By Ilia Stambler, PhD ilia.stambler@gmail.com
Contents:
Executive Summary
Project Description
The Need to Create a Roadmap to Lifespan Extension
International Longevity Alliance
Lifespan extension studies are vitally important for the development of new therapies and for addressing the population aging problem. Yet, there is a great diversity of approaches in the field. Hence, a roadmap to lifespan extension is needed.
The existing roadmaps are mostly partial and lack integrative capacity.
The proposed roadmap to lifespan extension will fill the gaps and will for the first time:
Analyze past approaches and make suggestions for the pursuit of healthy lifespan extension, while addressing the current needs and requirements.
Provide a truly comprehensive analysis of both core scientific and social determinants of lifespan extension.
The proposed roadmap will utilize an advanced IT platform allowing for gathering vast amounts of data, as well as data-mining, constant updates and cooperation.
Diverse and unique consultancy services will be developed as a result of the roadmap project, providing social normative and scientific methodological recommendations in the field of lifespan extension.
In the course of the project, collaboration, research and advocacy for lifespan extension will be activated.
The project will be performed by a select group of expert analysts and IT developers, while also engaging broad consultation and partnership of other experts in the field.
Current healthy lifestyle approaches are of only limited value for human lifespan extension [1].
-> Hence, the search for additional novel means and technologies for lifespan extension is necessary.
The deteriorative aging process is the main limiting factor of the human health and lifespan.
-> Hence the effort to ameliorate the aging process should receive the first priority in the pursuit of health and lifespan extension.
The deteriorative aging process either precipitates or lies at the root of chronic age-related diseases [2].
-> Hence lifespan extension studies, via amelioration of the aging process, will help design treatments for chronic age-related diseases.
Aging is an extremely complex problem and seeking a single “magic bullet” treatment or considering aging as merely a “damage repair” problem are not enough to achieve progress in the amelioration of aging and for healthy lifespan extension.
-> Hence the thorough knowledge aggregation and understanding of a vast array of mechanisms of aging and potential life-extending interventions is necessary to extend healthy lifespan.
The possibility of a significant lifespan extension has been proven on both theoretical biological grounds and experimental grounds in a variety of animal models that achieved a significant lifespan extension [3].
-> Yet the road toward human lifespan extension remains unclear and requires thorough elaboration.
There is a multitude of approaches to lifespan extension, based on a multitude of aging theories, research models and treatment modalities. The approaches are often disconnected and lack a unifying framework.
-> Hence, a thorough and critical evaluation of the existing work and selection of promising directions in the form of a roadmap is needed.
With the tremendous variety of studies and approaches, creating a comprehensive roadmap to life extension, that would analyze past developments and point to promising directions, is vitally needed. Several important endeavors to create such a roadmap have been made. Some examples include:
“The Common Denominator. A Research Agenda to Slow Aging and Slow Disease” by the Alliance for Aging Research (AAR) [4]
“Strategies for Engineered Negligible Senescence” of the SENS Research Foundation [5]
“Human Life Extension Program” of the Science for Life Extension Foundation [6]
“The Biology of Aging Platform” of the Russian Transhumanist Movement.
Also quite a few books about longevity contain breakdowns of promising directions for longevity research, for example: The future of aging: Pathways to human life extension (2010) [8].
These are important and pioneering projects, and their authors are close professional contacts of the authors of the present proposal, and will be approached for collaboration in the future [15].
Yet, all these attempts generally have several significant drawbacks. Hence, considerable additions and improvements are in order.
Some of the existing drawbacks and needs to fulfill can be summarized as follows:
The existing programs often present lists of potential research directions, rather than coherent and coordinated entities.
-> There is a need for integration between different elements and directions of the programs.
The existing program selections often appear arbitrary, uncritical and unsupported by weighted evidence.
-> There is a need to develop formal criteria for selection and inclusion of promising research directions.
The existing programs often include either very few elements (thus discarding a large array of factors affecting aging and lifespan) or so many seemingly unrelated elements that their operation becomes almost impossible.
-> There is a need to improve the accessibility and operability of the programs for lifespan extension research.
Most programs consider the effects of single factors and interventions for lifespan extension.
-> Crucially, there is a vital need for an integrative capacity that would determine the efficacy of particular potential life-extending interventions as well as the efficacy of their combinations.
Most existing programs are based on manual and low-tech approaches to data-mining and reviewing.
-> There is an urgent need to have a good Information Technology (IT) infrastructure that will make the process of roadmap creation iterative and interactive, and to allow handling massive amounts of data.
Most existing programs are produced by single authors or small teams.
-> There is a need for IT infrastructure to become an interactive hub for aging researchers and activists to create a “living and participatory roadmap”.
The existing programs are mainly based on former summary data with a considerable time lag after the data publication.
-> There is a need for good IT infrastructure to cope with the constantly changing data, providing the ability to obtain and update information continuously, as well as to produce periodical summary reports. This currently lacking ability may greatly facilitate the planning of future studies and efforts.
The existing programs often consider aging research just as purely and exclusively a scientific problem.
-> There is a crucial need to give due consideration of social, legislative, administrative, communal, economic, demographic, educational and even ethical factors that largely determine the development of lifespan extension research and translation of this research into practice.
The proposed roadmap to lifespan extension will aim to provide for the lacking needs and requirements.
The proposed roadmap to lifespan extension will also provide, for the first time, a truly comprehensive analysis, including both core scientific and social determinants.
The Roadmap will provide:
Scientific survey of the past approaches to lifespan extension and methodological suggestions, as well as forecasts for future development. Regarding the research gaps to be filled, the proposed roadmap, for the first time, will survey, critically analyze and forecast the feasibility of the accomplishment of lifespan extension.
Survey: Dominant research paradigms in the field will be analyzed with reference to theoretical, technological, empirical and experimental approaches to lifespan extension [3] – with a practical aim of extrapolating trends, identifying, classifying and rating the key factors and analytic tools [9].
Methodological recommendations: Based on the conducted surveys and ratings, research priorities promising for the pursuit of lifespan extension will be identified, and methodological recommendations will be provided, with specific reference to data-mining, basic research, animal and human testing.
Forecast: The trends in the current approaches to lifespan extension will be determined, including their continuity and limitations, thus providing a useful framework for research and investment planning.
IT infrastructure: Advanced IT infrastructure, based on Denigma (http://denigma.de] see below) will be utilized to assist in the analysis of the scientific approaches to lifespan extension, handling massive amounts of data and providing an interactive and updateable ecosystem.
Implications for therapy: The crucial connection between aging processes and age-related diseases will be emphasized. Hence, the directions for lifespan extension will be at the same time directions for chronic disease prevention [10].
Analysis of the social determinants and normative recommendations for lifespan extension. For the first time, the social determinants of lifespan extension will be analyzed with specific reference to the following:
Social and economic implications, opportunities and bottlenecks for lifespan extension in the population.
Social determinants of successful lifespan extension research, including organizational optimization and funding priorities.
Translation of lifespan extension results into clinical practice, including legislative, regulatory and organizational requirements.
Wide and egalitarian distribution of life-extending technologies, including legislative, regulatory and public health aspects.
Social activism and change of public attitude to lifespan extension research, including recommendations for public promotion and education on the subject of lifespan extension.
Extensive Social Network. Both for the purposes of scientific and social roadmap construction, the proposed project will include active social networking (mainly via the International Longevity Alliance http://longevityalliance.org and the Israeli Society for the Biology of Aging http://bioaging.org.il).
The proposed roadmap will be based on the unique databases, analytical and computational capabilities of the Denigma, which is a Digital Decipher Machine http://denigma.de (See the Appendix regarding the Denigma project).
The use of Denigma will provide the following advantages in creating the roadmap for lifespan extension:
Vast and diverse data. Based on Denigma, vast amounts of data on aging and lifespan extension studies have been and will be collected and continuously updated, including databases on particular research projects, scientists, centers and collaborations.
Advanced Information Technologies to assess Lifespan Interventions. Using advanced information technologies – such as semantic web and machine learning combined with statistics and information theory – the data will be analyzed considering the effects of single or combinations of various treatment factors (such as drugs, genes and lifestyle factors) on the healthspan and lifespan.
Evidence-based and formal criteria for prioritizing research directions. The comparative analysis of the actual effects of treatments will provide a scientific evidence-based and formal basis for selecting promising research directions as well as for their combination and integration within the roadmap.
Continuous updates and periodical summary reports. Insofar as Denigma allows a continuous inflow of information, the analyses can be constantly updated, with all the new trends and studies at the analyst’s fingertips. Yet, in addition, summary and focused reports on different trends and areas can be produced on the periodical basis, as required, using the latest available information.
Enhanced cooperation of longevity researchers. As Denigma is based on a distributed and open-source approach, cooperation and involvement of a large set of experts can be ensured.
Enhanced advocacy for longevity research. The IT platform of the Denigma, which will be built up during the roadmap development, will facilitate not just actual lifespan extension research, but also public advocacy for this research by providing a rich means of interaction, cooperation and visibility for the longevity research and advocacy community, both as co-creators and end-users of the roadmap to lifespan extension.
Consultancy and methodological recommendations
Using the information and expertise that we will gather, we will be able to provide unique consultancy and methodological recommendations about the field of lifespan extension.
The following areas are of particular interest:
Assisting researchers in planning their studies;
Assisting students choosing a career in the field;
Assisting developers and users of potential anti-aging and life-extending drugs and other treatments by showing evidence (or lack of evidence) for the efficiency of such treatments;
Assisting investors by facilitating the search for investment opportunities;
A more specific breakdown of potential consultancy and methodology services:
Guidelines for testing facilities for lifespan extension studies. Guidelines to create animal testing facilities for lifespan extension studies can be developed, on both an Academic basis and Do It Yourself Biology basis.
The set of methodological recommendations for setting up testing facilities can be used in Israel (if such a need and interest arise) or can be exported or outsourced to other countries.
Based on the gathered knowledge, methodological recommendations for testing life-extending drugs and other treatments can be developed and marketed, including recommendations for creating toolkits and automation devices for the testing process.
Providing the researchers with a powerful means of communication (linking) and data-mining.
Providing the researchers with focused datasets of evidence in support or counter-indication for a particular theory of aging and/or potential life-extending intervention.
Assisting students choosing a career in the field. A further set of recommendations may relate to encouraging the interest of students in the field of aging and longevity research, including:
Creation of visual aids
Learning materials
Directories including possibilities for studies, scholarships and jobs, in their areas
Assisting developers and users of potential anti-aging and life-extending drugs and other treatments by showing evidence (or lack of evidence) for the efficiency of such treatments. A set of recommendations can be made on potential anti-aging and life-extending drugs and treatments development and use:
Prediction of efficacy. The integrative and comparative analysis will allow developers and users to make predictive estimates for the efficacy of yet untested treatments, using such methods as mutual information, genetic networks and more.
Personalization of lifespan extending treatments. By correlation of treatments with actual health and lifespan metrics in defined and particular segments of the population, a database can be created concerning the effectiveness, safety, personalization, and interactions of potential lifespan extending drugs and other treatments.
Indication of physiological age. Using methods of semantic analysis, information theory and statistics, recommendations can be made for further studies regarding the correlation of age with health and disease status, in order to eventually produce a comprehensive expert system to determine personal physiological and biological age.
The system of recommendations for determining physiological and biological age, including estimates of the quality of life and performance in particular ages, will have the following applications:
Such a system will be crucial for devising criteria for retirement age based on actual performance and capacity (with obvious economic benefits).
Such a system will be also crucial for devising criteria for testing potential anti-aging and life-extending drugs and other interventions (when prolonged periods of testing and follow up are unfeasible).
Note: The area of consultancy regarding Assisting developers and users of potential anti-aging and life-extending drugs and other treatments may require prolonged research and is mentioned here as a possibility, and a potential promising direction of development.
Assisting investors by facilitating the search for investment opportunities. The proposed roadmap and consultancy services based on it will aid potential investors in their navigation in the field and pinpointing funding opportunities for the short and long term, with lower and higher risk levels.
Assisting policy-makers in prioritizing projects in the area of lifespan extension. With aging representing a major social problem, and biomedical research driving to provide solutions to ameliorate it, the proposed roadmap and consultancy will be invaluable for policy-makers.
Currently, several legislative proposals have been suggested in various countries, all arguing for the necessity to “make a plan” for the society to cope with the problem of aging, while taking into consideration the development of biomedical research and technology [11]. The current proposal for the roadmap to lifespan extension will, for the first time, attempt to actually make such a plan.
Analyzing social and economic constraints and opportunities for lifespan extension.
An indispensable part of the proposed roadmap to lifespan extension will be dedicated to the consideration of social and economic determinants and implications of lifespan extension and lifespan extension research.
In fact, during the creation of the roadmap to lifespan extension, a sort of think tank will be established, that will analyze and advise on the social constraints and opportunities along this road, including economic benefits and availability of resources, legislative and regulatory environment, communal distribution and public relations factors.
Developing normative recommendations.
Based on the social field analysis, normative legislative, regulatory, administrative and organizational recommendations will be developed, with special reference to:
Registering potential life-extending and anti-aging treatments;
Requirements for their short and long-term testing, criteria for their efficacy and safety;
Suggestions for funding priorities within the research and health care system, taking into consideration the crucial impact of aging on disease development;
Administrative and organizational requirements needed for the active promotion of life-extension research in Israel and elsewhere;
The rapid translation of the results of this research into medical and clinical practice;
Ultimately the wide and egalitarian distribution of life-extending technologies to the public.
The proposed Roadmap for Lifespan Extension is not an academic, purely descriptive project, but a proactive project, aiming to facilitate the achievement of the purpose of healthy lifespan extension for the population. Hence supportive advocacy and social networking components will be indispensable. The project will engage and activate the system that it aims to observe.
The proposed project will utilize a unique social support system – the International Longevity Alliance – whose aim is to strengthen worldwide public advocacy for life-extension research ([http://longevityalliance.org/) 12 [12)].
The International Longevity Alliance includes a broad and dedicated social network of international longevity activists and professionals, involving both scientific and social experts, that will assist in developing both the scientific arm and the social arm of the roadmap.
In turn, the support for the roadmap development will stimulate the development of the International Longevity Alliance and its aims.
The support of and by the International Longevity Alliance will be provided on the principles of distributed science and crowd-sourcing, while linking Israel into a wide network of international collaboration.
Through its active members and authors of this proposal, the International Longevity Alliance is strongly related to the Israeli Society for the Biology of Aging (http://bioaging.or.il). Formerly highly active, the Israeli Society for the Biology of Aging has been rather inactive in recent years, despite its obvious importance for the development of the field in Israel. The implementation of the proposed project will add vitality and impact to the Israeli Society for the Biology of Aging and eventually for the development of aging and lifespan extension science in Israel.
Thus, in summary, the result of the proposed roadmap will be a thorough and instructive analysis of the field of aging and longevity research and industry. Yet in addition, in the process of creating the roadmap, the entire field will be activated and encouraged, in Israel and abroad.
The roadmap development, including its analyses and recommendations, will be performed by the international team of experts who are the authors of this proposal, building on their previous extensive expertise in scientific meta-analysis, IT development, research design and health policy development, uniquely focusing on lifespan extension research [10].
Yet the project will also involve broad international consultation, cooperation and networking [13].
The tentative schedule for the project is 2 to 3 years:
1st year – Thorough survey of past lifespan extension research directions, building up and adjusting the IT infrastructure
2nd year – Developing methodological and normative recommendations for the development of the field of lifespan extension
3rd year (optional) – Establishing the consultancy services.
In this period, the costs will mainly cover salaries for the expert analysts and IT developers.
[1] Rizzuto, D., Orsini, N., Qiu, C., Wang, H-X, & Fratiglioni, L. (2012). Lifestyle, social factors, and survival after age 75: population based study, British Medical Journal, 345, e5568.
[2] Keyfitz, N. (1977). What difference would it make if cancer were eradicated? An examination of the Taeuber Paradox. Demography, 14 (4), 411-418; Rae, M. J., Butler, R. N., Campisi, J., de Grey, A. D. N. J., Finch, C. E., Gough, M., Martin, G. M., Vijg, J., Perrott, K. M., & Logan, B. J. (2010). The demographic and biomedical case for late-life interventions in aging, Science Translational Medicine, 2 (40), 40cm21.
[3] De Grey A and Rae M. Ending Aging. The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime, St. Martin’s Press, NY, 2007.
[4] The Common Denominator. A Research Agenda to Slow Aging and Slow Disease http://www.agingresearch.org/content/article/detail/8029/] http://www.healthspancampaign.org/research/research-agenda/
[5] http://www.sens.org/research/introduction-to-sens-research
[6] http://www.scienceagainstaging.com/ENG/index_ENG.html
[7; http://agingportfolio.org/] http://agingportfolio.org/index/category/id/134
[8] Fahy, G. M., West, M. D., Coles L. S., & Harris, S. B. (Eds). (2010). The future of aging: Pathways to human life extension. New York: Springer.
[9] Stambler I. A History of Life-extensionism in the 20th Century, PhD Dissertation, Graduate Program in Science, Technology and Society, Bar Ilan University, Israel, 2012.
[10] Rae, M. J., Butler, R. N., Campisi, J., de Grey, A. D. N. J., Finch, C. E., Gough, M., Martin, G. M., Vijg, J., Perrott, K. M., & Logan, B. J. (2010). The demographic and biomedical case for late-life interventions in aging, Science Translational Medicine, 2 (40), 40cm21.
[11] Law proposals in support of aging research and regenerative medicine in different countries. http://www.linkedin.com/groups/Law-proposals-in-support-aging-4893704.S.244799068?qid=12d3e127-c8c0-4dae-a07f-ed0af8c62a4e&trk=group_most_popular-0-b-ttl&goback=%2Egmp_4893704
[12] International Longevity Alliance groups in over 40 countries: https://www.facebook.com/groups/longevity.alliance/doc/429937660426393/
[13] Ilia Stambler. A History of Life-extensionism in the 20th Century, PhD Dissertation, Graduate Program in Science, Technology and Society, Bar Ilan University, Israel, 2012.
Ilia Stambler, David Blokh, Daniel Wuttke, Information Theory for Aging Research, 2013 http://www.denigma.de/experts/collaboration/28
Anton Kulaga and Daniel Wuttke, Denigma - Open Distributed Science for Aging Research, 2013 http://denigma.de/data/entry/open-distributed-science-for-aging-research
Edouard Debonneuil, European Innovation Partnership. Knowing Effects on Healthy Life Years, 2013 https://webgate.ec.europa.eu/eipaha/initiative/index/show/id/5
Daria Khaltourina (Ed.) Alcohol Catastrophe and Possibilities for State Policy to Overcome Alcohol-related Excessive Mortality in Russia, Lenand URSS, Moscow, 2008.
[14] Some of the partners of the proposing group include:
Aubrey de Grey, head of the Strategies for Engineered Negligible Senescence (SENS) Research Foundation (USA/UK) http://www.sens.org/
Joao Pedro de Magalhaes, head of the Integrative Genomics of Aging Group at the Institute of Integrative Biology, University of Liverpool, UK http://www.liv.ac.uk/integrative-biology/
And many more.
