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Mechanisms of Ageing and Development

Laura C D Pomatto, Patrick Y Sun, Kelvin J A Davies
Many consequences of ageing can be broadly attributed to the inability to maintain homeostasis. Multiple markers of ageing have been identified, including loss of protein homeostasis, increased inflammation, and declining metabolism. Although much effort has been focused on characterization of the ageing phenotype, much less is understood about the underlying causes of ageing. To address this gap, we outline the age-associated consequences of dysregulation of 'Adaptive Homeostasis' and its proposed contributing role as an accelerator of the ageing phenotype...
May 17, 2018: Mechanisms of Ageing and Development
Anastasios Kouroumalis, Eleni Mavrogonatou, Olga D Savvidou, Panayiotis J Papagelopoulos, Harris Pratsinis, Dimitris Kletsas
Intervertebral discs (IVDs) are the joints of the spine, mainly consisting of extracellular matrix (ECM) with a low number of cells embedded therein. Low cellularity stems from nutrient deprivation due to the lack of blood supply, as well as from the hypoxic and hyperosmotic conditions prevailing in the tissue. Intervertebral disc degeneration (IDD) has been firmly connected with low back pain, a major age-related disease, whereas degenerated discs have been characterized by increased proteolytic activity and accumulation of senescent cells...
May 17, 2018: Mechanisms of Ageing and Development
Rosita Gabbianelli, Marco Malavolta
No abstract text is available yet for this article.
May 17, 2018: Mechanisms of Ageing and Development
Shiraz Ahmad, Haseeb Valli, Karan R Chadda, James Cranley, Kamalan Jeevaratnam, Christopher L-H Huang
INTRODUCTION: Ageing and age-related bioenergetic conditions including obesity, diabetes mellitus and heart failure constitute clinical ventricular arrhythmic risk factors. MATERIALS AND METHODS: Pro-arrhythmic properties in electrocardiographic and intracellular recordings were compared in young and aged, peroxisome proliferator-activated receptor-γ coactivator-1β knockout (Pgc-1β-/- ) and wild type (WT), Langendorff-perfused murine hearts, during regular and programmed stimulation (PES), comparing results by two-way ANOVA...
May 12, 2018: Mechanisms of Ageing and Development
H Wolfe, A M Minogue, S Rooney, M A Lynch
The recognized role of neuroinflammation in the age-related deterioration of neuronal function highlights the importance of understanding the factors that control microglial activation. Microglia, as the immune cells of the brain, are the arbiters of the inflammatory profile in the brain. Normally they are maintained in a quiescent state by means of ligand-receptor interactions with neurons, within a prevailing anti-inflammatory microenvironment. The evidence indicates that, as the ageing process continues, microglia become activated, shift towards an inflammatory phenotype and alter the milieu in the brain...
May 11, 2018: Mechanisms of Ageing and Development
David Knupp, Pedro Miura
Circular RNAs (circRNAs) are a newly appreciated class of RNAs found across phyla that are generated most commonly from back-splicing of protein-coding exons. Recent profiling of circRNAs genome-wide has shown that hundreds of circRNAs dramatically increase in expression during aging in the brains of multiple organisms. No other class of transcripts has been found to show such a strong correlation with aging as circRNAs-could they be playing a role in the aging process? Here, we discuss the different methods used to profile circRNAs and discuss current limitations of these approaches...
May 10, 2018: Mechanisms of Ageing and Development
Junko Oshima, Hisaya Kato, Yoshiro Maezawa, Koutaro Yokote
Progeroid syndrome is a group of disorders characterized by the early onset of diseases that are associated with aging. Best known examples are Werner syndrome, which is adult onset and results from disease-causing DNA sequence variants in the RecQ helicase gene WRN, and Hutchison-Gilford progeria syndrome, which is childhood-onset and results from unique, recurrent disease-causing DNA sequence variants of the gene LMNA that encodes nuclear intermediate filaments. Related single gene RecQ disorders are Bloom syndrome and Rothmund-Thomson syndrome...
May 9, 2018: Mechanisms of Ageing and Development
Keetae Kim, Han Kyoung Choe
Aging is characterized by a progressive loss of several physiological functions that can cause various age-related disorders. Several factors have been identified as causes of aging to elucidate the decline in functions. Various aspects of physiological deterioration are controlled by the hypothalamus, a critical brain region that connects the neuroendocrine system to physiological functions. In addition, functional alterations in a set of agouti-related peptide/neuropeptide Y (AgRP/NPY) and pro-opiomelanocortin (POMC) neurons, a set of growth hormone-releasing hormone (GHRH) and somatostatin (SST) neurons, a set of arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) neurons, and a set of gonadotropin-releasing hormone (GnRH) and kisspeptin/neurokinin B/dynorphin (KNDy) neurons contribute to age-related physiological decline in energy metabolism, hormone regulation, circadian rhythm, and reproduction, respectively...
May 2, 2018: Mechanisms of Ageing and Development
M Liset Rietman, Annemieke M W Spijkerman, Albert Wong, Harry van Steeg, Alexander Bürkle, María Moreno-Villanueva, Thilo Sindlinger, Claudio Franceschi, Beatrix Grubeck-Loebenstein, Jürgen Bernhardt, P Eline Slagboom, Olivier Toussaint, Florence Debacq-Chainiaux, Ewa Sikora, Efstathios S Gonos, Nicolle Breusing, Wolfgang Stuetz, Daniela Weber, Tilman Grune, Andrea Basso, Francesco Piacenza, Marco Malavolta, Sebastiano Collino, Eugene H J M Jansen, W M Monique Verschuren, Martijn E T Dollé
Frailty among elderly people leads to an increased risk for negative health outcomes. To prevent frailty, we need a better understanding of the underlying mechanisms and early detection of individuals at risk. Both may be served by identifying candidate (bio)markers, i.e. biomarkers and markers, for the physical, cognitive, and psychological frailty domains. We used univariate (Rank-ANOVA) and multivariate (elastic net) approaches on the RASIG study population (age range: 35-74 years, n = 2220) of the MARK-AGE Study to study up to 331 (bio)markers between individuals with and without frailty for each domain...
April 29, 2018: Mechanisms of Ageing and Development
Olympia-Ekaterini Psathaki, Lena Dehnen, Paul Hartley, Achim Paululat
Here we show that a labyrinth channel compartment and slit diaphragms, which are the histological structures enabling insect nephrocytes ultrafiltration, are established during embryogenesis first by the garland nephrocytes (GCNs). The later pericardial nephrocytes, which represent the majority of functional nephrocytes in larvae and adults, lack these characteristic features at the embryonic stage. During larval development, a subpopulation of the pericardial cells survives and matures into functional nephrocytes (PCNs) displaying a fully differentiated slit diaphragm and a labyrinth channel compartment...
April 24, 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...
April 14, 2018: Mechanisms of Ageing and Development
Graham Pawelec
Since associations between lifespan and certain simple immune parameters such as T cell proliferative responses to mitogens were reported in the 1970´s, efforts to dissect out immune parameters correlating with morbidity and mortality have sought to define factors predicting individual longevity. Such "immune signatures" associating with defined clinical outcomes would represent biomarkers of "immunosenescence" that might also provide mechanistic insights into the ageing process. Because appropriate immune function is necessary for a healthy old age, a better understanding of immunosenescence contributing to frailty and death might allow interventions to improve personal and public health...
April 11, 2018: Mechanisms of Ageing and Development
Kimberly C Paul, Janet S Sinsheimer, Myles Cockburn, Jeff M Bronstein, Yvette Bordelon, Beate Ritz
OBJECTIVE: To investigate three expression-altering NFE2L2 SNPs and four PPARGC1α previously implicated SNPs and pesticides on Parkinson's disease (PD) risk and symptom progression. METHODS: In 472 PD patients and 532 population-based controls, we examined variants and their interactions with maneb and paraquat (MB/PQ) pesticide exposure on PD onset (logistic regression) and progression of motor symptoms and cognitive decline (n = 192; linear repeated measures)...
April 6, 2018: Mechanisms of Ageing and Development
Alexander M Vaiserman
Increasing evidence suggests that risk for age-related disease and longevity can be programmed early in life. In human populations, convincing evidence has been accumulated indicating that intrauterine growth restriction (IUGR) resulting in low birth weight (<2.5 kg) followed by postnatal catch-up growth is associated with various aspects of metabolic syndrome, type 2 diabetes and cardiovascular disease in adulthood. Fetal macrosomia (birth weight >4.5 kg), by contrast, is associated with high risk of non-diabetic obesity and cancers in later life...
April 4, 2018: Mechanisms of Ageing and Development
Maria De Luca
The extracellular matrix (ECM) is an intricate network that provides structural and anchoring support to cells in order to stabilize cell morphology and tissue architecture. The ECM also controls many aspects of the cell's dynamic behavior and fate through its ongoing, bidirectional interaction with cells. These interactions between the cell and components of the surrounding ECM are implicated in several biological processes, including development and adult tissue repair in response to injury, throughout the lifespan of multiple species...
April 4, 2018: Mechanisms of Ageing and Development
Ho-Jun Jeon, Young-Shin Kim, Joong-Gook Kim, Kyu Heo, Jung-Hoon Pyo, Masamitsu Yamaguchi, Joung-Sun Park, Mi-Ae Yoo
Chromatin change is one of the crucial causes of aging. Specifically, maintenance of heterochromatin stability is critical for cellular integrity, and its loss induces genomic instability and cellular aging. However, the causes and effects of heterochromatin instability in multicellular tissue aging still remain unclear. Here, in the adult Drosophila midgut, we report age-related loss of heterochromatin stability in enterocytes (ECs) due to the loss and dispersion of tri-methylated histone H3 Lys9 (H3K9me3) and heterochromatin protein 1 (HP1)...
April 3, 2018: Mechanisms of Ageing and Development
Mariam El Assar, Argentina Fernández, Alberto Sánchez-Ferrer, Javier Angulo, Leocadio Rodríguez-Mañas
Aging induces vascular dysfunction, representing the major risk factor for cardiovascular disease. Our aim was to ascertain specific vulnerability of vascular territories to aging by evaluating the progressive impact of aging on vascular function in four different vascular beds: aorta, mesenteric artery (MA), coronary artery (CA), and penile corpus cavernosum (CC) from 3, 6, 9, 12, 20 or 24 months-old male rats. Contractile/relaxant responses were evaluated in organ chambers (A/CC) and wire myographs (MA/CA)...
March 29, 2018: Mechanisms of Ageing and Development
Ryan P Barnes, Elise Fouquerel, Patricia L Opresko
Telomeres are dynamic nucleoprotein-DNA structures that cap and protect linear chromosome ends. Because telomeres shorten progressively with each replication, they impose a functional limit on the number of times a cell can divide. Critically short telomeres trigger cellular senescence in normal cells, or genomic instability in pre-malignant cells, which contribute to numerous degenerative and aging-related diseases including cancer. Therefore, a detailed understanding of the mechanisms of telomere loss and preservation is important for human health...
March 28, 2018: Mechanisms of Ageing and Development
Michaela Press, Tobias Jung, Jeannette König, Tilman Grune, Annika Höhn
The ubiquitin-proteasomal-system (UPS) and the autophagy-lysosomal-system (ALS) are both highly susceptible for disturbances leading to the accumulation of cellular damage. A decline of protein degradation during aging results in the formation of oxidatively damaged and aggregated proteins finally, resulting in failure of cellular functionality. Besides protein aggregation in response to oxidative damage, amyloids are a different type of protein aggregates able to distract proteostasis and interfere with cellular functionality...
March 23, 2018: Mechanisms of Ageing and Development
Peter Lenart, Jan Novak, Julie Bienertova-Vasku
Transposable elements (TEs) are powerful drivers of genome evolutionary dynamics but are principally deleterious to the host organism by compromising the integrity and function of the genome. The transposition of TEs may result in mutations and DNA damage. DNA double-strand breaks (DSBs), which may be caused by the transposition, are one of the processes directly linked to aging. TEs may thus be considered to constitute an internal source of aging and the frequency of transposition may, in turn, be considered to affect the pace of aging...
March 23, 2018: Mechanisms of Ageing and Development
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