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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
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...
July 8, 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
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 Cockayne Syndrome. 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...
June 23, 2018: Mechanisms of Ageing and Development
Jessica Bertschmann, Subhash Thalappilly, Karl Riabowol
No abstract text is available yet for this article.
June 18, 2018: Mechanisms of Ageing and Development
Valérie Haydont, Véronique Neiveyans, Hélène Zucchi, Nicolas O Fortunel, Daniel Asselineau
Deciphering the characteristics of dermal fibroblasts is critical to further understand skin ageing. We have conducted a genome-wide transcriptomic characterization of papillary (Fp) and reticular (Fr) fibroblasts extracted from human skin samples corresponding to younger and older adult ages. From this screen, biomarkers suitable for the assessment of chronological ageing were identified, and extrapolated to the context of photo-damaged skin. In particular, KANK4, ACAN, Col XI α1, and PSG1, were expressed at an increased level in both chronologically-aged and photo-damaged skin...
June 15, 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...
June 8, 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...
June 8, 2018: 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
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 30, 2018: Mechanisms of Ageing and Development
Jonas R Dias da Silva, Ivna Vidal Freire, Ícaro J S Ribeiro, Caroline Silva Dos Santos, Cezar Augusto Casotti, Djanilson Barbosa Dos Santos, Ana Angélica Leal Barbosa, Rafael Pereira
It is known that sarcopenia is a multifaceted phenomenon, which involves genetic, nutritional, hormonal and living habits aspects. Then, an integrated analysis, as a multivariate approach, could improve the comprehension about the determinants of sarcopenic state in old adults. The present study aimed to investigate the interaction among serum vitamin D, daily caloric and protein intake, lifestyle habits, ACE I/D gene polymorphism and sarcopenic state in community-dwelling old adults. One hundred one community-dwelling old adults were clinically stratified as sarcopenic or non-sarcopenic...
July 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...
July 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...
July 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...
July 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...
July 2018: Mechanisms of Ageing and Development
Olympia-Ekaterini Psathaki, Lena Dehnen, Paul S 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...
July 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)...
July 2018: Mechanisms of Ageing and Development
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