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A road map for European ageing research

Final Report Summary - WHYWEAGE (A road map for European ageing research)

Executive Summary:

Europe faces the immense challenge of unprecedented increase in life expectancy, which will become more intensive into the 21st century. Although this state of affairs is the essentially positive outcome from multiple improvements in health care and socioeconomic circumstances, it nevertheless leads to major pressure on all member and associated states of the European Union (EU) in terms of increasing prevalence of age-related health problems. There is urgent need for more basic research on the underpinning science of biological ageing, in order that it shall be possible to minimise dependency and improve health and quality of life for the rapidly growing numbers of older people. After some preparative efforts made in the Sixth Framework Programme (FP6), the time has come to federate the European research on ageing around commonly agreed perspectives, considering the need for progress in an area of great socioeconomic and political stakes for Europe. Therefore the next step to reinforce the constructive results arising from previous FPs was to establish a road map for European research on the molecular aspects of healthy human ageing. Based on an assessment of the state of the art in molecular gerontology and breakthroughs in biotechnology, we identified the main priorities of research for the next 10 to 15 years:

1. biomarkers of ageing and longevity
2. systems biology and its applications to biological ageing
3. oxidative stress, protein damage and maintenance
4. telomere biology
5. deoxyribonucleic acid (DNA) damage, mitochondria biology and senescence
6. targeting nuclear receptors in age-related diseases (particularly neurodegenerative disease and metabolic disease)
7. vascular ageing
8. immunosenescence and inflammation
9. metabolism and ageing
10. sarcopenia
11. skin ageing, elastic tissues and biotechnologies in skin biogerontology
12. clinical biogerontological research.

Project context and objectives:

Europe faces the immense challenge of unprecedented increase in life expectancy, which will become more intensive into the 21st century. Although this state of affairs is the essentially positive outcome from multiple improvements in health care and socioeconomic circumstances, it nevertheless leads to major pressure on all member and associated states of the European Union in terms of increasing prevalence of age-related health problems. There is urgent need for more basic research on the underpinning science of biological ageing, in order that it shall be possible to minimise dependency and improve health and quality of life for the rapidly growing numbers of older people. To achieve maximum efficacy and obtain relevant results rapidly, at this juncture it is necessary to better define the priorities of ageing research.

After some preparative efforts made in FP6, the time has come to federate the European research on ageing around commonly agreed perspectives, considering the need for progress in an area of great socioeconomic and political stakes for Europe. Therefore the next step to reinforce the constructive results arising from previous FPs was to establish a road map for European research on the molecular aspects of healthy human ageing. Based on an assessment of the state of the art in molecular gerontology and breakthroughs in biotechnology, we aimed to identify the main priorities for the next 10 to15 years.

To do so, we engaged an open and transparent mechanism to support a closely prepared and coordinated series of research workshops on identified topics that terminated in an all-encompassing integrative conference where the texts of final documents were negotiated.

We had already performed extensive Europe-wide surveying of the laboratories active in the field during the course of the FP6 Coordination Action 'Link-Age' (LSHM-CT-2005-513866), run by the coordinator of the present contract. Out of this survey, 11 topics on biogerontological themes have been selected. Each of these topics corresponds to a specific workshop that was held during the first 16 months of this support action. Here are the different selected themes currently considered as most relevant to human ageing research by the current and past coordinators of European projects:

1. Biomarkers of ageing
2. Vascular ageing
3. Mitochondria and senescence
4. Oxidative stress and protein damage; heat shock proteins
5. Telomeres nd DNA damage
6. Immunosenescence and inflammation
7. Obesity/ diabetes/ nutrition/ lipid and glucose metabolism
8. Muscle weakness and sarcopenia/ physical exercises
9. Skin age-related modifications and elastic tissues and skin ageing biotechnology
10. Nuclear receptors and systems biology in ageing
11. Clinical biogerontological studies.

Model systems have not been considered as such since we based the contract on molecular and cellular functions /structures altered with ageing. Many laboratories studying these alterations in model systems had already been selected through Link-Age and were de facto represented in all the workshops. Indeed model systems are often the best way to approach age-related alterations in molecular and cellular functions /structures. However, the final road map includes in its research themes a section titled 'systems biology' to emphasise the importance of this discipline in understanding the biology of ageing.

The organisation of each thematic workshop allowed the assessment of the state of the art and possible future achievements of the EU research on molecular basis of ageing.

The ultimate goals are:

1. to inform the various stakeholders including the European Commission (EC) dealing with scientific research via the production of a policy document entitled 'A road map for molecular gerontology research in Europe'. This final document will serve as a reference tool for further support of European policies on ageing.
2. to inform industry and point out potential areas of commercial interest and to favour the development of small and medium sized enterprises (SMEs) in Europe in the field of ageing research and services to old people so health status can be improved and quality of life at older age can be increased for the whole population in Europe and over the European frontiers.
3. to inform health care providers regarding current state of the art.
4. to inform the public.

These objectives were reached through the organisation of each thematic workshop, the summit conference, the conclusions and publications that arose from these discussions and through the establishment and regular updating of a website dedicated to all issues and objectives of WHYWEAGE.

The final aim of all the individual meetings was to establish a structure for the road map on the European research in ageing by answering the following questions: what are the current and potential themes of research and what is the current and potential work force of ageing research in Europe; how to maintain and develop further the current functional networks; what is the knowledge level of biological ageing in each of the current and potential topics and what is the state of the art as for the interactions between medicine, biology and social sciences; how to ameliorate (interdisciplinary) collaborations; what axes of research need to be developed in the next 10 to 15 years in Europe; how can we define priorities, what are the priorities according to the different stakeholders; who will be the recipients of the progress made considering the different stakeholders in presence (from scientists to socioeconomic benefits).

The writing of the 'road map for molecular gerontology research in Europe' itself was the essence of the project and is giving a state of the art on ageing research in Europe, on the axes of research that should be followed in the near and mid-term future and give suggestions on how ageing research should be pursued. Every partner of WHYWEAGE is internationally recognised as an expert in her/ his domain, which leads to a strong link between the support action and high top-level quality research. Current industrial representatives were associated to each workshop so translational research was directly considered, within the limits of industrial confidentiality, as expected.

During the second periodic report, the main objective was the dissemination of the results obtained during the course of the first period, mainly through the organisation of a joint conference with the FUTURAGE coordination action. There were three objectives to this multidisciplinary conference: to bring together the different actors involved in ageing research in Europe, to create successful networking between disciplines and last but not least to exchange ideas about how each other sees the future of ageing research in Europe. The objective of the FUTURAGE project is to deliver a road map on ageing, but on a larger discipline horizon, that is why we modified the WHYWEAGE road map to be more accessible for non-biogerontologists. This version will be integrated in the Futurage road map.

Project Results:

At the early beginning of the project, partners recruited participants to the different thematic workshops. Notices inviting applications have been spread namely via current relevant FP6 and already running FP7 projects, including the associate member of Link-Age Coordination Action. The call for participation has also been published in Nature (issue of September 2009). Applications sent by interested scientists included details of their academic qualifications and experiences, research interests and publications.

Each workshop was opened to around 20 participants to keep a right number allowing deep discussion on a brainstorming mode. It was decided to keep a few places for spontaneous application, however a very few applications have been received to participate to one or another workshop. The participants attended the workshop(s) essentially upon invitation by the organisers. Several industries or SMEs were also attending the different workshops.

The second step was to establish discussion groups on 12 specific themes linked to biogerontological research. The pre-selected topic addressed during these meetings were biomarkers of ageing; vascular ageing; oxidative stress and protein damage; mitochondria and senescence - telomeres and DNA damage (joint meeting); immunosenescence and inflammation; metabolism; muscle weakness and sarcopenia/ physical exercises; skin age-related modifications and elastic tissues - skin ageing biotechnology (joint meeting); nuclear receptors and systems biology; clinical biogerontological studies.

The final aim of all the individual meetings was to establish a structure for the road map on the European research in ageing by answering the following questions:

1. What are the current and potential themes of research and what is the current and potential work force of ageing research in Europe?
2. How to maintain and develop further the current functional networks?
3. What is the knowledge level of biological ageing in each of the current and potential topics and what is the state of the art as for the interactions between medicine, biology and social sciences?
4. How to ameliorate (interdisciplinary) collaborations?
5. What axes of research need to be developed in the next 10 to 15 years in Europe, how can we define priorities, what are the priorities according to the different stakeholders?
6. Who will be the recipients of the progress made considering the different stakeholders in presence (from scientists to socioeconomic benefits)?

One to three partners (or other scientists specifically invited) in this project were responsible for the organisation of one of the 11 workshops.

Each workshop did not exceed two days. The venues were chosen to favour creative thinking in a relaxed atmosphere. Each workshop included intense discussion on what research directions in each particular field should be prioritised to obtain maximum benefit within the foreseeable future. All the participants were asked to prepare their contributions to the workshop: a preliminary list (see above) of questions was sent to the participants before the workshop. The aim of the questionnaire was:

1. to identify lacks of knowledge in the topics being currently worked out,
2. to identify the new technological developments that could give rise to breakthroughs, to identify the technologies that are still in infancy and/or are promising as for the field, to identify the questions that cannot be answered due to technological vacuum,
3. to identify possible connections with adjacent fields or emerging field, in a transdisciplinary manner,
4. to identify possible future directions to follow and to propose mechanism(s) for setting the priorities.

Time was kept for brainstorming to identify potential sub-thematic relevant to the ageing research, innovative for both fundamental and translational research but not yet considered on an age-related point of view.

Conclusions from each workshop constituted the basic material for the writing of the road map for ageing research at the end of the project and were presented during the final integrative summit conference.

Each workshop included one or more European SMEs or industry to have them as actors in the development of future plans. Their presence was also useful as for identifying the technological /scientific gaps separating them from product development.

At the end of the meeting, two scientists were elected to represent, with the workshop leaders, their topic group at the final summit conference that took place in May 2010, near the end of the first reporting period of the project.

The 12 workshops, scientific in charge, dates and locations were:

1. workshop one (W1): Biomarkers of ageing and longevity. Alexander Bürkle and Stathis Gonos. Place: Athens. Dates: 26 to 28 February 2010.
2. W2. Vascular ageing. Jorge Erusalimsky. Place: Cardiff. Dates: 11 and 12 March 2010.
3. W3 (and W5). Mitochondria and senescence - telomeres and DNA damage. Pidder Jansen-Dürr, Thomas von Zglinicki and Alexander Bürkle. Place: Brussels. Dates: 26 and 27 March 2010.
4. W4. Oxidative stress, protein damage and protein maintenance. Bertrand Friguet, Grzegorz Bartosz and Csaba Soti. Place: Brussels. Dates: 19 and 20 November 2009
5. W6. Immunosenescence and inflammation. Graham Pawelec and Claudio Franceschi. Place: Bologna. Dates: 12 and 13 February 2010
6. W7. Metabolism. Hilde Nebb and Barbara Demeneix. Place: Paris. Date: 5 February 2010.
7. W8. Sarcopenia, muscle weakness and physical exercises. Gillian Butler-Browne. Place: Brussels. Dates: 22 and 23 March 2010.
8. W9 (and W11). Skin ageing and elastic tissues - skin ageing biotechnologies. Pascal Sommer, Michel Salmon, Christos Zouboulis, Brian Clark and Olivier Toussaint. Place: Brussels. Dates: 6 and 7 March 2010.
9. W10. Nuclear receptors and systems biology. Barbara Demeneix and Daryl Shanley. Place: Paris. Date: 4 February 2010.
10. W12. Clinical biogerontological studies. Christian Swine and Christos Zouboulis. Place: Brussels. Dates: 16 and 17 January 2010.

All the workshops were highly successful, many discussions took place about what should be the future of research in biogerontology at the European level. Participants also discussed about the needs in training, networking, multidisciplinarity and other themes directly or indirectly linked to research per se. As already mentioned, a total of 160 scientists attended at least one workshop. The gender distribution was 44 women for 116 men.

Amongst scientists who could not attend the workshops and had the obligation to refuse the invitation, a majority was women, which explained the low distribution in disfavour of the women. The participants came from 21 different countries: Austria (5), Belgium (9), Bulgaria (1), Czech Republic (1), Denmark (6), Finland (4), France (23), Germany (24), Greece (9), Hungary (3), Israel (3), Italy (19), Lithuania (1), Norway (1), Poland (3), Portugal (1), Spain (8), Sweden (5), Switzerland (2), the Netherlands (5), United Kingdom (27) which is a good representation of European countries (both EU members and associates).

Following the 11 workshops, The final summit conference gave the opportunity to the elected representatives of each individual topic meetings to meet and exchange ideas that have been discussed during the smaller workshops. Reports arising from each topic meeting were presented and debated during the conference. All elected representatives of individual topic meeting were responsible for the presentation of their own report in front of the other participants.

The major aim of the conference was to agree upon the final road map to be presented to the commission. A programme was set up but participants soon realised that it had to be continuously changed following the ongoing of the work during the conference and debates.

The conference was held from Monday 17 May till Wednesday 19 May after lunch. The conference finished with the presentation of the road map outlines in presence of the scientific officer of the project. This presentation was followed by a press conference.

Progress of the conference

On the first day, each group of delegates presented the report of their workshop to the other participants. Time was kept for discussion and questions. At the end of the day, one delegate per group met with the coordinator and the manager to discuss the structure the road map should take. Workshops delegates present at the discussion were for W1: Alexander Bürkle; W2: Jorge Erusalimsky; W3 and W5: Thomas von Zglinicki; W4: Bertrand Friguet; W6: Graham Pawelec; W7: David Gems; W8: Gillian Butler-Browne; W9 and W11: Pascal Sommer; W10: Adrianna Maggi; W12: Michael Theodorakis, as well as the coordinator Olivier Toussaint and the manager Béatrice Rayet.

At the end of this meeting, an agreement on the following structure has been reached:

Executive summary

State of the art: brief overview of the field (The idea was to merge these parts but actually the states of the art were so specific that they were kept as there are).

Recommendations. Understanding the biology of ageing (Encompass: how to have better clinical studies, how to have better functional evaluation of patients - subjects, ageing mechanisms, how to improve new/ better protocols): each workshop fills in with their own content

1. How could we design interventional strategies?
2. 'Infrastructures' (longitudinal studies, biobases, imaging, support of gender based studies, ethical considerations etc.).

What are the needs in term of training and dissemination (dissemination networking and training) to be merged between the different workshops report.

Industrial involvement, industrial relevance, social impact, to be merged between the different workshops report.

This structure was then presented to the rest of the assembly. Everybody agreed on the suggested road map structure.

On the second day, the workshops delegates re-wrote their report in view of the road map structure and the manager compiled and centralised all the reports before sending them as a unique document to all summit conference participants. On the late afternoon, participants had read the whole document and met for discussion. It was important that every participant to the conference agreed on the whole document. Questions and arguments were exchanged during this meeting.

On the first half of the morning of the third and last day, each workshop delegates prepared two short five-lines paragraphs, the first one on the justification of their thematic workshop and the second on the major research priority for the development of their field in the future. The compilation of these workshops statement was presented in front of the scientific officer and the press representatives already present in the room.

The conference has been highly successful, the road map has been finalised after the conference and this work package is now ended.

During the first period, the main dissemination activity has been the Press conference held right after the summit conference declaration on 19 May 2010. Eight journalists came to the conference (beside the participants who stayed in the room): two from the Belgian daily paper 'le Soir', one from the Belgian daily paper 'vers l'avenir', one from the Belga press agency, the editor of the 'mutualités socialistes' newsletter and the person in charge for the 'fonds de la recherche scientifique' (FNRS) newsletter. Two left the room before the manager could ask their affiliation. The project was also presented in the Facultés Universitaires Notre-Dame de la Paix (FUNDP) magazine Libre-Cours in June 2010.

During the second period, close collaboration has been set up with the FUTURAGE programme (see http://www.futurage.group.shef.ac.uk/) whose objective is to deliver a road map for ageing research but on a larger discipline horizon. Together with the Futurage action, we co-organised a multidisciplinary conference on ageing research in Europe. Beside Futurage and WHYWEAGE, several other support actions and research projects have been invited to participate in order to cross link results and views concerning ageing in Europe and its consequences. These projects are Diamap (see http://www.diamap.eu/) 'a road map for diabetes research in Europe' that included a chapter on ageing and diabetes, Predict (see http://www.predicteu.org/) entitled 'increasing the participation of elderly in clinical trials', Courage in Europe - collaborative research on ageing in Europe (see http://www.courageproject.eu/) Ancien - assessing needs of care in European nations (see http://www.ancien-longtermcare.eu/) Ahead III - assessment of hearing in the elderly: aging and degeneration - integration through Immediate Intervention (see http://www.ahead.polimi.it/) EuroVisionNet - connecting vision research (see http://www.eurovisionnet.eu/) Gefos - genetic factors for osteoporosis consortium (see http://www.gefos.org/).

We also had the opportunity to hear about two very new FP7 supported project in biology of ageing, the IDEAL and the Switchbox projects (no website available at the time of report writing).

Potential Impact:

We identified the main priorities of research in biogerontology for the next 10 to 15 years: biomarkers of ageing and longevity; systems biology and its applications to biological ageing; oxidative stress, protein damage and maintenance; telomere biology, DNA damage, mitochondria biology and senescence; targeting nuclear receptors in age-related diseases (particularly neurodegenerative disease and metabolic disease); V of ageing and longevity; systems biology and its applications to biological ageing; oxidative stress, protein damage and maintenance; telomere biology, DNA damage, mitochondria biology and senescence; targeting nuclear receptors in age-related diseases (particularly neurodegenerative disease and metabolic disease); vascular ageing; immunosenescence and inflammation; metabolism and ageing; sarcopenia; skin ageing, elastic tissues and biotechnologies in skin biogerontology and clinical biogerontological research. Through the report containing all the details about how and why these priorities were set, the EC has access to the results of the consultation of the field of biogerontology about the research priorities. Engaging into this research will increase biomedical knowledge and help greatly to minimise dependency and improve health and quality of life for the rapidly growing numbers of older people.

List of websites:

web address: http://www.whyweage.eu

Contact details:

Olivier Toussaint

WHYWEAGE project coordinator

FNRS senior research associate

University of Namur

51, rue de Bruxelles, 5000, Namur

Tel: +32-817-24132

Fax: +32-817-24135

E-mail: olivier.toussaint@fundp.ac.be