Structural neuroimaging in preclinical dementia: from microstructural deficits and grey matter atrophy to macroscale connectomic changes.
Abstract The last decade has witnessed a proliferation of neuroimaging studies characterising brain changes associated with Alzheimer's disease (AD), where both widespread atrophy and 'signature' brain regions have been implicated. In parallel, a prolonged latency period has been established in AD, with abnormal cerebral changes beginning many years before symptom onset. This raises the possibility of early therapeutic intervention, even before symptoms, when treatments could have the greatest effect on disease-course modification. Two important prerequisites of this endeavour are (1) accurate characterisation or ...
Source: Ageing Research Reviews - October 20, 2016 Category: Genetics & Stem Cells Authors: Mak E, Gabel S, Mirette H, Su L, Williams GB, Waldman A, Wells K, Ritchie K, Ritchie C, O'Brien J Tags: Ageing Res Rev Source Type: research

Sex Differences in the Prevalence and Incidence of Mild Cognitive Impairment: A Meta-Analysis.
CONCLUSION: The only statistically significant finding emerging from this study was that women have a higher prevalence of non-amnestic MCI. To better understand sex differences in the preclinical stages of dementia, studies must better characterize the etiology of the cognitive impairment. PMID: 27771474 [PubMed - as supplied by publisher] (Source: Ageing Research Reviews)
Source: Ageing Research Reviews - October 18, 2016 Category: Genetics & Stem Cells Authors: Au B, Dale-McGrath S, Tierney MC Tags: Ageing Res Rev Source Type: research

Molecular pathology endpoints useful for aging studies.
MOLECULAR PATHOLOGY ENDPOINTS USEFUL FOR AGING STUDIES. Ageing Res Rev. 2016 Oct 6;: Authors: Niedernhofer LJ, Kirkland JL, Ladiges W Abstract 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. ...
Source: Ageing Research Reviews - October 5, 2016 Category: Genetics & Stem Cells Authors: Niedernhofer LJ, Kirkland JL, Ladiges W Tags: Ageing Res Rev Source Type: research

Nutrition for the ageing brain: towards evidence for an optimal diet.
Sijben J, Spencer JP, Thuret S, van de Rest O, Vandewoude M, Wesnes K, Williams RJ, Williams RS, Ramirez M Abstract 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 nutr...
Source: Ageing Research Reviews - October 2, 2016 Category: Genetics & Stem Cells Authors: Vauzour D, Robles MC, Miquel-Kergoat S, Andres-Lacueva C, Bánáti D, Barberger-Gateau P, Bowman GL, Caberlotto L, Clarke R, Hogervorst E, Kiliaan AJ, Lucca U, Manach C, Minihane AM, Mitchell ES, Perneczky R, Perry H, Roussel AM, Schuermans J, Sijben J, S Tags: Ageing Res Rev Source Type: research

Life and death in the trash heap: the ubiquitin proteasome pathway and UCHL1 in brain aging, neurodegenerative disease and cerebral Ischemia.
Abstract 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 lipid...
Source: Ageing Research Reviews - September 30, 2016 Category: Genetics & Stem Cells Authors: Graham SH, Liu H Tags: Ageing Res Rev Source Type: research

Targeting chaperones, heat shock factor-1, and unfolded protein response: Promising therapeutic approaches for neurodegenerative disorders.
Abstract 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. Notably, the cellular system is equipped wi...
Source: Ageing Research Reviews - September 30, 2016 Category: Genetics & Stem Cells Authors: Bose S, Cho J Tags: Ageing Res Rev Source Type: research

Sarcopenic obesity or obese sarcopenia: a cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis.
Abstract 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 c...
Source: Ageing Research Reviews - September 30, 2016 Category: Genetics & Stem Cells Authors: Kalinkovich A, Livshits G Tags: Ageing Res Rev Source Type: research

ER stress and impaired autophagy flux in neuronal degeneration and brain injury.
Discussion of DHA functions is focused on modulating ER stress and autophagy in regard to its neuroprotection and anti-tumor functions. PMID: 27594375 [PubMed - as supplied by publisher] (Source: Ageing Research Reviews)
Source: Ageing Research Reviews - August 31, 2016 Category: Genetics & Stem Cells Authors: Yin Y, Sun G, Li E, Kiselyov K, Sun D Tags: Ageing Res Rev Source Type: research

Nutrition in early life and age-associated diseases.
Abstract 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. These mechanisms are a) changes in tissue structure,...
Source: Ageing Research Reviews - August 31, 2016 Category: Genetics & Stem Cells Authors: Tarry-Adkins JL, Ozanne SE Tags: Ageing Res Rev Source Type: research

Inflammation and frailty in the elderly: A systematic review and meta-analysis.
In conclusion, frailty and pre-frailty are associated with higher inflammatory parameters and in particular CRP and IL-6. Further longitudinal studies are needed. PMID: 27592340 [PubMed - as supplied by publisher] (Source: Ageing Research Reviews)
Source: Ageing Research Reviews - August 30, 2016 Category: Genetics & Stem Cells Authors: Soysal P, Stubbs B, Lucato P, Luchini C, Solmi M, Peluso R, Sergi G, Isik AT, Manzato E, Maggi S, Maggio M, Prina AM, Cosco TD, Wu YT, Veronese N Tags: Ageing Res Rev Source Type: research

Cutting back on the essentials; can manipulating intake of specific amino acids modulate health and lifespan?
Abstract 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 elici...
Source: Ageing Research Reviews - August 24, 2016 Category: Genetics & Stem Cells Authors: Brown-Borg HM, Buffenstein R Tags: Ageing Res Rev Source Type: research

Calorie restriction in humans: An update.
Abstract 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, ...
Source: Ageing Research Reviews - August 16, 2016 Category: Genetics & Stem Cells Authors: Most J, Tosti V, Redman LM, Fontana L Tags: Ageing Res Rev Source Type: research

Anti-aging pharmacology: promises and pitfalls.
Abstract 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 ...
Source: Ageing Research Reviews - August 10, 2016 Category: Genetics & Stem Cells Authors: Vaiserman AM, Lushchak OV, Koliada AK Tags: Ageing Res Rev Source Type: research

Skin Aging and Oxidative Stress: Equol's Anti-Aging Effects via Biochemical and Molecular Mechanisms.
Abstract Oxygen in biology is essential for life. It comes at a cost during normal cellular function, where reactive oxygen species (ROS) are generated by oxidative metabolism. Human skin exposed to solar ultra-violet radiation (UVR) dramatically increases ROS production/oxidative stress. It is important to understand the characteristics of human skin and how chronological (intrinsic) aging and photo-aging (extrinsic aging) occur via the impact of ROS production by cascade signaling pathways. The goal is to oppose or neutralize ROS insults to maintain good dermal health. Botanicals, as active ingredients, represen...
Source: Ageing Research Reviews - August 8, 2016 Category: Genetics & Stem Cells Authors: Lephart ED Tags: Ageing Res Rev Source Type: research

The lysosomal storage disease continuum with ageing-related neurodegenerative disease.
Abstract 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. The lysosome should no lo...
Source: Ageing Research Reviews - August 7, 2016 Category: Genetics & Stem Cells Authors: Lloyd-Evans E, Haslett L Tags: Ageing Res Rev Source Type: research

Cockayne syndrome: Clinical features, model systems and pathways.
Abstract 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). It has been considered a progeria, and many of...
Source: Ageing Research Reviews - August 5, 2016 Category: Genetics & Stem Cells Authors: Karikkineth AC, Scheibye-Knudsen M, Fivenson E, Croteau DL, Bohr VA Tags: Ageing Res Rev Source Type: research

Chaperone mediated autophagy in aging: Starve to prosper.
Abstract 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. CMA operates at basal conditions in most mammalian cell models ...
Source: Ageing Research Reviews - July 29, 2016 Category: Genetics & Stem Cells Authors: Xilouri M, Stefanis L Tags: Ageing Res Rev Source Type: research

Cerebral Circulation in Aging.
Abstract Cerebral circulation is known to be protected by the regulatory function against the hypoperfusion that will affect the cognitive function as a result of brain ischemia and energy failure. The regulatory function includes cerebrovascular autoregulation, chemical control, metabolic control, and neurogenic control, and those compensatory mechanisms can be influenced by hypertension, atherosclerosis, cardiac diseases, cerebrovascular diseases and aging. On the other hand, large and/or small infarction, intracranial hemorrhage, subarachnoid hemorrhage, atherosclerosis, amylod angiopathy are also more directly...
Source: Ageing Research Reviews - July 29, 2016 Category: Genetics & Stem Cells Authors: Nagata K, Yamazaki T, Takano D, Maeda T, Fujimaki Y, Nakase T, Sato Y Tags: Ageing Res Rev Source Type: research

Targeting mTOR signaling by polyphenols: a new therapeutic target for ageing.
Abstract Current aging research is aimed not only at the promotion of longevity, but also at improving ‎health span‎ through the‎ discovery and development‎ of new therapeutic strategies‎‏‎ by investigating ‎molecular and ‎cellular ‎pathways involved in cellular senescence.‎ Understanding the mechanism of action ‎of ‎polyphenolic compounds targeting mTOR (mechanistic target of rapamycin) and related pathways opens up new directions ‎‎to revolutionize ways to slow down the ‎onset and development of age-dependent degeneration. Herein, we will ‎discu...
Source: Ageing Research Reviews - July 20, 2016 Category: Genetics & Stem Cells Authors: Pazoki-Toroudi H, Amani H, Ajami M, Nabavi SF, Braidy N, Devi KP, Nabavi SM Tags: Ageing Res Rev Source Type: research

The more the better? A meta-analysis on effects of combined cognitive and physical intervention on cognition in healthy older adults.
Abstract Both cognitive intervention and physical exercise benefit cognitive function in older adults. It has been suggested that combined cognitive and physical intervention may induce larger effects than cognitive or physical intervention alone, but existing literature has shown mixed results. This meta-analysis aimed at assessing the efficacy of combined intervention on cognition by comparing combined intervention to control group, cognitive intervention and physical exercise. Eligible studies were controlled trials examining the effects of combined intervention on cognition in older adults without known cognit...
Source: Ageing Research Reviews - July 12, 2016 Category: Genetics & Stem Cells Authors: Zhu X, Yin S, Lang M, He R, Li J Tags: Ageing Res Rev Source Type: research

Hutchinson-Gilford Progeria Syndrome: a premature aging disease caused by LMNA gene mutations.
Abstract Products of the LMNA gene, primarily lamin A and C, are key components of the nuclear lamina, a proteinaceous meshwork that underlies the inner nuclear membrane and is essential for proper nuclear architecture. Alterations in lamin A and C that disrupt the integrity of the nuclear lamina affect a whole repertoire of nuclear functions, causing cellular decline. In humans, hundreds of mutations in the LMNA gene have been identified and correlated with over a dozen degenerative disorders, referred to as laminopathies. These diseases include neuropathies, muscular dystrophies, lipodystrophies, and premature a...
Source: Ageing Research Reviews - June 28, 2016 Category: Genetics & Stem Cells Authors: Gonzalo S, Kreienkamp R, Askjaer P Tags: Ageing Res Rev Source Type: research

Nutritional strategies to optimise cognitive function in the aging brain.
Abstract Old age is the greatest risk factor for most neurodegenerative diseases. During recent decades there have been major advances in understanding the biology of aging, and the development of nutritional interventions that delay aging including calorie restriction (CR) and intermittent fasting (IF), and chemicals that influence pathways linking nutrition and aging processes. CR influences brain aging in many animal models and recent findings suggest that dietary interventions can influence brain health and dementia in older humans. The role of individual macronutrients in brain aging also has been studied, wi...
Source: Ageing Research Reviews - June 25, 2016 Category: Genetics & Stem Cells Authors: Wahl D, Cogger VC, Solon-Biet SM, Waern RV, Gokarn R, Pulpitel T, Cabo R, Mattson MP, Raubenheimer D, Simpson SJ, Le Couteur DG Tags: Ageing Res Rev Source Type: research

A synopsis on Aging - theories, mechanisms and future prospects.
Abstract Answering the question as to why we age is tantamount to answering the question of what is life itself. There are countless theories as to why and how we age, but, until recently, the very definition of aging - senescence - was still uncertain. Here, we summarize the main views of the different models of senescence, with a special emphasis on the biochemical processes that accompany aging. Though inherently complex, aging is characterized by numerous changes that take place at different levels of the biological hierarchy. We therefore explore some of the most relevant changes that take place during aging ...
Source: Ageing Research Reviews - June 24, 2016 Category: Genetics & Stem Cells Authors: da Costa JP, Vitorino R, Silva GM, Vogel C, Duarte AC, Rocha-Santos T Tags: Ageing Res Rev Source Type: research

Cystatin C in aging and in Alzheimer's disease.
Abstract Under normal conditions, the function of catalytically active proteases is regulated, in part, by their endogenous inhibitors, and any change in the synthesis and/or function of a protease or its endogenous inhibitors may result in inappropriate protease activity. Altered proteolysis as a result of an imbalance between active proteases and their endogenous inhibitors can occur during normal aging, and such changes have also been associated with multiple neuronal diseases, including Amyotrophic Lateral Sclerosis (ALS), rare heritable neurodegenerative disorders, ischemia, some forms of epilepsy, and Alzhei...
Source: Ageing Research Reviews - June 18, 2016 Category: Genetics & Stem Cells Authors: Mathews PM, Levy E Tags: Ageing Res Rev Source Type: research

The emerging role of Notch pathway in ageing: focus on the related mechanisms in age-related diseases.
Abstract Notch signaling is an evolutionarily conserved pathway, which is fundamental for the development of all tissues, organs and systems of human body. Recently, a considerable and still growing number of studies have highlighted the contribution of Notch signaling in various pathological processes of the adult life, such as age-related diseases. In particular, the Notch pathway has emerged as major player in the maintenance of tissue specific homeostasis, through the control of proliferation, migration, phenotypes and functions of tissue cells, as well as in the cross-talk between inflammatory cells and the i...
Source: Ageing Research Reviews - June 16, 2016 Category: Genetics & Stem Cells Authors: Balistreri CR, Madonna R, Melino G, Caruso C Tags: Ageing Res Rev Source Type: research

Can 'calpain-cathepsin hypothesis' explain Alzheimer neuronal death?
Abstract Neurons are highly specialized post-mitotic cells, so their homeostasis and survival depend on the tightly-regulated, continuous protein degradation, synthesis, and turnover. In neurons, autophagy is indispensable to facilitate recycling of long-lived, damaged proteins and organelles in a lysosome-dependent manner. Since lysosomal proteolysis under basal conditions performs an essential housekeeping function, inhibition of the proteolysis exacerbates level of neurodegeneration. The latter is characterized by an accumulation of abnormal proteins or organelles within autophagic vacuoles which reveal as 'gra...
Source: Ageing Research Reviews - June 11, 2016 Category: Genetics & Stem Cells Authors: Yamashima T Tags: Ageing Res Rev Source Type: research

Aging in Rothmund-Thomson Syndrome and Related RECQL4 Genetic Disorders.
Abstract Rothmund-Thomson Syndrome (RTS) is a rare autosomal recessive disease which manifests several clinical features of accelerated aging. These findings include atrophic skin and pigment changes, alopecia, osteopenia, cataracts, and an increased incidence of cancer for patients carrying RECQL4 germline mutations. Mutations in RECQL4 are responsible for the majority of cases of RTS. RECQL4 belongs to RECQ DNA helicase family which has been shown to participate in many aspects of DNA metabolism. In the past several years, accumulated evidence indicates that RECQL4 is important not only in cancer development but...
Source: Ageing Research Reviews - June 6, 2016 Category: Genetics & Stem Cells Authors: Lu L, Jin W, Wang LL Tags: Ageing Res Rev Source Type: research

Macular thickness and volume in the elderly: a systematic review.
en TL Abstract Ageing leads to a number of changes in the body including the macula. Detailed imaging using optical coherence tomography have enabled in vivo studies of how macula changes with age. Here we systematically review 49 studies (9,115 participants and 11,577 eyes) to provide an overview of how ageing manifests in the macula of the elderly focusing on clinical relevant measures that are thicknesses and volumes of different macular areas. Ageing seems to increase center point foveal thickness. Ageing does not seem to change the center subfield thickness significantly. Ageing decreases the inner and outer ...
Source: Ageing Research Reviews - May 31, 2016 Category: Genetics & Stem Cells Authors: Subhi Y, Forshaw T, Sørensen TL Tags: Ageing Res Rev Source Type: research

From DNA damage to functional changes of the trabecular meshwork in aging and glaucoma.
tti A Abstract Glaucoma is a degenerative disease of the eye. Both the anterior and posterior segments of the eye are affected, extensive damage being detectable in the trabecular meshwork and the inner retina-central visual pathway complex. Oxidative stress is claimed to be mainly responsible for molecular damage in the anterior chamber. Indeed, oxidation harms the trabecular meshwork, leading eventually to endothelial cell decay, tissue malfunction, subclinical inflammation, changes in the extracellular matrix and cytoskeleton, altered motility, reduced outflow facility and (ultimately) increased IOP. Moreover, ...
Source: Ageing Research Reviews - May 26, 2016 Category: Genetics & Stem Cells Authors: Saccà SC, Gandolfi S, Bagnis A, Manni G, Damonte G, Traverso CE, Izzotti A Tags: Ageing Res Rev Source Type: research

Bloom's Syndrome: Why Not Premature Aging?: A comparison of the BLM and WRN helicases.
Abstract Genomic instability is a hallmark of cancer and aging. Premature aging (progeroid) syndromes are often caused by mutations in genes whose function is to ensure genomic integrity. The RecQ family of DNA helicases is highly conserved and plays crucial roles as genome caretakers. In human, mutations in three RecQ genes - BLM, WRN, and RECQL4 - give rise to Bloom's syndrome (BS), Werner syndrome (WS), and Rothmund-Thomson's syndrome (RTS), respectively. WS is a prototypic premature aging disorder; however, the clinical features present in BS and RTS do not indicate accelerated aging. The BLM helicase has pivo...
Source: Ageing Research Reviews - May 25, 2016 Category: Genetics & Stem Cells Authors: Renty C, Ellis NA Tags: Ageing Res Rev Source Type: research

Impact of Lysosome Status on Extracellular Vesicle Content and Release.
Abstract Extracellular vesicles (EVs) are nanoscale size bubble-like membranous structures released from cells. EVs contain RNA, lipids and proteins and are thought to serve various roles including intercellular communication and removal of misfolded proteins. The secretion of misfolded and aggregated proteins in EVs may be a cargo disposal alternative to the autophagy-lysosomal and ubiquitin-proteasome pathways. In this review we will discuss the importance of lysosome functionality for the regulation of EV secretion and content. Exosomes are a subtype of EVs that are released by the fusion of multivesicular bodi...
Source: Ageing Research Reviews - May 25, 2016 Category: Genetics & Stem Cells Authors: Eitan E, Suire C, Zhang S, Mattson MP Tags: Ageing Res Rev Source Type: research

Senescent endothelial cells: potential modulators of immunosenescence and ageing.
We describe the possibility that age-related changes in Toll-like receptors (TLRs) and microRNAs can affect the phenotypes of senescent endothelial cells and immune cells via a negative feedback loop aimed at restraining the excessive pro-inflammatory response. This review also addresses the following questions: how do senescent endothelial cells influence ageing or age-related changes in the inflammatory burden; what is the connection between ECs and immunosenescence, and what are the crucial hypothetical pathways linking endothelial cells and the immune system during ageing. PMID: 27235855 [PubMed - as supplied by p...
Source: Ageing Research Reviews - May 24, 2016 Category: Genetics & Stem Cells Authors: Pantsulaia I, Ciszewski WM, Niewiarowska J Tags: Ageing Res Rev Source Type: research

Non-invasive brain stimulation of the aging brain: state of the art and future perspectives.
Abstract Favored by increased life expectancy and reduced birth rate, worldwide demography is rapidly shifting to older ages. The golden age of aging is not only an achievement but also a big challenge because of the load of the elderly on social and medical health care systems. Moreover, the impact of age-related decline of attention, memory, reasoning and executive functions on self-sufficiency emphasizes the need of interventions to maintain cognitive abilities at a useful degree in old age. Recently, neuroscientific research explored the chance to apply Non-Invasive Brain Stimulation (NiBS) techniques (as tran...
Source: Ageing Research Reviews - May 20, 2016 Category: Genetics & Stem Cells Authors: Tatti E, Rossi S, Innocenti I, Rossi A, Santarnecchi E Tags: Ageing Res Rev Source Type: research

Telomere-Associated Aging Disorders.
Abstract Telomeres are dynamic nucleoprotein-DNA structures that cap and protect linear chromosome ends. Several monogenic inherited diseases that display features of human premature aging correlate with shortened telomeres, and are referred to collectively as telomeropathies. These disorders have overlapping symptoms and a common underlying mechanism of telomere dysfunction, but also exhibit variable symptoms and age of onset, suggesting they fall along a spectrum of disorders. Primary telomeropathies are caused by defects in the telomere maintenance machinery, whereas secondary telomeropathies have some overlapp...
Source: Ageing Research Reviews - May 19, 2016 Category: Genetics & Stem Cells Authors: Opresko PL, Shay JW Tags: Ageing Res Rev Source Type: research

Biomarkers to identify and isolate senescent cells.
Abstract Aging is the main risk factor for many degenerative diseases and declining health. Senescent cells are part of the underlying mechanism for time-dependent tissue dysfunction. These cells can negatively affect neighbouring cells through an altered secretory phenotype: the senescence-associated secretory phenotype (SASP). The SASP induces senescence in healthy cells, promotes tumour formation and progression, and contributes to other age-related diseases such as atherosclerosis, immune-senescence and neurodegeneration. Removal of senescent cells was recently demonstrated to delay age-related degeneration an...
Source: Ageing Research Reviews - May 18, 2016 Category: Genetics & Stem Cells Authors: Matjusaitis M, Chin G, Sarnoski EA, Stolzing A Tags: Ageing Res Rev Source Type: research

Disorders of lysosomal acidification-the emerging role of v-ATPase in aging and neurodegenerative disease.
Abstract Autophagy and endocytosis deliver unneeded cellular materials to lysosomes for degradation. Beyond processing cellular waste, lysosomes release metabolites and ions that serve signaling and nutrient sensing roles, linking the functions of the lysosome to various pathways for intracellular metabolism and nutrient homeostasis. Each of these lysosomal behaviors is influenced by the intraluminal pH of the lysosome, which is maintained in the low acidic range by a proton pump, the vacuolar ATPase (v-ATPase). New reports implicate altered v-ATPase activity and lysosomal pH dysregulation in cellular aging, longe...
Source: Ageing Research Reviews - May 15, 2016 Category: Genetics & Stem Cells Authors: Colacurcio DJ, Nixon RA Tags: Ageing Res Rev Source Type: research

Ataxia-Telangiectasia (A-T): An Emerging Dimension of Premature Ageing.
Abstract A-T is a prototype genome instability syndrome and a multifaceted disease. A-T leads to neurodegeneration - primarily cerebellar atrophy, immunodeficiency, oculocutaneous telangiectasia (dilated blood vessels), vestigial thymus and gonads, endocrine abnormalities, cancer predisposition and varying sensitivity to DNA damaging agents, particularly those that induce DNA double-strand breaks. With the recent increase in life expectancy of A-T patients, the premature ageing component of this disease is gaining greater awareness. The complex A-T phenotype reflects the ever growing number of functions assigned t...
Source: Ageing Research Reviews - May 11, 2016 Category: Genetics & Stem Cells Authors: Shiloh Y, Lederman HM Tags: Ageing Res Rev Source Type: research

Impaired protein degradation in FTLD and related disorders.
l A PMID: 27166223 [PubMed - as supplied by publisher] (Source: Ageing Research Reviews)
Source: Ageing Research Reviews - May 6, 2016 Category: Genetics & Stem Cells Authors: Götzl JK, Lang CM, Haass C, Capell A Tags: Ageing Res Rev Source Type: research

Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases.
Abstract As regulators of bioenergetics in the cell and the primary source of endogenous reactive oxygen species (ROS), dysfunctional mitochondria have been implicated for decades in the process of aging and age-related diseases. Mitochondrial DNA (mtDNA) is replicated and repaired by nuclear-encoded mtDNA polymerase γ (Pol γ) and several other associated proteins, which compose the mtDNA replication machinery. Here, we review evidence that errors caused by this replication machinery and failure to repair these mtDNA errors results in mtDNA mutations. Clonal expansion of mtDNA mutations results in mito...
Source: Ageing Research Reviews - April 29, 2016 Category: Genetics & Stem Cells Authors: DeBalsi KL, Hoff KE, Copeland WC Tags: Ageing Res Rev Source Type: research

Intramembrane Proteolysis within lysosomes.
g P Abstract Regulated intramembrane proteolysis is of pivotal importance in a diverse set of developmental and physiological processes. Altered intramembrane substrate turnover may be associated with neurodegeneration, cancer and impaired immune function. In this review we will focus on the intramembrane proteases which have been localized in the lysosomal membrane. Members of the γ-secretase complex and γ-secretase activity are found in the lysosomal membrane and are discussed to contribute to intracellular amyloid β production. Mutant or deficient γ-secretase may cause disturbed lysosomal...
Source: Ageing Research Reviews - April 29, 2016 Category: Genetics & Stem Cells Authors: Schröder B, Saftig P Tags: Ageing Res Rev Source Type: research

Preserving the longevity of long-lived type II collagen and its implication for cartilage therapeutics.
Abstract Human life expectancy has been steadily increasing at a rapid rate, but this increasing life span also brings about increases in diseases, dementia, and disability. A global burden of disease 2010 study revealed that hip and knee osteoarthritis ranked the 11th highest in terms of years lived with disability. Wear and tear can greatly influence the quality of life during ageing. In particular, wear and tear of the articular cartilage have adverse effects on joints and result in osteoarthritis. The articular cartilage uses longevity of type II collagen as the foundation around which turnover of proteoglycan...
Source: Ageing Research Reviews - April 27, 2016 Category: Genetics & Stem Cells Authors: Tiku ML, Madhan B Tags: Ageing Res Rev Source Type: research

Lysosomal cathepsins and their regulation in aging and neurodegeneration.
Abstract Lysosomes and lysosomal hydrolases, including the cathepsins, have been shown to change their properties with aging brain a long time ago, although their function was not really understood. The first biochemical and clinical studies were followed by a major expansion in the last 20 years with the development of animal disease models and new approaches leading to a major advancement of understanding of the role of physiological and degenerative processes in the brain at the molecular level. This includes the understanding of the major role of autophagy and the cathepsins in a number of diseases, including ...
Source: Ageing Research Reviews - April 24, 2016 Category: Genetics & Stem Cells Authors: Stoka V, Turk V, Turk B Tags: Ageing Res Rev Source Type: research

The crucial impact of lysosomes in aging and longevity.
In conclusion, this review aims at critically examining the nature and pliability of the different layers, in which lysosomes are involved as a control hub for aging and longevity. PMID: 27125853 [PubMed - as supplied by publisher] (Source: Ageing Research Reviews)
Source: Ageing Research Reviews - April 24, 2016 Category: Genetics & Stem Cells Authors: Carmona-Gutierrez D, Hughes AL, Madeo F, Ruckenstuhl C Tags: Ageing Res Rev Source Type: research

Association between Fat Free Mass and Glucose Homeostasis: Common knowledge revisited.
ne IJ PMID: 27112523 [PubMed - as supplied by publisher] (Source: Ageing Research Reviews)
Source: Ageing Research Reviews - April 21, 2016 Category: Genetics & Stem Cells Authors: Perreault K, Lagacé JC, Brochu M, Dionne IJ Tags: Ageing Res Rev Source Type: research

Synaptic pathology: a shared mechanism in neurological disease.
Abstract Synaptic proteomes have evolved a rich and complex diversity to allow the exquisite control of neuronal communication and information transfer. It is therefore not surprising that many neurological disorders are associated with alterations in synaptic function. As technology has advanced, our ability to study the anatomical and physiological function of synapses in greater detail has revealed a critical role for both central and peripheral synapses in neurodegenerative disease. Synapse loss has a devastating effect on cellular communication, leading to wide ranging effects such as network disruption withi...
Source: Ageing Research Reviews - April 19, 2016 Category: Genetics & Stem Cells Authors: Henstridge CM, Pickett E, Spires-Jones TL Tags: Ageing Res Rev Source Type: research

Neuroprotective effects of the catalytic subunit of telomerase: a potential therapeutic target in the Central Nervous System.
Barreto GE Abstract Senescence plays an important role in neurodegenerative diseases and involves key molecular changes induced by several mechanisms such as oxidative stress, telomere shortening and DNA damage. Potential therapeutic strategies directed to counteract these molecular changes are of great interest for the prevention of the neurodegenerative process. Telomerase is a ribonucleoprotein composed of a catalytic subunit (TERT) and a RNA subunit (TERC). It is known that the telomerase is involved in the maintenance of telomere length and is a highly expressed protein in embryonic stages and decreases in a...
Source: Ageing Research Reviews - April 15, 2016 Category: Genetics & Stem Cells Authors: González-Giraldo Y, Forero DA, Echeverria V, Gonzalez J, Ávila-Rodriguez M, Garcia-Segura LM, Barreto GE Tags: Ageing Res Rev Source Type: research

Age-related changes in AMPK activation: Role for AMPK phosphatases and inhibitory phosphorylation by upstream signaling pathways.
Abstract AMP-activated protein kinase (AMPK) is a fundamental regulator of energy metabolism, stress resistance, and cellular proteostasis. AMPK signaling controls an integrated signaling network which is involved in the regulation of healthspan and lifespan e.g. via FoxO, mTOR/ULK1, CRCT-1/CREB, and SIRT1 signaling pathways. Several studies have demonstrated that the activation capacity of AMPK signaling declines with aging, which impairs the maintenance of efficient cellular homeostasis and enhances the aging process. However, it seems that the aging process affects AMPK activation in a context-dependent manner ...
Source: Ageing Research Reviews - April 5, 2016 Category: Genetics & Stem Cells Authors: Salminen A, Kaarniranta K, Kauppinen A Tags: Ageing Res Rev Source Type: research

Cholesterol Metabolism: A Review of How Ageing Disrupts the Biological Mechanisms Responsible for its Regulation.
Abstract Cholesterol plays a vital role in the human body as a precursor of steroid hormones and bile acids, in addition to providing structure to cell membranes. Whole body cholesterol metabolism is maintained by a highly coordinated balancing act between cholesterol ingestion, synthesis, absorption, and excretion. The aim of this review is to discuss how ageing interacts with these processes. Firstly, we will present an overview of cholesterol metabolism. Following this, we discuss how the biological mechanisms which underpin cholesterol metabolism are effected by ageing. Included in this discussion are lipoprot...
Source: Ageing Research Reviews - March 31, 2016 Category: Genetics & Stem Cells Authors: Morgan AE, Mooney KM, Wilkinson SJ, Pickles NA, Mc Auley MT Tags: Ageing Res Rev Source Type: research

Regenerative function of immune system: Modulation of muscle stem cells.
Abstract Ageing is characterised by progressive deterioration of physiological systems and the loss of skeletal muscle mass is one of the most recognisable, leading to muscle weakness and mobility impairments. This review highlights interactions between the immune system and skeletal muscle precursor cells (widely termed satellite cells or myoblasts) to influence satellite cell behaviour during muscle regeneration after injury, and outlines deficits associated with ageing. Resident neutrophils and macrophages in skeletal muscle become activated when muscle fibres are damaged via stimuli (e.g. contusions, strains, ...
Source: Ageing Research Reviews - March 30, 2016 Category: Genetics & Stem Cells Authors: Saini J, McPhee JS, Al-Dabbagh S, Stewart CE, Al-Shanti N Tags: Ageing Res Rev Source Type: research

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer's disease.
ute;M Abstract It is now well established, at least in animal models, that exercise elicits potent pro-cognitive and pro-neurogenic effects. Alzheimer's disease (AD) is one of the leading causes of dementia and represents one of the greatest burdens on healthcare systems worldwide, with no effective treatment for the disease to date. Exercise presents a promising non-pharmacological option to potentially delay the onset of or slow down the progression of AD. Exercise interventions in mouse models of AD have been explored and have been found to reduce amyloid pathology and improve cognitive function. More recent st...
Source: Ageing Research Reviews - March 30, 2016 Category: Genetics & Stem Cells Authors: Ryan SM, Kelly ÁM Tags: Ageing Res Rev Source Type: research