic regulation of gene expression is extensive. Epigenetic control of transcription requires the function of protein complexes whose specific biochemical activities, such as histone mono-ubiquitylation, affect chromatin compaction and, consequently activation or repression of gene expression. Complexes composed of Polycomb Group (PcG) proteins promote transcriptional silencing while those containing trithorax group (trxG) proteins promote transcriptional activation...
September 2018: Mechanisms of Ageing and Development
Ana Dolinar, Metka Ravnik-Glavač, Damjan Glavač
Amyotrophic lateral sclerosis is a rapidly progressing neurodegenerative disease. Decades of research show that the etiology of this disease is affected by genetic, epigenetic and environmental factors rather than limited by a patient's genotype. The interaction between these factors is complex, and research has only begun to unravel this issue. The main epigenetic mechanisms, DNA methylation, miRNA, and histone modifications, can explain a portion of the disease complexity. However, the interplay among the epigenetic mechanisms themselves and with genetic factors remains largely uncharacterized...
September 2018: Mechanisms of Ageing and Development
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