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Steve Hill Interviews Sarah Constantin of The Longevity Research Institute

Steve Hill Interviews Sarah Constantin of The Longevity Research Institute

Sarah Constantin
Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by our allies at the Life Extension Advocacy Foundation (LEAF) on May 9th, 2018. In this article Mr. Hill interviews Dr. Sarah Constantin, a researcher with a focus on machine learning at The Longevity Research Institute. This is an excellent article, especially if you want to learn more of the hard science behind longevity research. The topics of the interview range from deep learning being applied to pharmacology, to optimal mouse strains, and ideal areas of research to target age-related diseases.

~Bobby Ridge, Assistant Editor, June 30, 2019

Today, we have an interview with the Longevity Research Institute, a new group that launched in April 2018. The goal of the Institute is to identify therapies that can demonstrably extend healthy human lifespan by 2030 at the latest.

Searching for longevity

There are dozens of compounds and therapies that have been demonstrated to increase the lifespan of mammals. Recently, there have been some impressive examples of rejuvenation in animals using a variety of approaches, including partial cellular reprogramming, stem cell therapy, and senescent cell removal. More importantly, in many of these studies, age-related diseases have been delayed or even reversed.

Unfortunately, very few of these studies have had independent follow-ups or replication, and that is slowing down progress. The Longevity Research Institute is aiming to bridge the gap between basic science and commercial drug development.

It has chosen the field of aging research as its area of focus for one simple reason: age-related diseases are the leading cause of death globally. Heart disease, stroke, cancer, diabetes, Parkinson’s, Alzheimer’s and many more diseases are all caused by the various processes of aging.

The data from hundreds of animal studies tell us that aging is not a one-way process and that the rate of aging is something we can slow down or even reverse. Experimental results show that we can increase the healthy lifespan of animals significantly and delay the onset of age-related diseases in doing so. If we could translate those findings to humans, we could potentially increase the healthy period of life, known as health span, or even increase our lifespan beyond current norms while remaining healthy.

The majority of aging research consists of basic science that focuses on the mechanisms of aging, studies involving invertebrates like worms or fruit flies, and experiments that examine the effect of therapies on biomarkers of aging. However, the Longevity Research Institute believes that the way to find effective treatments that could translate to humans is by testing interventions on mammals to see if they increase lifespan or if they delay or reverse symptoms of aging, such as frailty, cognitive decline, and the prevalence of age-related diseases. Robust mammalian lifespan studies are quite rare in aging research due to their long duration and thus cost; the Institute believes they are worth doing despite this challenge.

Its philosophy is to be skeptical of results that depend on too many uncertain assumptions, such as particular mechanisms of aging or analogies between invertebrate and human biology. It believes that the closest way to measure the health and lifespan of a human is to measure the same things in mammals.

Replicating and Extending Lifespan Results

The majority of studies that have been shown to increase lifespan are rarely independently replicated to confirm the findings. There are therapies that, decades later, still have had no follow-up, and the Longevity Research Institute would like to change this situation.

To that end, it will be engaged in grant writing to obtain funds so that researchers studying aging will be able to conduct lifespan studies in mice and rats. The Longevity Research Institute also plans to commission its own studies and contract research organizations to carry them out.

It has a long list of promising interventions and is considering becoming involved with carboxyfullerenes, epithalamin, and stem cell transplants, for example. It is also interested in testing combinations of therapies to see if they have synergistic effects.

As translational research on aging is really a new, uncharted territory, the Institute is working with the Interventions Testing Program and METRICS to design reproducible animal studies. As part of that process, it will be testing genetically heterogeneous animals and using blind, randomized studies to reduce bias. A blind experiment is an experiment in which information about the test is hidden from participants, to reduce or eliminate bias, until after a trial outcome is known.

Best practices and transparency

Establishing best practices and protocol for translational aging research is a top priority here, and its work could help set the stage for future translational efforts. If superbly designed research protocols can be designed and made accessible to everyone, then they could be a real help in standardizing aging research and ensuring that the quality of results is the best it can be.

As part of its commitment to transparency and knowledge sharing, a condition of funding projects is that all experimental data will be made freely available to the public, as will pre-registration of experimental designs. The Institute will further protect this open science initiative by using blockchain technology to make immutable, publicly accessible records of everything it does.

We had the opportunity to talk with Sarah Constantin, Ph.D. and one of the key figures at the Longevity Research Institute, about their work. Sarah is a data scientist specializing in machine learning.

Your group believes that we need to conduct lifespan studies in mice in order to confirm that something might translate. However, some researchers believe that using multiple biomarkers of aging allows them to project, within a reasonable margin of error, changes to potential lifespan. This is becoming more relevant as the accuracy of biomarkers, and the use of comprehensive biomarker panels, becomes more commonplace. How do you respond to this?

There’s some very interesting stuff going on with biomarkers of aging.  We’re able to predict mortality with AUCs of 0.8-0.9, which is quite good, with aging biomarkers, including things like blood panels of inflammatory and metabolic markers, DNA methylation, and phenotypic markers such as BMI and frailty. Some of these biomarkers are things we’re planning to measure in our animal studies, and they should give us interim results on whether the interventions we’re testing affect the predictors of aging. I still believe that we can be most confident in whether a treatment promotes longevity when we’ve tracked its effects throughout an organism’s lifespan. We do know of examples (such as calorie restriction in primates) in which it’s equivocal whether the treatment extends lifespan but it clearly improves age-related biomarkers, and you have to do a lifespan study to distinguish those cases.

Advances in deep learning and systems pharmacology are allowing us to project interactions and potential therapies far more efficiently than ever before. What are your thoughts on these approaches, and will you be looking to use them in your work?

The deep learning and systems pharmacology approaches are actually where I started in biotech; I did machine learning at Recursion Pharmaceuticals, which is taking those approaches for doing phenotypic screens for genetic disease treatments. I think they’re really useful for drug discovery, at the beginning of the pipeline, where they can enable you to search a wider space of drug candidates. At LRI, we’re starting all the way at the other end of the pipeline, with drugs that have already been tested and shown promise in vivo. However, once we make some progress on those, then yes, it could make sense to start doing some of these machine learning-enabled approaches.

What is the ideal mouse strain for aging research, particularly lifespan studies, in your view?

Well, the Interventions Testing Program at the National Institute of Aging is using three-way heterozygous mouse crosses, which I think is the ideal. A single inbred strain of mouse doesn’t have much genetic diversity, so often what you’re testing is the effect of a treatment on that particular strain of mouse, and the results won’t transfer to another strain.

The use of progeria mice is common in aging research due to the shorter study time, but these models are often criticized as not being representative of true aging; what are your thoughts on the prevalence of progeria mice in aging research, and are they a relevant model for what we are trying to achieve?

I think progeria mice are an imperfect proxy. There are a lot of different kinds of progeria, and they exhibit some but not all of the typical symptoms of natural aging.  I’d have more confidence in studies done on aged mice than progeric mice.

We see that you have a strong commitment to ensuring public access to scientific knowledge. What inspired you to make such a wonderful and strong commitment to open science?

Well, coming from a data science background, I’m hyper-aware of how easy it is to fool yourself with data.  You can massage anything into a spurious result if you test enough hypotheses and pick your subgroups artfully. Really, the best way to guard against that is to share the raw data so that people can run their own analyses. Making science more open is how you make it more trustworthy.

Is there a publically viewable list of the targets that you are interested in testing?

The list is still evolving, but some of the first things we’re looking into testing are carboxyfullerenes, which seem to have neuroprotective and life-extending effects, and epithalamin, which is a pineal gland-derived peptide that’s been reported to extend lifespan and even reduce human mortality. Both of these are sort of in the sweet spot of not being the subject of that much research to date, but what there is is very promising, so the value of information is high.

What is likely to be your first target for studies, and what is the rationale behind your choice?

I think people should know that there’s a lot of low-hanging fruit in aging research — treatments that we have reason to believe might work but that we’d still have to test. The misperceptions are either that life extension is so speculative that we’ll never get there or that we already know how to do it and you just have to take the right supplements to live forever. I think the reality is that we’ll have to do a lot of experimental work, but it’s highly possible that, in time, we might find something that extends healthy lifespan in humans.

We would like to thank Sarah for taking the time to do this interview with us, and we look forward to seeing her team’s progress in the near future.

Steve Hill serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

Jim Mellon Announces Launch of New Book – Juvenescence: Investing in the Age of Longevity – Press Release by Biogerontology Research Foundation

Jim Mellon Announces Launch of New Book – Juvenescence: Investing in the Age of Longevity – Press Release by Biogerontology Research Foundation

Biogerontology Research Foundation


London, UK: Biogerontology Research Foundation Trustee Jim Mellon announces the publication of his newest book, Juvenescence: Investing in the Age of Longevity.

The book is a comprehensive summary of the emerging longevity industry, including profiles of longevity companies, investment opportunities, and aims to chart the major ideas of the geroscience’s thought-leaders and the vast implications this will have on economies and societies.

Often referred to as the British Warren Buffett, Billionaire Jim Mellon is well known for identifying major emerging trends before they become mainstream. Mellon made his wealth by investing in emerging markets throughout the 1990s. After many years of research and investing in the life science sector, Jim announced his vision for the emergence of the nascent longevity industry at Master Investor, one of the UK’s leading investor show in March of 2017, which was attended by over five thousand investors and entrepreneurs.

“The Biogerontology Research Foundation is proud to support what we feel will come to be seen as a landmark publication in the modern history of biogerontology. Jim has put an enormous amount of thought and effort into this new book, and has interviewed many of the field’s leading scientists in his research. The field of geroscience and the emerging longevity industry are both sure to prosper from very well-respected business personalities like Jim Mellon championing the longevity industry and projecting that it will become the world’s largest industry. Further, governments and policy makers should note the pressing need for a paradigm shift in medicine and healthcare away from ‘sick care’ toward comprehensive and disease-preventative healthspan extension. We are proud to have Jim as a Trustee of the Biogerontology Research Foundation and look forward to helping him lend mainstream credibility to the field and actionability to the dawning longevity industry” said Franco Cortese, Deputy Director & Trustee of the Biogerontology Research Foundation.

In 2012, Jim published his best-seller Cracking the Code, which summarized his vision for the future of the life science sector. In 2017, he announced his intention to focus much of his time and assets on the emerging longevity industry and make substantial investments into this area.

Jim and long-time co-author Al Chalabi toured many academic institutions, biopharmaceutical companies, and Silicon Valley tech companies to learn about the latest research and to understand the rapidly advancing field of longevity. Juvenescence highlights the technologies they deem the most likely to generate substantial longevity dividends and create sustainable and profitable industries. They travelled through the US and Europe, interviewing geroscience’s leading scientists and thought-leaders and provide an objective survey of their findings well as a detailed vision for the industry’s future and the most appropriate investment opportunities within the dawning longevity industry.

 

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Earlier this year Jim Mellon announced the formation of Juvenescence Limited, a company investing in the longevity biotechnology. Since then the company announced investments in several high-profile longevity companies including Insilico Medicine, Inc, a Baltimore-based leader in artificial intelligence for drug discovery, biomarker development, and aging research.

About the Biogerontology Research Foundation:

The Biogerontology Research Foundation is a UK non-profit research foundation and public policy center seeking to fill a gap within the research community, whereby the current scientific understanding of the ageing process is not yet being sufficiently exploited to produce effective medical interventions. The BGRF funds and conducts research which, building on the body of knowledge about how ageing happens, aims to develop biotechnological interventions to remediate the molecular and cellular deficits which accumulate with age and which underlie the ill-health of old age. Addressing ageing damage at this most fundamental level will provide an important opportunity to produce the effective, lasting treatments for the diseases and disabilities of ageing, required to improve quality of life in the elderly. The BGRF seeks to use the entire scope of modern biotechnology to attack the changes that take place in the course of ageing, and to address not just the symptoms of age-related diseases but also the mechanisms of those diseases.

Biogerontology Research Foundation Launches Campaign for Photographic Biomarkers of Age

Biogerontology Research Foundation Launches Campaign for Photographic Biomarkers of Age

Biogerontology Research Foundation


Thursday, August 31st, 2017, London, UK: The Biogerontology Research Foundation announces the launch of a crowdfunding campaign, MouseAge, to develop and test photographic biomarkers of ageing in mice in collaboration with scientists from Harvard University, University of Oxford, Youth Laboratories and Insilico Medicine. The project’s aim is to develop novel biomarkers of ageing in mice for the purposes of testing the effect of healthspan and lifespan-extending interventions. The project is now live at Lifespan.io, a crowdfunding platform for ageing research institutions that has launched several successful campaigns for SENS Research Foundation, International Longevity Alliance and CellAge.

“One of the most fundamental challenges in ageing research today is the development of robust and reliable biomarkers of ageing to serve as the basis by which the efficacy of lifespan and healthspan-extending interventions can be tested. Humans live a long time, and testing the effect of geroprotective interventions in humans using lifespan gains as the main criterion for success would be wildly impractical, necessitating long and costly longitudinal studies. By developing accurate biomarkers of ageing, the efficacy of potential geroprotective interventions could instead be tested according to changes in study participants’ biomarkers of ageing. While significant attention is paid to the development of highly accurate biomarkers of ageing, less attention is paid to developing actionable biomarkers of ageing that can be tested inexpensively using the tools at hand to the majority of researchers and clinicians. The Biogerontology Research Foundation chose to support MouseAge.org because photographic biomarkers of ageing represents a highly actionable alternative to more expensive measures of biological age.” said Franco Cortese, Deputy Director & Trustee of the Biogerongology Research Foundation.

The project utilizes Insilico Medicine’s novel deep learning platforms to correlate changes in physical appearance with biological and chronological age. Insilico is leading the pack in the intersection of deep learning and ageing research, and is well known for its use of advances in genomics, big data analysis, and deep learning for in silico drug discovery and drug repurposing for ageing and age-related diseases. The Biogerontology Research Foundation has collaborated with Insilico Medicine in the development of actionable and practical biomarkers of ageing before through their Ageing.AI project, and both organizations hope that MouseAge is the next in a long line of continuing research into the development of actionable biomarkers of ageing via the intersection of longevity research and deep learning.

“There are many experiments conducted around the world that examine lifespan in mice. The artificially intelligent MouseAge system will help determine which interventions make mice look younger. The plan is to develop an accurate predictor of mouse biological age based on images of mice and then apply transfer learning techniques to other datasets and data types,” said Vadim Gladyshev, MouseAge Research Lead and Professor of Medicine at Brigham and Women’s Hospital, Harvard Medical School.

Milestones for the project include the design of standardized protocols for creating photos and videos of mice, developing a mobile app and server infrastructure for image data collection, developing and testing the project’s main algorithm for mouse age prediction, optimizing feature extraction to investigate visual biomarkers of ageing in mice, creating a central data repository for the project’s data, utilizing transfer learning techniques to make these methods applicable to other model organisms, and ultimately using transfer learning techniques to develop photographic biomarkers of ageing in humans. The project’s principal investigator is Anastasia Georgievskaya, co-founder of Youth Laboratories, a company working at the intersection of ageing research, AI and machine vision, with the ultimate goal of using facial imageing data to predict patient health status.

The ultimate end-goal of MouseAge is to develop an intuitive mobile app to be used by researchers across the globe free of charge, where users can take images of model organisms and have the project’s DP-based algorithms perform age-assessment of images uploaded by users of the app. Both the organizations and researchers behind MouseAge are united in their belief in the promise of AI to accelerate ageing research and to streamline the development of effective healthspan-extending interventions for use in human patients, and hope that MouseAge comes to be remembered as an important landmark in the ongoing paradigm shift away from costly and inefficient sick-care and toward morbidity compression and effective healthspan extension for the benefit of all.

“Ageing research is the most altruistic cause that can generate billions of quality-adjusted life years over time and save the global economy. We are very happy to contribute to and support the MouseAge project. Our Young.AI system for tracking multiple biomarkers during human ageing is currently in the alpha stage and is launching in the fall. However, the biological relevance of many of the biomarkers and interventions is yet to be established, and the MouseAge project contributes to the body of fundamental science required to bridge AI and longevity research. Please support the MouseAge project on LifeSpan.io to contribute to this grand effort”, said Alex Zhavoronkov, PhD, Chief Science Officer of the Biogerontology Research Foundation.

About the Biogerontology Research Foundation:

The Biogerontology Research Foundation is a UK non-profit research foundation and public policy center seeking to fill a gap within the research community, whereby the current scientific understanding of the ageing process is not yet being sufficiently exploited to produce effective medical interventions. The BGRF funds and conducts research which, building on the body of knowledge about how ageing happens, aims to develop biotechnological interventions to remediate the molecular and cellular deficits which accumulate with age and which underlie the ill-health of old age. Addressing ageing damage at this most fundamental level will provide an important opportunity to produce the effective, lasting treatments for the diseases and disabilities of ageing, required to improve quality of life in the elderly. The BGRF seeks to use the entire scope of modern biotechnology to attack the changes that take place in the course of ageing, and to address not just the symptoms of age-related diseases but also the mechanisms of those diseases.