Total and specific serum IgE decreases with age in patients with allergic rhinitis,asthma and insect allergy but not in patients with atopic dermatitis

Concerning allergic diseases, the incidence of allergic symptoms, as well as their severity, seems to decrease with age. The decline of onset of allergic symptoms observed in ageing might result from a decrease of serum total and specific IgE. Atopic disorders are complex diseases that involve interactions among several physiological systems, e.g. skin, lung, mucosae, and the immune system. It was the aim of this study to compare the effects of age on total and specific IgE in patients with atopic dermatitis (AD), allergic rhinitis or asthma, and insect allergy, respectively.     

Atherosclerosis,oxidation and endometriosis

Endometriosis affects younger women of childbearing age. Atherosclerosis is considered as a disease of the old and increases with the ageing process. Both diseases are characterized by the increased presence of activated macrophages and associated increases in growth promoting activity and the production of inflammatory cytokines. In this review, we propose that oxidative stress and the presence of forms of oxidized low-density lipoprotein (LDL) might contribute to both Atherosclerosis and Endometriosis.     

Atherosclerosis,Oxidation and Endometriosis

Endometriosis affects younger women of childbearing age. Atherosclerosis is considered as a disease of the old and increases with the ageing process. Both diseases are characterized by the increased presence of activated macrophages and associated increases in growth promoting activity and the production of inflammatory cytokines. In this review, we propose that oxidative stress and the presence of forms of oxidized low-density lipoprotein (LDL) might contribute to both Atherosclerosis and Endometriosis.     

NF-κB pathway activators as potential ageing biomarkers: targets for new therapeutic strategies

Chronic inflammation is a major biological mechanism underpinning biological ageing process and age-related diseases. Inflammation is also the key response of host defense against pathogens and tissue injury. Current opinion sustains that during evolution the host defense and ageing process have become linked together. Thus, the large array of defense factors and mechanisms linked to the NF-κB system seem to be involved in ageing process. This concept leads us in proposing inductors of NF-κB signaling pathway as potential ageing biomarkers. On the other hand, ageing biomarkers, represented by biological indicators and selected through apposite criteria, should help to characterize biological age and, since age is a major risk factor in many degenerative diseases, could be subsequently used to identify individuals at high risk of developing age-associated diseases or disabilities. In this report, some inflammatory biomarkers will be discussed for a better understanding of the concept of biological ageing, providing ideas on eventual working hypothesis about potential targets for the development of new therapeutic strategies and improving, as consequence, the quality of life of elderly population.     

Potential biomarkers of ageing

Life span in individual humans is very heterogeneous.Thus, the ageing rate, measured as the decline of functional capacity and stress resistance, is different in every individual. There have been attempts made to analyse this individual age, the so-called biological age, in comparison to chronological age. Biomarkers of ageing should help to characterise this biological age and, as age is a major risk factor in many degenerative diseases,could be subsequently used to identify individuals at high risk of developing age-associated diseases or disabilities.Markers based on oxidative stress, protein glycation,inflammation, cellular senescence and hormonal deregulation are discussed.     

Mechanisms of ageing: public or private?

Ageing--the decline in survival and fecundity with advancing age is caused by damage to macromolecules and tissues. Ageing is not a programmed process, in the sense that no genes are known to have evolved specifically to cause damage and ageing. Mechanisms of ageing might therefore not be expected to be as highly conserved between distantly related organisms as are mechanisms of development and metabolism. However, evidence is mounting that modulators of the rate of ageing are conserved over large evolutionary distances. As we discuss in this review, this conservation might stem from mechanisms that match reproductive rate to nutrient supply.     

Endocrine regulation of ageing

Over the past 15 years it has become clear that mutations in genes that regulate endocrine signalling pathways can prolong lifespan. Lifespan can be increased by altered endocrine signalling in a group of cells or a single tissue, which indicates that crosstalk between tissues functions to coordinate ageing of the organism. These endocrine pathways might serve as targets for the manipulation of the ageing process and prevention of age-related diseases.     

Epigenetic age prediction

Advanced age is the main common risk factor for cancer, cardiovascular disease and neurodegeneration. Yet, more is known about the molecular basis of any of these groups of diseases than the changes that accompany ageing itself. Progress in molecular ageing research was slow because the tools predicting whether someone aged slowly or fast (biological age) were unreliable. To understand ageing as a risk factor for disease and to develop interventions, the molecular ageing field needed a quantitative measure; a clock for biological age. Over the past decade, a number of age predictors utilising DNA methylation have been developed, referred to as epigenetic clocks. While they appear to estimate biological age, it remains unclear whether the methylation changes used to train the clocks are a reflection of other underlying cellular or molecular processes, or whether methylation itself is involved in the ageing process. The precise aspects of ageing that the epigenetic clocks capture remain hidden and seem to vary between predictors. Nonetheless, the use of epigenetic clocks has opened the door towards studying biological ageing quantitatively, and new clocks and applications, such as forensics, appear frequently. In this review, we will discuss the range of epigenetic clocks available, their strengths and weaknesses, and their applicability to various scientific queries.     

Reactive oxygen species target specific tryptophan site in the mitochondrial ATP synthase

The release of reactive oxygen species (ROS) as side products of aerobic metabolism in the mitochondria is an unavoidable consequence. As the capacity of organisms to deal with this exposure declines with age, accumulation of molecular damage caused by ROS has been defined as one of the central events during the ageing process in biological systems as well as in numerous diseases such as Alzheimer's and Parkinson's Dementia. In the filamentous fungus Podospora anserina, an ageing model with a clear defined mitochondrial etiology of ageing, in addition to the mitochondrial aconitase the ATP synthase alpha subunit was defined recently as a hot spot for oxidative modifications induced by ROS. In this report we show, that this reactivity is not randomly distributed over the ATP Synthase, but is channeled to a single tryptophan residue 503. This residue serves as an intra-molecular quencher for oxidative species and might also be involved in the metabolic perception of oxidative stress or regulation of enzyme activity. A putative metal binding site in the proximity of this tryptophan residue appears to be crucial for the molecular mechanism for the selective targeting of oxidative damage.     

Hemostasis and ageing

On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related Diseases was held in Palermo, Italy. The lecture of D. Mari on Hemostasis and ageing is summarized herein. Physiological ageing is associated with increased plasma levels of many proteins of blood coagulation together with fibrinolysis impairment. This may be of great concern in view of the known association between vascular and thromboembolic diseases and ageing. On the other hand, centenarians are characterized by a state of hypercoagulability and possession of several high-risk alleles and well-known atherothrombotic risk markers but this appears to be compatible with longevity and/or health. Parameters considered risk factors for atherosclerotic vascular diseases in young people may lose their biological significance in advanced age and assume a different role.     

Mitochondrial DNA mutations and ageing

The mechanism by which we age has sparked a huge number of theories, and is an area of intense debate. As the elderly population rises, the importance of elucidating these mechanisms is becoming more apparent as age is the single biggest risk factor for a number of diseases such as cancer, diabetes and neurodegenerative disease. Mitochondrial DNA (MtDNA) mutations have been shown to accumulate in cells and tissues during the ageing process; however the question as to whether these mutations have a causal role in the ageing process remains an area of uncertainty. Here we review the current literature, and discuss the evidence for and against a causal role of mtDNA mutations in ageing and in the pathogenesis of age-related disease.     

Endothelial Cell Senescence and Age-Related Vascular Diseases

Advanced age is an independent risk factor for ageing-related complex diseases,such as coronary artery disease,stroke,and hypertension,which are common but life threatening and related to the ageing-associated vascular dysfunction.On the other hand,patients with progeria syndromes suffer from serious atherosclerosis,suggesting that the impaired vascular functions may be critical to organismal ageing,or vice versa.However,it remains largely unknown how vascular cells,particularly endothelial cell,become senescent and how the senescence impairs the vascular functions and contributes to the age-related vascular diseases over time.Here,we review the recent progress on the characteristics of vascular ageing and endothelial cell senescence in vitro and in vivo,evaluate how genetic and environmental factors as well as autophagy and stem cell influence endothelial cell senescence and how the senescence contributes to the agerelated vascular phenotypes.such as atherosclerosis and increased vascular stiffness,and explore the possibility whether we can delay the age-related vascular diseases through the control of vascular ageing.     

Effects of d‐galactose‐induced ageing on the heart and its potential interventions

Ageing is a strong independent risk factor for disability, morbidity and mortality. Post‐mitotic cells including those in the heart are a particular risk to age‐related deterioration. As the occurrence of heart disease is increasing rapidly with an ageing population, knowledge regarding the mechanisms of age‐related cardiac susceptibility and possible therapeutic interventions needs to be acquired to prevent advancing levels of heart disease. To understand more about the ageing heart, numerous aged animal models are being used to explore the underlying mechanisms. Due to time‐consuming for investigations involving naturally aged animals, mimetic ageing models are being utilized to assess the related effects of ageing on disease occurrence. d ‐galactose is one of the substances used to instigate ageing in various models, and techniques involving this have been widely used since 1991. However, the mechanism through which d ‐galactose induces ageing in the heart remains unclear. The aim of this review was to comprehensively summarize the current findings from in vitro and in vivo studies on the effects of d ‐galactose‐induced ageing on the heart, and possible therapeutic interventions against ageing heart models. From this review, we hope to provide invaluable information for future studies and based on the findings from experiments involving animals, we can inform possible therapeutic strategies for the prevention of age‐related heart diseases in clinical settings.     

Mitochondria-targeted antioxidants and metabolic modulators as pharmacological interventions to slow ageing

Populations in many nations today are rapidly ageing. This unprecedented demographic change represents one of the main challenges of our time. A defining property of the ageing process is a marked increase in the risk of mortality and morbidity with age. The incidence of cancer, cardiovascular and neurodegenerative diseases increases non-linearly, sometimes exponentially with age. One of the most important tasks in biogerontology is to develop interventions leading to an increase in healthy lifespan (health span), and a better understanding of basic mechanisms underlying the ageing process itself may lead to interventions able to delay or prevent many or even all age-dependent conditions. One of the putative basic mechanisms of ageing is age-dependent mitochondrial deterioration, closely associated with damage mediated by reactive oxygen species (ROS). Given the central role that mitochondria and mitochondrial dysfunction play not only in ageing but also in apoptosis, cancer, neurodegeneration and other age-related diseases there is great interest in approaches to protect mitochondria from ROS-mediated damage. In this review, we explore strategies of targeting mitochondria to reduce mitochondrial oxidative damage with the aim of preventing or delaying age-dependent decline in mitochondrial function and some of the resulting pathologies. We discuss mitochondria-targeted and -localized antioxidants (e.g.: MitoQ, SkQ, ergothioneine), mitochondrial metabolic modulators (e.g. dichloroacetic acid), and uncouplers (e.g.: uncoupling proteins, dinitrophenol) as well as some alternative future approaches for targeting compounds to the mitochondria, including advances from nanotechnology.     

Realistic population dynamics in epidemiological models: the impact of population decline on the dynamics of childhood infectious diseases. Measles in Italy as an example

Most contributions in the field of mathematical modelling of childhood infectious diseases transmission dynamics have focused on stationary or exponentially growing populations. In this paper an epidemiological model with realistic demography is used to investigate the impact of the non-equilibrium conditions typical of the transition to sustained below replacement fertility (BRF) recently observed in a number of western countries, upon the transmission dynamics of measles. The results depend on the manner we model the relation between the (changing) age distribution of the population and contacts. Under some circumstances the transitional ageing phase typical of BRF populations might complexly interact with epidemiological variables leading to (i) a substantial reduction in the amount of vaccination effort required for eliminating the disease; (ii) a significant magnification of the perverse impact of vaccination in terms of the burden of severe age related morbidity.     

Vitality diagnostics and preventive medicine for the well-being of people at advanced age

This paper emphasises the importance of vitality diagnostics in relation to healthy ageing and prevention of age-associated diseases. Ageing, reducing the reserve capacity, decreases the adaptability of various systems and increases the risk of functional disorders. The early recognition and treatment of functional disorders in vitality diagnostics laboratories provides an opportunity to prevent or delay the onset of degenerative diseases related to advanced age.     

Fingerprinting the diseased prostate: associations between BPH and prostate cancer

Two of the most common diseases which occur in ageing men relate to their prostate. BPH and prostate cancer are prevalent diseases which have an impact on most men as they age. The advent of gene expression analysis has provided an opportunity to examine these diseases in a novel fashion. These analyses, to date, have revealed associations between these two diseases which have not been previously identified. These commonalities include global genetic changes which occur throughout the prostates in individuals with these diseases. Understanding the fingerprints of these diseases is providing novel markers and treatment strategies for both BPH and prostate cancer.     

Telomeres and human disease: ageing, cancer and beyond

Telomere length and telomerase activity are important factors in the pathobiology of human disease. Age-related diseases and premature ageing syndromes are characterized by short telomeres, which can compromise cell viability, whereas tumour cells can prevent telomere loss by aberrantly upregulating telomerase. Altered functioning of both telomerase and telomere-interacting proteins is present in some human premature ageing syndromes and in cancer, and recent findings indicate that alterations that affect telomeres at the level of chromatin structure might also have a role in human disease. These findings have inspired a number of potential therapeutic strategies that are based on telomerase and telomeres.