Objective Age-related changes in the immune system, also known as ‘immunosenescence’, have a huge detrimental impact on the health of our ageing populations. However, the extent and mechanisms of the changes, and thus possible routes to prevention or alleviation, are largely unknown. We propose to analyse immunosenescence with unprecedented resolution by determining in large cohorts of volunteers the changes with age in circulating levels of ~140 subtypes of immune system cells and ~25 immune molecules, including cytokines and antibodies. We will also quantify age-related immune dysfunction, and notably autoreactivity, by determining the specificity and level of key circulating autoantibodies and their correlation with contractions in the B & T cell repertoire in our large general population ageing cohorts. Underlying genetic and major environmental factors -- including life style choices like smoking, diet, alcohol intake and, physical activity as well as transmissible viral infections -- will be systematically analysed. The analyses will build on our studies on levels of immune system cell subsets and inflammatory biomarkers in genetically well characterized population cohorts, and will be followed up by examining sorted circulating cells for ageing-related shifts in transcriptional profiles and function. For these targetted experiments, our focus,will be on cell types that show the greatest changes with age and/or are most critical for immune responsiveness; and from volunteers selected based on their genetic and epidemiological exposure profiles. Studies will be facilitated by complementary expertise of the participating centres, capitalising on unique bioresources. Overall, the advances in knowledge should better elucidate pathways of immunosenescence, reveal new biomarkers for early diagnosis of immune dysfunction, and point to target cells and molecules that can be supplemented or activated for eventual prevention or alleviation of ageing-related immune dysfunction. Fields of science natural sciencescomputer and information sciencesdata sciencemedical and health sciencesclinical medicinerheumatologymedical and health sciencesbasic medicineneurologymultiple sclerosismedical and health sciencesbasic medicineimmunologyautoimmune diseasesmedical and health scienceshealth sciencesnutrition Programme(s) H2020-EU.3.1. - SOCIETAL CHALLENGES - Health, demographic change and well-being Main Programme H2020-EU.3.1.1. - Understanding health, wellbeing and disease Topic(s) PHC-01-2014 - Understanding health, ageing and disease: determinants, risk factors and pathways Call for proposal H2020-PHC-2014-2015 See other projects for this call Sub call H2020-PHC-2014-two-stage Funding Scheme RIA - Research and Innovation action Coordinator CONSIGLIO NAZIONALE DELLE RICERCHE Net EU contribution € 2 514 062,50 Address PIAZZALE ALDO MORO 7 00185 Roma Italy See on map Region Centro (IT) Lazio Roma Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 514 062,50 Participants (4) Sort alphabetically Sort by Net EU contribution Expand all Collapse all THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE United Kingdom Net EU contribution € 2 227 855,26 Address TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 227 855,26 UNIVERSITAET INNSBRUCK Austria Net EU contribution € 700 000,00 Address INNRAIN 52 6020 Innsbruck See on map Region Westösterreich Tirol Innsbruck Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 700 000,00 ALTA RICERCA E SVILUPPO IN BIOTECNOLOGIE SRLU Italy Net EU contribution € 200 000,00 Address VIA FIORENTINA 151 53100 Siena See on map SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed. Yes Region Centro (IT) Toscana Siena Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 200 000,00 THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD United Kingdom Net EU contribution € 208 082,24 Address WELLINGTON SQUARE UNIVERSITY OFFICES OX1 2JD Oxford See on map Region South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 208 082,24