Editorial [Hot Topic:Drug Targets in Ageing and Age-Associated Diseases (Executive Editors: C. Caruso and E. Jirillo)]

Ageing is a post-maturational process that, due to a diminished homeostatic capacity and increased vulnerability, reduces responsiveness to environmental stimuli. Nowdays, individuals can live until 80-120 years but this increase in lifespan is not free of disabilities and diseases. Therefore, current attempts are aimed at finding out drug targets by which one may correct functional deficits in ageing and/or prevent age-associated diseases. Current knowledge on ageing and age-associated diseases and anti-ageing therapies will be reviewed in this issue of Current Pharmaceutical Design. Jirillo and associates [1] will discuss the state of the art of anti-ageing therapies with special reference to immunosenescence, Alzheimer's disease, cardiovascular diseases and diet and age-related diseases. Henson and associates [2] will examining the role of CTLA-4 and PD-1 in regulating immune response and their therapeutic potential in the elderly. Amadio and associates [3] will show that the RNA-binding protein ELAV/HuR can affect, post-transcriptionally, the fate of HSP70 mRNA following H2O2-mediated oxidative stress in SH-SY5Y human neuroblastoma cells. An impairment of this regulatory mechanism may lead to the defective cellular response to oxidative stress as evidenced in cerebral senescence. Porcellini and associates [4] will discuss on the role of α-1-anti-chymotrypsin (ACT) in Alzheimer's disease and the development of compounds able to interfere with ACT biological activity. Lanni and associates [5] will focus on p53 which has been involved in ageing and Alzheimer's disease. With ageing a conformational change of p53 occurs which impairs its ability to activate an apoptotic program when cells are exposed to noxious stimuli. Balistreri and associates [6] will demonstrate a correlation between the polymorphisms of TLR4 and CD14 genes and Alzheimer's disease with special reference to the +896A/G TLR4 single nucleotide polymorphism. Listì and associates [7] will report that -765G COX-2 and -1708A 5-LO single nucleotide polymorphisms are independent positive risk factors for developing myocardial infarction, thus allowing to determine which patients to treat with specific inhibitors of the eicosanoids or their enzymes. Iacoviello and associates [8] will show that high thyroid stimulating hormone levels in chronic heart failure patients are independently associated with a greater likelihood of heart failure progression, thus supporting prospective studies for establishing the most appropriate treatment of clinical hypothyroidism in such patients. Chiloiro and associates [9] will examine the relationship between moderate obesity and glucose metabolism, insulin sensitivity and suspected fatty liver in children. Results will clarify that moderately obese children exhibit a clear increase of insulin and insulin resistance which may lead to a future metabolic syndrome. Di Renzo and associates [10] will investigate the effect of body fat mass on the relationships between -174G/C IL-6 promoter gene polymorphism, IL-6 circulating level and insulin resistance. Data will show that fat mass percentage is a major determinant of increase in IL-6 production and insulin resistance. Trosko [11] will emphasize the need to provide elderly subjects with a correct dietary intake that might also affect stem cells, whose alterations can compromise the ageing of that organ. Mocchegiani and associates [12] will demonstrate that the association “zinc plus selenium” improves humoral immunity in old subjects after influenza vaccination. Furthermore, the association “zinc plus niacin (a precursor of NAD+)” in elderly is in progress. Magrone and associates [13-15] will investigate the ability of red wine polyphenols to promote the in vitro release from human healthy peripheral blood mononuclear cells of regulatory, proinflammatory and antiinflammatory cytokines as well as of immunoglobulins. The involvement of polyphenols in the activation of p38 and ERK1/2 as well as nitric oxide production will be discussed. Collectively, in vitro data will show that a moderate use of red wine in humans is able to elicit at cellular and molecular levels a protective response for the host mostly in age-related disorders.