Actionable Biomarkers for Human Longevity Recommendation
TOTAL SCORE: 11
Score
A1 (Feasibility increased by continuance of pandemic): 0
A2 (Necessity increased by covid pandemic): 0
A3 (political viability): +1
B1 (Relevance to the specific goal of increasing HALE by 5 years by 2035): +1
B2 (Relevance to general goal of biomedical healthy life extension): +1
C1 (Market readiness applicability): +1
C2 (Project readiness): +1
C3 (Move to market readiness): +1
D1 (Actionability): +1
D2 (Degree of measurability): 0
D3 (Degree of leveraging cross-sector inputs): +1
D4 (Awareness of international context): 0
D5 (Resourcefulness): +1
D6 (Reorganisation): +1
E (Disruptiveness): +1
F (Dividends - does the recommendation aid in social activity and inclusivity?): 0
Point of Comparison: The report refers directly to the need for actionable biomarkers in the paragraph: “Dr Riccardo Marioni of the University of Edinburgh told us that, ideally, biomarkers should be inexpensive, so they can be used at the population level, and as minimally invasive as possible.” There is however no explicit acknowledgement that this is the current stumbling block in attaining the 2035 goal, nor any thorough exploration of how existing resources can be repurposed in order to take the shortest possible route to attaining a minimum viable panel.
RECOMMENDATION SUMMARY
Biomarkers are a measurable indicator of some biological state or condition. They are often measured and evaluated to examine normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Biomarkers are used in many scientific fields. “Biomarkers of aging” are biomarkers that could predict functional capacity at some later age better than will chronological age. Stated another way, biomarkers of aging would give the true "biological age", which may be different from the chronological age. Validated biomarkers of aging would allow for testing interventions to extend lifespan, because changes in the biomarkers would be observable throughout the lifespan of the organism. Although maximum lifespan would be a means of validating biomarkers of aging, it would not be a practical means for long-lived species such as humans because longitudinal studies would take far too much time. Ideally, biomarkers of aging should assay the biological process of ageing and not a predisposition to disease, should cause a minimal amount of trauma to assay in the organism, and should be reproducibly measurable during a short interval compared to the lifespan of the organism.
Metrics for tangible progress are absolutely essential components of any government strategic agenda. Governments must be able to monitor and describe biomedical progress. It will be impossible to make concrete claims regarding global progress in biotechnology - and in preventive medicine in particular - without an agreed panel of biomarkers. In medicine, a biomarker is a measurable indicator of the severity or presence of some disease state, and are capable of serving as a standard metric for industrial output in the global Longevity Industry. While the state of science, advanced biomedicine and the science of Longevity in particular are quite advanced in the UK, there is a clear paucity of practical developments in the specific realm of biomarkers of ageing, and in the development of panels of ageing biomarkers that can be used to assess differences in biological age vs. chronological age, and to measure the effects of lifestyle and therapeutic interventions on biological age. This is a similar situation to the current state of AI for precision and preventive medicine, in which there is a lot of work going on in science and academia, but a visible lag in the practical real-world implementation of that science into practice.
The importance of benchmarking Longevity Biomarkers and Biomarker Panels by their ratio of accuracy vs. actionability, rather than just their accuracy, cannot be understated. In order for this domain of technologies to actually accelerate the translation of Longevity theory into practice, and enable short-term progress in the extension of Healthy Human Longevity, they need to consist of biomarkers that are market-ready, and obtainable to the majority of doctors, clinicians and nation’s citizenry.
Why is a minimum sufficient panel of biomarkers necessary? 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 optimise the existing toolkit of regenerative medicine to address the damage of aging, which is already thoroughly researched. And thus out of this paradigm shift occurred from it arose the field of rejuvenation biotechnology. Now once again, the technology is ahead of the science, the funding, and the political leadership. 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 ageing and to determine how to optimise their implementation. But this is not a biotechnology problem, but a data mining, analysis and management problem. And moreover, in many countries, to various degrees, large-scale data mining, analysis and management is a question of political coordination.
Consider this as one example of recently discovered “minimum sufficient” biomarkers: There have been positive developments in the formulation of precise biomarkers of ageing that can be used to estimate biological age and mortality risk based on Deep Learning analysis of standard blood biomarkers, which is not as precise as the most precise available biomarkers of ageing (DNA Methylation clocks), but which are precise enough, and which can be implemented by any researcher, doctor and clinician that has access to routine blood tests. Similarly, there have been biomarkers of ageing that are constructed using deep learning-based analysis of photographs in mice, which could quite easily be extended to humans. As one possibility, given the increasing resolution capabilities of smart-phones, the development of photographic biomarkers of ageing (e.g. of the face, or the eye) could be a very actionable area of research to focus on.
As the Precision Health industry is growing, we will see an increasing emphasis on the creation and validation of a wide diversity of Biomarkers of Aging, which will enable the extension of healthspan and the maintenance of optimal health for the population via continuous AI-empowered monitoring of fluctuations in personalized Biomarkers of Aging.
P4 (Preventive, Predictive, Personalized and Participatory) Medicine, being the cornerstone of lifespan and healthspan extension, will be the central platform for the utilization of a wide array of Longevity Biomarkers for healthcare by both the general public, and by progressive governments seeking to optimise their population-level National Healthy Longevity.
Support and development of Biomarkers of Human Longevity has been a priority of Aging Analytics Agency and its parent company, Deep Knowledge Group, for many years, and, indeed, one of the factors that influenced its first investment in the Longevity Industry in 2014 (in Insilico Medicine, which has gone on to hold Series A and B rounds from other investors including Wuxi AppTec, Pavilion Capital, Qiming Venture Partners,Eight Roads, F-Prime Capital, Lilly Asia Ventures, Sinovation Ventures, Baidu Ventures, Pavilion Capital, Bold Capital Partners, and others) precisely due to its strengths not only in AI and deep learning for Longevity research and drug development, but also for its work relating to Biomarkers of Human Longevity.
In 2019, Aging Analytics Agency produced and released ‘Biomarkers of Longevity: Current state, Challenges and Opportunities Landscape Overview 2019”, which market the first public disclosure of its ongoing study into the current state and future trajectory of this domain.
That special case study that performed a benchmarking of human biomarkers of aging and Longevity according to their degree of actionability (a weighted metric that analyzed their level of precision and accuracy vs. factors that determine how easily they can be implemented on a massive scale, such as cost, invasiveness, and broad adoptability).
In Q1 2021, we are following up on this report with a new, open-access, extended and enhanced edition, titled ‘The Rising Wave of Human Biomarkers of Longevity: Landscape Overview 2021’, along with an associated IT-Platform to make the report’s key conclusions, take-awyas and predictions maximally usable and understandable for Longevity scientists, companies, investors, policy makers and the general public.
The project uses comprehensive analytical frameworks 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 importance of benchmarking Longevity Biomarkers and Biomarker Panels by their ratio of accuracy vs. actionability, rather than just their accuracy, cannot be understated. In order for this domain of technologies to actually accelerate the translation of Longevity theory into practice, and enable short-term progress in the extension of Healthy Human Longevity, they need to consist of biomarkers that are market-ready, and obtainable to the majority of doctors, clinicians and nation’s citizenry.
We now have biomarkers and biomarker panels that are market ready, actionable enough (i.e., with comparatively low cost and invasiveness) to be developed, applied and used at scale, and accurate enough to prove useful in validating the safety and effectiveness of lifestyle, behavioural and Precision Medicine-focused interventions, and to track their changes on individual and population-level Healthy Longevity.
With this in place, the Longevity Industry (as well as national governments) have no excuse not to use them for the purposes of therapeutic validation on the one hand, and optimization of population health on the other.
The upcoming project is produced by Aging Analytics Agency for Deep Knowledge Group’s international Longevity policy-focused subsidiary and open-access Longevity Industry knowledge and collaboration platform, Longevity.International, in order to foster a maximum degree of international collaboration and transparency.
It is our hope that releasing the report and IT-Platform in an open-access manner via Longevity.International will encourage scientists, companies and other industry stakeholders to make their own contributions to the platform, in an effort to eventually arrive at a robust and consensus framework
Using this data the report provides advice to the industry leaders for the conception, development and maturation of their action plans, providing insurance organizations with a tool to improve their customer services and risk pricing principles, and to policy makers, in order to combat the problem of Ageing Population and realise that opportunity of National Healthy Longevity.
The project is designed to offer key strategic recommendations regarding technologies and biomarkers implementations within the reach of companies, entities and nations in order to assist them in optimizing their developmental action plans and strategies, providing specialized guidance for business and investment core decisions. It delivers:
1. A "most comprehensive" list of single biomarkers of aging and panels, their advantages and strengths, disadvantages and weaknesses, and future perspectives, challenges and opportunities with a focus on technologies currently used for assessment.
2. Concrete analysis of recent novel biomarkers of aging just entering R&D processes today, emerging tools, and novel assay platforms awaiting approval or standardization for clinical implementation, one step away of being market-ready within the next several years.
3. Highlights respecting why AI platforms will come to be a necessary and indispensable component of Longevity biomarker discovery, research and development.
4. Overview of different categories of panels, whether for Research Use Only or Approved for Clinical Use.
5. Classification of most advanced ageing biomarkers (ageing clocks), their combinations with AI systems, and SWOT and Technology Readiness Level (TRL) analysis of each category with reviews of example use cases and action points. Overview of ageing biomarker mobile applications currently on the market.
6. Brief overview of ageing clock application in the insurance industry, concerning technological, and ethical aspects.
7. Conclusions and practical recommendations regarding the application of ageing clocks.
The parties with early access to this report will gain expertise in the current state of ageing biomarkers technology and market, insights about relative technological and economical traits of each biomarker group, and their applicability in various healthcare industries, as well as the insurance industry (which we will be discussing in detail in a future article in the present series).
The project is designed to providing all stakeholders, including companies, investors, governmental and policy-focused organizations, as well as the general public with:
1. Concrete deep analysis of which biomarkers and biomarker panels are available today; its strengths and weaknesses, their accuracy, availability and current actionability, their strength, and weaknesses, technology readiness levels (TRLs), and peculiarities of each type of Longevity biomarkers related to its uses for real-time and precision monitoring of health status, and biological age.
2. Tangible estimations of which biological age biomarkers and implementations are consolidated, or their current conditioning stage for precision assessment of health status and endpoints of clinical trials and therapies, the use in insurance risk assessments.
3. Highlights regarding the role of digital biomarkers, and AI platforms and how they will become necessary and indispensable components of ageing and Longevity biomarker discovery, research, development and users daily use; overview of mobile apps containing actionable biomarkers or ageing clocks.
It is our hope that this open-source platform will serve as an ideal starting group to galvanise the UK government’s own efforts towards the support, development and dissemination of a truly actionable consensus panel of market-ready biomarkers of human ageing and Longevity.
There is however a risk that the UK Governments and governmental or political strategic bodies may make one or both of the following errors:
1. They might assume that the missing bridge on the road to HALE-extending preventive medicine is still progress in biotech methods, rather than increased precision and personalisation.
2. They might assume that because the current scientific quest for ever more precise biomarkers is not slowing down, that we don’t yet have a set of biomarkers precise and sufficiently actionable enough to take immediate action. As such government strategic bodies therefore risk limiting their strategic ambitions with regard to time frames.
Thus, we recommend that the government make the development of both precise and actionable, implementable panels of ageing biomarkers one of their top priorities, and formulate a specific task-force for the formulation of a road-map that enables increased governmental support (both monetary and non-monetary) to scientists, non-profits and start-ups working on the development of both effective and practical panels of biomarkers of ageing.
Score
A1 (Feasibility increased by continuance of pandemic): 0
A2 (Necessity increased by covid pandemic): 0
A3 (political viability): +1
B1 (Relevance to the specific goal of increasing HALE by 5 years by 2035): +1
B2 (Relevance to general goal of biomedical healthy life extension): +1
C1 (Market readiness applicability): +1
C2 (Project readiness): +1
C3 (Move to market readiness): +1
D1 (Actionability): +1
D2 (Degree of measurability): 0
D3 (Degree of leveraging cross-sector inputs): +1
D4 (Awareness of international context): 0
D5 (Resourcefulness): +1
D6 (Reorganisation): +1
E (Disruptiveness): +1
F (Dividends - does the recommendation aid in social activity and inclusivity?): 0
Point of Comparison: The report refers directly to the need for actionable biomarkers in the paragraph: “Dr Riccardo Marioni of the University of Edinburgh told us that, ideally, biomarkers should be inexpensive, so they can be used at the population level, and as minimally invasive as possible.” There is however no explicit acknowledgement that this is the current stumbling block in attaining the 2035 goal, nor any thorough exploration of how existing resources can be repurposed in order to take the shortest possible route to attaining a minimum viable panel.
RECOMMENDATION SUMMARY
Biomarkers are a measurable indicator of some biological state or condition. They are often measured and evaluated to examine normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Biomarkers are used in many scientific fields. “Biomarkers of aging” are biomarkers that could predict functional capacity at some later age better than will chronological age. Stated another way, biomarkers of aging would give the true "biological age", which may be different from the chronological age. Validated biomarkers of aging would allow for testing interventions to extend lifespan, because changes in the biomarkers would be observable throughout the lifespan of the organism. Although maximum lifespan would be a means of validating biomarkers of aging, it would not be a practical means for long-lived species such as humans because longitudinal studies would take far too much time. Ideally, biomarkers of aging should assay the biological process of ageing and not a predisposition to disease, should cause a minimal amount of trauma to assay in the organism, and should be reproducibly measurable during a short interval compared to the lifespan of the organism.
Metrics for tangible progress are absolutely essential components of any government strategic agenda. Governments must be able to monitor and describe biomedical progress. It will be impossible to make concrete claims regarding global progress in biotechnology - and in preventive medicine in particular - without an agreed panel of biomarkers. In medicine, a biomarker is a measurable indicator of the severity or presence of some disease state, and are capable of serving as a standard metric for industrial output in the global Longevity Industry. While the state of science, advanced biomedicine and the science of Longevity in particular are quite advanced in the UK, there is a clear paucity of practical developments in the specific realm of biomarkers of ageing, and in the development of panels of ageing biomarkers that can be used to assess differences in biological age vs. chronological age, and to measure the effects of lifestyle and therapeutic interventions on biological age. This is a similar situation to the current state of AI for precision and preventive medicine, in which there is a lot of work going on in science and academia, but a visible lag in the practical real-world implementation of that science into practice.
The importance of benchmarking Longevity Biomarkers and Biomarker Panels by their ratio of accuracy vs. actionability, rather than just their accuracy, cannot be understated. In order for this domain of technologies to actually accelerate the translation of Longevity theory into practice, and enable short-term progress in the extension of Healthy Human Longevity, they need to consist of biomarkers that are market-ready, and obtainable to the majority of doctors, clinicians and nation’s citizenry.
Why is a minimum sufficient panel of biomarkers necessary? 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 optimise the existing toolkit of regenerative medicine to address the damage of aging, which is already thoroughly researched. And thus out of this paradigm shift occurred from it arose the field of rejuvenation biotechnology. Now once again, the technology is ahead of the science, the funding, and the political leadership. 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 ageing and to determine how to optimise their implementation. But this is not a biotechnology problem, but a data mining, analysis and management problem. And moreover, in many countries, to various degrees, large-scale data mining, analysis and management is a question of political coordination.
Consider this as one example of recently discovered “minimum sufficient” biomarkers: There have been positive developments in the formulation of precise biomarkers of ageing that can be used to estimate biological age and mortality risk based on Deep Learning analysis of standard blood biomarkers, which is not as precise as the most precise available biomarkers of ageing (DNA Methylation clocks), but which are precise enough, and which can be implemented by any researcher, doctor and clinician that has access to routine blood tests. Similarly, there have been biomarkers of ageing that are constructed using deep learning-based analysis of photographs in mice, which could quite easily be extended to humans. As one possibility, given the increasing resolution capabilities of smart-phones, the development of photographic biomarkers of ageing (e.g. of the face, or the eye) could be a very actionable area of research to focus on.
As the Precision Health industry is growing, we will see an increasing emphasis on the creation and validation of a wide diversity of Biomarkers of Aging, which will enable the extension of healthspan and the maintenance of optimal health for the population via continuous AI-empowered monitoring of fluctuations in personalized Biomarkers of Aging.
P4 (Preventive, Predictive, Personalized and Participatory) Medicine, being the cornerstone of lifespan and healthspan extension, will be the central platform for the utilization of a wide array of Longevity Biomarkers for healthcare by both the general public, and by progressive governments seeking to optimise their population-level National Healthy Longevity.
Support and development of Biomarkers of Human Longevity has been a priority of Aging Analytics Agency and its parent company, Deep Knowledge Group, for many years, and, indeed, one of the factors that influenced its first investment in the Longevity Industry in 2014 (in Insilico Medicine, which has gone on to hold Series A and B rounds from other investors including Wuxi AppTec, Pavilion Capital, Qiming Venture Partners,Eight Roads, F-Prime Capital, Lilly Asia Ventures, Sinovation Ventures, Baidu Ventures, Pavilion Capital, Bold Capital Partners, and others) precisely due to its strengths not only in AI and deep learning for Longevity research and drug development, but also for its work relating to Biomarkers of Human Longevity.
In 2019, Aging Analytics Agency produced and released ‘Biomarkers of Longevity: Current state, Challenges and Opportunities Landscape Overview 2019”, which market the first public disclosure of its ongoing study into the current state and future trajectory of this domain.
That special case study that performed a benchmarking of human biomarkers of aging and Longevity according to their degree of actionability (a weighted metric that analyzed their level of precision and accuracy vs. factors that determine how easily they can be implemented on a massive scale, such as cost, invasiveness, and broad adoptability).
In Q1 2021, we are following up on this report with a new, open-access, extended and enhanced edition, titled ‘The Rising Wave of Human Biomarkers of Longevity: Landscape Overview 2021’, along with an associated IT-Platform to make the report’s key conclusions, take-awyas and predictions maximally usable and understandable for Longevity scientists, companies, investors, policy makers and the general public.
The project uses comprehensive analytical frameworks 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 importance of benchmarking Longevity Biomarkers and Biomarker Panels by their ratio of accuracy vs. actionability, rather than just their accuracy, cannot be understated. In order for this domain of technologies to actually accelerate the translation of Longevity theory into practice, and enable short-term progress in the extension of Healthy Human Longevity, they need to consist of biomarkers that are market-ready, and obtainable to the majority of doctors, clinicians and nation’s citizenry.
We now have biomarkers and biomarker panels that are market ready, actionable enough (i.e., with comparatively low cost and invasiveness) to be developed, applied and used at scale, and accurate enough to prove useful in validating the safety and effectiveness of lifestyle, behavioural and Precision Medicine-focused interventions, and to track their changes on individual and population-level Healthy Longevity.
With this in place, the Longevity Industry (as well as national governments) have no excuse not to use them for the purposes of therapeutic validation on the one hand, and optimization of population health on the other.
The upcoming project is produced by Aging Analytics Agency for Deep Knowledge Group’s international Longevity policy-focused subsidiary and open-access Longevity Industry knowledge and collaboration platform, Longevity.International, in order to foster a maximum degree of international collaboration and transparency.
It is our hope that releasing the report and IT-Platform in an open-access manner via Longevity.International will encourage scientists, companies and other industry stakeholders to make their own contributions to the platform, in an effort to eventually arrive at a robust and consensus framework
Using this data the report provides advice to the industry leaders for the conception, development and maturation of their action plans, providing insurance organizations with a tool to improve their customer services and risk pricing principles, and to policy makers, in order to combat the problem of Ageing Population and realise that opportunity of National Healthy Longevity.
The project is designed to offer key strategic recommendations regarding technologies and biomarkers implementations within the reach of companies, entities and nations in order to assist them in optimizing their developmental action plans and strategies, providing specialized guidance for business and investment core decisions. It delivers:
1. A "most comprehensive" list of single biomarkers of aging and panels, their advantages and strengths, disadvantages and weaknesses, and future perspectives, challenges and opportunities with a focus on technologies currently used for assessment.
2. Concrete analysis of recent novel biomarkers of aging just entering R&D processes today, emerging tools, and novel assay platforms awaiting approval or standardization for clinical implementation, one step away of being market-ready within the next several years.
3. Highlights respecting why AI platforms will come to be a necessary and indispensable component of Longevity biomarker discovery, research and development.
4. Overview of different categories of panels, whether for Research Use Only or Approved for Clinical Use.
5. Classification of most advanced ageing biomarkers (ageing clocks), their combinations with AI systems, and SWOT and Technology Readiness Level (TRL) analysis of each category with reviews of example use cases and action points. Overview of ageing biomarker mobile applications currently on the market.
6. Brief overview of ageing clock application in the insurance industry, concerning technological, and ethical aspects.
7. Conclusions and practical recommendations regarding the application of ageing clocks.
The parties with early access to this report will gain expertise in the current state of ageing biomarkers technology and market, insights about relative technological and economical traits of each biomarker group, and their applicability in various healthcare industries, as well as the insurance industry (which we will be discussing in detail in a future article in the present series).
The project is designed to providing all stakeholders, including companies, investors, governmental and policy-focused organizations, as well as the general public with:
1. Concrete deep analysis of which biomarkers and biomarker panels are available today; its strengths and weaknesses, their accuracy, availability and current actionability, their strength, and weaknesses, technology readiness levels (TRLs), and peculiarities of each type of Longevity biomarkers related to its uses for real-time and precision monitoring of health status, and biological age.
2. Tangible estimations of which biological age biomarkers and implementations are consolidated, or their current conditioning stage for precision assessment of health status and endpoints of clinical trials and therapies, the use in insurance risk assessments.
3. Highlights regarding the role of digital biomarkers, and AI platforms and how they will become necessary and indispensable components of ageing and Longevity biomarker discovery, research, development and users daily use; overview of mobile apps containing actionable biomarkers or ageing clocks.
It is our hope that this open-source platform will serve as an ideal starting group to galvanise the UK government’s own efforts towards the support, development and dissemination of a truly actionable consensus panel of market-ready biomarkers of human ageing and Longevity.
There is however a risk that the UK Governments and governmental or political strategic bodies may make one or both of the following errors:
1. They might assume that the missing bridge on the road to HALE-extending preventive medicine is still progress in biotech methods, rather than increased precision and personalisation.
2. They might assume that because the current scientific quest for ever more precise biomarkers is not slowing down, that we don’t yet have a set of biomarkers precise and sufficiently actionable enough to take immediate action. As such government strategic bodies therefore risk limiting their strategic ambitions with regard to time frames.
Thus, we recommend that the government make the development of both precise and actionable, implementable panels of ageing biomarkers one of their top priorities, and formulate a specific task-force for the formulation of a road-map that enables increased governmental support (both monetary and non-monetary) to scientists, non-profits and start-ups working on the development of both effective and practical panels of biomarkers of ageing.