The glia doctrine: Addressing the role of glial cells in healthy brain ageing
Publication date: October 2013 Source:Mechanisms of Ageing and Development, Volume 134, Issue 10 Author(s): Erlend A. Nagelhus , Mahmood Amiry-Moghaddam , Linda H. Bergersen , Jan G. Bjaalie , Jens Eriksson , Vidar Gundersen , Trygve B. Leergaard , J. Preben Morth , Jon Storm-Mathisen , Reidun Torp , Kristine B. Walhovd , Tone Tønjum Glial cells in their plurality pervade the human brain and impact on brain structure and function. A principal component of the emerging glial doctrine is the hypothesis that astrocytes, the most abundant type of glial cells, trigger major molecular processes leading to brain ageing. ...
Source: Mechanisms of Ageing and Development - November 7, 2014 Category: Geriatrics Source Type: research

DNA damage response, bioenergetics, and neurological disease: The challenge of maintaining brain health in an aging human population
Publication date: October 2013 Source:Mechanisms of Ageing and Development, Volume 134, Issue 10 Author(s): Lene Juel Rasmussen , Yosef Shiloh , Linda H. Bergersen , Miriam Sander , Vilhelm A. Bohr , Tone Tønjum (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - November 7, 2014 Category: Geriatrics Source Type: research

A parallel randomized trial on the effect of a healthful diet on inflammageing and its consequences in European elderly people: Design of the NU-AGE dietary intervention study
Discussion The NU-AGE study is the first dietary intervention investigating the effect of a healthful diet providing targeted nutritional recommendations for optimal health and quality of life in apparently healthy European elderly. Results of this intervention will provide evidence on the effect of a healthful diet on the prevention of age related decline. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

The NIA Interventions Testing Program Announces the 2014 Solicitation of Proposals
Publication date: January 2014 Source:Mechanisms of Ageing and Development, Volume 135 (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Splicing factor 3B1 hypomethylation is associated with altered SF3B1 transcript expression in older humans
Publication date: January 2014 Source:Mechanisms of Ageing and Development, Volume 135 Author(s): Alice C. Holly , Luke C. Pilling , Dena Hernandez , Benjamin P. Lee , Andrew Singleton , Luigi Ferrucci , David Melzer , Lorna W. Harries Ageing in man is associated with changes to the splicing factor pool. A proportion of splicing factors are regulated during ageing by mechanisms involving the Ataxia Telangiectasia Mutated (ATM) gene, but the factors that determine the remaining proportion have yet to be identified. DNA methylation is known to be an important regulatory mechanism of gene expression. We assessed age-associa...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Crosstalk between mitochondrial stress signals regulates yeast chronological lifespan
Publication date: January 2014 Source:Mechanisms of Ageing and Development, Volume 135 Author(s): Elizabeth A. Schroeder , Gerald S. Shadel Mitochondrial DNA (mtDNA) exists in multiple copies per cell and is essential for oxidative phosphorylation. Depleted or mutated mtDNA promotes numerous human diseases and may contribute to aging. Reduced TORC1 signaling in the budding yeast, Saccharomyces cerevisiae, extends chronological lifespan (CLS) in part by generating a mitochondrial ROS (mtROS) signal that epigenetically alters nuclear gene expression. To address the potential requirement for mtDNA maintenance in this respon...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Natural killer cell development and maturation in aged mice
Publication date: January 2014 Source:Mechanisms of Ageing and Development, Volume 135 Author(s): Eleni Beli , David M. Duriancik , Jonathan F. Clinthorne , Taehyung Lee , Sungjin Kim , Elizabeth M. Gardner The effect of aging on natural killer cell homeostasis is not well studied in humans or in animal models. We compared natural killer (NK) cells from young and aged mice to investigate age-related defects in NK cell distribution and development. Our findings indicate aged mice have reduced NK cells in most peripheral tissues, but not in bone marrow. Reduction of NK cells in periphery was attributed to a reduction of th...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Stress and aging at the nuclear gateway
Publication date: January 2014 Source:Mechanisms of Ageing and Development, Volume 135 Author(s): Boris Fichtman , Amnon Harel The nuclear pore complex (NPC) is a massive molecular machine embedded in the nuclear envelope and controlling traffic into and out of the cell nucleus. Here, we describe some of the outstanding research questions concerning the NPC, its assembly and functions. We also discuss recent findings that link the NPC and its immediate surroundings to the process of cellular aging. Scaffold and barrier nucleoporins are two major types of protein building blocks that make up the NPC. Surprisingly, these t...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Age-related vascular gene expression profiling in mice
Publication date: January 2014 Source:Mechanisms of Ageing and Development, Volume 135 Author(s): Christos Rammos , Ulrike B. Hendgen-Cotta , Rene Deenen , Julia Pohl , Pia Stock , Christian Hinzmann , Malte Kelm , Tienush Rassaf Increasing age involves a number of detrimental changes in the cardiovascular system and particularly on the large arteries. It deteriorates vascular integrity and leads to increased vascular stiffness entailing hypertension with increased cardiovascular morbidity and mortality. The consequences of continuous oxidative stress and damages to biomolecules include altered gene expression, genomic i...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Cockayne Syndrome group B protein stimulates NEIL2 DNA glycosylase activity
Publication date: January 2014 Source:Mechanisms of Ageing and Development, Volume 135 Author(s): Maria D. Aamann , Christina Hvitby , Venkateswarlu Popuri , Meltem Muftuoglu , Lasse Lemminger , Cecilie K. Skeby , Guido Keijzers , Byungchan Ahn , Magnar Bjørås , Vilhelm A. Bohr , Tinna Stevnsner Cockayne Syndrome is a segmental premature aging syndrome, which can be caused by loss of function of the CSB protein. CSB is essential for genome maintenance and has numerous interaction partners with established roles in different DNA repair pathways including transcription coupled nucleotide excision repair and ba...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Healthy aging diets other than the Mediterranean: A focus on the Okinawan diet
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 Author(s): Donald Craig Willcox , Giovanni Scapagnini , Bradley J. Willcox The traditional diet in Okinawa is anchored by root vegetables (principally sweet potatoes), green and yellow vegetables, soybean-based foods, and medicinal plants. Marine foods, lean meats, fruit, medicinal garnishes and spices, tea, alcohol are also moderately consumed. Many characteristics of the traditional Okinawan diet are shared with other healthy dietary patterns, including the traditional Mediterranean diet, DASH diet, and Portfolio...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

The role of low-grade inflammation and metabolic flexibility in aging and nutritional modulation thereof: A systems biology approach
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 Author(s): Dulce Calçada , Dario Vianello , Enrico Giampieri , Claudia Sala , Gastone Castellani , Albert de Graaf , Bas Kremer , Ben van Ommen , Edith Feskens , Aurelia Santoro , Claudio Franceschi , Jildau Bouwman Aging is a biological process characterized by the progressive functional decline of many interrelated physiological systems. In particular, aging is associated with the development of a systemic state of low-grade chronic inflammation (inflammaging), and with progressive deterioration of metabol...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Adipose tissue, diet and aging
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 Author(s): Mauro Zamboni , Andrea P. Rossi , Francesco Fantin , Giulia Zamboni , Salvatore Chirumbolo , Elena Zoico , Gloria Mazzali Age related increase in body fat mass, visceral adipose tissue (AT), and ectopic fat deposition are strongly related to worse health conditions in the elderly. Moreover, with aging higher inflammation in adipose tissue may be observed and may contribute to inflammaging. Aging may significantly affect AT function by modifying the profile of adipokines produced by adipose cells, reducin...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Nutrition, diet and immunosenescence
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 Author(s): Mònica Maijó , Sarah J. Clements , Kamal Ivory , Claudio Nicoletti , Simon R. Carding Ageing is characterized by immunosenescence and the progressive decline in immunity in association with an increased frequency of infections and chronic disease. This complex process affects both the innate and adaptive immune systems with a progressive decline in most immune cell populations and defects in activation resulting in loss of function. Although host genetics and environmental factors, such as ...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Present and future of anti-ageing epigenetic diets
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 Author(s): Maria Giulia Bacalini , Simonetta Friso , Fabiola Olivieri , Chiara Pirazzini , Cristina Giuliani , Miriam Capri , Aurelia Santoro , Claudio Franceschi , Paolo Garagnani The rapid technological advancements achieved in the last years have boosted the progressive identification of age-associated epigenetic changes. These studies not only contribute to shed light on the molecular basis of ageing and age-related diseases but, given the plasticity of epigenetic modifications, also provide the basis for anti-...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Reprint of: Musculoskeletal system in the old age and the demand for healthy ageing biomarkers
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 Author(s): Sebastiano Collino , François-Pierre Martin , Leonidas G. Karagounis , Marie Noelle Horcajada , Sofia Moco , Claudio Franceschi , Martin Kussmann , Elizabeth Offord Population ageing has emerged as a major demographic trend worldwide due to improved health and longevity. This global ageing phenomenon will have a major impact on health-care systems worldwide due to increased morbidity and greater needs for hospitalization/institutionalization. As the ageing population increases worldwide, there is ...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Effect of resistance-type exercise training with or without protein supplementation on cognitive functioning in frail and pre-frail elderly: Secondary analysis of a randomized, double-blind, placebo-controlled trial
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 Author(s): Ondine van de Rest , Nikita L. van der Zwaluw , Michael Tieland , Jos J. Adam , Gert Jan Hiddink , Luc J.C. van Loon , Lisette C.P.G.M. de Groot Physical activity has been proposed as one of the most effective strategies to prevent cognitive decline. Protein supplementation may exert an additive effect. The effect of resistance-type exercise training with or without protein supplementation on cognitive functioning in frail and pre-frail elderly people was assessed in a secondary analysis. Two 24-week, do...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Nutrition and protein energy homeostasis in elderly
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 Author(s): Yves Boirie , Béatrice Morio , Elodie Caumon , Noël J. Cano Protein-energy homeostasis is a major determinant of healthy aging. Inadequate nutritional intakes and physical activity, together with endocrine disturbances are associated with of sarcopenia and frailty. Guidelines from scientific societies mainly address the quantitative aspects of protein and energy nutrition in elderly. Besides these quantitative aspects of protein load, perspective strategies to promote muscle protein synthesis...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Maintenance of a healthy trajectory of the intestinal microbiome during aging: A dietary approach
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 Author(s): Marco Candela , Elena Biagi , Patrizia Brigidi , Paul W. O’Toole , Willem M. De Vos Sharing an intense transgenomic metabolism with the host, the intestinal microbiota is an essential factor for several aspects of the human physiology. However, several age-related factors, such as changes diet, lifestyle, inflammation and frailty, force the deterioration of this intestinal microbiota–host mutualistic interaction, compromising the possibility to reach longevity. In this scenario, the NU-AGE pr...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Cognitive decline, dietary factors and gut–brain interactions
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 Author(s): Barbara Caracciolo , Weili Xu , Stephen Collins , Laura Fratiglioni Cognitive decline in elderly people often derives from the interaction between aging-related changes and age-related diseases and covers a large spectrum of clinical manifestations, from intact cognition through mild cognitive impairment and dementia. Epidemiological evidence supports the hypothesis that modifiable lifestyle-related factors are associated with cognitive decline, opening new avenues for prevention. Diet in particular has ...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Water-loss dehydration and aging
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 Author(s): Lee Hooper , Diane Bunn , Florence O. Jimoh , Susan J. Fairweather-Tait This review defines water-loss and salt-loss dehydration. For older people serum osmolality appears the most appropriate gold standard for diagnosis of water-loss dehydration, but clear signs of early dehydration have not been developed. In older adults, lower muscle mass, reduced kidney function, physical and cognitive disabilities, blunted thirst, and polypharmacy all increase dehydration risk. Cross-sectional studies suggest a wat...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Micronutrient–gene interactions related to inflammatory/immune response and antioxidant activity in ageing and inflammation. A systematic review
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 Author(s): Eugenio Mocchegiani , Laura Costarelli , Robertina Giacconi , Marco Malavolta , Andrea Basso , Francesco Piacenza , Rita Ostan , Elisa Cevenini , Efstathios S. Gonos , Daniela Monti Recent longitudinal studies in dietary daily intake in human centenarians have shown that a satisfactory content of some micronutrients within the cells maintain several immune functions, a low grade of inflammation and preserve antioxidant activity. Micronutrients (zinc, copper, selenium) play a pivotal role in maintaining a...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Iron status in the elderly
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 Author(s): Susan J. Fairweather-Tait , Anna A. Wawer , Rachel Gillings , Amy Jennings , Phyo K. Myint Iron deficiency anaemia is prevalent in older age, particularly after the age of 80. Serum ferritin concentrations also decline, although there is no evidence to suggest that changes in iron stores are an inevitable consequence of ageing. Chronic inflammation is a common condition in older people, making the measurement of iron status difficult, and it is likely that elevated levels of circulating hepcidin are resp...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Reprint of: A parallel randomized trial on the effect of a healthful diet on inflammageing and its consequences in European elderly people: Design of the NU-AGE dietary intervention study
Discussion The NU-AGE study is the first dietary intervention investigating the effect of a healthful diet providing targeted nutritional recommendations for optimal health and quality of life in apparently healthy European elderly. Results of this intervention will provide evidence on the effect of a healthful diet on the prevention of age related decline. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Combating inflammaging through a Mediterranean whole diet approach: The NU-AGE project's conceptual framework and design
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 Author(s): Aurelia Santoro , Elisa Pini , Maria Scurti , Giustina Palmas , Agnes Berendsen , Anna Brzozowska , Barbara Pietruszka , Anna Szczecinska , Noël Cano , Nathalie Meunier , C.P.G.M. de Groot , Edith Feskens , Susan Fairweather-Tait , Stefano Salvioli , Miriam Capri , Patrizia Brigidi , Claudio Franceschi The development of a chronic, low grade, inflammatory status named “inflammaging” is a major characteristic of ageing, which plays a critical role in the pathogenesis of age-related diseas...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Special Issue Title Page
Publication date: March–April 2014 Source:Mechanisms of Ageing and Development, Volumes 136–137 (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Nar1 deficiency results in shortened lifespan and sensitivity to paraquat that is rescued by increased expression of mitochondrial superoxide dismutase
Publication date: June 2014 Source:Mechanisms of Ageing and Development, Volume 138 Author(s): Wei Zhao , Bing Xiong Fang , Yu Jie Niu , Yi Na Liu , Bin Liu , Qi Peng , Jiang Bin Li , Brian M. Wasko , Joseph R. Delaney , Brian K. Kennedy , Yousin Suh , Zhong Jun Zhou , Matt Kaeberlein , Xin Guang Liu Saccharomyces cerevisiae Nar1p is an essential Fe/S protein that exhibits striking similarity to bacterial iron-only hydrogenases. Nar1p is required for the maturation of cytosolic and nuclear, but not of mitochondrial Fe/S proteins, and plays a role in modulating sensitivity to oxygen in both yeast and Caenorhabditis elegan...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

PPM1B depletion induces premature senescence in human IMR-90 fibroblasts
Publication date: June 2014 Source:Mechanisms of Ageing and Development, Volume 138 Author(s): Jeong Hyeon Park , Tracy K. Hale , Rebecca Jane Smith , Tian Yang p53 and NF-κB are key transcription factors in regulating the gene expression program of cellular and organismal senescence. PPM1B is a member of the protein phosphatase 2C family and plays a role in negatively regulating p53 and NF-κB thereby possibly attenuating the gene expression program of cellular senescence. Here, possible involvement of PPM1B in replicative senescence has been investigated using the in vitro aging model of IMR-90 cells. PPM1B ...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

The hallmarks of fibroblast ageing
Publication date: June 2014 Source:Mechanisms of Ageing and Development, Volume 138 Author(s): Julia Tigges , Jean Krutmann , Ellen Fritsche , Judith Haendeler , Heiner Schaal , Jens W. Fischer , Faiza Kalfalah , Hans Reinke , Guido Reifenberger , Kai Stühler , Natascia Ventura , Sabrina Gundermann , Petra Boukamp , Fritz Boege Ageing is influenced by the intrinsic disposition delineating what is maximally possible and extrinsic factors determining how that frame is individually exploited. Intrinsic and extrinsic ageing processes act on the dermis, a post-mitotic skin compartment mainly consisting of extracellular m...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Diet fatty acid profile, membrane composition and lifespan: An experimental study using the blowfly (Calliphora stygia)
We report three experiments using the blowfly Calliphora stygia, where this theory was tested by manipulation of dietary fat profile. Although the fat profile of the larval diet resulted in small alterations of individual membrane fatty acids, it had no effect on the peroxidation index (PI) of membrane lipids and furthermore had no effect on maximum lifespan. Similarly, manipulation of the fat profile of the adult diet resulted in small changes in individual fatty acids, but had no effect on the PI of membrane lipids. There was a small increase in maximum lifespan when adult diet was supplemented with PUFA in form of veget...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Aging effects on oxidative phosphorylation in rat adrenocortical mitochondria
Publication date: June 2014 Source:Mechanisms of Ageing and Development, Volume 138 Author(s): Paola Solinas , Hisashi Fujioka , Tomas Radivoyevitch , Bernard Tandler , Charles L. Hoppel Does aging in itself lead to alteration in adrenocortical mitochondrial oxidative phosphorylation? Mitochondria from Fischer 344 (F344) rats (6 and 24 months old), Brown Norway rats (6 and 32 months old) and F344-Brown Norway hybrid rats (6 and 30 months old) were compared. Mitochondria were isolated from extirpated adrenal cortex. The yields of mitochondria were quantitatively similar in all rat strains irrespective of age. In order to ...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

The N-glycan profile of placental membrane glycoproteins alters during gestation and aging
This study represents the first N-glycan profiling of placental cell membrane proteins. These data represent a basis for future research on the N-glycome of placental proteins in different (patho)physiological conditions. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Inflamm-aging does not simply reflect increases in pro-inflammatory markers
Publication date: July 2014 Source:Mechanisms of Ageing and Development, Volume 139 Author(s): Vincent Morrisette-Thomas , Alan A. Cohen , Tamàs Fülöp , Éléonor Riesco , Véronique Legault , Qing Li , Emmanuel Milot , Françis Dusseault-Bélanger , Luigi Ferrucci Many biodemographic studies use biomarkers of inflammation to understand or predict chronic disease and aging. Inflamm-aging, i.e. chronic low-grade inflammation during aging, is commonly characterized by pro-inflammatory biomarkers. However, most studies use just one marker at a time, sometimes leading to conflic...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Exercise enhances wound healing and prevents cancer progression during aging by targeting macrophage polarity
Publication date: July 2014 Source:Mechanisms of Ageing and Development, Volume 139 Author(s): Jorming Goh , Warren C. Ladiges Physical activity, which can include regular and repetitive exercise training, has been shown to decrease the incidence of age-related diseases. Aging is characterized by aberrant immune responses, including impaired wound healing and increased cancer risk. The behavior and polarized phenotype of tissue macrophages are distinct between young and old organisms. The balance of M1 and M2 macrophages is altered in the aged tissue microenvironment, with a tilt towards an M2-dominant macrophage populat...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Age-specific bone tumour incidence rates are governed by stem cell exhaustion influencing the supply and demand of progenitor cells
Publication date: July 2014 Source:Mechanisms of Ageing and Development, Volume 139 Author(s): Richard B. Richardson Knudson's carcinogenic model, which simulates incidence rates for retinoblastoma, provides compelling evidence for a two-stage mutational process. However, for more complex cancers, existing multistage models are less convincing. To fill this gap, I hypothesize that neoplasms preferentially arise when stem cell exhaustion creates a short supply of progenitor cells at ages of high proliferative demand. To test this hypothesis, published datasets were employed to model the age distribution of osteochondroma,...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Similar patterns of clonally expanded somatic mtDNA mutations in the colon of heterozygous mtDNA mutator mice and ageing humans
Publication date: July 2014 Source:Mechanisms of Ageing and Development, Volume 139 Author(s): Holly L. Baines , James B. Stewart , Craig Stamp , Anze Zupanic , Thomas B.L. Kirkwood , Nils-Göran Larsson , Douglass M. Turnbull , Laura C. Greaves Clonally expanded mitochondrial DNA (mtDNA) mutations resulting in focal respiratory chain deficiency in individual cells are proposed to contribute to the ageing of human tissues that depend on adult stem cells for self-renewal; however, the consequences of these mutations remain unclear. A good animal model is required to investigate this further; but it is unknown whether ...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Rapamycin prevents strong phosphorylation of p53 on serine 46 and attenuates activation of the p53 pathway in A549 lung cancer cells exposed to actinomycin D
Publication date: July 2014 Source:Mechanisms of Ageing and Development, Volume 139 Author(s): Małgorzata Krześniak , Artur Zajkowicz , Iwona Matuszczyk , Marek Rusin The activation of the p53 pathway by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a molecule that mimics metabolic stress, is attenuated by rapamycin, an inhibitor of mTOR kinase, immunosuppressant, and cancer drug. Rapamycin also extends lifespan in experimental animals. Because AICAR is a relatively weak activator of p53, we investigated whether stimulation of p53 by the strong activator actinomycin D is also sensitive to the inhibitory effect...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Relationship between heat shock protein 70 expression and life span in Daphnia
Publication date: July 2014 Source:Mechanisms of Ageing and Development, Volume 139 Author(s): Charles Schumpert , Indhira Handy , Jeffry L. Dudycha , Rekha C. Patel The longevity of an organism is directly related to its ability to effectively cope with cellular stress. Heat shock response (HSR) protects the cells against accumulation of damaged proteins after exposure to elevated temperatures and also in aging cells. To understand the role of Hsp70 in regulating life span of Daphnia, we examined the expression of Hsp70 in two ecotypes that exhibit strikingly different life spans. Daphnia pulicaria, the long lived ecoty...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Short-term rapamycin treatment in mice has few effects on the transcriptome of white adipose tissue compared to dietary restriction
Publication date: September 2014 Source:Mechanisms of Ageing and Development, Volume 140 Author(s): Wilson C. Fok , Carolina Livi , Alex Bokov , Zhen Yu , Yidong Chen , Arlan Richardson , Viviana I. Pérez Rapamycin, a drug that has been shown to increase lifespan in mice, inhibits the target of rapamycin (TOR) pathway, a major pathway that regulates cell growth and energy status. It has been hypothesized that rapamycin and dietary restriction (DR) extend lifespan through similar mechanisms/pathways. Using microarray analysis, we compared the transcriptome of white adipose tissue from mice fed rapamycin or DR-diet ...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Ageing-related responses to antiangiogenic effects of sunitinib in atherosclerosis-prone mice
Publication date: September 2014 Source:Mechanisms of Ageing and Development, Volume 140 Author(s): Brian Meehan , Delphine Garnier , Alexander Dombrovsky , Karrie Lau , Esterina D’Asti , Nathalie Magnus , Janusz Rak Antiangiogenic therapies in cancer exert their effects in the context of age-related comorbidities, which affect the entirety of the vascular system. Among those conditions, the impact of atherosclerosis is especially prevalent, but poorly understood, and not reflected in mouse models routinely used for testing antiangiogenic therapeutics. Our earlier work suggested that these obstacles can be overcome...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Dietary advanced glycation end products are associated with decline in memory in young elderly
Publication date: September 2014 Source:Mechanisms of Ageing and Development, Volume 140 Author(s): Rebecca K. West , Erin Moshier , Irit Lubitz , James Schmeidler , James Godbold , Weijing Cai , Jaime Uribarri , Helen Vlassara , Jeremy M. Silverman , Michal Schnaider Beeri We recently reported that serum methylglyoxal (sMG) is associated with a faster rate of decline in a global measure of cognition in the very elderly. We here provide for the first time evidence in which high levels of dietary AGE (dAGE) are associated with faster rate of decline in memory in 49 initially non-demented young elderly (p =0.012 in mixed r...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Epigenetic regulation of tissue factor inducibility in endothelial cell senescence
In this study, we show that senescent human umbilical vein endothelial cells lose their ability to induce tissue factor (TF), a transmembrane protein with important roles in hemostasis and cancer progression, in response to thrombin or – independently of cell-surface receptors – phorbol-12-myristate-13-acetate. This phenomenon could not be explained by senescence-related alterations in the downstream signal transduction cascade or by accelerated TF mRNA degradation. Rather, using chromatin immuno-precipitation we could show that loss of TF gene inducibility during senescence occurs following chromatin remodelli...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Trajectories of physiological dysregulation predicts mortality and health outcomes in a consistent manner across three populations
Publication date: Available online 20 October 2014 Source:Mechanisms of Ageing and Development Author(s): Emmanuel Milot , V. Morissette-Thomas , Qing Li , Linda P. Fried , Luigi Ferrucci , Alan A. Cohen Mechanistic and evolutionary perspectives both agree that aging involves multiple integrated biochemical networks in the organism. In particular, the homeostatic physiological dysregulation (PD) hypothesis contends that aging is caused by the progressive breakdown of key regulatory processes. However, nothing is yet known about the specifics of how PD changes with age and affects health. Using a recently validated measur...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Short and long telomeres increase risk of amnestic mild cognitive impairment
Publication date: Available online 22 October 2014 Source:Mechanisms of Ageing and Development Author(s): Rosebud O. Roberts , Lisa A. Boardman , Ruth H. Cha , V. Shane Pankratz , Ruth A. Johnson , Teresa J.H. Christianson , Lewis R. Roberts , Ronald C. Petersen Peripheral blood telomere length has been associated with age-related conditions including Alzheimer's disease (AD). This suggests that telomere length may identify subjects at increased risk of AD. Thus, we investigated the associations of peripheral blood telomere length with amnestic mild cognitive impairment (aMCI), a putative precursor of AD, among Mayo Clin...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

p16INK4A mediates age-related changes in mesenchymal stem cells derived from human dental pulp through the DNA damage and stress response
Publication date: November–December 2014 Source:Mechanisms of Ageing and Development, Volumes 141–142 Author(s): Xingmei Feng , Jing Xing , Guijuan Feng , Dan Huang , Xiaohui Lu , Suzhe Liu , Wei Tan , Liren Li , Zhifeng Gu Mesenchymal stem cells derived from human dental pulp (DP-MSCs) are characterized by self-renewal and multi-lineage differentiation, which play important roles in regenerative medicine. Autologous transfers, as non-immunogenic, constitute the safest approach in cellular transplantations. However, their use may be limited by age-related changes. In the study, we compared DP-MSCs isolated fr...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Mitochondrial chaperone TRAP1 activates the mitochondrial UPR and extends healthspan in Drosophila
Publication date: November–December 2014 Source:Mechanisms of Ageing and Development, Volumes 141–142 Author(s): Rehan M. Baqri , Arielle V. Pietron , Rewatee H. Gokhale , Brittany A. Turner , Laurie S. Kaguni , Alexander W. Shingleton , Sam Kunes , Kyle E. Miller The molecular mechanisms influencing healthspan are unclear but mitochondrial function, resistance to oxidative stress and proteostasis are recurring themes. Tumor necrosis factor Receptor Associated Protein 1 (TRAP1), the mitochondrial analog of Hsp75, regulates levels of reactive oxygen species in vitro and is found expressed at higher levels in t...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Lifelong maintenance of composition, function and cellular/subcellular distribution of proteasomes in human liver
Publication date: November–December 2014 Source:Mechanisms of Ageing and Development, Volumes 141–142 Author(s): Elena Bellavista , Morena Martucci , Francesco Vasuri , Aurelia Santoro , Michele Mishto , Alexander Kloss , Elisa Capizzi , Alessio Degiovanni , Catia Lanzarini , Daniel Remondini , Alessandro Dazzi , Sara Pellegrini , Matteo Cescon , Miriam Capri , Stefano Salvioli , Antonia D’Errico-Grigioni , Burkhardt Dahlmann , Gian Luca Grazi , Claudio Franceschi Owing to organ shortage, livers from old donors are increasingly used for transplantation. The function and duration of such transplanted liv...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Escherichia coli carbon source metabolism affects longevity of its predator Caenorhabditis elegans
Publication date: November–December 2014 Source:Mechanisms of Ageing and Development, Volumes 141–142 Author(s): Ana María Brokate-Llanos , Andrés Garzón , Manuel J. Muñoz Nutrition is probably the most determinant factor affecting aging. Microorganisms of the intestinal flora lay in the interface between available nutrients and nutrients that are finally absorbed by multicellular organisms. They participate in the processing and transformation of these nutrients in a symbiotic or commensalistic relationship. In addition, they can also be pathogens. Alive Escherichia coli OP50 are ...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Vascular and extravascular distribution of the ATP-binding cassette transporters ABCB1 and ABCC1 in aged human brain and pituitary
Publication date: November–December 2014 Source:Mechanisms of Ageing and Development, Volumes 141–142 Author(s): Hans-Gert Bernstein , Gloria Hölzl , Henrik Dobrowolny , Jens Hildebrandt , Kurt Trübner , Markus Krohn , Bernhard Bogerts , Jens Pahnke ATP-binding cassette (ABC) transporters play an increasing role in the understanding of pathologic peptide deposition in neurodegenerative diseases (NDs), such as Alzheimer's and Parkinson's. To describe the location of the most important ABC transporters for NDs in human brain tissue, we investigated ABCB1 and ABCC1 immunohistologically in the adult hum...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research

Analyzing feed-forward loop relationship in aging phenotypes: Physical activity and physical performance
We present evidence of feed-forward loop relationships and positive association between physical activity and performance levels, which are components of frailty, using measures from 431 high functioning women initially aged 70–79 years followed over 7 visits. Physical activity levels were assessed using a questionnaire. Grip strength was measured using a handheld dynamometer and usual walking speed was measured over 4-m. The results suggest that a reduction in physical activity would not only degrade physical performance, but it would further reduce physical activity through declines in physical performance. As both...
Source: Mechanisms of Ageing and Development - November 3, 2014 Category: Geriatrics Source Type: research