Evelyne Yehudit Bischof, MD, MPH, FEFIM, is a professor at Shanghai University of Medicine and Health Sciences, a visiting professor at Tel Aviv University School of Medicine, and chief physician for internal medicine in Renji University Hospital of Jiatong School of Medicine. This means that she is a perfect example of a modern longevity professional, living a busy life and sharing her time between several clinics all around the world, high-profile conferences, and top-notch research organizations. She is also a star in the rising field of longevity medicine, which is focused on countering aging across the lifespan in a personalized, evidence-based, and data-driven way.
You are obviously not the regular type of professor and researcher that I usually speak with; you’re primarily a practicing clinician, a medical doctor. Could you briefly tell me about your journey in medicine that finally brought you to the longevity field?
I’m an internal medicine specialist, and most of my life, I have been in academic university hospital settings. My residency and fellowship were both in Switzerland and in China, mostly in the University Hospital of Basel, in the department of internal medicine, intensive and emergency care and oncology. Medical oncology is almost my second specialty, certification missing, and it’s definitely my main research focus. During the time in Switzerland, and also in collaboration with my universities here in China (primarily Fudan Cancer Hospital and Renji University Hospital), I was working on a project on the intersection of aging and cancer.
As we know, aging and cancer have a huge overlap in terms of pathways, molecular presentation, and clinical presentation: all types of symptoms, comorbidities, polypharmacy, frailty, toxicities that are seen in cancer patients and/or oldest-old cancer patients, as we called it back in 2012-2014, since now we have better definitions for that.
On one hand, this is the work of internists to make a differential diagnosis from complex presentation of various symptoms. Plenty of comorbidities, of algorithms (we call it often clinical reasoning in differential diagnosis) that we are running in our heads as internists to make the proper diagnostic and then treatment, looking at all the systems. Then, on the other hand, being an oncologist in a medical and hemato-oncology ward, especially seeing those patients suffering from cancer. We often make amendments of the protocols for patients over the age of 60, as they are in most cases not included in the randomized controlled trials that are taken as a necessary evidence base for clinical guidelines.
This is what brought me to the longevity field. When I began to work in it, I started connecting with people who are powering longevity medicine with the tools that it needs: AI and computational science. I got introduced to people like Dr. Wei-Wu He from Human Longevity, where I started working as a concierge physician, to Dr. Kai-Fu Li, the godfather of artificial intelligence, and many others, such as Prof. David Sinclair, with whom we also published in Lancet Healthy Longevity on aging as a disease.
I’d like to specifically acknowledge Prof. Alex Zhavoronkov, my first mentor in the longevity field, especially in terms of AI and data science, which as a medical doctor, I knew absolutely nothing about. Together with him, we published a number of papers, including those on the first attempt to define longevity medicine in Nature Aging with Dr. Kai-Fu Lee. That was my journey to where I am now, working between Israel, Switzerland, China, and the USA as a clinician in oncology and ICU wards, and as longevity physician at HLI (Prof. Craig Venter’s clinic) and with my own concierge longevity patients all around the world.
Since you mentioned old patients, some research suggests that centenarians and supercentenarians are better protected against cancer. I wonder if you have looked into this.
This is actually one of the most important recent findings in geroncology, the field that we are pioneering. I just fulfilled one of my life dreams: to build a Sino-Swiss Geroncology Center network, with our university hospitals in Shanghai and Basel working now together in clinic and research. We have departments of geroncology, dealing with oldest-old cancer patients, implementing longevity diagnostics such as biological age measurements, PO longevity monitoring, NLP and other parameters that we then fuel into an AI machine learning platform.
We are aiming to soon publish a number of papers informing about the current practice and then to create global RCTs that can produce clinical guidelines for those oldest-old cancer patients but also to show how longevity medicine is implemented right now already in the “sick-care” hospital setting. It is not a plan anymore; it has been happening for the past two years, and we are working on creating evidence-based approaches, validation steps, and responsible medical approaches.
Longevity medicine is not at all a private longevity lounge-based approach only. As a clinician and academic professor, it is important for me to send this message to doctors, patients and all stakeholders. Ultimately, this is the way how to scale healthy longevity for all, healthy and sick people, across all healthcare systems.
We know that old age is the number one risk factor for cancer. This said, the development of diagnostic biomarkers has led us to identify, using multi-omics rather than just genomics, that centenarians and almost-centenarians do have a very interesting profile of oncoprotective genes and, of course, suppression of oncogenes, especially in the promoter methylation pathway. We don’t know enough, but it seems that methylation of oncogenes and oncosuppressors is altered in those centenarians, and this is how they are protected – in addition, of course, to things like lifestyle.
There’s also something very interesting going on in proteomics. It seems that some of the enzymatic pathways, not only the mTOR pathway or the hypoxic pathway, but also some others, like TGF and several less-known ones seem also to be involved, including those we see in the most aggressive cancers, like pancreatic cancer, triple-negative breast cancer. So, yes, centenarians seem to be somehow protected.
Let’s talk about longevity medicine. I heard one researcher saying that basically all medicine is longevity medicine, since medicine fights diseases, and diseases shorten life. This is obviously an oversimplification, but what is longevity medicine, and how it is different, paradigm-wise?
First, I must mention that we have officially created the Healthy Longevity Medicine Society, which has been announced at the ARDD conference and Singapore NUS conference, basically positioning longevity medicine as a medical discipline. The society will further accelerate transitioning from geroscience, which is very well established, to actual, practical longevity medicine. Prof. Andrea Maier from Singapore is the first elected president, I am the vice president, and we have a stellar executive committee, with Professors Nir Barzilai, James Kirkland, Tom Rando, and Harold Pincus, so we have all the fields of longevity medicine represented, including mental and neurodegenerative fields.
We are currently writing a white paper on the definition of healthy longevity medicine. There is no consensus; nobody’s claiming to have the ultimate definition. However, there is a paper in Nature Aging from early 2021 by Dr. Kai-Fu Li, Dr. Zhavoronkov and me as AI-powered precision medicine based on biological age restoration toward individual optimal biological age, the age of the individual’s optimal performance, and another one in Lancet Healthy Longevity called “Upskilling Longevity Physicians” that is being cited now by Google as the definition of the field. At our first in-person meeting of the HLMS, we defined healthy longevity medicine as a field that aims to optimize the healthspan across the lifespan.
Longevity medicine encompasses all the disciplines in the medical field. One could say that it’s the most collaborative, the most interdisciplinary and multidisciplinary, interactive discipline, because all fields in medicine at some point will be looking not on how to cure sickness or detect it early (prevention) but on how to detect the risks of ever developing sickness and to optimize and enhance health in order to extend healthy lifespan and ensure the optimal performance of an individual at a specific point of time (so it is 3-dimensional). Also, we’re powered not only by AI but also by geroscience and computational science. Again, this is a major simplification and just one aspect of the field.
It is important to stress that healthy longevity medicine as we see it is purely evidence-based, purely scientific. It sits next to disciplines such as endocrinology, oncology, cardiology, etc. You can position it either under internal medicine or as a separate field. At the same time, it is extremely inclusive and collaborative.
Researchers in the longevity field are still at odds with each other about the very nature of aging, and arguably, we don’t have a single proven anti-aging intervention, although we do have proven interventions that reduce mortality. So, how do you treat your patients?
Yes, it is important to set the message straight. Working with longevity patients at the moment means primarily having a set of diagnostics and monitoring on the highest possible level with the highest possible granularity that is not seen in any other medical field.
There are two legs to this. See, I like to simplify things as a German. One leg is diagnostics, and the other one is therapeutics. Of course, our therapeutic leg is still research-in-progress, it’s still not validated or evidence-based, but I am optimistic, seeing the RCTs on the way, that we will soon see more of the credible healthy longevity interventions in the medical field.
How about commercially available devices and supplements?
We do have many devices and supplements on the market, but we are not there yet with actual evidence on most of them. I would love to see (and again, I am positive that we will) clinical trials at the intersection of science and clinic, such as by Prof. Brian Kennedy or Prof. Nir Barzilai, who are conducting high level research on the potential pharmacologics. As a physician, not only do I want to see evidence, but first and foremost, I need to follow the principle “do no harm.”
Admittedly, in the therapeutic area, we have very little, besides highly established interventions related to lifestyle and nutrition. Hopefully, therapeutics will arise. But, here’s the point: people tend to complain that we’re doing longevity medicine without having actionable items once the diagnostic is conducted. However, many people might not realize that if we do not establish and validate protocols of diagnostics that will allow us to draw conclusions, we will never be able to validate the therapeutics that are either already there or are being developed. For this, we need data, structural longitudinal monitoring, and data mining.
If you ask me how I work with my patients right now, I have three sorts of patients. One is the sick care, I won’t talk about them now, of course. Then, there are longevity patients. Some of them are, of course, very advanced, and they require 24/7 work. Then there are also some patients who are not so intense in their program. Those have higher levels of automatic and self-monitoring that I review periodically.
How do I follow up? With various measurement, including measuring the biological age in different organs and systems using different biological aging clocks, mostly deep aging clocks, but not only – that’s in addition to all other values and parameters, like the blood values, heart rate variability, visceral fat, etc. The final manifestation of my success or lack thereof is whether their biological age has improved or not.
It’s an interesting notion about longevity medicine being sort of a practical arm of the longevity field as a whole. I wanted to ask you about biomarkers of aging. Basically, those have the same problem as interventions do. They should be a cornerstone of longevity medicine, but just as with the interventions, we arguably still don’t have reliable and clinically proven biomarkers of aging, or maybe we do? Which ones do you use in your practice?
In literature, you mostly see proposed biomarkers of aging. Some of them are validated, coming from the various medical disciplines, especially geriatrics and internal medicine, etc. While it’s an oversimplification, there are quantitative and qualitative biomarkers – something that I can measure precisely, and something that I can only measure via proxy – scores, questionnaires, etc. The scientific field, of course, mostly trusts quantitative biomarkers, and we are seeing amazing teams all over the world working on various aspects of it, so I am very hopeful that soon we will start seeing more and more validation and biomarkers entering clinical practice.
There are things that I can measure directly, and then, there are things I measure by proxy, such as frailty – we have plenty of frailty scores, indices, questionnaires, etc. There, we always have some biases, of course. In terms of potential biomarkers of aging, we could be encouraged to responsibly measure them in trial settings even if they’re not perfect, because the more markers we use, the better we can actually validate which ones are applicable and advance the field. Of course, we should not cause harm, such as imposing fear or worry on patients based on a still unvalidated measurement.
A core term on the biomarker front is biological age. Various clocks that measure it are being developed, and some have been published. The field of deep aging clocks that use deep neural networks is booming and bringing good results. We see good tools in hematological aging clock, photoaging clocks, epigenetic clocks, and others. I’m really looking forward to the development of better physiological aging clocks and microbiome aging clocks. Finally, I also see the rise of brain aging clocks in middle-term future. However, as we often stress, we are still refining them and learning, and we see how crucial it is to integrate various clocks because the most important point here is that every cell, organ, and system of the body is aging at a different pace!
Let’s not forget reproductive scores, those are very important. I’m also looking forward to seeing more system- and organ-specific clocks. For instance, today, we have developments in cardiological aging clocks. We are also developing with colleagues oncological aging clocks. I think it’s very important for us all to finally move to a new era of diagnosing and treating cancer, where we will be able to say not only that the patient has this and this risk factors, but once the patient already has cancer, how do we devise optimal treatment protocols?
So, I see plenty of great developments in the biomarkers of human longevity. I think it’s very important for people to understand that measuring one parameter over time is very important, it gives you the longitudinal perspective.
Medicine is never black and white, but the right phrasing would be that there is just a huge number of potential parameters. Even now, we are already looking at hundreds of parameters, and this is why we need AI. Soon we’ll be looking at millions of those, and human intelligence will not be able to capture it. So, we need a symbiosis of human and artificial intelligence in order to derive and validate biomarkers of human longevity.
You kind of answered my next question, which was about AI and longevity, by explaining probably the main reason why we need AI in the field, but maybe you would like to add something?
AI and computational science are indeed crucial for the field of longevity medicine – also in medicine as a whole, of course, but especially in longevity medicine. First, we need them to develop biomarkers that can help us validate therapeutics and track therapeutic outcomes.
As I said, for me, longevity medicine is one of the most complex disciplines in medicine, simply because it has to implement all the findings from all medical fields. So, round-the-clock monitoring of several hundred parameters from every patient that demand huge amounts of storage and of AI inputs. Otherwise, we won’t be able to make sense of this enormous, heterogenic, multi-modal mess. Without AI, we’d never be able to actually say which of those parameters make sense, how they interact with each other, what can we derive from them, and how can we use it in future clinical trials, for diagnostics, and so on.
It’s also very important to mention that we shouldn’t fear applying AI, because it can help us. That said, of course, I’m not promoting replacing physicians with AI. I don’t think we’ll ever see that, at least I hope not. Human intelligence is still very important, because at the moment, AI cannot copy our emotions, and a lot of the decisions and algorithms are based on our feelings that we develop as practicing physicians. This is also why I feel that longevity physicians need to spend significant time in sick care in order to be properly able to add enough human intelligence to AI in longevity medicine.
Finally, I will quote Peter Diamantis, whom I deeply admire as an expert in the field. He said that there will come a time when not integrating AI into medical practice will be considered malpractice. My point here would be that as physicians, we should responsibly pick the best of all tools to advance our field for the benefit of patients (and humans in general).
I know that you are passionate about educating physicians on longevity medicine, which is logical since you need to recruit people somehow. Are you actively working on this?
Yes, I have been passionate about educating healthcare professionals for many years, and I am very actively involved. Together with the team (especially Prof. Alex Zhavoronkov and myself, but also other volunteers, physicians and scientists) we have developed the first course curriculum for longevity medicine for physicians. This course is for free, because we want as many physicians as possible to educate themselves on the basics of longevity medicine.
We used the COVID time in order to develop this introductory course in longevity medicine tailored for clinicians, but of course, they are not the only audience. It is now a large education hub, free for all, launched in various countries, including via the NHS! Now, we also have the advanced course, a much longer one (we call them Longevity Medicine for Physicians 101 and 201), where participants not only can learn but can also get CME certification, accredited by AMA, American Medical Association, which means it’s approved worldwide (let me tell you, it’s a huge achievement).
It’s open for everyone, but we were especially motivated by the lack of such course for physicians. Soon, the adjusted versions of the courses will be implemented in the medical curricula for medical students – this is another dream of mine that is becoming a reality, which makes me very happy.
We are developing a new course that will be launched soon – Longevity Medicine for Veterinarians. This is very important, right? This will not only discuss how to make a dog and a cat live longer but also how to translate from animals to humans since most studies are done in animals. Prof. Matt Kaeberlein and other scientists have done tremendous work in this field, and it is very important to present those findings to physicians. Longevity Medicine for Investors will be the next one, and then Longevity Medicine for Athletes, and Longevity Medicine for the Oldest Old.
Most of all, I am proud that this course has been launched on national platforms. It’s already been available for two years on the NHS platform, so that UK doctors can access it, and we are now implementing this course for medical curriculum in medical schools, which is a dream come true. Medical students will actually have it as an obligatory part of their medical curriculum – first in Tel-Aviv University, and then in other countries, including China. We hope that other countries will follow soon.
I personally also educate doctors one-on-one or in small groups, training them in longevity medicine. These are mostly CEOs of hospitals that are opening now departments of longevity medicine in their university clinics. It makes me happy that the leadership of hospitals, not just the doctors, is asking for systematic training. This is crucial for them if they want to innovate, to implement longevity medicine in their hospitals. We are talking about combining sick care and longevity medicine in one hub in a university hospital, such as Sheba Medical Center in Israel, which is one of the top ten hospitals in the world according to the Newsweek ranking.
As a longevity physician trying to educate others about longevity medicine, have you encountered any pushback from physicians or the medical establishment?
Let’s say I don’t experience pushbacks or skepticism. Of course, there had been some caution as recently as three or four years ago, it’s understandable. Today, I see the opposite. I’ve been a part of the European Federation of internal Medicine for many years and a part of their board. That’s the hub for all internists in Europe.
This year, at the European Congress of Internal Medicine, the go-to event for us, like the World Economic Forum for economists, the top of the top plenary session was about longevity medicine. I was presenting, and I was allowed to invite a co-speaker, so I had Dr. Felipe Sierra, former director of the NIA’s Division of Aging Biology, who is now the CSO of Hevolution, and we spoke in the plenary session on longevity medicine, in front of all these internists from all around the world. This is another dream come true, and basically a revolution. I think this shows just how much the mindset has changed.
I’m actually getting a lot of questions from physicians about how they can learn, how they can educate themselves in longevity medicine. I talk with many CEOs, with hospital leadership, insurance companies, public health leaders, politicians. Since the field requires a lot of innovation in terms of technology, education, and infrastructure, progress in some places can be at a different pace. Our foremost concern is the patient’s safety, and this requires a very prudent approach, such as randomized controlled trials and approvals on many levels. I want to finish on a very positive note. I see revolutionary changes, and I’m very happy about this momentum, and that’s why we need all hands on deck.
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October 2, 2022
Thanks for publishing this article. Professors Evelyne Bischof and Alex Zhavoronkov and their teams are doing some of the most important and effective initiatives I know of for fighting aging. They recognized early that superior technology in the form of AI Tools (DNN, machine learning, etc.) were necessary for leaps in some medical research. In addition to developing the excellent Longevity Medicine for Physicians courses, they are individually models of passion and purpose helping all of humanity.
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