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Ageing Research Reviews

L J Niedernhofer, J L Kirkland, W Ladiges
The first clinical trial aimed at targeting fundamental processes of aging will soon be launched (TAME: Targeting Aging with Metformin). In its wake is a robust pipeline of therapeutic interventions that have been demonstrated to extend lifespan or healthspan of preclinical models, including rapalogs, antioxidants, anti-inflammatory agents, and senolytics. This ensures that if the TAME trial is successful, numerous additional clinical trials are apt to follow. But a significant impediment to these trials remains the question of what endpoints should be measured? The design of the TAME trial very cleverly skirts around this based on the fact that there are decades of data on metformin in humans, providing unequaled clarity of what endpoints are most likely to yield a positive outcome...
October 6, 2016: Ageing Research Reviews
David Vauzour, Maria Camprubi-Robles, Sophie Miquel-Kergoat, Cristina Andres-Lacueva, Diána Bánáti, Pascale Barberger-Gateau, Gene L Bowman, Laura Caberlotto, Robert Clarke, Eef Hogervorst, Amanda J Kiliaan, Ugo Lucca, Claudine Manach, Anne-Marie Minihane, Ellen Siobhan Mitchell, Robert Perneczky, Hugh Perry, Anne-Marie Roussel, Jeroen Schuermans, John Sijben, Jeremy P E Spencer, Sandrine Thuret, Ondine van de Rest, Maurits Vandewoude, Keith Wesnes, Robert J Williams, Robin S B Williams, Maria Ramirez
As people age they become increasingly susceptible to chronic and extremely debilitating brain diseases. The precise cause of the neuronal degeneration underlying these disorders, and indeed normal brain ageing remains however elusive. Considering the limits of existing preventive methods, there is a desire to develop effective and safe strategies. Growing preclinical and clinical research in healthy individuals or at the early stage of cognitive decline has demonstrated the beneficial impact of nutrition on cognitive functions...
October 3, 2016: Ageing Research Reviews
Alexander Kalinkovich, Gregory Livshits
Sarcopenia, an age-associated decline in skeletal muscle mass coupled with functional deterioration, may be exacerbated by obesity leading to higher disability, frailty, morbidity and mortality rates. In the combination of sarcopenia and obesity, the state called sarcopenic obesity (SOB), some key age- and obesity-mediated factors and pathways may aggravate sarcopenia. This review will analyze the mechanisms underlying the pathogenesis of SOB. In obese adipose tissue (AT), adipocytes undergo hypertrophy, hyperplasia and activation resulted in accumulation of pro-inflammatory macrophages and other immune cells as well as dysregulated production of various adipokines that together with senescent cells and the immune cell-released cytokines and chemokines create a local pro-inflammatory status...
October 1, 2016: Ageing Research Reviews
Shambhunath Bose, Jungsook Cho
Protein misfolding, which is known to cause several serious diseases, is an emerging field that addresses multiple therapeutic areas. Misfolding of a disease-specific protein in the central nervous system ultimately results in the formation of toxic aggregates that may accumulate in the brain, leading to neuronal cell death and dysfunction, and associated clinical manifestations. A large number of neurodegenerative diseases in humans, including Alzheimer's, Parkinson's, Huntington's, and prion diseases, are primarily caused by protein misfolding and aggregation...
October 1, 2016: Ageing Research Reviews
Steven H Graham, Hao Liu
The ubiquitin proteasome pathway (UPP) is essential for removing abnormal proteins and preventing accumulation of potentially toxic proteins within the neuron. UPP dysfunction occurs with normal aging and is associated with abnormal accumulation of protein aggregates within neurons in neurodegenerative diseases. Ischemia disrupts UPP function and thus may contribute to UPP dysfunction seen in the aging brain and in neurodegenerative diseases. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1), an important component of the UPP in the neuron, is covalently modified and its activity inhibited by reactive lipids produced after ischemia...
October 1, 2016: Ageing Research Reviews
Neal B McKinnon, Denise M Connelly, Charles L Rice, Susan W Hunter, Timothy J Doherty
Although much of the literature on neuromuscular changes with aging has focused on loss of muscle mass and isometric strength, deficits in muscle power are more pronounced with aging and may be a more sensitive measure of neuromuscular degeneration. This review aims to identify the adaptations to the neuromuscular system with aging, with specific emphasis on changes that result in decreased muscle power. We discuss how these changes in neuromuscular performance can affect mobility, and ultimately contribute to an increased risk for falls in older adults...
September 30, 2016: Ageing Research Reviews
Wei Cai, Kai Zhang, Peiying Li, Ling Zhu, Jing Xu, Boyu Yang, Xiaoming Hu, Zhengqi Lu, Jun Chen
Current understanding on the mechanisms of brain injury and neurodegeneration highlights an appreciation of multicellular interactions within the neurovascular unit (NVU), which include the evolution of blood-brain barrier (BBB) damage, neuronal cell death or degeneration, glial reaction, and immune cell infiltration. Aging is an important factor that influences the integrity of the NVU. The age-related physiological or pathological changes in the cellular components of the NVU have been shown to increase the vulnerability of the NVU to ischemia/reperfusion injury or neurodegeneration, and to result in deteriorated brain damage...
September 30, 2016: Ageing Research Reviews
Robert M Brosh
No abstract text is available yet for this article.
September 29, 2016: Ageing Research Reviews
Thomas J LaRocca, Christopher R Martens, Douglas R Seals
As our world's population ages, cardiovascular diseases (CVD) will become an increasingly urgent public health problem. A key antecedent to clinical CVD and many other chronic disorders of aging is age-related arterial dysfunction, characterized by increased arterial stiffness and impaired arterial endothelial function. Accumulating evidence demonstrates that diet and nutrition may favorably modulate these arterial functions with aging, but many important questions remain. In this review, we will summarize the available information on dietary patterns and nutritional factors that have been studied for their potential to reduce arterial stiffness and improve endothelial function with age, with an emphasis on: 1) underlying physiological mechanisms, and 2) emerging areas of research on nutrition and arterial aging that may hold promise for preventing age-related CVD...
September 28, 2016: Ageing Research Reviews
Rik Mencke, Jan-Luuk Hillebrands
Klotho is an anti-ageing protein that functions in many pathways that govern ageing, like regulation of phosphate homeostasis, insulin signaling, and Wnt signaling. Klotho expression levels and levels in blood decline during ageing. The vascular phenotype of Klotho deficiency features medial calcification, intima hyperplasia, endothelial dysfunction, arterial stiffening, hypertension, and impaired angiogenesis and vasculogenesis, with characteristics similar to aged human arteries. Klotho-deficient phenotypes can be prevented and rescued by Klotho gene expression or protein supplementation...
September 27, 2016: Ageing Research Reviews
Tuo Yang, Yang Sun, Zhengyu Lu, Rehana K Leak, Feng Zhang
As human life expectancy rises, the aged population will increase. Aging is accompanied by changes in tissue structure, often resulting in functional decline. For example, aging within blood vessels contributes to a decrease in blood flow to important organs, potentially leading to organ atrophy and loss of function. In the central nervous system, cerebral vascular aging can lead to loss of the integrity of the blood-brain barrier, eventually resulting in cognitive and sensorimotor decline. One of the major of types of cognitive dysfunction due to chronic cerebral hypoperfusion is vascular cognitive impairment and dementia (VCID)...
September 27, 2016: Ageing Research Reviews
Jane L Tarry-Adkins, Susan E Ozanne
The prevalence of age-associated disease is increasing at a striking rate globally. It is known that a strong association exists between a suboptimal maternal and/or early-life environment and increased propensity of developing age-associated disease, including cardiovascular disease (CVD), type-2 diabetes (T2D) and obesity. The dissection of underlying molecular mechanisms to explain this phenomenon, which is known as 'developmental programming' is still emerging; however three common mechanisms have emerged in many models of developmental programming...
September 1, 2016: Ageing Research Reviews
Yan Yin, George Sun, Eric Li, Kirill Kiselyov, Dandan Sun
Autophagy is a highly controlled lysosome-mediated function in eukaryotic cells to eliminate damaged or aged long-lived proteins and organelles. It is required for restoring cellular homeostasis in cell survival under multiple stresses. Autophagy is known to be a double-edged sword because too much activation or inhibition of autophagy can disrupt homeostatic degradation of protein and organelles within the brain and play a role in neuronal cell death. Many factors affect autophagy flux function in the brain, including endoplasmic reticulum (ER) stress, oxidative stress, and aging...
September 1, 2016: Ageing Research Reviews
Holly M Brown-Borg, Rochelle Buffenstein
With few exceptions, nutritional and dietary interventions generally impact upon both old-age quality of life and longevity. The life prolonging effects, commonly observed with dietary restriction reportedly are linked to alterations in protein intake and specifically limiting the dietary intake of certain essential amino acids. There is however a paucity of data methodically evaluating the various essential amino acids on health- and lifespan and the mechanisms involved. Rodent diets containing either lower methionine content, or tryptophan, than that found in commercially available chow, appear to elicit beneficial effects...
August 25, 2016: Ageing Research Reviews
Jasper Most, Valeria Tosti, Leanne M Redman, Luigi Fontana
Calorie restriction (CR), a nutritional intervention of reduced energy intake but with adequate nutrition, has been shown to extend healthspan and lifespan in rodent and primate models. Accumulating data from observational and randomized clinical trials indicate that CR in humans results in some of the same metabolic and molecular adaptations that have been shown to improve health and retard the accumulation of molecular damage in animal models of longevity. In particular, moderate CR in humans ameliorates multiple metabolic and hormonal factors that are implicated in the pathogenesis of type 2 diabetes, cardiovascular diseases, and cancer, the leading causes of morbidity, disability and mortality...
August 17, 2016: Ageing Research Reviews
Emyr Lloyd-Evans, Luke Haslett
Lysosomal storage diseases and diseases of ageing share many features both at the physiological level and with respect to the mechanisms that underlie disease pathogenesis. Although the exact pathophysiology is not exactly the same, it is astounding how many similar pathways are altered in all of these diseases. The aim of this review is to provide a summary of the shared disease mechanisms, outlining the similarities and differences and how genetics, insight into rare diseases and functional research has changed our perspective on the causes underlying common diseases of ageing...
August 8, 2016: Ageing Research Reviews
Ajoy C Karikkineth, Morten Scheibye-Knudsen, Elayne Fivenson, Deborah L Croteau, Vilhelm A Bohr
Cockayne syndrome (CS) is a disorder characterized by a variety of clinical features including cachectic dwarfism, severe neurological manifestations including microcephaly and cognitive deficits, pigmentary retinopathy, cataracts, sensorineural deafness, and ambulatory and feeding difficulties, leading to death by 12 years of age on average. It is an autosomal recessive disorder, with a prevalence of approximately 2.5 per million. There are several phenotypes (1, 2 and 3) and complementation groups (CSA and CSB), and overlaps with xeroderma pigmentosum (XP)...
August 6, 2016: Ageing Research Reviews
Maria Xilouri, Leonidas Stefanis
The major lysosomal proteolytic pathways essential for maintaining proper cellular homeostasis are macroautophagy, chaperone-mediated autophagy (CMA) and microautophagy. What differentiates CMA from the other types of autophagy is the fact that it does not involve vesicle formation; the unique feature of this pathway is the selective targeting of substrate proteins containing a CMA-targeting motif and the direct translocation into the lysosomal lumen, through the aid of chaperones/co-chaperones localized both at the cytosol and the lysosomes...
July 30, 2016: Ageing Research Reviews
Pinar Soysal, Brendon Stubbs, Paola Lucato, Claudio Luchini, Marco Solmi, Roberto Peluso, Giuseppe Sergi, Ahmet Turan Isik, Enzo Manzato, Stefania Maggi, Marcello Maggio, A Matthew Prina, Theodore D Cosco, Yu-Tzu Wu, Nicola Veronese
The pathogenesis of frailty and the role of inflammation is poorly understood. We examined the evidence considering the relationship between inflammation and frailty through a systematic review and meta-analysis. A systematic literature search of papers providing data on inflammatory biomarkers and frailty was carried out in major electronic databases from inception until May 2016. From 1856 initial hits, 35 studies (32 cross-sectional studies n=3232 frail, n=11,483 pre-frail and n=8522 robust, and 563 pre-frail+robust; 3 longitudinal studies n=3402 participants without frailty at baseline) were meta-analyzed...
November 2016: Ageing Research Reviews
Alexander M Vaiserman, Oleh V Lushchak, Alexander K Koliada
Life expectancy has grown dramatically in modern times. This increase, however, is not accompanied by the same increase in healthspan. Efforts to extend healthspan through pharmacological agents targeting aging-related pathological changes are now in the spotlight of geroscience, the main idea of which is that delaying of aging is far more effective than preventing the particular chronic disorders. Currently, anti-aging pharmacology is a rapidly developing discipline. It is a preventive field of health care, as opposed to conventional medicine which focuses on treating symptoms rather than root causes of illness...
November 2016: Ageing Research Reviews
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