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Sub-cellular Biochemistry

Raj N Kalaria, Yoshiki Hase
Proper functioning of the brain is dependent on integrity of the cerebral vasculature. During ageing, a number of factors including aortic or arterial stiffness, autonomic dysregulation, neurovascular uncoupling and blood-brain barrier (BBB) damage will define the dynamics of brain blood flow and local perfusion. The nature and extent of ageing-related cerebrovascular changes, the degree of involvement of the heart and extracranial vessels and the consequent location of tissue pathology may vary considerably...
2019: Sub-cellular Biochemistry
Terry J Aspray, Tom R Hill
Osteoporosis is a "skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture" which, in light of demographic change, is becoming an increasing burden on health care worldwide. Increasing age and female gender are associated with the condition, although a wider range of clinical risk factors are being used increasingly to identify those at risk of osteoporosis and its most important sequelae, fracture.While osteoporosis and fracture have long been associated with women in the post-menopausal age, fracture incidence increases because of the ageing of our population...
2019: Sub-cellular Biochemistry
Ray Kreienkamp, Susana Gonzalo
The structural nuclear proteins known as "lamins" (A-type and B-type) provide a scaffold for the compartmentalization of genome function that is important to maintain genome stability. Mutations in the LMNA gene -encoding for A-type lamins- are associated with over a dozen of degenerative disorders termed laminopathies, which include muscular dystrophies, lipodystrophies, neuropathies, and premature ageing diseases such as Hutchinson Gilford Progeria Syndrome (HGPS). This devastating disease is caused by the expression of a truncated lamin A protein named "progerin"...
2019: Sub-cellular Biochemistry
Sergio Claudio Saccà, Carlo Alberto Cutolo, Tommaso Rossi
Many diseases are related to age, among these neurodegeneration is particularly important. Alzheimer's disease Parkinson's and Glaucoma have many common pathogenic events including oxidative damage, Mitochondrial dysfunction, endothelial alterations and changes in the visual field. These are well known in the case of glaucoma, less in the case of neurodegeneration of the brain. Many other molecular aspects are common, such as the role of endoplasmic reticulum autophagy and neuronal apoptosis while others have been neglected due to lack of space such as inflammatory cytokine or miRNA...
2019: Sub-cellular Biochemistry
Veronika Piskovatska, Olha Strilbytska, Alexander Koliada, Alexander Vaiserman, Oleh Lushchak
Aging, as a physiological process mediated by numerous regulatory pathways and transcription factors, is manifested by continuous progressive functional decline and increasing risk of chronic diseases. There is an increasing interest to identify pharmacological agents for treatment and prevention of age-related disease in humans. Animal models play an important role in identification and testing of anti-aging compounds; this step is crucial before the drug will enter human clinical trial or will be introduced to human medicine...
2019: Sub-cellular Biochemistry
Mark Ross, Hannah Lithgow, Lawrence Hayes, Geraint Florida-James
Exercise in young adults has been consistently shown to improve various aspects of physiological and psychological health but we are now realising the potential benefits of exercise with advancing age. Specifically, exercise improves cardiovascular, musculoskeletal, and metabolic health through reductions in oxidative stress, chronic low-grade inflammation and modulating cellular processes within a variety of tissues. In this this chapter we will discuss the effects of acute and chronic exercise on these processes and conditions in an ageing population, and how physical activity affects our vasculature, skeletal muscle function, our immune system, and cardiometabolic risk in older adults...
2019: Sub-cellular Biochemistry
Carolyn Ann Sarbacher, Jaroslava T Halper
We begin this chapter by describing normal characteristics of several pertinent connective tissue components, and some of the basic changes they undergo with ageing. These alterations are not necessarily tied to any specific disease or disorders, but rather an essential part of the normal ageing process. The general features of age-induced changes, such as skin wrinkles, in selected organs with high content of connective or soft tissues are discussed in the next part of the chapter. This is followed by a section dealing with age-related changes in specific diseases that fall into at least two categories...
2019: Sub-cellular Biochemistry
Frédéric Bonté, Dorothée Girard, Jean-Christophe Archambault, Alexis Desmoulière
The skin provides the primary protection for the body against external injuries and is essential in the maintenance of general homeostasis. During ageing, resident cells become senescent and the extracellular matrix, mainly in the dermis, is progressively damaged affecting the normal organization of the skin and its capacity for repair. In parallel, extrinsic factors such as ultraviolet irradiation, pollution, and intrinsic factors such as diabetes or vascular disease can further accelerate this phenomenon...
2019: Sub-cellular Biochemistry
Lei Zhang, Matthew J Yousefzadeh, Yousin Suh, Laura J Niedernhofer, Paul D Robbins
Ageing is defined by the loss of functional reserve over time, leading to a decreased tissue homeostasis and increased age-related pathology. The accumulation of damage including DNA damage contributes to driving cell signaling pathways that, in turn, can drive different cell fates, including senescence and apoptosis, as well as mitochondrial dysfunction and inflammation. In addition, the accumulation of cell autonomous damage with time also drives ageing through non-cell autonomous pathways by modulation of signaling pathways...
2019: Sub-cellular Biochemistry
Sonja Brosel, Michael Strupp
The world's population is ageing due to increased hygiene and improved medical care. Dizziness and imbalance frequently affect the elderly and is most common among individuals over the age of 60. In this age group approximately 30% of the population experience these debilitating symptoms at some point. They contribute to falls and frailty, which often result in hospitalization causing tremendous cost for the health care systems, and increased mortality. To make the matters worse balance disorders are often complex...
2019: Sub-cellular Biochemistry
Noémie Gensous, Claudio Franceschi, Stefano Salvioli, Paolo Garagnani, Maria Giulia Bacalini
During the past decades, life expectancy of subjects with Down syndrome (DS) has greatly improved, but age-specific mortality rates are still important and DS subjects are characterized by an acceleration of the ageing process, which affects particularly the immune and central nervous systems. In this chapter, we will first review the characteristics of the ageing phenomenon in brain and in immune system in DS and we will then discuss the biological hallmarks of ageing in this specific population. Finally, we will also consider in detail the knowledge on epigenetics in DS, particularly DNA methylation...
2019: Sub-cellular Biochemistry
Pradeep Kumar Sacitharan
The increase in global lifespan has in turn increased the prevalence of osteoarthritis which is now the most common type of arthritis. Cartilage tissue located on articular joints erodes during osteoarthritis which causes pain and may lead to a crippling loss of function in patients. The pathophysiology of osteoarthritis has been understudied and currently no disease modifying treatments exist. The only current end-point treatment remains joint replacement surgery. The primary risk factor for osteoarthritis is age...
2019: Sub-cellular Biochemistry
Sydney M A Juan, Paul A Adlard
With an increasingly ageing population that is expected to double by 2050 in the U.S., it is paramount that we further understand the neurological changes that occur during ageing. This is relevant not only in the context of "pathological" ageing, where the development of many neurodegenerative disorders is typically a feature of only the older population (and indeed, age is the primary risk factor for many conditions such as Alzheimer's disease), but also for what is considered to be "normal" or "healthy" ageing...
2019: Sub-cellular Biochemistry
Lauren Walker, Kirsty E McAleese, Daniel Erskine, Johannes Attems
This chapter describes the main neuropathological features of the most common age associated neurodegenerative diseases including Alzheimer's disease, Lewy body diseases, vascular dementia and the various types of frontotemporal lobar degeneration. In addition, the more recent concepts of primary age-related tauopathy and ageing-related tau astrogliopathy as well as chronic traumatic encephalopathy are briefly described. One section is dedicated to cerebral multi-morbidity as it is becoming increasingly clear that the old brain is characterised by the presence of multiple pathologies (to varying extent) rather than by one single, disease specific pathology alone...
2019: Sub-cellular Biochemistry
Peter J Barnes
Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis are regarded as a diseases of accelerated lung ageing and show all of the hallmarks of ageing, including telomere shortening, cellular senescence, activation of PI3 kinase-mTOR signaling, impaired autophagy, mitochondrial dysfunction, stem cell exhaustion, epigenetic changes, abnormal microRNA profiles, immunosenescence and a low grade chronic inflammation due to senescence-associated secretory phenotype (SASP). Many of these ageing mechanisms are driven by exogenous and endogenous oxidative stress...
2019: Sub-cellular Biochemistry
Ludmila Müller, Svetlana Di Benedetto, Graham Pawelec
Aging leads to numerous changes that affect all physiological systems of the body including the immune system, causing greater susceptibility to infectious disease and contributing to the cardiovascular, metabolic, autoimmune, and neurodegenerative diseases of aging. The immune system is itself also influenced by age-associated changes occurring in such physiological systems as the endocrine, nervous, digestive, cardio-vascular and muscle-skeletal systems. This chapter describes the multidimensional effects of aging on the most important components of the immune system...
2019: Sub-cellular Biochemistry
Jane L Tarry-Adkins, Susan E Ozanne
The prevalence of age-associated disease is increasing at a striking rate globally and there is evidence to suggest that the ageing process may actually begin before birth. It has been well-established that the status of both the maternal and early postnatal environments into which an individual is exposed can have huge implications for the risk of developing age-associated disease, including cardiovascular disease (CVD), type-2 diabetes (T2D) and obesity in later life. Therefore, the dissection of underlying molecular mechanisms to explain this phenomenon, known as 'developmental programming' is a highly investigated area of research...
2019: Sub-cellular Biochemistry
Fabio Dall'Olio
Glycosylation is one of the most frequent post-translational modification of proteins. Many membrane and secreted proteins are decorated by sugar chains mainly linked to asparagine (N-linked) or to serine or threonine (O-linked). The biosynthesis of the sugar chains is mainly controlled by the activity of their biosynthetic enzymes: the glycosyltransferases. Glycosylation plays multiple roles, including the fine regulation of the biological activity of glycoproteins. Inflammaging is a chronic low grade inflammatory status associated with aging, probably caused by the continuous exposure of the immune system to inflammatory stimuli of endogenous and exogenous origin...
2018: Sub-cellular Biochemistry
Babukrishna Maniyadath, Namrata Shukla, Ullas Kolthur-Seetharam
As the popular adage goes, all diseases run into old age and almost all physiological changes are associated with alterations in gene expression, irrespective of whether they are causal or consequential. Therefore, the quest for mechanisms that delay ageing and decrease age-associated diseases has propelled researchers to unravel regulatory factors that lead to changes in chromatin structure and function, which ultimately results in deregulated gene expression. It is therefore essential to bring together literature, which until recently has investigated gene expression and chromatin independently...
2018: Sub-cellular Biochemistry
Kathleen Mikkelsen, Vasso Apostolopoulos
Vitamin B contributes to the overall health and wellbeing, including that of energy metabolism, methylation, synthesis and DNA repair and proper immune function. Deficiency in B vitamins has been linked to neurocognitive disorders, mitochondrial dysfunction, immune dysfunction and inflammatory conditions. In ageing populations B vitamin deficiency has been linked to cardiovascular disorders, cognitive dysfunction, osteoporosis and methylation disorders and can increase the risk of developing degenerative diseases, particularly cardiovascular disease, cognitive diseases and osteoporosis...
2018: Sub-cellular Biochemistry
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