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 8, 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 6, 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 30, 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 30, 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 21, 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 13, 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 29, 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 26, 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 25, 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 19, 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 17, 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 12, 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 7, 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 - June 1, 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 27, 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 26, 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 26, 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 25, 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 21, 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 20, 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 19, 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 16, 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 12, 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 7, 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 30, 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 30, 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 28, 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 25, 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 25, 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 22, 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 20, 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 16, 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 6, 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 - April 1, 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 31, 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 31, 2016 Category: Genetics & Stem Cells Authors: Ryan SM, Kelly ÁM Tags: Ageing Res Rev Source Type: research

Roles of the tyrosine isomers meta-tyrosine and ortho-tyrosine in oxidative stress.
Abstract The damage to cellular components by reactive oxygen species, termed oxidative stress, both increases with age and likely contributes to age-related diseases including Alzheimer's disease, atherosclerosis, diabetes, and cataract formation. In the setting of oxidative stress, hydroxyl radicals can oxidize the benzyl ring of the amino acid phenylalanine, which then produces the abnormal tyrosine isomers meta-tyrosine or ortho-tyrosine. While elevations in m-tyrosine and o-tyrosine concentrations have been used as a biological marker of oxidative stress, there is emerging evidence from bacterial, plant, and ...
Source: Ageing Research Reviews - March 31, 2016 Category: Genetics & Stem Cells Authors: Ipson BR, Fisher AL Tags: Ageing Res Rev Source Type: research

Noradrenergic modulation of emotional memory in aging.
This study briefly reviews this timely line of research with a specific focus on aging. After having identified surprisingly few studies that investigated emotional memory in older adults from a neurobiological perspective, we found a significant interaction between noradrenergic activity and emotional memory enhancement in older adults. This pattern of data are explained both in terms of a top-down modulation of behavioral processes (e.g., changes in priority and individual goals) and in terms of greater activity of noradrenergic system during aging. Altogether, both behavioral and genetic variations studies (e.g., Alpha ...
Source: Ageing Research Reviews - March 18, 2016 Category: Genetics & Stem Cells Authors: Mammarella N, Domenico AD, Palumbo R, Fairfield B Tags: Ageing Res Rev Source Type: research

Werner Syndrome: Clinical Features, Pathogenesis and Potential Therapeutic Interventions.
Abstract Werner syndrome (WS) is a prototypical segmental progeroid syndrome characterized by multiple features consistent with accelerated aging. It is caused by null mutations of the WRN gene, which encodes a member of the RECQ family of DNA helicases. A unique feature of the WRN helicase is the presence of an exonuclease domain in its N-terminal region. Biochemical and cell biological studies during the past decade have demonstrated involvements of the WRN protein in multiple DNA transactions, including DNA repair, recombination, replication and transcription. A role of the WRN protein in telomere maintenance c...
Source: Ageing Research Reviews - March 15, 2016 Category: Genetics & Stem Cells Authors: Oshima J, Sidorova JM, Monnat RJ Tags: Ageing Res Rev Source Type: research

Aging in Two Languages: Implications for Public Health.
Abstract With the population aging and a dramatic increase in the number of senior citizens, public health systems will be increasingly burdened with the need to deal with the care and treatment of individuals with dementia. We review evidence demonstrating how a particular experience, bilingualism, has been shown to protect cognitive function in older age and delay onset of symptoms of dementia. This paper describes behavioral and brain studies that have compared monolingual and bilingual older adults on measures of cognitive function or brain structure and reviews evidence demonstrating a protective effect of bi...
Source: Ageing Research Reviews - March 15, 2016 Category: Genetics & Stem Cells Authors: Bialystok E, Abutalebi J, Bak TH, Burke DM, Kroll JF Tags: Ageing Res Rev Source Type: research

Functional neuroimaging of normal aging: declining brain, adapting brain.
Abstract Early functional neuroimaging research on normal aging brain has been dominated by the interest in cognitive decline. In this framework the age-related compensatory recruitment of prefrontal cortex, in terms of executive system or reduced lateralization, has been established. Further details on these compensatory mechanisms and the findings reflecting cognitive decline, however, remain the matter of intensive investigations. Studies in another framework where age-related neural alteration is considered adaptation to the environmental change are recently burgeoning and appear largely categorized into three...
Source: Ageing Research Reviews - March 14, 2016 Category: Genetics & Stem Cells Authors: Sugiura M Tags: Ageing Res Rev Source Type: research

Introduction and overview of the special issue "Brain imaging and aging": The new era of neuroimaging in aging research.
Introduction and overview of the special issue "Brain imaging and aging": The new era of neuroimaging in aging research. Ageing Res Rev. 2016 Mar 11; Authors: Furukawa K, Ishiki A, Tomita N, Onaka Y, Saito H, Nakamichi T, Hara K, Kusano Y, Ebara M, Arata Y, Sakota M, Miyazawa I, Totsune T, Okinaga S, Okamura N, Kudo Y, Arai H Abstract It is well known that the brain is one of the organs particularly affected by aging in terms of function, relative to the gastrointestinal tract and liver, which exhibit less functional decline. There is also a wide range of age-related neurological disorders s...
Source: Ageing Research Reviews - March 11, 2016 Category: Genetics & Stem Cells Authors: Furukawa K, Ishiki A, Tomita N, Onaka Y, Saito H, Nakamichi T, Hara K, Kusano Y, Ebara M, Arata Y, Sakota M, Miyazawa I, Totsune T, Okinaga S, Okamura N, Kudo Y, Arai H Tags: Ageing Res Rev Source Type: research

Periodic acid-Schiff granules in the brain of aged mice: from amyloid aggregates to degenerative structures containing neo-epitopes.
e; C, Vilaplana J Abstract Brain ageing in mice leads to the progressive appearance and expansion of degenerative granular structures frequently referred as "PAS granules" because of their positive staining with periodic acid-Schiff (PAS). PAS granules are present mainly in the hippocampus, although they have also been described in other brain areas such as piriform and entorhinal cortices, and have been observed in other mammals than mice, like rats and monkeys. PAS granules have been identified as a wide range of brain deposits related to numerous neurodegenerative diseases, such as amyloid deposits, n...
Source: Ageing Research Reviews - March 9, 2016 Category: Genetics & Stem Cells Authors: Manich G, Cabezón I, Augé E, Pelegrí C, Vilaplana J Tags: Ageing Res Rev Source Type: research

Lysosomal cell death mechanisms in aging.
oya P Abstract Lysosomes are degradative organelles essential for cell homeostasis that regulate a variety of processes, from calcium signaling and nutrient responses to autophagic degradation of intracellular components. Lysosomal cell death is mediated by the lethal effects of cathepsins, which are released into the cytoplasm following lysosomal damage. This process of lysosomal membrane permeabilization and cathepsin release is observed in several physiopathological conditions and plays a role in tissue remodeling, the immune response to intracellular pathogens and neurodegenerative diseases. Many evidences ind...
Source: Ageing Research Reviews - March 3, 2016 Category: Genetics & Stem Cells Authors: Gómez-Sintes R, Ledesma MD, Boya P Tags: Ageing Res Rev Source Type: research

What lysosomes actually tell us about Parkinson's disease?
Abstract Parkinson's disease is a common neurodegenerative disorder of unknown origin mainly characterized by the loss of neuromelanin-containing dopaminergic neurons in the substantia nigra pars compacta and the presence of intraneuronal proteinaceous inclusions called Lewy bodies. Lysosomes are dynamic organelles that degrade, in a controlled manner, cellular components delivered via the secretory, endocytic, autophagic and phagocytic membrane-trafficking pathways. Increasing amounts of evidence suggest a central role of lysosomal impairment in PD aetiology. This review provides an update on how genetic evidence...
Source: Ageing Research Reviews - March 3, 2016 Category: Genetics & Stem Cells Authors: Bourdenx M, Dehay B Tags: Ageing Res Rev Source Type: research

iPSCs-based anti-aging therapies: Recent discoveries and future challenges.
z BG, Gallardo ME Abstract The main biological hallmarks of the aging process include stem cell exhaustion and cellular senescence. Consequently, research efforts to treat age-related diseases as well as anti-aging therapies in general have recently focused on potential 'reprogramming' regenerative therapies. These new approaches are based on induced pluripotent stem cells (iPSCs), including potential in vivo reprogramming for tissue repair. Another possibility is targeting pathways of cellular senescence, eg, through modulation of p16INK4a signaling and especially inhibition of the nuclear factor kappa-light-chai...
Source: Ageing Research Reviews - February 24, 2016 Category: Genetics & Stem Cells Authors: Pareja-Galeano H, Sanchis-Gomar F, Pérez LM, Emanuele E, Lucía A, Gálvez BG, Gallardo ME Tags: Ageing Res Rev Source Type: research

Regulatory development of geriatric medicines: To GIP or not to GIP?
Abstract Geriatric patients represent the main users of medicines, but are historically often minimally included in clinical trials, resulting in a gap in the knowledge of the benefit/risk balance of medicines in this heterogeneous population. As the worldwide population is aging, the need for safe and effective medicines for older patients is proportionally increasing. The aim of this review is to provide an overview of the current regulatory status of the development of geriatric medicines, the encountered challenges and the view of the involved stakeholders, coming to the conclusion whether it is necessary or n...
Source: Ageing Research Reviews - February 17, 2016 Category: Genetics & Stem Cells Authors: De Spiegeleer B, Wynendaele E, Bracke N, Veryser L, Taevernier L, Degroote A, Stalmans S Tags: Ageing Res Rev Source Type: research

Brain Fluorodeoxyglucose (FDG) PET in dementia.
Abstract The purpose of this article is to present a selective and concise summary of fluorodeoxyglucose (FDG) positron emission tomography (PET) in dementia imaging. FDG PET is used to visualize a downstream topographical marker that indicates the distribution of neural injury or synaptic dysfunction, and can identify distinct phenotypes of dementia due to Alzheimer's disease (AD), Lewy bodies, and frontotemporal lobar degeneration. AD dementia shows hypometabolism in the parietotemporal association area, posterior cingulate, and precuneus. Hypometabolism in the inferior parietal lobe and posterior cingulate/prec...
Source: Ageing Research Reviews - February 11, 2016 Category: Genetics & Stem Cells Authors: Kato T, Inui Y, Nakamura A, Ito K Tags: Ageing Res Rev Source Type: research

Apolipoprotein E (APOE) ε4 and episodic memory decline in Alzheimer's disease: A review.
Apolipoprotein E (APOE) ε4 and episodic memory decline in Alzheimer's disease: A review. Ageing Res Rev. 2016 Feb 10; Authors: Mohamad EH, Antoine P, Amouyel P, Lambert JC, Pasquier F, Kapogiannis D Abstract A growing body of research has examined the relationship between episodic memory decline, the cognitive hallmark of Alzheimer's disease (AD), and the presence of Apolipoprotein E ε4 (APOE ε4) allele, a major genetic risk factor for the disease. Our review attempts to summarize and critically evaluate this literature. We performed a systematic search for studies assessing ep...
Source: Ageing Research Reviews - February 10, 2016 Category: Genetics & Stem Cells Authors: Mohamad EH, Antoine P, Amouyel P, Lambert JC, Pasquier F, Kapogiannis D Tags: Ageing Res Rev Source Type: research

Walking ability to predict future cognitive decline in old adults: a scoping review.
th CJ Abstract Early identification of individuals at risk for cognitive decline may facilitate the selection of those who benefit most from interventions. Current models predicting cognitive decline include neuropsychological and/or biological markers. Additional markers based on walking ability might improve accuracy and specificity of these models because motor and cognitive functions share neuroanatomical structures and psychological processes. We reviewed the relationship between walking ability at one point of (mid)life and cognitive changes at follow-up. A systematic literature search identified 20 longitud...
Source: Ageing Research Reviews - February 6, 2016 Category: Genetics & Stem Cells Authors: Kikkert LH, Vuillerme N, Campen JP, Hortobágyi T, Lamoth CJ Tags: Ageing Res Rev Source Type: research