http://www.immunityageing.com The most accessed research articles published by Immunity & Ageing 2012-04-23T00:00:00Z This paper pays attention to the modifiable lifestyle factors such as diet and nutrition thatmight influence life extension and successful ageing. Previous data reported that in Sicily, thebiggest Mediterranean island, there are some places where there is a high frequency of malecentenarians with respect to the Italian average. The present data show that in SicaniMountain zone there are more centenarians with respect to the Italian average. In fact, in fivevillages of Sicani Mountains, there were 19 people with an age range of 100-107 years oldfrom a total population of 18,328 inhabitants. So, the centenarian number was 4.32-foldhigher than the national average (10.37 vs. 2.4/10,000); the female/male ratio was 1.1:1 in thestudy area, while the national ratio is 4.54:1. Unequivocally, their nutritional assessmentshowed a high adherence to the Mediterranean nutritional profile with low glycemic indexfood consumed. To reach successful ageing it is advisable to follow a diet with low quantityof saturated fat and high amount of fruits and vegetables rich in phytochemicals. http://www.immunityageing.com/content/9/1/10 Sonya Vasto Claudia Rizzo Calogero Caruso Immunity & Ageing 2012, null:10 2012-04-23T00:00:00Z doi:10.1186/1742-4933-9-10 /content/figures/1742-4933-9-10-toc.gif Immunity & Ageing 1742-4933 ${item.volume} 10 2012-04-23T00:00:00Z PDF The demographic and social changes of the past decades have determined improvements in public health and longevity. So, the number of centenarians is increasing as a worldwide phenomenon. Scientists have focused their attention on centenarians as optimal model to address the biological mechanisms of "successful and unsuccessful ageing". They are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases, such as cardiovascular diseases and cancer. Thus, particular attention has been centered on their genetic background and immune system. In this review, we report our data gathered for over 10 years in Sicilian centenarians. Based on results obtained, we suggest longevity as the result of an optimal performance of immune system and an over-expression of anti-inflammatory sequence variants of immune/inflammatory genes. However, as well known, genetic, epigenetic, stochastic and environmental factors seem to have a crucial role in ageing and longevity. Epigenetic is associated to ageing, as demonstrated in many studies. In particular, ageing is associated with a global loss of methylation state. Thus, the aim of our future studies will be to analyze the weight of epigenetic changes in ageing and longevity. http://www.immunityageing.com/content/9/1/8 Carmela Balistreri Giuseppina Candore Giulia Accardi Manuela Bova Silvio Buffa Matteo Bulati Giusi Forte Florinda Listi Adriana Martorana Marisa Palmeri MariaValeria Pellicano Loredana Vaccarino Letizia Scola Domenico Lio Giuseppina Colonna-Romano Immunity & Ageing 2012, null:8 2012-04-23T00:00:00Z doi:10.1186/1742-4933-9-8 /content/figures/1742-4933-9-8-toc.gif Immunity & Ageing 1742-4933 ${item.volume} 8 2012-04-23T00:00:00Z PDF World population has experienced continuous growth since 1400 A.D. Current projections show a continued increase - but a steady decline in the population growth rate - with the number expected to reach between 8 and 10.5 billion people within 40 years. The elderly population is rapidly rising: in 1950 there were 205 million people aged 60 or older, while in 2000 there were 606 million. By 2050, the global population aged 60 or over is projected to expand by more than three times, reaching nearly 2 billion people 1. Most cancers are age-related diseases: in the US, 50% of all malignancies occur in people aged 65-95. 60% of all cancers are expected to be diagnosed in elderly patients by 2020 2. Further, cancer-related mortality increases with age: 70% of all malignancy-related deaths are registered in people aged 65 years or older 3. Here we introduce the microscopic aspects of aging, the pro-inflammatory phenotype of the elderly, and the changes related to immunosenescence. Then we deal with cancer disease and its development, the difficulty of treatment administration in the geriatric population, and the importance of a comprehensive geriatric assessment. Finally, we aim to analyze the complex interactions of aging with cancer and cancer vaccinology, and the importance of this last approach as a complementary therapy to different levels of prevention and treatment. Cancer vaccines, in fact, should at present be recommended in association to a stronger cancer prevention and conventional therapies (surgery, chemotherapy, radiation therapy), both for curative and palliative intent, in order to reduce morbidity and mortality associated to cancer progression. http://www.immunityageing.com/content/9/1/4 Paolo Mazzola Saba Radhi Leonardo Mirandola Giorgio Annoni Marjorie Jenkins Everardo Cobos Maurizio Chiriva-Internati Immunity & Ageing 2012, null:4 2012-04-17T00:00:00Z doi:10.1186/1742-4933-9-4 /content/figures/1742-4933-9-4-toc.gif Immunity & Ageing 1742-4933 ${item.volume} 4 2012-04-17T00:00:00Z XML Ageing is a challenge for any living organism and human longevity is a complex phenotype. With increasing life expectancy, maintaining long-term health, functionality and well-being during ageing has become an essential goal. To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health. In this article we briefly discuss relevant topics on ageing and longevity with particular focus on dietary patterns of centenarians and nutrient-sensing pathways that have a pivotal role in the regulation of life span. Finally, we also discuss the potential role of Nrf2 system in the pro-ageing signaling emphasizing its phytohormetic activation. http://www.immunityageing.com/content/9/1/9 Sergio Davinelli D. Craig Willcox Giovanni Scapagnini Immunity & Ageing 2012, null:9 2012-04-23T00:00:00Z doi:10.1186/1742-4933-9-9 /content/figures/1742-4933-9-9-toc.gif Immunity & Ageing 1742-4933 ${item.volume} 9 2012-04-23T00:00:00Z PDF Healthy ageing and longevity in humans result from a number of factors, including genetic background, favorable environmental and social factors and chance.In this article we aimed to overview the research on the biological basis of human healthy ageing and longevity, discussing the role of epidemiological, genetic and epigenetic factors in the variation of quality of ageing and lifespan, including the most promising candidate genes investigated so far. Moreover, we reported the methodologies applied for their identification, discussing advantages and disadvantages of the different approaches and possible solutions that can be taken to overcome them. Finally, we illustrated the recent approaches to define healthy ageing and underlined the role that the emerging field of epigenetics is gaining in the search for the determinants of healthy ageing and longevity. http://www.immunityageing.com/content/9/1/6 Alberto Montesanto Serena Dato Dina Bellizzi Giuseppina Rose Giuseppe Passarino Immunity & Ageing 2012, null:6 2012-04-23T00:00:00Z doi:10.1186/1742-4933-9-6 /content/figures/1742-4933-9-6-toc.gif Immunity & Ageing 1742-4933 ${item.volume} 6 2012-04-23T00:00:00Z XML The trace element zinc is essential for the immune system, and zinc deficiency affects multiple aspects of innate and adaptive immunity. There are remarkable parallels in the immunological changes during aging and zinc deficiency, including a reduction in the activity of the thymus and thymic hormones, a shift of the T helper cell balance toward T helper type 2 cells, decreased response to vaccination, and impaired functions of innate immune cells. Many studies confirm a decline of zinc levels with age. Most of these studies do not classify the majority of elderly as zinc deficient, but even marginal zinc deprivation can affect immune function. Consequently, oral zinc supplementation demonstrates the potential to improve immunity and efficiently downregulates chronic inflammatory responses in the elderly. These data indicate that a wide prevalence of marginal zinc deficiency in elderly people may contribute to immunosenescence. http://www.immunityageing.com/content/6/1/9 Hajo Haase Lothar Rink Immunity & Ageing 2009, null:9 2009-06-12T00:00:00Z doi:10.1186/1742-4933-6-9 /content/figures/1742-4933-6-9-toc.gif Immunity & Ageing 1742-4933 ${item.volume} 9 2009-06-12T00:00:00Z XML Aging is associated with a decline in immune function (immunosenescence), a situation known to correlate with increased incidence of cancer, infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. A decrease in functional competence of individual natural killer (NK) cells is found with advancing age. Macrophages and granulocytes show functional decline in aging as evidenced by their diminished phagocytic activity and impairment of superoxide generation. There is also marked shift in cytokine profile as age advances, e.g., CD3+ and CD4+ cells decline in number whereas CD8+ cells increase in elderly individuals. A decline in organ specific antibodies occurs causing reduced humoral responsiveness. Circulating melatonin decreases with age and in recent years much interest has been focused on its immunomodulatory effect. Melatonin stimulates the production of progenitor cells for granulocytes-macrophages. It also stimulates the production of NK cells and CD4+ cells and inhibits CD8+ cells. The production and release of various cytokines from NK cells and T-helper lymphocytes also are enhanced by melatonin. Melatonin presumably regulates immune function by acting on the immune-opioid network, by affecting G protein-cAMP signal pathway and by regulating intracellular glutathione levels. Melatonin has the potential therapeutic value to enhance immune function in aged individuals and in patients in an immunocompromised state. http://www.immunityageing.com/content/2/1/17 Venkatramanujam Srinivasan Georges Maestroni Daniel Cardinali Ana Esquifino S. Pandi-Perumal Sandra Miller Immunity & Ageing 2005, null:17 2005-11-29T00:00:00Z doi:10.1186/1742-4933-2-17 /content/figures/1742-4933-2-17-toc.gif Immunity & Ageing 1742-4933 ${item.volume} 17 2005-11-29T00:00:00Z XML The success of biomedical researches has led to improvement in human health and increased life expectancy. An unexpected consequence has been an increase of age-related diseases and, in particular, neurodegenerative diseases. These disorders are generally late onset and exhibit complex pathologies including memory loss, cognitive defects, movement disorders and death. Here, it is described as the use of simple animal models such as worms, fishes, flies, Ascidians and sea urchins, have facilitated the understanding of several biochemical mechanisms underlying Alzheimer's disease (AD), one of the most diffuse neurodegenerative pathologies. The discovery of specific genes and proteins associated with AD, and the development of new technologies for the production of transgenic animals, has helped researchers to overcome the lack of natural models. Moreover, simple model systems of AD have been utilized to obtain key information for evaluating potential therapeutic interventions and for testing efficacy of putative neuroprotective compounds. http://www.immunityageing.com/content/9/1/3 Marta Di Carlo Immunity & Ageing 2012, null:3 2012-04-16T00:00:00Z doi:10.1186/1742-4933-9-3 /content/figures/1742-4933-9-3-toc.gif Immunity & Ageing 1742-4933 ${item.volume} 3 2012-04-16T00:00:00Z PDF The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses or bacteria and other pathogens. During evolution the human organism was set to live 40 or 50 years; today, however, the immune system must remain active for much a longer time. This very long activity leads to a chronic inflammation that slowly but inexorably damages one or several organs: this is a typical phenomenon linked to ageing and it is considered the major risk factor for age-related chronic diseases. Alzheimer's disease, atherosclerosis, diabetes and even sarcopenia and cancer, just to mention a few – have an important inflammatory component, though disease progression seems also dependent on the genetic background of individuals. Emerging evidence suggests that pro-inflammatory genotypes are related to unsuccessful ageing, and, reciprocally, controlling inflammatory status may allow a better chance of successful ageing. In other words, age-related diseases are "the price we pay" for a life-long active immune system: this system has also the potential to harm us later, as its fine tuning becomes compromised. Our immune system has evolved to control pathogens, so pro-inflammatory responses are likely to be evolutionarily programmed to resist fatal infections with pathogens aggressively. Thus, inflammatory genotypes are an important and necessary part of the normal host responses to pathogens in early life, but the overproduction of inflammatory molecules might also cause immune-related inflammatory diseases and eventually death later. Therefore, low responder genotypes involved in regulation of innate defence mechanisms, might better control inflammatory responses and age-related disease development, resulting in an increased chance of long life survival in a "permissive" environment with reduced pathogen load, medical care and increased quality of life. http://www.immunityageing.com/content/2/1/8 Federico Licastro Giuseppina Candore Domenico Lio Elisa Porcellini Giuseppina Colonna-Romano Claudio Franceschi Calogero Caruso Immunity & Ageing 2005, null:8 2005-05-18T00:00:00Z doi:10.1186/1742-4933-2-8 /content/figures/1742-4933-2-8-toc.gif Immunity & Ageing 1742-4933 ${item.volume} 8 2005-05-18T00:00:00Z XML We describe the inflammation pathway from Cholesterol to Aging. Interleukin 6 mediated inflammation is implicated in age-related disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimer's disease and some forms of Arthritis and Cancer. Statins and Bisphosphonates inhibit Interleukin 6 mediated inflammation indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion. Polyphenolic compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated inflammation by direct inhibition of the signal transduction pathway. Therapeutic targets for the control of all the above diseases should include inhibition of Interleukin-6 mediated inflammation. http://www.immunityageing.com/content/4/1/1 Sota Omoigui Immunity & Ageing 2007, null:1 2007-03-20T00:00:00Z doi:10.1186/1742-4933-4-1 /content/figures/1742-4933-4-1-toc.gif Immunity & Ageing 1742-4933 ${item.volume} 1 2007-03-20T00:00:00Z XML