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Biomarkers of Longevity 2.0: The Shift Toward Actionable, AI-Empowered Biomarkers of Aging, Health and Longevity

- By Franco Cortese, Partner at Deep Knowledge Group and Longevity.Capital

Key Points

        

  • The use of biomarkers is an indispensable component of Longevity industry analytics and assessment. It is the foundation upon which measurement of Healthy Longevity and the effectiveness of Longevity therapeutics is built. 

  • Biomarkers are also the primary metric in P4 (precision, preventive, personalized and participatory) medicine, which involves continuous monitoring of the progress of a disease state and recommending a series of corrective interventions in response, to keep patients’ state of health in an optimal mode for as long as possible.

  • Aggregating biomarkers of aging (rather than biomarkers of disease) is particularly difficult however, as they must be sought in populations of healthy people rather than from among the health data of the hospital populations. 

  • Furthermore, as the scope of P4 medicine broadens, the number of biomarkers and technologies will increase rapidly in the coming years. This makes the implementation of P4 medicine impractical by current, manual means.

  • Some possible solutions to these problems include the use of AI for the development of an optimal panel of biomarkers of aging, for the analysis of individual patients’ biomarkers of aging, and for orchestrating therapeutic interventions in response to fluctuations in those biomarkers.

  • As the number of data points increases, it becomes not only optimal, but strictly necessary, to use AI and big data analysis for these purposes. This is one of the foremost goals of the recently-established Longevity AI Consortium at King's College London.

       

I have worked with the Deep Knowledge Group and its various subsidiary and partner organizations in a number of capacities over the past three years. Before serving as Deputy Director of Aging Analytics Agency, I served as Deputy Director of the Biogerontology Research Foundation, and a member of its Board of Trustees, from 2017 - 2018. One of the projects I am most proud of during my tenure there was spearheading the Biogerontology Research Foundation’s part of a multi-institution project to classify aging as a disease during the World Health Organization’s most recent round of revisions to their International Classification of Disease (ICD-11) - a health care classification system that providing a framework of diagnostic codes for classifying diseases, which serves as the example followed by the majority of developed nations' drug regulatory agencies for determining which conditions are officially classified as diseases and, therefore, which conditions can be targeted by therapeutic interventions, tested, and ultimately approved.

        

The result of our proposal was the introduction by the World Health Organization of a new extension code for aging-related diseases - XT9T - that can be applied to both new and existing diseases. While the addition of an extension code for ‘aging-related’ via ICD-11 does not amount to classifying aging as a disease in full, it is a step in the right direction, and brings us one step closer to getting the World Health Organization to recognize aging as a pathological process with identifiable and quantifiable clinical indications, which can be intervened upon so as to enable human healthspan extension, compression of morbidity and prevention of age-related disease, during subsequent ICD revision processes.

These efforts are about much more than just theory or semantics. Aubrey de Grey remarked when asked about the impact of the new extension code, XT9T: “The ICD is not just a taxonomy. It greatly influences how drugs are prescribed in most nations, because a physician’s justification for writing a prescription must typically be documented in terms of an ICD code describing the diagnosis. As such, the addition of an extension code to denote aging may have a really huge impact on the financial rewards that drug developers can expect to reap if they bring treatments for age-related ill-health to the market.”

         

One of the strongest conclusions I reached in working towards the classification of aging as a disease is the incredibly pressing need not just for biomarkers of aging, but the need for actionable biomarkers that could be put into practice today to measure the effectiveness of healthspan-extending interventions today. It is biomarkers of aging and longevity, which can serve as a proxy measure of the effectiveness of longevity-focused therapies, that will pave the way to getting approval for drugs not on the basis of single, narrowly-classified diseases, but on their effects on aging itself, and will lay the necessary regulatory infrastructure needed for the rapid industrialization of longevity to scale, as well as to allow governments to measure the effectiveness of their efforts to increase national Healthy Longevity, a goal that a number of longevity-progressive governments are now keenly moving forward towards.

         

Now, through our work with Dr. Richard Siow and the Longevity AI Consortium at King’s College London, we are striving to fill this unmet gap and transforming this goal into reality, through the development of AI-empowered technologies and solutions to the development of actionable biomarkers of aging, health and longevity to scale. One special function of the Longevity AI Consortium will be the development of an optimal panel of biomarkers of aging - a specific niche where the implementation is lagging behind the science.

            

The present article, which is an excerpt from my guest chapter in the upcoming book, “Longevity Industry 1.0: Defining the Biggest and Most Complex Industry in Human History, co-authored by Deep Knowledge Group Co-Founders Dmitry Kaminskiy and Margaretta Colangelo, aims to outline the need for actionable biomarkers of aging, health and longevity, how AI will be the major driver for achieving it in the coming years, and Deep Knowledge Group’s plans and activities focused on turning these potentials into concrete realities.

 

What are Biomarkers of Aging?

         

How do we know when a biomarker is a biomarker of aging? It depends on how it is sourced. The current approach to biomarkers is to take them from people at various stages of a disease’s known progress, which in practice means sourcing them from hospital patients. Isolating biomarkers of aging, however, means collecting data which marks the difference between healthy people with as little trace of officially recognised disease as possible. This presents a challenge because whereas hospital patients remain in dedicated areas, and are available for analysis at the doctor's convenience, collecting biomarkers of aging means collecting vast amounts of data from the daily lives of people who have no reason to be in a hospital. There are however options available for aggregating such data, such as the devices which come under the AgeTech umbrella, which will find their user base among those suffering from aging but not officially-recognized disease per-se.

          

It is important in technology never to let the perfect be the enemy of good, especially when the technology is of great humanitarian significance. For example, in the early 2000s, enthusiastic proponents of the application of regenerative medicine to aging were urging governments, entrepreneurs and thought-leaders to make this a priority. They argued that technology was ahead of the science and the funding, and that while a great deal remains to be discovered about the mechanisms of aging, we already know enough to optimize the existing toolkit of regenerative medicine to address the damage of aging, which is already thoroughly researched. And thus out of this paradigm shift arose the now rapidly-rising Longevity Industry.

 

Now once again, the technology is ahead of the science and the funding. And, once again, a paradigm shift is due. Presently the necessary biotechnologies for the implementation of P4 medicine technologies and therapies are already in place. What is needed now is big data analytics to develop optimal panels of biomarkers of aging and to determine how to optimize their implementation with maximum precision.

         

There is however a risk that governments and governmental or political and strategic bodies may make one or both of the following errors:

             

  • They might assume that the missing bridge on the road to Health Adjusted Lide Expectancy-extending P4 medicine is still largely a scientific problem, rather than one of practical technological implementation.

  • They might assume that, because the current scientific quest for ever more precise biomarkers is not slowing down, we don’t yet have a set of biomarkers precise and sufficiently actionable to take immediate action. 

 

As such, government strategic bodies therefore risk limiting their strategic ambitions with regard to time frames.

         

For example, in the UK, Theresa May’s government has announced a commitment to adding 5 extra years on the nation’s HALE by 2035, and Aging Analytic Agency has advised the UK’s recently-formed All-Party Parliamentary Group for Longevity that actionable biomarkers of aging will be necessary to meet this goal, and to measure the effectiveness of their development plans to extend National Healthy Longevity.

                

It is therefore desirable that such bodies have access to a panel of biomarkers which are not only comprehensive but also actionable. A panel of less precise but easily implementable biomarkers of aging would be much more useful much sooner, than an extremely precise and comprehensive panel of biomarkers of aging that is too hard or expensive to translate easily into widespread practical and clinical use across nations.

The Need for Actionable Biomarkers of Aging and Longevity

        

The development of precise and actionable biomarkers of aging is one of the most prevalent and important areas of longevity research today, as well as an area where practical implementation is lagging behind the science. This is one of the most important diagnostic services that could be offered, and yet it does not receive the attention it deserves compared to the amount of tangible benefits it can deliver.

           

For example, a panel of aging biomarkers was developed recently which is based on Deep Learning analysis of standard blood biomarkers, which is less precise than the more precise available biomarkers of aging (e.g., DNA Methylation clocks), but which is nonetheless precise enough, and can be implemented by any researcher, doctor and clinician that has access to routine blood tests.

         

As a further example of actionability, consider that biomarkers of aging have been constructed using Deep Learning-based analysis of photographs of mice, which could quite easily be extended to humans. Their accuracy alone is not enough to make them a research priority, but the increasing video capabilities of smart-phones means that this rapid development of photographic biomarkers of aging (e.g. of the face or the eye) could now be a very actionable area of research whose practical level of precision and accuracy will develop quite rapidly in coming years.

           

However, the use of AI in longevity R&D is lagging behind in its application to geroscience. While there is a small handful of companies that are working at this frontier, the overall proportion in comparison to the total size of the longevity industry is still quite small. Deep Knowledge Ventures has been identifying and supporting companies working on the frontlines of AI for Longevity since 2014, when it provided the seed funding for Insilico Medicine, now a leader in the application of AI for Longevity research, drug discovery and biomarker development.

The Launch of the Longevity AI Consortium at King’s College London

 

Last week Europe’s first Longevity AI Consortium (LAIC) launched at King's College London with strategic and financial support from Deep Knowledge Group and the Biogerontology Research Foundation. 

          

AI for Longevity is an underrepresented sector in the Longevity Industry despite having more potential to increase Healthy Longevity in the short term than any other sector. The Longevity AI Consortium will work to facilitate the shift from treatment to prevention and from preventive medicine to real-world precision health. The initial aim will be to identify novel longevity and healthy ageing biomarkers to accelerate diagnosis of age-related health decline. Then researchers will develop personalized physical, mental and financial health to better implement and promote healthy lifestyles for longevity, such as modifying patterns in sleep, nutrition, physical activity, environmental exposure and financial planning.

           

The initial focus will be on core longevity academic-industry R&D, including the development of biomarkers of aging and novel implementation of life and health data analytics. In 2020, after achieving several key scientific and funding milestones, AI-enabled solutions for physical, mental and financial wellness will become a major focus, and an AI Longevity Accelerator will be launched to serve as a much-needed bridge between start-ups and major UK investors, creating for the first time a dedicated infrastructure for increased investments and developments in this important sector.

As part of its continuing development efforts over the next several years, the Consortium will expand to include centers in Switzerland, Israel, Singapore, United States and Japan through a £7 million commitment from Deep Knowledge Ventures.

      

The Consortium will serve as the leading R&D hub and industry-academic hotspot for advanced AI-driven AI-driven personalized preventive diagnostics, prognostics and therapeutics.This represents a paradigm shift from treatment to prevention and a new frontier - from precision medicine to precision health, enabling the UK to become the #1 global hub for the application of AI to Longevity and Precision Health. Precision Health through AI will be developed by a combination of AI-Driven Precision Diagnostics, AI-Driven Advanced Prognostics, Personalised Treatment Optimization, and AI-Driven Preventative Treatment. 

         

Some of the major focus areas of the Consortium include:

         

  • Frontier applications of artificial intelligence in aging research, longevity R&D and the development of biomarkers of health and longevity, and the paradigm shift from disease treatment and sick care to preventive medicine, and from preventive medicine to precision health.

  • Facilitating a shift toward actionable biomarkers of aging, including the identification of biomarkers of health, longevity and aging that have the highest ratios of accuracy and precision vs. actionability, expense and ease-of-implementation, and the benchmarking of biomarkers that can be used in practice today

  • Emerging trends and novel paradigms relating to both the creation and application of life data collected on a massive scale from healthy individuals and used in scientifically-backed, quantifiable, tangible and precise ways to preserve and maintain an optimal state of health

  • Leveraging the disruptive and accelerative impact that AI is having on Longevity R&D and the practical implementation and clinical translation of Longevity technologies and therapeutics

  • Frontier applications of AI for financial wellness over extended periods of healthy Longevity, and the maintenance and optimization of “wealthspan” to complement advances in “healthspan”, including the application of AI assistants and “robo-advisors” for personal financial management, and the utilization of novel forms of financial data to enable AI-empowered AgeTech and WealthTech services

  • Novel methods of using AI to optimize psychological wellness, social activity, promote neuroplasticity and combat loneliness and social isolation among elderly
     

Biomarkers of Longevity 2019: New Special Analytical Case Study by Aging Analytics Agency

      

Biomarkers of Longevity: Current state, Challenges and Opportunities Landscape Overview 2019” is an open-access special analytical case study published earlier this month by Aging Analytics Agency that uses a comprehensive analytical framework to rank and benchmark existing panels of biomarkers of aging, health and Longevity according to their ratios of accuracy vs. actionability, identifying the panels of biomarkers that can have the greatest impact on increasing both individual and national Healthy Longevity in the next few years.

 

 

The report was officially launched and presented at the recent AI for Longevity Summit at King’s College London, organized by the Longevity AI Consortium with the strategic support of Deep Knowledge GroupAging Analytics Agency, the Biogerontology Research Foundation and others.

The summit featured talks from top executives from Prudential, HSBC, AXA Insurance, NVIDIA, Microsoft, Babylon Health, Insilico Medicine, Longevity.Capital, Longevity Vision Fund, Juvenescence, Deep Knowledge Ventures, and the UK All-Party Parliamentary Group for Longevity.

The use of biomarkers is an indispensable component of industry analytics and assessment. It is the foundation upon which measurement of Healthy Longevity and the effectiveness of P4 (Precision, Preventive, Personalized, Participatory) Medicine and Longevity therapeutics is built. The report is designed as an in-depth review of the state of the art in biomarkers of biological age to advise private and public sector participants effectively.

The report was produced to offer a panoramic review of the global landscape of aging and Longevity biomarkers, containing selected lists, rankings and enhanced profiles of more than 50 Single Biomarkers directly correlated with the trajectories of age-related diseases and syndromes, and exceeding 100 diverse biomarker panels for analytical data-driven comparisons that allow an optimal integration of multiple biomarkers for practical use, achieving highly actionable monitoring systems for healthcare, clinical practice, translational research, frontier developments that exploit the current conditioning of the rising Longevity industry, and the execution of public policies aiming to increase National Healthy Longevity that will result in a renaissance never seen before in economic and social dynamics.

 

In addition to their purely descriptive and analytical approaches, the report is designed to make key strategic recommendations, and to offer guidance regarding biomarker implementations, technologies and techniques within the reach of companies and nations today, in order to equip them with the tools necessary for optimizing their strategy and action plans, providing specialized guidelines for business, investment and policy decision making.

   

 

The report delivers a most comprehensive list of single biomarkers and biomarker panels of biological age together with extensive and enhanced profiles: their advantages, disadvantages, future perspectives, challenges and opportunities, with a focus on technologies currently used for assessment; concrete analysis of routine, advanced and novel biomarkers of aging, emerging tools and platforms, and insights about the impact of these biomarkers on health systems and clinical practice.

 

A special treatment tracing the role of Digital Biomarkers and AI platforms as necessary and indispensable components of the Longevity biomarker industry is also delivered, highlighting the fact that AI and data science are increasingly necessary to handle the increasing volume of biomarker, life and health data.

Conclusions

       

  • Deep Knowledge Group and the Biogerontology Research Foundation were pivotal in their strategic and financial support of the launch of the Longevity AI Consortium at King’s College London, which is working to leverage the industry-academic strengths of the region and marshal them towards the intensive application of AI to leading-edge areas of Longevity R&D.

  • A special focus for Longevity AI Consortium will be the use of AI for the development of an optimal, actionable panel of biomarkers of aging, and devoting AI-driven R&D to neglected areas of research in Longevity and P4 Medicine.

  • It is important in any domain of science or technology never to let the perfect be the enemy of good. It is desirable therefore to develop a minimum viable panel (MVP) of biomarkers: a panel of biomarkers which though not as precise as possible are precise enough and easily implementable. In order to kickstart a global discussion on the possibility of an MVP biomarker panel, Aging Analytics Agency has recently published a special analytical case study specifically on this topic, entitled Biomarkers of Longevity: Current State, Challenges and Opportunities 2019 Landscape Overview

  • Deep Knowledge Group will continue to support the development of AI-driven, actionable biomarkers of aging, health and Longevity through its involvement in the Longevity AI Consortium and its recently-announced AI Longevity Accelerator Program, and through the efforts of its Longevity-focused hybrid investment subsidiary fund, Longevity.Capital, which is heavily prioritizing the AI for Longevity and AI for Longevity FinTech, AgeTech and WealthTech sectors.

 

The Longevity AI Consortium established by Ageing Research at King’s (ARK) at King's College London serves as a leading academic-industry R&D hub for AI-driven personalised and preventive diagnostics, prognostics and therapeutics. The advances in genetics, artificial intelligence and the growing availability of health data present an opportunity to develop advanced personalised consumer and patient care. The aims of the Longevity AI Consortium include the identification of novel longevity and healthy ageing biomarkers, accelerated diagnosis of age-related health decline, with increased accuracy, refining demographic and clinical methods to facilitate recruitment, retention and ongoing reappraisal, the development of personalised physical, mental and financial health and longevity to better implement and promote effective healthy lifestyles for longevity, such as modifying patterns in sleep, nutrition, physical activity, environmental exposure and financial planning.

       

Longevity.Capital is a hybrid investment fund specifically focused on the Longevity Industry, backed by seasoned professionals who have been active in both the investment banking and Longevity industries for 25+ years, long before the sector was recognized as a serious prospect by the overwhelming majority of investors. The fund employs advanced InvestTech solutions for investment de-risking, including portfolio diversification across the full scope of the Longevity industry (biomedicine, finance, tech), and formulates its investment strategy based on sophisticated industry intelligence and comparative analytics provided by the world-leading Longevity Analytics entity Aging Analytics Agency, which uses hundreds of quantitative and fact-based parameters to identify prospective investment targets for the fund, utilizing multidimensional analytical frameworks as complex as the industry itself.

         

Deep Knowledge Group is a consortium of commercial and non-profit organizations active on many fronts in the realm of DeepTech and Frontier Technologies (AI, Longevity, FinTech, GovTech, InvestTech), ranging from scientific research to investment, entrepreneurship, media, analytics and more. Its subsidiaries and associated organisations include Deep Knowledge Ventures, Longevity.Capital, AI-Pharma.Capital, Longevity FinTech Company, Deep Knowledge Analytics, Aging Analytics Agency, Biogerontology Research Foundation, Longevity Swiss Foundation, Longevity International UK - Secretariat for the UK All-Party Parliamentary on Longevity, and the Longevity AI Consortium at King’s College London.

      

Aging Analytics Agency is the world’s premier provider of industry analytics on the topics of Longevity, Precision Preventive Medicine and Economics of aging, and the convergence of technologies such as AI and Digital Health and their impact on healthcare. The company provides strategic consulting services in fields related to Longevity, and currently serves as the primary source of analytics for the specialized hybrid hedge fund Longevity.Capital, as well as the UK All-Party Parliamentary Group for Longevity. It is also an Official Member Organization of the United Nations NGO Committee on Ageing.

        

The Biogerontology Research Foundation is the UK’s oldest charity focused on Longevity and on expediting the coming paradigm shift from disease treatment to personalized precision prevention. It was the main initial donor that provided financial and organisational support to Longevity International UK for the purpose of establishing the All-Party Parliamentary Group for Longevity. It was also actively involved in the successful initiative of adding a new extension code for “age-related diseases” (XT9T) accepted in 2018 by the World Health Organization during the last revisions of its International Classification of Diseases framework.