The Current State of Longevity Science

AI will accelerate real-world implementations of Longevity Science, enabling a paradigm shift from Precision Medicine to Precision Health.

Our three previous articles on the Longevity industry raised a great deal of interest. Some thought that our projections were too bold, while others including several scientists who work in the field of Geroscience, thought that our projections were too conservative and that our article seemed overly skeptical about current progress in aging research. In this article, we take a deep dive into the current state of Longevity Science, with an emphasis on practical applications and recent scientific progress. We explain why investors may underestimate the current rate of progress, why scientists may overestimate the current rate of progress, and how we address these disproportions using AI to produce tangible, quantifiable metrics that enable assessment and forecasting in a realistic and practical way.

As the Longevity industry has matured, the level of scientific and technological complexity has increased. Unlike the days when the Longevity industry was synonymous with biomedical gerontology, the biological science sectors of the industry are now extremely broad, consisting of disparate technological strands - geroscience, geriatrics, regenerative medicine, precision medicine - all advancing simultaneously. It's a challenge to perceive the scale of the Longevity sphere - even for those who work in the industry. Experts in each sector within the Longevity industry lack a comprehensive understanding of the entire industry, so it's difficult for them to make predictions for the industry as a whole.

Data science and AI are becoming the central factors driving progress in the industry. Predictive analytics in Longevity science is already complex and multidimensional, and AI intensifies these challenges. Aging Analytics Agency, the first company to achieve relevant predictive success in the Longevity industry, did so by applying the type of quantitative analytical frameworks normally used for advanced or commoditized industries such as the aerospace sector or financial markets, to the Longevity industry.

Biomarkers

The use of biomarkers is an indispensable component of analysis in this industry. Biomarkers are the foundation upon which the effectiveness of Longevity therapeutics is measured. Biomarkers are also the primary metric in P4 medicine, which involves continuously monitoring the progress of a disease state and recommending a series of corrective interventions to keep health in an optimal state for as long as possible.

Although aggregating biomarkers of aging (rather than biomarkers of disease) is particularly difficult, they must be sought in populations of healthy people, rather than from the health data of hospital populations. Furthermore, as the scope of P4 medicine broadens, the number of biomarkers and technologies will increase rapidly to the thousands in the coming years. This makes the implementation of P4 medicine impractical by current manual means.

Potential 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.

AI Center for Longevity

Aging Analytics Agency and its parent company, Deep Knowledge Ventures, are currently working toward the establishment of an AI Center for Longevity in London 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 this AI Longevity Center 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 desirable 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 is publishing a report on the subject later this year, entitled Biomarkers of Longevity: List of Most Comprehensive Biomarkers of Aging and Optimized Minimally Required Actionable Panels of Biomarkers.

CONTENTS

INTRODUCTION

Current predictions vary wildly on the prospect of seriously intervening in aging and achieving appreciable healthy life extension by scientific means. The Longevity industry is so multifaceted as to potentially defy analysis. Even the biological science sectors of the industry are extremely broad, consisting of disparate technological strands. Aging Analytics Agency was the first company to succeed in developing a valid, relevant and utilizable Longevity Industry analytical framework, dividing the industry into various sectors and sub-sectors, then applying to it the analytic approach first developed for other multi-faceted, innovation-dense, high-technology driven industries such as aerospace and finance. These sectors have been the subject of years of analysis by Aging Analytics Agency, which we aim to summarize in this series of articles.

THE ROLE OF AI IN LONGEVITY SCIENCE

P4 Medicine (Personalized, Precision, Preventive and Participatory) relies on the ability to continuously monitor individual patients’ responses to treatments and continuously recommend adjustments. This requires an advanced system of metrics. P4 emerged from a series of paradigm shifts which gave rise to a diversification of Longevity science. This explosion of resulting synergies means that the science of Longevity will soon be comprised of tens of thousands of elements, and to predict the effects of all of them on human health is an almighty challenge for strategists, and for this reliable metrics are essential. The major tool for devising metrics will be AI. For these reasons Aging Analytics Agency have long considered AI the major engine of Longevity science and industry. This however requires the intensive development of panels of actionable biomarkers of aging, with AI as the main analytical and coordinating engine.

BIOMARKERS OF AGING

Gathering biomarkers of aging means collecting vast amounts of data from the daily lives of people who have no reason to be in hospital. There are however options available for aggregating such data, such as the use of AI for the development of an optimal panel of biomarkers of aging. It is important to achieve a panel of biomarkers which are both comprehensive and actionable so that scientists, healthcare practitioners and policy-makers do not overestimate their timeframes. Aging Analytics Agency is planning to publish a report profiling biomarkers in an attempt to offer an idea of how such a panel could be identified.

AI LONGEVITY CENTERS

Biomarkers for aging are also an essential factor in Aging Analytics Agency's strategic agenda, which includes recommendations for the establishment of AI Centers for Longevity across the United Kingdom, Asia and other Longevity progressive countries and regions, and for the success of Longevity-related government initiatives worldwide, especially those that seek to seize the Longevity dividend. As AI becomes increasingly integrated into every aspect of biomedical R&D, and the practical implementation of P4 medicine, the rate of progress is set to increase dramatically. In order to expedite this process and leverage the use of AI for Longevity and preventive medicine research to its maximum capacity, Aging Analytics Agency and its parent company, Deep Knowledge Ventures, are currently supporting the establishment of AI Centers for Longevity in the UK.

THE ROAD AHEAD

Aging Analytics Agency predicts that in the next few years a network of powerful tech hubs will spring up across the Longevity-progressive countries documented in its various analytical reports, that will establish favorable legal infrastructures for advanced biomedical companies, who under the proper scrutiny and with the use of aging biomarkers, will move away from model organisms and towards a more human-centered approach for therapeutic validation, especially for those therapies that have already crossed the bridge from geroscience R&D towards P4 medicine and practical implementation. The road ahead for Longevity is less a matter of improving the constituent technologies and more a matter of enhancing data aggregation, management and analysis. The best research areas to watch in order to monitor progress are listed with some brief words on the prospects and difficulties facing each one.

NEXT STEPS

Aging Analytics Agency has accomplished the monitoring of this complex and multidimensional landscape with the use of diverse metrics covering every facet of the industry: analytic methods for judging the developmental stage and market readiness of technologies, initially used for assessing and monitoring progress in aerospace, finance and other high-technology driven industries, to biotech, biomedicine and Longevity. It is by such methods that Aging Analytics Agency will continue to optimize the trajectory of the industry , as well as by supporting the establishment of AI Centers for Longevity, and the launch of the Longevity-focused hybrid hedge fund Longevity.Capital.

INTRODUCTION

Predictions differ wildly on the prospect of seriously intervening in aging and achieving radical or appreciable healthy life extension by scientific means. The tools, techniques and technologies required to extend Healthy Longevity are already in a sufficient state of maturity to be applied today. Many experts agree that although more extreme extension of Healthy Longevity will require therapies still being developed and validated, there are existing interventions that could have appreciable effects today. But this might not appear to be the case if one only looks at government demographic projections, which presuppose only very modest extension of healthy functional lifespan, if any. The reason for this disparity of opinion is that Longevity is now an extremely complex emerging global industry.

Some may not think of it as such, perhaps still equating progress in Longevity with linear progress in geroscience, or perhaps as a combination of geroscience and the application of regenerative medicine to aging. But even this view is outdated. In the past decade, the combination of technologies that will escort the global population to longer, healthier, more productive lives has expanded and diversified. The Longevity industry has advanced well beyond geroscience and now occupies a point of convergence between digital, biotechnological, and financial technologies, working together in various ways through governmental coordination across the globe.

Even the biological science sectors of the industry are extremely broad, consisting of disparate technological strands. In the past century we have seen the emergence of curiosity-driven basic research into aging in the form of biogerontology, the immediate applications of this knowledge in the form of biomedical gerontology, the exploration of regenerative medicine for aging, and the emergence of the precision approaches. All of these strands are advancing simultaneously, creating substantial synergetic and complexity-intensifying effects.

Due to the rise of P4 medicine, doctors are now on the brink of a revolution in their daily operations as investors were 100 years ago, when it took as long as a week to consider and enact a single trade deal. Today we have high-frequency trading empowered by AI, and consequently a rapid succession of trade decisions based on rapid precision-enhanced data analysis.

Digital Transformation

Biomedical research is facing a similar digital transformation, whereby data science and AI revolutionize and accelerate testing. Before long, anything related to aging and Longevity will consist of a rapid succession of precisely calculated micro-interventions (e.g. micro-dosages) administered in response to continuous monitoring of fluctuations in biomarkers of aging in order to restore them to normal levels long before the actual onset of disease. The rate of progress in aging research is currently limited by a reliance on the use of model organisms to assess the safety and efficacy of therapeutics. But when dealing with aging, this method will become increasingly ineffective due to the vast genetic difference between the aging processes in model organisms and humans, as digital technologies allow for the possibility of a more rapid human-centered approach to testing.

Why are predictions so diverse? Two reasons:

When experts make varying predictions on the future success of aging science, very often each is considering only progress in his or her own particular domain, and no one person’s expertise is comprehensive enough to make predictions about so diverse a science, or the confluence of factors that will eventually produce results.
As with the digital transformation of finance in the last century, a transformation in one sector can act as an accelerant to the whole industry. We will increasingly come to see the use of AI-driven monitoring of fluctuations in biomarkers, and AI-coordinated application of micro-interventions to normalize them. No one expert from any one sector has the analytic means, or experience in the full, multi-sector and multi-domain scope of the Longevity Industry to predict the results of this.

One might assume that an industry this multifaceted would defy analysis. Instead the task of analysis falls to those with the powerful enough analytical tools to divide the industry into its individual components and measure the progress in each sector and sub-sector individually. In fact, Aging Analytics Agency has found that Longevity as an entire industry can be divided into Geroscience R&D, P4 (Personalized, Precision, Preventive and Participatory) Medicine, AgeTech, and Novel Financial Systems.

Longevity Industry Framework

These sectors have been the subject of years of analysis by Aging Analytics Agency. We have been publishing this series of reports in order to disseminate the major insights and conclusions of this analysis as widely as possible and to galvanize the optimization of the global Longevity Industry as a whole. We believe that with proper frameworks for integration of digital, medical and financial technologies in place the prospect of appreciable healthy life extension is more than simply science-fiction, and indeed will serve as a necessary solution to the looming crisis of the Silver Tsunami.

The first article in our weekly Longevity Newsletter, The Longevity Industry will be the Biggest and Most Complex Industry in Human History, provided a broad overview of this complex landscape, We stated that the challenges of realistic assessment and forecasting of such a complex industry are substantial, but not unsolvable. There already exist established practices for forecasting and assessment in other complex high-tech industries, especially taking into account progress in big data analysis and AI for forecasting, scenario building and modeling, which can be adapted for use in Longevity. Aging Analytics Agency was the first to apply these practices to Longevity, formulating relevant, quantitative analytical frameworks for Longevity industry assessment, benchmarking, forecasting and optimization.

The quantitative and tangible assessment of technologies, methods, therapies and companies within the Longevity space necessitates the use of novel approaches to technological, scientific and industry benchmarking, utilizing methodologies like Technology Readiness Levels (TRLs), which use the expertise of science and technology professionals to assess the market-readiness of products and services, and forecast when their clinical translation will become a reality.

The second article, The Future of the Longevity Financial Industry, explained that the financial industry has a particularly special role to play in the ongoing development of the global Longevity sphere at the present juncture. It will be necessary for novel financial systems to be developed which monetize Healthy Longevity, and repeatedly reinvest in the technologically-reinvigorated working population, if they are to survive the silver tsunami.

The third article, Longevity as New Government Strategy, explained the need for governmental coordination in integrating digital and financial technologies in order to bring about these financial reforms. Any government wishing to seize the Longevity Dividend must develop a national (and international) Longevity development strategy. To this end, Aging Analytics Agency is adjusting its analytical focus to include government development plans, and is engaged in dialogue with several government related organizations in their efforts to ensure that their strategic focus remains firmly on attaining synergy, and is keen to open dialogue with any Longevity-progressive governments in the formulation of their metrics for success.

THE ROLE OF AI IN LONGEVITY SCIENCE

Finance is not the only quadrant of the Longevity industry broad and complex enough to find itself in need of government-level planning and digital integration order to advance further. Aging Analytics Agency routinely puts P4 (preventive, personalized, precision and participatory) at the center of its strategic agenda.

The first segment of the Longevity Industry is Geroscience R&D - the segment of biomedical science and research that aims to treat the root causes of aging. Some of the most early-stage forms of geroscience attempt to treat aging as an engineering issue to be solved using advanced biomedical engineering. These areas are at the very forefront of biotech and biomedicine, and so even these alone require highly specialized approaches to assessment and forecasting, beyond those that have proven adequate for the biotech industry generally.

This is the now iconic mindmap from Longevity Industry Landscape Overview, Vol I: The Science of Longevity. It illustrates the full range of scientific institutions and expertise working in the scientific sub-sectors of the Longevity industry on the cusp of 2018. The graphic, and the report itself (described as a ‘Leviathan’ in the popular online media), was the first of a kind and since then a similar format of infographic has featured in all of Aging Analytics Agency’s ‘Landscape Overview’ reports.

In the early 2000s, enthusiastic proponents of the application of regenerative medicine to aging were arguing that “the science was ahead of 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 identified. And thus a paradigm shift occurred: toward a more repair-oriented approach, the pursuit of a goal named “rejuvenation biotechnology” (the use of regenerative medicine to repair aged tissue). Now this time the technology is ahead of the policy, and the practical healthcare and medical frameworks of developed countries, necessitating a paradigm shift toward greater prevention, personalization, precision and patient participation, utilizing all available tools and technologies that are market-ready today to optimize citizens’ Healthy Longevity.

This layering on of paradigms, and the explosion of synergies that this will produce, means that by the normal methods of assessment, the science of Longevity will soon be comprised of tens of thousands of components, and to predict the effects of all of them on human health is already an incredibly complex challenge. The major tool for managing this will be AI. Hence why Aging Analytics Agency have long considered AI the major engine and driver of future Longevity science and industry.

This is especially true of P4 medicine itself. P4 is defined by the fact that its constituent leading-edge technologies have already achieved a state of market-readiness and clinical implementation. As such, when different strands of geroscience R&D reach a state of validation sufficient for their practical implementation, they cross over from R&D and into the scope of P4 medicine.

Given that P4 medicine, by definition, consists of those Longevity-relevant technologies and techniques that are in practice today, what remains to be done in terms of actually applying them for the extension of Healthy Longevity is largely a matter of data mining, analysis and management, driven by advances in biomedicine, data science and Artificial Intelligence. For example, as AI for R&D in drug discovery becomes more sophisticated, drugs will become more customized to specific diseases and even specific patients. Drug development companies will transition from the current form of “blockbuster drugs” (standard drug formulations applicable to many millions of patients) to P4 medicine, tailoring drugs to specific patient cases based on age, gender, ethnicity, state of health and genetics.

The current state of medicine and healthcare is currently being disrupted by the application of P4 medicine, causing a shift away from "one-treatment-fits-all" blockbuster drugs and towards personalized, precision, preventive and participatory diagnostics, prognostics and therapeutics.

The first and second “P” in P4 Medicine are ‘personalized’ and ‘precision’, which refer to the drugs and treatments that will be designed and applied using precise, individually-tailored methods of dosing, cocktail compositions of micro-dosages, and efficient methods of delivery. Such advances also represent a move toward greater prevention (the third “P” in P4 Medicine), and a shift away from reactionary treatments and towards optimized disease prevention, by the application of micro-dosages of drugs long before the underlying pathology develops into actual chronic disease. Healthy Longevity means prevention rather than treatment, through the maintenance of optimal states of health via continuous monitoring of biomarkers, and micro-adjustments in therapeutic, lifestyle and behavioral regimes to normalize those biomarkers.

This eclectic range of biotechnologies owe their “preventive medicine” status to the fact that each can be applied (and micro-adjusted) in response to continuous monitoring of biomarkers.

The fourth “P” in P4 Medicine is “participatory”, which refers to the increasingly active role that patients are taking in managing their own health, culminating in a situation where citizens are empowered with the tools, approaches and services capable of enabling continual micro-adjustments to their behavioral, lifestyle and therapeutic regimens in response to continuous AI-empowered monitoring of micro-changes in biomarkers that measure state of health and predict risk of diseases long before their actual onset and progression. This paradigm is described very precisely in the book “The Patient as CEO: How Technology Empowers the Healthcare Consumer” by Robin Farmanfarmanian.

These changes are already being embraced by the medical communities and healthcare systems of progressive countries. In coming years, as P4 becomes the new norm, the new definition of failure will be when patients are forced to get doctors involved. In a world in which P4 medicine triumphs, citizens will have no need to engage with doctors until the very end of life.

Advances in P4 Medicine will converge and culminate in the emergence of a new paradigm of “Precision Health”, which denotes the continuous stabilization of health and the maximum-obtainable maintenance of a young biological age via the routine application of P4 medicine in response to ongoing fluctuations in biomarkers of aging and health.

The term Precision Health is becoming increasingly common. The term refers to the idea that the ideal and most comprehensive case of P4 Medicine will naturally and inevitably lead to a state of Precision Health, where diseases and other sub-optimal forms of health are delayed for as long as possible, until near the very end of life.

The role of AI in P4 medicine is already remarkably apparent, especially in places such as the UK, USA, Switzerland and Singapore. For example we have seen very proactive efforts by the UK government, both through their AI Industrial Grand Challenge and their aging Industrial Grand Challenge, to rapidly apply AI to preventive medicine, advanced biomedicine and digital health, and the recent establishment of the All-Party Parliamentary Group for Longevity, where Aging Analytics Agency was proactively involved.

Furthermore, its high degree of complexity necessitates not only innovative frameworks for general benchmarking and forecasting, but also for the general assessment of its technologies’ and therapies basic safety and efficacy. Take, for example, the common use of model organisms to assess the safety and efficacy of therapeutics.

Not only do new methods of standard industry benchmarking and forecasting need to be developed to combat the issues of overcomplexity and multidimensionality in the Longevity Industry, but new methods of testing the basic safety and efficacy of Longevity and Precision Health diagnostics, prognostics and therapeutics need to be adapted as well, moving away from the use of model organisms, towards a more human-centric approach.

While this works well enough for single diseases, it will become increasingly ineffective when applied to Longevity therapeutics due to the vast genetic difference between the aging processes in model organisms and humans. This situation has created an urgent need for a shift away from model organisms and towards more human-centered approaches for safety and efficacy testing, utilizing comprehensive yet actionable panels of biomarkers of aging in patient populations.

As the Longevity, Preventive Medicine and Precision Health industries are grown and developed to scale, we will see an increasing emphasis on the creation and validation of a wide diversity of biomarkers of aging come into use, which will enable the extension of healthspan and the maintenance of optimal health for the majority of citizens' lifespans via continuous, AI-empowered monitoring of fluctuations in personalized biomarkers of aging.

BIOMARKERS OF AGING

The continuous monitoring of small changes in health, and the continuous and commensurate micro-adjustment of treatments in response, requires an agreed panel of biomarkers. Furthermore metrics for tangible progress are absolutely essential component of any strategic agenda. Governments must be able to monitor all biomedical strands of the industry. It will be impossible to make concrete claims regarding progress in biotechnology - and in preventive medicine in particular without such biomarkers. And this is a challenge in itself.

What are biomarkers?

In medicine, a biomarker (an abbreviation of “biological marker”) is a measurable indicator of a biological state or condition. In practice, biomarkers are used to measure the severity or presence of some specific disease state, and can be used in disease diagnosis and prognosis.

Biomarkers are used in numerous kinds of research, both in vitro and in vivo, and almost always include human studies. Although individual biomarkers are difficult to classify, scientists nonetheless identify three specific types: exposure biomarkers, effect biomarkers, and susceptibility biomarkers. These can be used as indicators for several purposes. For example, a biomarker can confirm or disprove the disease risk in an individual, or negative effect which pathogenic agents or their metabolites, chemicals or organic substances have caused. Or, biomarkers could reveal an individual’s sensitivity to specific effects of treatments, and thereby provide the necessary advice for future treatments.

Digital Biomarkers

Biomarkers are typically classified as molecules which have properties that allow them to be measured in biological samples in clinical settings. But what if we measure people's health outside the clinic with the help of everyday devices such as a phone? Thanks to advances in digital technology we now have access to a whole new form of measurable indicator: digital biomarkers. Digital biomarkers are like any other biomarker, but measured through gadgets. Digital biomarkers are defined as objective, quantifiable physiological and behavioral data that are collected and measured by means of digital devices such as portables, wearables, implantables and digestibles. This data can be used not only to confirm the presence of any kind of disease but to predict and, moreover, prevent all possible pathologies.

Nowadays digital biomarkers are widely studied in order to reveal the broad spectrum of possible uses, and to revolutionize current methods of patient health state monitoring and disease outcomes prediction. According to Digital Biomarkers Journal, a multidisciplinary-by-design open access journal that bridges the disciplines of computer science, engineering, biomedicine, regulatory science and informatics, digital biomarkers represent an opportunity to capture clinically meaningful, objective data.

Digital biomarkers could be the breakthrough bioscience has been waiting for, which is why not only individuals and health care providers but also many companies have grabbed the opportunity with both hands. Breathometer, Xsensio, Scailyte AG, Nightingale Health, FEET ME, xbird, Mindstrong Health, Serimmune, IXICO, etc., are top private companies that successfully carry out the mission of digital biomarker popularization. They are known for the development of unique sensing platforms and chips, human liquid testing systems, devices for health monitoring, single-cell profiling devices, and providing unique information that fuels development of new diagnostics, vaccines, and therapeutics. All of these enable novel approaches for preventing and treating a great many diseases.

Source: Karger.com

Digital biomarkers could potentially reorganize the whole Pharma industry and become an integral part of the drug development process. Due to the sensitivity and precision they provide, digital biomarkers can be used to improve clinical trials of drugs. While testing a treatment, finding the appropriate dosage, and looking for side effects, this new form of indicator reveals a drug's efficacy and toxicity for individual patients.

In 2017 the Digital Biomarkers Journal provided a deep analysis of the modern pharmaceutical business model and how it implements digital biomarkers. According to the article, in the case of some illnesses, digital biomarkers can improve the understanding of the natural history of a disease through more continuous measurement of objective health data. Such information may become priceless in situations where symptom presence and severity is more variable and disease prevention and treatment necessitates a more individualized approach to each patient. The past few years have seen increased interest in digital biomarkers and in expanding the scope of their application. We expect to see digital biomarkers eventually become routine in patient care.

Pharmaceutical companies and health systems like GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, Roche, Verily Life Sciences, Biogen, support experiments and strategic initiatives that cover a wide spectrum of therapeutic areas involving different devices. The aim of these experiments is to help increase knowledge about disease progression by various means, including digital biomarkers. e.g. Digital biomarkers enable advanced detection of the onset of certain conditions such as Parkinson's disease, multiple sclerosis, and Alzheimer's disease.

PatientsLikeMe and Biogen partnership has provided promising results from a new study that demonstrates wearable devices collecting and sharing physical activity measurement in patients with multiple sclerosis.
Neurotrack has measured cognitive ability remotely to assess cognition in patients with Alzheimer disease.

Roche has developed a smartphone-based monitoring system (right) to capture voice-related information, which will be useful for those suffering from Parkinson's disease. The app measures Parkinson's disease fluctuations.

What are aging biomarkers?

Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor healthy 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 only, e.g. between the young and even younger, with no traces of any officially recognized diseases.

This presents a challenge because biomarkers research must be adjusted to different ages, races, states of health and lifestyles of the test subjects used in the research, normally hospital patients yielding vast quantities of medical data. But whereas the hospital patients that would ordinarily be used for biomarker research remain in dedicated areas (e.g. hospital beds), 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 hospital, e.g. healthy people who are biologically thirty-five. There are however options available for aggregating data from such demographics.

In order to achieve an optimal panel of aging biomarkers for precision diagnosis data must be taken using multiple health variables from people who are not currently patients. This is an almost entirely impractical task to do manually.

One option, which is a special focus of Aging Analytics Agency, is the use of AI for the development of an optimal panel of biomarkers of aging – a specific niche where the 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.

The growing prospect of AI-derived actionable biomarkers of aging is described very well in a recent scientific article by Alex Zhavoronkov, CEO of Insilico Medicine. Insilico Medicine is the leading company working on this specific topic, and Deep Knowledge Ventures provided Insilico Medicine with its seed funding in 2014.

The diagnostic technologies of the future will be grounded in bodies of data which are incomprehensibly vast, spanning every determining stage in the development of pathology, from the exposome to the genome.

The diagnostic technologies of the future should be anchored to panels of aging biomarkers digitally obtained. This will enable the current state of health of each patient to be continually and precisely monitored, allowing the effectiveness of interventions and micro-adjustments to interventions to be continuously assessed in detail, enabling an unprecedented degree of precision and prevention in biomedicine, and an unprecedented degree of prescience in biomedical research. This, in a nutshell is the nature of the aforementioned digital transformation of the Longevity industry.

The third “P” of precision medicine: personalization. Changes in an individual’s biomarkers are tracked in response to ongoing treatment.

The Need for a Minimum Viable Panel (MVP) of Biomarkers

It is important in technology never to let the perfect be the enemy of good, especially when the technology is of great humanitarian significance. Aging Analytics Agency has observed a tendency among governments and political strategic bodies to make the error of assuming 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 enough and actionable enough to take immediate action.

As such government strategic bodies 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, whereas Aging Analytic Agency has subsequently advised the UK’s newly formed APPG for Longevity that a much more relevant timeline would be 2025, provided that actionable biomarkers with sufficient accuracy are utilized. This aspiration better reflects real current rate and state of scientific and technological innovation.

The ongoing shift toward diverse and actionable biomarkers of aging is described very well in a recent scientific article by Alex Zhavoronkov, CEO of Insilico Medicine.

It is important therefore to develop and promote the widespread use of a panel of biomarkers which are not only comprehensive but also immediately actionable. A panel of less precise but easily implementable biomarkers of aging would be much better than an extremely precise and comprehensive panel of biomarkers of aging that is too hard or expensive to translate easily into widespread practical use across nations.

As an example of minimum viable biomarkers, consider that a set of of aging biomarkers was developed recently which is based on Deep Learning analysis of standard blood biomarkers, which is less accurate than the most precise available biomarkers of aging (DNA Methylation clocks), but which is nonetheless good enough, and can be implemented by any researcher, doctor and clinician that has access to routine blood tests.

As a further example, 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 these 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.

Gathering aging biomarkers means collecting data which marks the difference between healthy people only, e.g. between the young and even younger, with no traces of any officially recognized diseases. The continuous monitoring of small changes in such biomarkers, and the continuous and commensurate micro-adjustment of treatments in response, allows for some de facto reversal of biological age.

However, the use of AI in 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.

An MVP panel of biomarkers will make the biotech sector of Longevity much more lean, and dynamic. It will allow for a more rapid assessment period, which in turn will allow for a rapid succession of experiments with microdoses of different treatment and drugs.

It is not uncommon for scientists to prefer such a mode of research. There are already communities of scientists secretly experimenting upon themselves with small interventions and geroprotectors such as metformin. And a hundred years earlier, in an age of simpler and fewer laws, self-experimentation was common and comparatively uncontroversial.

Aging Analytics Agency’s Upcoming Report - Biomarkers of Longevity: Most Comprehensive and Minimum Required Panels of Biomarkers of Aging

In order to expedite the development of an MVP panel of aging biomarkers which is internationally useful, Aging Analytics Agency is planning to “get the ball rolling” on discussions in an upcoming report entitled Biomarkers of Longevity: Most Comprehensive / Minimal Required Actionable Panels of Biomarkers of Aging.

The report introduces the concept of biomarkers and then summarizes the research already conducted into aging biomarkers thus far. It then profiles and examines the strengths and weaknesses of each - in terms of precision, cost, practicality, readiness - and identifies a subset which are sufficiently comprehensive to have immediate utility. Our hope is that this document may shed some light on the possibility of a threshold for an MVP biomarker panel for aging.

AI LONGEVITY CENTER

As scope of P4 medicine grows, and the number of relevant biomedical interventions increases rapidly to the thousands in coming years, the number of associated biomarkers will increase to tens of thousands. Only AI is capable of handling and coordinating all this data.

In order to effectively execute the paradigm shift from Precision Medicine to Precision Health, and enable citizens to become the CEOs of their own health through the combination of near-continuous monitoring of biomarkers of aging and combined with high-frequency therapeutic micro-adjustments to normalize small deviations in those biomarkers long before the actual occurrence of disease, it will soon become necessary to utilize AI to manage, analyze and execute the process of monitoring and therapeutic adjustments.

While today AI has an incredibly impactful role to play in terms of accelerating the rate of progress in P4 Medicine R&D, very soon it will become a strictly necessary component of its practical implementation due to the sheer volume of data involved.

In order to help accelerate the use and adoption of AI for both Longevity R&D, and its practical implementation within the scope of P4 medicine, Aging Analytics Agency is working alongside several like-minded organizations to establish the first UK-based AI Longevity Centre. A special focus for this AI Longevity Centre will be the use of AI for the development of an optimal panel of biomarkers of aging, and work on important but comparatively neglected and underrepresented areas of biomarkers of aging R&D.

In the UK there are currently 4 major AI Centers for Healthcare, in various major hubs across the country, such as the new AI Center for Value Based Healthcare at King’s College. However, none of them have a specific focus on Longevity and preventive medicine. While these centers do serve as a proof-of-concept for the viability of an AI Center for Longevity, they do not adequately address the need for a complete AI for Longevity R&D hub capable of developing leading solutions, products and services that apply AI to the specific purpose of extending Healthy Longevity.

There are only 3 institutions in the world actively trying to establish what are effectively AI Centers for Longevity. These are the US-based Buck Institute for Research on Aging, Y Combinator, and the US-based AI Precision Health Institute (AI-PHI) at the University of Hawaii Cancer Center. Only the AI-PHI has actually succeeded in establishing such a center in practice.

The intensive application of AI to all stages of Longevity and Preventive Medicine R&D has the potential to rapidly accelerate the clinical translation of both validated and experimental diagnostics, prognostics and therapeutics, to empower patients to become the CEOs of their own health through continuous AI-driven monitoring of minor fluctuations in biomarkers, and the rapid development of the global Longevity Industry to scale.

As such Aging Analytics Agency and its parent company, Deep Knowledge Ventures, is working on the development of several leading AI Centers for Longevity, which would apply the latest advances in AI, Precision Health, Preventive Medicine and Biomarkers of Aging to accelerate the development of technologies, procedures and services to increase the UK’s National Healthy Longevity.

The choice of location (currently undisclosed) for the first AI Longevity Centre in the UK is a place with a unique combination of resources, departments and technologies for both AI and Longevity. The centre is being established this year (2019) will be further developed in 2020, and we expect it to be the first of several such centers across the UK. The first Longevity AI Center in the UK will be the first ever platform for the production of comprehensive cloud computing systems for developing multifactorial panels of biomarkers of ageing, and aims to identify a minimum recommended panel of biomarkers to be implemented into clinical diagnostic facilities or partnership projects.

These may include different academic institutions, healthcare providers such as clinics, diagnostic laboratories and AI healthcare companies. The concept for the AI Centre for Longevity will be to provide free of charge access to this cloud computing system, with our partners contributing different types of data and joint development and validation of biomarkers. Our partners will gain access to the cloud service and the AI capabilities of the Centre to develop and validate new experimental markers.

Key areas of focus will include how AI can be implemented so that the diverse data sources can be more effectively mined and analyzed. The nature of the data to be collected remains to be established, and identification of appropriate facilities required to process such digitized data linked with current health status of individuals. The Longevity AI Centre also represents a significant opportunity for commercialization of the technologies and biomarkers identified through the research partnerships. It is likely there will be numerous spin-off companies created, and financial companies can be provided with specific services.

For example data from voice recognition and health status would be valuable for insurance companies. As the development of biomarkers of wellness and Longevity will be collected from people of all age groups (since aging starts from the time of conception) and ethnic backgrounds and correlated to genetic and environmental factors, this will enhance the global profile for the Centre.

One additional area of research that the AI Center for Longevity will focus on is the establishment of a dense ecosystem of unmanned, deep-dignostic P4 medicine booths in key metropolitan clusters of the UK. creation of a nation-wide network of unmanned preventive diagnostics booths across the UK.

This has already been launched in China by the company Ping AN Doctor, which plans to install 300,000 such unmanned booths in populated public spaces, wherein each booth will cover 5,000 citizens.

Considering that the UK has a population of 67 million citizens, the UK should model the scope of these booths after the example of China, which would translate to 13,500 such booths, if we assume a single booth to cover 5,000 citizens.

It is important to note that this project should not necessitate any novel R&D, but just an emulation of the existing efforts being made in China. These booths would not aim to offer deep or broad preventive care, or the deepest levels of preventive diagnostics and prognostics available, but would include simple preventive diagnostics (including visual recognition, and possible blood and urine analysis) capable of enabling regular monitoring of changes in conditions and results, and should be in locations that make it convenient for citizens to have check-ups at these booths one time per month.

These booths should be connected via the NHS cloud computing system to provide deeper, AI-enabled analysis based on the simple diagnostic tools and methods described above. They should also be integrated with user's digital devices (including mobile phones and wearables).

This is another example of an initiative that is not complex, and does not require intensive efforts at innovation, but rather the simple optimization and application of existing technologies. It can be considered to be for the most part a data aggregation and management issue, rather than project requiring any kind of medical innovation whatsoever.

Following the successful development of the first AI Longevity Centre, we suggest that it expand its operations and establish some prototypical AI Centre for Financial Wellness. Whereas the AI Centre for Longevity would focus on optimizing health into old age, this centre would focus on the application of AI to the creation of methods and technologies to promote wellness in the elderly in all aspects of life besides health, ranging from financial wellness, continuing education, happiness, psychological wellbeing, neuroplasticity and active social involvement.

In addition to its focus on the synergetic application of AI, biomarkers of aging and Longevity, the AI Centre for Longevity also plans on dedicating resources to R&D in other niches in which the levels of practical, real-world implementation are lagging behind advancements in science.

These include the implementation of microbiome diagnostics and therapeutics, as well as recent advancements and innovations in advanced cosmetics in particular. The microbiome has in recent years come to be regarded in scientific circles as a very strong, actionable and measurable indicator of bodily health, while microbiome therapeutics (including, for example, microbiota transplants) has also come to be recognized for its very high ratio of effectiveness vs. ease-of-implementation and low risk profile.

Similarly, whereas most areas of the cosmetics industry are still dominated by scientifically unvalidated claims, there is an increasing amount of emerging validated approaches that are emerging. In particular, these include creams and injections based on patient-specific stem cell lines, and much more recently, the areas of (1) facial rejuvenation via restoration of the skin microbiome to its youthful state, and (2) the use of AI analytics to formulate personalized treatment regimes for wrinkled skin, dry skin and dandruff.

One additional point of focus should be on the development of microbiome-based approaches to improving the efficacy of drug development and delivery, either by utilizing changes in the microbiome to enhance the absorption and deliver of oral drugs, or modifying the specific dosing of drugs in accordance with the personalized specifics of patients' microbiomes. One specific partner for this specific niche could be Atlas Biomed, a leading precision medicine clinic in London that has a strong focus on microbiome diagnostics and therapeutics.

Aging Analytics Agency’s upcoming industry landscape overview reports. These will follow in the format of previous non-regional reports in the Longevity Industry Landscape Overview series. Longevity Industry and the Microbiome covers the development of microbiome-based approaches to improving the efficacy of drug development and delivery, and Longevity and Advancing Cosmetic industry covers the development of creams and injections based on patient-specific stem cell lines.

Aging Analytics Agency is also in dialogue with a number of third-parties on the subject of roadmapping the establishment of additional centers in key R&D, academic, industrial metropolitan centers throughout the UK, such as Birmingham, Liverpool and Edinburgh, with the aforementioned AI and Healthcare across the UK, thereby providing a proof-of-concept for purposes of the proposal.

THE ROAD AHEAD

Only the work of mass health data aggregation stands between us and a coming new age of precision diagnostics and prognostics based on aging biomarkers obtained from whole populations, in which AI analysis and automation using advanced mathematical tools and algorithms makes predictions and recommendations based on thousands of data points for each person. With each year, we will see increasingly precise and comprehensive diagnostics and prognostics, which, when combined with subsequent further advances in AI, will amount to a degree of predictive power which opens the doors to a whole new industry.

Aging Analytics Agency predicts that in the next few years a network of powerful tech hubs will spring up across the world’s Longevity-progressive countries documented in our reports, that will compete with each other to establish the most favorable legal infrastructures and legislative ecosystems for advanced biomedical companies that, under the proper scrutiny, will test on human rather than model organisms.

These will not be traditional biotech hubs like California’s Silicon Valley or Switzerland’s Health Valley. They will be powerful ecosystems that utilize the full scope of P4 medicine managed in real-time by AI, and will feature several distinct hallmarks including:

AI data management, analysis and integration
High frequency biomarker monitoring and therapeutic micro-adjustments
Biomarkers-based P4 medicine for aging
More favorable legal frameworks for clinical trials on humans

At the time of the Apollo 11 mission, the prerequisite sciences for space travel -- rocketry, Newtonian physics, mathematics and basic astronomy -- were already centuries old. It was the added enhancements of precision and predictiveness, brought about by digitization, with substantial government initiative, commitment and funding thrown in, which opened the door to another world.

Likewise, from this point on, advancing the Longevity industry is less a matter of improving its constituent sciences and technologies and more a matter of enhancing their precision through data aggregation. This is a far cry from the alternative priority of investing in basic research into “frontier technologies” in the hope of remote future breakthroughs which, though potentially revolutionary, are still decades away from fruition.

Aging Analytics Agency itself is not averse to investment in the full spectrum of technologies that comprise the Longevity industry, from short-term palliative solutions such as AgeTech which can be implemented within months, to radical life extending rejuvenation biotechnologies which may not add a single year of healthy life for decades. But others are taking a more conservative and yet efficient approach that can go a long way toward establishing a bridge between Longevity startups in need of relevant amounts of investments, and conservative investors, as described in the second article in this weekly series. In the case of Longevity.Capital, for example, only 10% of its investments will be in startups pursuing technologies which are still years away from validation and practical implementation (and therefore still necessarily dragging along at the testing model organisms stage). 90% of its investments will be in technologies that are either implementable in practice today or at a point of validation and TRL level that indicates the feasibility of its practical implementation within the next 3-5 years.

Most Promising Domains of Geroscience

Aging Analytics Agency monitors each domain of geroscience closely. The following are some of the research areas, people and organizations to put on one’s watchlist if one wishes to get an overview of which are progressing the fastest. Also added are a few words about the rate of progress of each, and the difficulties currently faced by each going forward.

Senolytics

Senescent cells, also known as “zombies cells”, are cells that refuse to die well after they are due to be replaced. Scientists believe that they speed up aging and create favorable conditions for pathologies when they build up in our body. A major interest of gerontologists is creating specific and low side-effect drugs that can induce death of senescent cells, referred to as senolytics. The aim of senolytic research is to prevent or delay age-associated conditions, and many known potentially senolytic drugs are under intensive investigation. The main difficulty for finding remedies to this obstacle is that the science behind cellular senescence is not yet completely understood. The link between cellular senescence and aging needs to be further researched.

People to watch

Ned David
Chris Gibson
James Kirkland

Companies to watch

Senolytic Therapeutics
Cleara Biotech
Unity Biotechnology
Oisín Biotechnologies
Recursion Pharmaceuticals
Mayo Clinic

Influencer infographics are a staple of Aging Analytics Agency reports. It is important for purposes of relevant industry analytics to recognise the pivotal role of investors, scientists and influencers of popular opinions (the latter having ramifications for political will, another pivotal factor frequently discussed in this series of articles).

Geroprotectors

Geroprotectors are chemicals with the ability to slow down aging and age-related diseases. Usually, they achieve this through interplay with the key aging-associated signaling axes in cells. Two of the most well-known geroprotectors, rapamycin and metformin, have already been validated extensively in model organisms. The challenge that remains is for gerontologists to find natural mimetics of validated synthetic drugs. The reason for this is that natural occurring mimetics should be less toxic and more bioavailable. This makes geroprotectors a very promising field of aging science and pharmacology industry. Of all the domains listed here geroprotectors are the closest to practical implementation with several examples of real-world use even today, many functioning as natural mimetics of various `tried-and-tested substances such as metformin, etc.

People to watch

Alex Zhavoronkov
Alexey Moskalev
Vadim Gladydhev
David Sinclair

Companies and organizations to watch

SENS Foundation
resTORbio
Insilico Medicine

Another format of infographic common in Aging Analytics Agency reports. The Agency has profiled and kept abreast of the great many academic events and publications touching on every aspect of the science.

Gene therapy

Gene therapy is precision treatment for fixing deficient genes. It is achieved through editing genes by delivering replacement genetic code to cells packed inside viruses. This can be done to germ cells as well as with adult organisms. Multiple systems of gene editing have been developed and the most recent - CRISPR - is a major subject of media hype and scrutiny. The potential of gene therapy is vast and its possible uses innumerable. In particular it is an eventual key component in rejuvenation biotechnology, mentioned below. Anti-aging gene therapies had received a great deal of publicity in recent years and has made headlines with its various lurches forward. Prominent Harvard geneticist George Church, via his company Rejuvenate Bio, has recently delivered 45 gene therapies to provide aging reversal and found the combined treatment effective against obesity, diabetes, osteoarthritis, cardiac damage and kidney disease. They expect to get the treatment in the hands of actual patients by around 2025
.

People to watch

George Church
James M. Wilson

Companies and organizations to watch

AVROBIO
AveXis
Bluebird Bio
Homology Medicines
Uniqure NV
REGENXBIO Inc.
MeiraGTx
Voyager Therapeutics

Since late 2017 Aging Analytics Agency has been painstaking identifying geroscience institutes around the world, cataloging by region. Lists such as this first appeared in Longevity Industry Landscape Overview vol 1: The Science of Longevity.

Cell therapies

Stem cell therapy is used to regenerate tissues and organs. There has already been some reported success in regenerating seriously damaged tissues and organs. Cellular therapies also include personalized cancer treatment by modified T-cells, also known as CAR T-cell therapies. The field is now booming and in 2018 a Nobel Prize in relevant T-cell research was received by James P. Allison and Tasuku Honjo. Several CAR T-cell therapy products have been approved by the FAD already. Over 240 CAR-T clinical trials are running. The field of immuno-oncology is attracting billions of dollars in investment and a great deal of interest from pharma. Transplantation of therapeutic stem cell populations could be used to treat a number of diseases, such as blindness, muscular dystrophy, myocardial infarction, stroke, missing teeth, wounds, Alzheimer’s disease, and so on. There were 33 ongoing phase III clinical trials of cell therapies and 16 of gene-modified cell therapies, including CAR T-cell therapies, at the end of 2018.

People to watch

Michael West
Robert Preti
Chris Mason
Emile Nuwaysir
Daniel Kota

Companies and organizations to watch

BlueRock Therapeutics
Celularity
Hemostemix
Aperion Biologics
Celyad
Kite Pharma

Aging Analytics Agency’s recognition of the importance of politics and finance as pivotal to the future growth of the Longevity industry necessitates the monitoring of events and publications outside the academic and scientific world.

Caloric restriction mimetics

Calorie restriction (CR) mimetics is a class of drug candidate that can mimic the anti-aging effects that occur naturally due to a decrease in calorie intake of 20-50%. This process happens without any harmful side-effects such as malnutrition. It works by targeting key signaling pathways such as the rapamycin pathway. Today, there are no validated CR mimetic drugs for human consumption, but this field under intensive investigation. This explanation for the huge interest in this domain is that calorie restriction has already been shown to extend the lives of various laboratory organisms - from yeast and nematoda to rodents. CR mimetics is being thoroughly investigated, but the field holds limited promise in humans. It is perhaps implementable within a decade or so, but its benefits (the possible success of the mimicry itself) are an unknown quantity (even if the effects of actual calorie restriction are well documented).

People to watch

David Sinclair
Leonard Guarente
Guido Kroemer
Eric Ravussin

Company to watch

Elysium

Infographic from Aging Analytics Agency’s 2019 report The Science of Longevity in the UK Landscape Overview Q4 2018. The United kingdom is of special interest to Aging analytics Agency due to its detailed industrial strategy which explicitly seeks to address the “Aging Society” as a major challenge. It is therefore a subject of multiple updated case studies per year.

Regenerative Medicine

Regenerative medicine is the repair of damaged (or aged) tissues and organs, e.g. by regenerating human cells, artificially engineering tissues and organs to renew their functionality, and regrowing and repairing damaged, lost or aged cells, tissue or organs. The application of regenerative medicine to aging is called “rejuvenation biotechnology”, the most fully elaborated strategy for which is SENS (Strategies for Engineered negligible Senescence), an action plan for repairing aged tissue based on a “damage report” consisting of a list of manifest differences between old and young cells and tissues.

A typical example of a problem of aging amenable to regenerative medicine solutions would be stem cell exhaustion. This can reduce the efficiency of the immune system, and lead to muscle loss, a decline in bone mass and slow wound healing. A solution to this obstacle, therefore, could significantly extend healthspan. A regenerative medical solutions would be to find a way to enhance the activity of stem cells. The difficulty with this approach are also typical of regenerative medical solutions: it can lead to unwanted side effects, as the stem cells can senesce at an accelerated rate, resulting in premature aging. Slowing their activity, on the other hand, can cause premature aging as well. There’s a clear need, therefore, for finding the “sweet spot” for stem cell activity and guiding the cells in that direction. We also need further development of effective tools to operate on stem cells in the tissues and either replace or rejuvenate them.

People to watch

Anthony Atala
Aubrey de Grey
Judith Campisi

Companies and organizations to watch

AgeX Therapeutics
BioTime
SENS Research Foundation
Buck Institute for Research on Aging.

Ovarian rejuvenation

Menopause negatively affects women's lives as it leads to a hormone imbalance and a number of associated problems. Headaches, racing heart, urinary urgency, and weight gain are only some of those. But women always have eggs inside their ovaries (even during postmenopause). A lot of eggs just stay dormant. Ovarian rejuvenation is a new approach to re-awake egg maturation and development. Its could lead to a more normal physical and mental state in 40+ women by removing menopause and postmenopause symptoms. Also, it could slow down aging by keeping hormone balance typical for reproductive years. All-in-all it could decrease the number of woman’s disability-adjusted life years as it allows them to maintain health and wellbeing. Modern approaches to ovarian rejuvenation include PRP (Platelet Rich Plasma) injections, and injections of the patient's own fat stem cells directly into the ovaries.

People to watch

Judith Campisi
John Jackson
David Barad

Companies and organizations to watch

Inovium
The Buck Institute for Research on Aging Center for Female Reproductive Longevity
Center for Human Reproduction
Robinson Research Institute
New Hope Fertility Center

Another graphic from Longevity Industry Landscape Overview vol I, the Science of Longevity. Here laboratories themselves are identified rather than companies. Note that the concentric circles represent increasing decrees of disruptiveness, with palliative technologies such as geriatrics represented by the outer ring and disruptive interventions in core aging processes at the centre.

Immune System Rejuvenation

People of advanced age frequently face immune dysfunction in their innate and adaptive immune systems. This type of age-related condition is known as immunosenescence. This leads to chronic inflammations, chronic diseases and higher rates of infection. The task of immune system rejuvenation is to stimulate and support the indigenous immune system to restore and maintain its optimal, youthful functionality. Established rejuvenation practice include stem cells recovery, thymus rejuvenation, and modulation of hormone production. Immune system rejuvenation is relatively far from practical implementation, but with some low hanging fruit, e.g. people are already experimenting with altering their own immune system through fasting, so there is a great deal of experimental data is easily obtainable.

People to watch

Eric Verdin
Joan Mannick
Bobby Brooke
Valter Longo

Companies and organizations to watch

resTORbio
Serimmune
Institute for Education, Research, and Scholarships (IFERS)

With the rapid development of the Longevity industry, the number of events dedicated to this topic has increased proportionately. These events differ in a number of ways including target audience, central topics being covered, entrance fee range, location, venue, etc. Potential participants need to be aware of such conferences details while planning which conferences to attend. This report aims to serve as a guide in this type of decision making, which also includes a cost-benefit analysis of the conferences themselves. Aging Analytics Agency's report Top-30 Longevity Conferences 2019-2020 presents the Top-30 conferences related to Longevity, providing key facts and figures on each. The Top-30 conferences chosen for this list, from 150 Longevity-themed conferences in total, satisfy the following criteria: 1) They are well attended, with a large number of speakers as well as participants 2)They include at least one panel on the topic of Longevity 3) They feature speakers who are professionals in the industry.

Domain: Inflammaging

Aging impacts how cells communicate with each other, which can cause inflammaging: a constant state of low-level body-wide inflammation, which in turn brings about several aging-related conditions. Countering inflammaging would improve the immune system’s activity and could mitigate many aging-related conditions. Cells communicate with each other by sending chemical signals of various kinds. This ability is one respect in which aging can be a “contagious” process, for example how senescent cells can urge other cells—even in other tissues—to undergo senescence themselves. Senescent cells release pro-inflammatory molecules that contribute to a general state of inflammation in the body. This condition is associated with aging and many aging-related diseases including Alzheimer’s, atherosclerosis, Type II diabetes, and cancer, and can hinder the function of adult stem cells. Constant inflammation can even accelerate telomere attrition, which then promotes cellular senescence.

People to watch

Philipp Leucht
C. Franceschi
Keith L. Kirkwood
Anne Marie Josephson
Judith Campisi
Remi-Martin Laberge

Companies and organizations to watch

Buck Institute for Research on Aging
NYU School of Medicine
SENS Research Foundation
National Institute of Arthritis and Musculoskeletal and Skin Diseases

Domain: Biogerontology

Basic research into the biology of aging. Although those with a more utilitarian approach to gerocience would prefer to prioritize translational research rather than the pursuit of a fully comprehensive theory of how aging occurs, theoretical biogerontology still has much to achieve, and is likely to hold unforeseen promise. It has already proved essential to the kind of intelligence gathering which enables interventions in other domains listed here such as senolytics and mimetics, and it is impossible to tell what new doors further research may uncover. Biogerontology has in its sights the eventuality of a “robust theory of aging”, a theory that ties together all the different mechanisms of aging and explains the relationship between them. The theory would predict how any change of the involved factors will affect the aging process. The development of such a theory would prove audacious but impactful, and a proof of concept is expected around the year 2030.

People to watch

Michael R. Rose
Steven N. Austad
Cynthia Kenyon
Richard A. Miller

Companies and organizations to watch

Oxford University
Cambridge University
University College London
University of Swansea
Newcastle University
Edinburgh University
Stanford University
Buck Institute for Aging Research
Biogerontology Research Foundation

Domain : Biomarkers of Aging

The search for a reliable panel of biomarkers for aging opens up enough doors that it constitutes an entire domain of geroscience in itself. It is also unique among these domains as it approaches the intersection between the P4 and geroscience quadrants of the industry (as illustrated in the sector diagram near the beginning of this article), not to mention a major synergy between digital and biotech sectors. Success in this domain is a much lower hanging fruit than is commonly supposed, due to the overlooked possibility of a minimum viable panel of biomarkers, described above.

People to watch

Alex Zhavoronkov
Morten Scheibye-Knudsen
Lee Uhn

Companies and organizations to watch

Insilico Medicine
Exscientia
bioAge
Sophia Genetics
Gachon University Gil Medical Center
University of Copenhagen
University of Alberta
Biogerontology Research Foundation

NEXT STEPS

All of this makes for a very eclectic landscape and subject for analysis. Aging Analytics Agency has accomplished this analysis with the use of diverse metrics covering every facet of the industry. In all its publications, operations and engagements, Aging Analytics Agency is concerned exclusively with practical implementation of these technologies as soon as possible, for the benefit of as much of humanity alive today as possible. In these articles we offer a glimpse of our analytical framework, and have done our best to make it as simple as possible for the average reader. However, given the reality of the industry in its current and foreseeable state of development, nothing less than an extremely sophisticated analysis could possibly suffice for the purposes of investor confidence, and as such overviews such as these only scratch the surface of the depth of current and future analysis.

Aging Analytics Agency's 3-D Longevity Industry Analytical Framework, whose production was necessitated by the complexities of the sector, and required in order to obtain a tangible and pragmatic understanding of the industry in order to structure investment strategy in a relevant way.

We have applied the standard of analytic methods normally used in assessing and monitoring progress in aerospace and other high-technology driven industries marked by a rapid pace of innovation and new technology adoption -- to the scientific sectors of the Longevity industry, geroscience R & D, regenerative medicine and P4 medicine.

The analytical frameworks used by Aging Analytics Agency for Longevity Industry analysis, benchmarking and forecasting have been in a continuous state of development and refinement for the past five years, and now utilize several dozens of specifically-weighted, quantitative metrics to measure the present-state readiness and validation, future prospects, therapeutic depth and breadth, and scope of companies’ therapeutic, diagnostic and/or prognostic pipeline.

Analysts of the aerospace industry devised a concrete metric for describing the progress of a technological component of an industry from its earliest conception to an application of a technology in its final form: the technology readiness level (TRL), a knowledge-based standard and shorthand for evaluating the maturity of a technology or invention. TR1 is the lowest level of technology readiness and TR9 is the highest.

And as illustrated here, Aging Analytics Agency also take a divide-and-conquer approach to Longevity industry Industry analysis, benchmarking and forecasting. While such an analysis may seem daunting and many of the benefits lie more than a decade in the future, the need for such an analysis it is an encouraging sign of how far the industry has matured since a decade ago when progress could be understood linearly in terms of basic geroscience research.

In order to conduct effective analysis, benchmarking and forecasting for the Longevity Industry, analysts and investors need to utilize analytical frameworks and methodologies at least equal to the levels of complexity, multidimensionality and intersectionality of the Longevity Industry’s constituent technologies, domains of science and companies.

Aging Analytics Agency has and will continue to refine their systems of comparative analysis systems over the next several years, refining the specific metrics used to conduct its market studies, as well as the mathematical formulas used to combine them, and the advanced visualization techniques used to make their forecasts, ranking and determinations as clear as possible. They will continue to increase and enhance the breadth, depth and overall re-tunability of these analytical frameworks, and to extend them to additional relevant domains, including benchmarking of projects and initiatives in the realms of the Longevity Financial Industry and Longevity politics, governance and national development plans.

Caption: An infographic from Aging Analytics Agency’s upcoming Precision Medicine Clinic Landscape Overview 2019: Most Advanced Clinics, Technologies and Methods analytical report, illustrating the comparative levels of sophistication of an example precision medicine clinic’s various technologies and services.

It was necessary to begin the process of developing these analytical frameworks early, and to continue to evolve the approaches used for assessment, benchmarking and forecasting continuously, in step with the rapidly shifting dynamics of Longevity. We are now standing at the dawn of a golden age of Artificial Intelligence that will deliver significant progress in the development of comprehensive yet actionable panels of biomarkers of aging in the next few years, and rapidly-intensifying dynamics of progress on the forefront of preventive medicine, precision health and advanced biomedicine. These will form the central drivers of a vast, multi-faceted industry which will penetrate and disrupt surrounding industries including biotechnology and finance. Its end product is, after all, humanity's most valuable asset upon which all other assets depend: years of healthy functional active life.

The proprietary reports of Aging Analytics Agency utilize a variety of insightful comparative analyses, including company harmonization analyses showing how companies compare in terms of the ratio of their strengths in key areas including scientific validation, business development, marketing, financial position, executive management composition, technology pipelines and other relevant domains.

Aging Analytics Agency and its parent company Deep Knowledge Ventures will continue its mission to strategically assist, support, and optimize the trajectory of development of the global Longevity Industry by developing and refining its advanced analytical methodologies of in order to keep up with its multiplying growth and complexity, as well as by supporting the establishment of AI Centers for Longevity, and the launch of the Longevity-focused hybrid hedge fund Longevity.Capital.

CONCLUSIONS

The Science of Longevity, much like the broader Longevity Industry itself, is a field unprecedented in its levels of complexity, multidimensionality and intersectionality. The typical approaches for analysis, benchmarking and forecasting developed for use in the biotech and biomedical industries are not adequate when applied to the Science of Longevity. New methods and approaches for quantitative, tangible analysis, benchmarking and forecasting are necessitated by these unprecedented levels of complexity, and they need to be at least as sophisticated and multidimensional as the specific domain they are being applied to. This is the mission that Aging Analytics Agency has been dedicated to for the past five years: the development and continuing refinement of novel analytical frameworks that are relevant in the face of the Longevity Industry’s complexity.

As developments in the Science of Longevity reach maturity and become implementable in practice, they fall under the domain of P4 Medicine, which consists of the entire scope of personalized, preventive, precision and participatory prognostics, diagnostics and therapeutics capable of maximizing citizens’ Healthy Longevity, and maintaining an optimal state of health for as long as possible.
One of the most important areas of Longevity scientific R&D is the development of biomarkers of aging - measurable indicators that can be used to estimate an individual’s biological age, and test the effect of interventions on biological age. Biomarkers of aging lay the necessary groundwork to test the safety and effect of Longevity interventions.
Even more important is the development of actionable biomarkers of aging, which can be thought of as the “minimum viable” panel of aging biomarkers: ones which have optimal levels of precision and accuracy vs. actionability (i.e. expense, ease of implementation, etc), thus enabling their accelerated implementation into practical use.
Also important are ongoing shifts in how biomarkers of aging are sources and developed. Whereas historically the majority of such biomarkers came from persons of ill-health, there is an increasingly recognized need to begin sourcing them from a healthy populations that differ from each other in terms of their age, state of health, ethnicity, and sex. Moving forward, we will begin to see increasing levels of aging biomarker personalization, and the actual “minimum viable” panel of biomarkers used in practice by any given person will come to be highly tailored to their unique age, sex, ethnicity, current state of health, genetics and so on.
The continued development of implementable biomarkers of aging will quite rapidly lay the foundation for the paradigm shift from Precision Medicine to Precision Healthy, enabling citizens to become the CEOs of their own health via near-continuous monitoring of fluctuations in biomarkers of aging, and the application of therapeutic “micro-adjustments” to normalize those biomarkers when they deviate from their youthful optimum on an ongoing basis. Health management on both the personal and national level today is operating in much the same way that financial trading operated 50 years ago, involving low-frequency transactions measured no in microseconds, but in days. As P4 medicine progresses, the entire healthcare, medical and health management paradigm will shift towards high-frequency diagnostics and therapeutics, enabling the normalization of deviations in biomarkers with very small adjustments in near real-time.
As both the number of biomarkers of aging and the number of practically-implementable interventions increases from tens or hundreds to thousands, the need for AI to manage and coordinate all those data points in order to formulate the most optimum ongoing therapeutic adjustments becomes increasingly necessary. Whereas now AI’s most pivotal role is in accelerating Longevity scientific R&D, its central role within Longevity and P4 medicine will quickly come to be the management of citizen’s everyday P4 diagnostic, prognostic and therapeutic regimens.
Aging Analytics Agency and its parent company, Deep Knowledge Ventures, are currently working toward the establishment of several AI Centers for Longevity in the UK and Asia, as well as complementary AI Centers for Lifetime Wellness, which will focus on R&D for all non-medical (financial, psychological, social) aspects of lifelong wellness, functionality, independence and happiness.
As the industry grows ever more elaborate, there is an increasing need for dedicated centers such as this focusing on providing companies and researchers active in this space with advanced AI-driven support, to conduct cutting-edge R&D on the application of AI to the development of actionable and practically-realizable biomarkers of aging, in order to accelerate the coming paradigm shift from Precision Medicine to Precision Health, and enable citizens to take control of their own Healthy Longevity.

In this article we have sought to provide a general introduction to the science of Longevity, and its major components. A comprehensive overview of this area would require a great deal more space. But we did highlight the fact that the next significant hurdle in the advancement of the industry is digital integration, and that in the next few years the enhanced precision this provides will create a paradigm shift and open the doors to a wide array of R & D applications. This enhanced precision will be grounded in panels of actionable biomarkers for aging obtained partly via digital wearable devices. This will enable the rapid assessment of the efficiency of treatments, and the equally rapid identification of the appropriate prevention and restoration of those age-associated changes. To put it simply: The core of Longevity Science will be Biomarkers and AI-Technology.

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This article was written by Margaretta Colangelo and Dmitry Kaminskiy with input from the Aging Analytics Agency team.

Dmitry Kaminskiy is General Partner of Deep Knowledge Ventures, Founding Partner of Longevity.Capital, Founder of Aging Analytics Agency, and Founder of Deep Knowledge Analytics. Dmitry is the Head of International Development of the Secretariat for the UK All-Party Parliamentary Group for Longevity, Managing Trustee of the Biogerontology Research Foundation. Dmitry is based in London.

Margaretta Colangelo is Managing Partner of Deep Knowledge Ventures and Managing Partner of Longevity.Capital. She is Co-Founder of Aging Analytics Agency, Co-founder of Deep Knowledge Analytics, and Co-founder of Longevity.Capital. Margaretta serves on the Advisory Board of the AI Precision Health Institute at the University of Hawai‘i Cancer Center. Margaretta is based in San Francisco.

Deep Knowledge Ventures is a leading investment fund focused on the synergetic convergence of DeepTech, frontier technologies and technological megatrends, renowned for its use of sophisticated analytical system for investment target identification and due-diligence. Major investment sectors include AI, Precision Medicine, Longevity, Blockchain and InvestTech. @DeepTech_VC

Deep Knowledge Group Showcase Page

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. @AgingAnalytics

Longevity.Capital is a specialized Longevity-Focused Hedge Fund with enhanced liquidity that uses hybrid investment technologies to combine the profitability of venture funds with the liquidity of hedge funds, significantly de-risking the interests of LPs and providing the best and most promising Longevity companies with relevant amounts of investment.

Longevity Capital LinkedIn Page

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