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Ferrara, Italy

Remondini D.,University of Bologna | Salvioli S.,University of Bologna | Salvioli S.,BioPharmaNet Laboratory | Francesconi M.,University of Bologna | And 7 more authors.
Molecular BioSystems | Year: 2010

Human aging is associated with complex alterations that contribute to remodelling of physiological processes and ultimately manifests in loss of tissue/organ function. Peripheral blood T cells do not escape this phenomenon and undergo profound remodelling with aging. Thus, investigating the effects of aging on T cells transcriptomics and identifying the underlying regulatory mechanisms can be of extreme importance to understand the aging process in the Immune System (IS). To this aim, we performed an analysis of gene expression data of T cells collected from peripheral blood of 25 healthy human donors of different age from 25 to more than 95 years, in order to characterize changes that occur throughout the entire adult lifespan. By means of microarray analysis, we observed large groups of genes exhibiting non-monotonic expression patterns over time: such behaviour, that could not be observed in typical "two-group" experiments (e.g. young vs. old people) highlights similarities in gene expression profiles of young and "successfully aged" individuals. Genes whose expression profiles change during lifespan were grouped into three main patterns (eigenmodes) to which different biological functions were significantly associated. The analysis of KEGG pathways to which these genes belong indicated that the biological processes altered in T cell aging are not only those typically associated with immune cells (Jak-STAT signalling, T cell receptor signalling, cytokine-cytokine receptor interactions, etc.) but also some not specific of immune cells, such as long-term depression, PPAR and mTOR signalling, glucose and glutathione metabolism, suggesting that T cell aging may be representative of a more generalised aging phenomenon. Thus, the T cell may represent a useful cellular model to study organismal aging. We further searched for over-represented transcription factor binding sites (TFBSs) in the promoter regions of genes clustered by similarity of their age-related patterns to evidence possible co-regulation. A comparison between over-representation of TFBSs and the time course of the corresponding transcription factor (TF) expression levels revealed that a restricted group of TFs may play a central role in driving aging-specific changes in gene expression of T cells. © 2010 The Royal Society of Chemistry.

Zironi I.,University of Bologna | Zironi I.,Institute For Biomedical Technologies Itb | Gaibani P.,University of Bologna | Remondini D.,University of Bologna | And 12 more authors.
Mechanisms of Ageing and Development | Year: 2010

Aging is a complex process resulting from, among other, dynamic non-linear interactions between genetics and environment. Centenarians are the best example of successful aging in humans, as they escaped from, or largely postponed, major age-related diseases. Ionic fluxes changes play a key role in several patho-physiological cellular processes, but their relation to human aging is largely unexplored. In the present study we have compared patch-clamp potassium (K+) current recordings from dermal fibroblasts (DF) obtained from young, elderly and centenarian donors. We found that in DF from elderly donors, but not from centenarians, K+ current amplitude is significantly smaller with respect to DF from young donors. Moreover, cell membrane capacitance of DF from elderly donors is smaller with respect to young donors and centenarians. We also observed that the voltage-gated Shaker Kv1.1 channel is expressed in higher percentage of elderly's and centenarian's DF than young's, whereas the large-conductance calcium-activated K+ (BKCa) channel β1 subunit is expressed in lower percentage of centenarian's DF than in elderly's and young's. The maintenance of young K+ currents and the peculiar age-related remodeling of K+ channel subtypes in centenarian's DF is likely associated with successful aging and might provide a predictive marker of longevity. © 2010 Elsevier Ireland Ltd.

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