From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing

Understanding the basic biology of human ageing is a key milestone in attempting to ameliorate the deleterious consequences of old age. This is an urgent research priority given the global demographic shift towards an ageing population. Although some molecular pathways that have been proposed to contribute to ageing have been discovered using classical biochemistry and genetics, the complex, polygenic and stochastic nature of ageing is such that the process as a whole is not immediately amenable to biochemical analysis. Thus, attempts have been made to elucidate the causes of monogenic progeroid disorders that recapitulate some, if not all, features of normal ageing in the hope that this may contribute to our understanding of normal human ageing. Two canonical progeroid disorders are Werner’s syndrome and Hutchinson-Gilford progeroid syndrome (also known as progeria). Because such disorders are essentially phenocopies of ageing, rather than ageing itself, advances made in understanding their pathogenesis must always be contextualised within theories proposed to help explain how the normal process operates. One such possible ageing mechanism is described by the cell senescence hypothesis of ageing. Here, we discuss this hypothesis and demonstrate that it provides a plausible explanation for many of the ageing phenotypes seen in Werner’s syndrome and Hutchinson-Gilford progeriod syndrome. The recent exciting advances made in potential therapies for these two syndromes are also reviewed

Association between interleukin 2 polymorphisms and haplotypes and gastric cancer

Univ Sagrado Coracao USC, Bauru, BrazilUniv Fed Sao Paulo UNIFESP, Sao Paulo, BrazilUniv Fed Sao Paulo UNIFESP, Sao Paulo, BrazilWeb of Scienc

Analysis of SNAP25 mRNA expression and promoter DNA methylation in brain areas of Alzheimer’s Disease patients

Alzheimer's Disease (AD) is the most common cause of dementia in elderly people. the presynaptic terminal is an important site of pathological changes in AD, leading to synaptic loss in specific brain regions, such as in the cortex and hippocampus. in this study, we investigated synaptosomal-associated protein, 25-kDa (SNAP25) mRNA levels and promoter DNA methylation in post mortem brain tissues (entorhinal and auditory cortices and hippocampus) from healthy elderly and AD subjects as well as in peripheral blood leukocytes of young, healthy elderly and AD patients. mRNA quantification was performed by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) using the Delta Delta C-T method and promoter DNA methylation was quantified by mass spectrometry using the Sequenom EpiTYPER platform. We observed a significant decrease in SNAP25 expression in AD across all the three brain regions in relation to the healthy elderly subjects, suggesting impairment in synaptic function. the changes in the auditory cortex reflected those observed in the hippocampus and entorhinal cortex, the primary areas affected in AD. However, no AD-associated differences in SNAP25 promoter DNA methylation were observed suggesting that other mechanisms may be involved in mediating the observed gene expression changes. (C) 2012 IBRO. Published by Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Disciplina Genet, Dept Morfol & Genet, São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Neurol Clin, Dept Neurol Neurocirurgia, São Paulo, BrazilFac Med Marilia FAMEMA, Hemoctr, Genet Lab, Marilia, SP, BrazilMcGill Univ, Dept Psychiat, Douglas Hosp Res Ctr, Montreal, PQ, CanadaKings Coll London, Inst Psychiat, London WC2R 2LS, EnglandUniv Sagrado Coracao, Bauru, SP, BrazilUniversidade Federal de São Paulo, Disciplina Genet, Dept Morfol & Genet, São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Neurol Clin, Dept Neurol Neurocirurgia, São Paulo, BrazilWeb of Scienc