1,721,650 research outputs found
Effects of extremely low frequency (ELF) pulsed electromagnetic fields (PEMFs) on immunocompetent cells
No full textThe effects of the exposure of mitogen-stimulated human lymphocytes from young and aged subjects to low-frequency pulsed electromagnetic fields (PEMFs) were studied, by measuring cell proliferation, production and utilization of interleukin-2 (IL-2) and the expression of IL-2 receptors. Moreover, data are presented about DNA repair, cell survival and genotoxic effects in cultures exposed to PEMFs. PEMFs increased DNA synthesis, and the effect was more pronunced in the cells from very old subjects. Moreover a higher percentage of IL-2 receptor-positive cells and T-activated lymphocytes was found in the exposed cultures. No effects were found as far as DNA repair and genotoxic effects are concerned
Inflammaging and human longevity in the omics era
No full textInflammaging is a recent theory of aging originally proposed in 2000 where data and conceptualizations regarding the aging of the immune system (immunosenescence) and the evolution of immune responses from invertebrates to mammals converged. This theory has received an increasing number of citations and experimental confirmations. Here we present an updated version of inflammaging focused on omics data â particularly on glycomics â collected on centenarians, semi-supercentenarians and their offspring. Accordingly, we arrived to the following conclusions: i) inflammaging has a structure where specific combinations of pro- and anti-inflammatory mediators are involved; ii) inflammaging is systemic and more complex than we previously thought, as many organs, tissues and cell types participate in producing pro- and anti-inflammatory stimuli defined âmolecular garbageâ; iii) inflammaging is dynamic, can be propagated locally to neighboring cells and systemically from organ to organ by circulating products and microvesicles, and amplified by chronic age-related diseases constituting a âlocal fireâ, which in turn produces additional inflammatory stimuli and molecular garbage; iv) an integrated Systems Medicine approach is urgently needed to let emerge a robust and highly informative set/combination of omics markers able to better grasp the complex molecular core of inflammaging in elderly and centenarians
Resistance to apoptosis in CTLL-2 cells overexpressing B-Myb is associated with B-Myb-dependent bcl-2 induction
No full textTranscriptional regulators of the Myb family play important roles in cell proliferation, differentiation, and survival. To investigate the role of Myb proteins in the regulation of apoptosis, we studied the apoptotic response of interleukin 2-dependent CTLL-2 cells stably transfected with B-Myb. B-Myb-overexpressing cells showed a diminished cytokine dependence and were resistant to apoptosis induced by doxorubicin, ceramide, and dexamethasone, Overexpression of B-Myb was associated with enhanced expression of bcl-2, which was dependent, at least in part, on increased transcription. In transient transfection assays in T-lymphoblastic cells, B-Myb was able to stimulate the promoter activity of the bcl-2 5' flanking region linked to the chloramphenicol acetyltransferase reporter gene. A segment of the bcl-2 promoter (nucleotides +34 to +58 relative to the transcription initiation site) contained a putative Myb-binding site and was shown to specifically interact with B-Myb and to confer B-Myb responsiveness to a bcl-2/chloramphenicol acetyltransferase reporter construct. These results indicate that B-Myb promotes T cells survival by enhancing the expression of bcl-2 and identify bcl-2 as a B-Myb target gene regulated in a DNA binding-dependent manner
Role of mitochondrial DNA in longevity, aging and age-related diseases in humans: a reappraisal.
No full textThe genetic variability of H. sapiens mitochondrial DNA (mtDNA) can be either
germ-line inherited or somatically acquired, and its effect on aging and
longevity as well as on the pathogenesis of complex age-related diseases is a hot
topic. Here we illustrate the complexity of such studies, related to the large
genetic variability of mtDNA in different populations and the fact that the rate
of the aging process is different in different cells, tissues and organs. As far
as concern Alzheimer's disease, the accumulation of somatic mutations in several
tissues have been investigated, as well as the inherited mtDNA variability.
However, the issue is still controversial and further studies are needed to
clarify the role of mtDNA variants in Alzheimer's disease. This review is aimed
to summarize the most recent advances in this field. By high throughput mtDNA
sequencing and the study of large cohorts of ethnically homogeneous
subjects/patients, it is now possible to perform high dimensionality studies in
order to clarify the genetic associations among several inherited mtDNA variants
and longevity or age-associated diseases in humans
Impact of Nutrition on Adult Vaccination Efficacy
No full textAfter introductory chapters devoted to the safe production and distribution of vaccines, the book addresses the question of adult vaccination in the framework of a life-course approach to vaccination. It presents the proceedings of multidisciplinary expert discussions with an excellent summary of the current state of knowledge on adult vaccination in various diseases, as well as an overview of the professionals involved and the obstacles to achieving greater vaccine uptake, and how these may be addressed.
The book systematically discusses the major vaccine-preventable diseases, as well as regulatory issues in vaccine provision, and presents the results of an expert meeting designed to identify the obstacles to vaccination, and solutions for addressing these barriers. It goes on to extend the discussion beyond the traditional boundaries of human health to encompass the “one health” concept.
The book is intended for all those with an interest in vaccination, including physicians (from a wide range of disciplines including geriatrics/gerontology, infectious diseases, pediatrics, internal medicine, and other non-organ specialties), other healthcare professionals, pharmacists, representatives of the pharmaceutical industry and regulatory bodies (EMEA, national authorities), policymakers, the media and the general public
Senescence associated macrophages and "macroph-aging": are they pieces of the same puzzle?
No full textLiterature review in support of adjuvanticity/immunogenicity assessment of proteins
Full text linkBased on the risk assessment of genetically modified plants, according to Implementing Regulation (EU) No 503/201321 “In cases when known functional aspects of the newly expressed protein or structural similarity to known strong adjuvants may indicate possible adjuvant activity, the applicant shall assess the possible role of these proteins as adjuvants”. To further investigate the topic, an EFSA procurement was launched requesting a comprehensive literature review and critically appraisal on adjuvanticity and immunogenicity of proteins. A systematic literature search and critical review was performed, identifying 299 relevant publications. From the evaluation of the relevant literature emerged that: i) a clear classification of adjuvant and immunogens of proteins cannot be done; ii) structural features able to modulate adjuvanticity and immunogenicity are mainly ascribed to therapeutic proteins and in the context of allergenicity and cross-reactivity; iii) factors affecting the propensity of a protein to stimulate immune response are aggregation, thermal processing, digestion, food matrix, among others; iv) different proteins are described to have immunomodulatory effects; v) risk assessment of adjuvant and immunogenic behaviour of proteins requires specific methodologies that can be adapted from other fields; vi) adjuvanticity and immunogenicity of Cry proteins in certain experimental conditions seems plausible but due to low dosage, oral route of administration, food and feed processing and digestion, it is unlikely to emerge as a safety issue in food and feed; vii) eliciting an immune response is a very complex matter as the body responds to immune offence by inducing many processes. Based on these considerations, it is expected that the availability of new humanized animal models and the possibility to deploy artificial intelligent systems on the vastity of human data will become a general direction aiming to help answering specific questions relating to the immune systems, including the adjuvanticity and immunogenicity of food/feed proteins
Toward precision interventions and metrics of inflammaging
No full textInflammaging describes a chronic, systemic, low-grade inflammatory state that is recognized as a major risk factor for age-related diseases (ARDs) and a pivotal convergence point of multiple biological mechanisms involved in aging. Here, we discuss the heterogeneity of inflammaging, proposing that it emerges as a consequence of each individual’s lifelong exposures to inflammatory stimuli, shaped by a unique combination of genetics, lifestyle, socioeconomic conditions and environmental factors such as infections and pollution. Through this lens, we then discuss measuring inflammaging, describing the development of inflammatory clocks that quantify inflammatory age and show strong associations with ARD incidence as well as how other aging clocks intersect with inflammaging. Finally, we consider interventions that may counteract inflammaging, including nutritional interventions, physical activity and gerotherapies such as senolytics. We propose that deepening our knowledge of the individual nature of inflammaging stands to enhance our understanding of personalized aging trajectories and inform precision interventions
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