Dr. João Pedro de Magalhães is a Professor at the University of Liverpool, England, where he studies aging and longevity at the genetic level, and he is also an affiliate Principal Investigator in the Neuroendocrinology and Aging Group at the University of Coimbra, Portugal. Dr. de Magalhães has built the Human Ageing Genomic Resources (HAGR), a curated database of genes related to aging. He recently published an article on the subject of life-extending drugs.We took the opportunity to interview him on his article along with his thoughts about the current state and future trajectory of life extension research.
João, first off, I really loved your most recent article published in Drug Discovery Today. It was great to read a birds-eye-view take on the longevity field from someone who has been on its forefront for so long. What was your motivation for writing the piece?
Thank you, I am really glad you liked my recent article.
Back in September 2020, I did a talk at the Aging Research and Drug Discovery meeting and played with some of the data in our GenAge and DrugAge databases on genes and drugs associated with aging and longevity. I noticed that the number of drugs associated with aging has been increasing exponentially, while the number of genes has sort of plateaued. I mentioned this in my talk, and I thought it would be a nice basis for an article as well. Then we also did some analysis of investment and companies working in longevity, which confirmed my suspicions that there is a growing investment in the area. So, I thought this would be a really nice topic for a brief article, highlighting the growth in the longevity biotech industry.
One of my main takeaways from the article was that there are reasons for cautious optimism in the field. Is that a fair representation of your views? And, if so, what are the biggest reasons why we should be optimistic? What approaches are you most excited about?
Yes, I am cautiously optimistic about the development of longevity drugs in particular, what I call in my article “longevity pharmacology”. I think the discovery that aging and longevity can be manipulated in animals has really changed the field; we have seen a rapid and significant growth in the study of aging. And there are a number of companies now starting to focus on longevity. So, I think there is a sense of energy in the field that I find very interesting and positive. Keep in mind, of course, that most of these companies and approaches will fail, but if only one of them succeeds, that will be groundbreaking.
Do you think your level of optimism now has been increasing, decreasing, or holding steady over the years? And if it has changed, why?
My optimism regarding developing interventions in aging has increased, again because of the manipulations of aging in animal models, and the growing number of longevity drugs and companies in the anti-aging biotech industry. So compared to 20 years ago when I started working in aging, nowadays, aging is a proper field of study; it is an established branch of science. Aging and longevity are still small when compared to other fields, like cancer or Alzheimer’s disease, but aging is picking up pace and growing in excitement, people, and funding.
Of course, the future is uncertain, and there are reasons for pessimism too. For example, you mention that many biotech companies are focused on translating only a few of the possible strategies that have emerged, and we could benefit from a more diverse set of approaches. What do you see as some of the other main bottlenecks to the longevity field?
I think the crucial bottleneck in the longevity field is the time it takes to do experiments. And really there is no way around it, no matter how much money and how much technology we have, you still need to do longevity and aging studies, at least in animal models. And that remains as the main bottleneck of research: the fact that we need to do long, time-consuming experiments to test any intervention or gene for aging.
We have another issue I think as well in that we don’t fully understand the process of aging. In fact, I don’t think we understand the causes of human aging yet. There are a number of hypotheses and pathways that we know about, but in humans, none are proven; perhaps human aging is actually different from what everybody is focusing on. Hence why I say we need to be more creative.
In the piece, you mention the TAME trial. Do you think this will represent a paradigm shift for the field? Will other studies start to follow their model or could it potentially be more of a one-off?
I am very excited about the TAME trial, I think it will be a wonderful proof of concept for developing clinical trials for aging. Even if the trial itself is a failure, it will be a tremendous learning experience for the field, and it will pave the way for future similar studies. My guess would be that we will learn a lot of lessons on how to conduct such studies from the TAME trial, even if most likely some tweaking will be necessary in the future. Science is a gradual process; you go step-by-step improving and learning. And the TAME trial is a great step in the right direction but not the final destination.
Along similar lines, the NIA announced last week that it will be funding clinical trials targeting aging. Of course, the FDA still requires an approval to be disease-specific, but we haven’t seen a funding announcement like this from the NIA before. On a scale from business-as-usual to we should be celebrating in the streets, how big of a deal is this?
I don’t know the background to the announcement, but I take it as a very positive sign that the field as a whole is becoming more translational; indeed, this is one of the points I make in my recent article. Again, it’s a long journey, and we need to take it step by step, but this is another step in the right direction.
I also want to ask about what’s next for you and your lab. Can you give us a little tease about what you are most excited about that we should be on the lookout for in the near future?
We have several different projects that I’m excited about. We are looking into single cell sequencing in the context of aging, which is a very interesting approach to untangle cell interactions, and potentially even tissue interactions in the context of aging. I think this is a very underexplored topic in aging. We’re also doing some work on long-lived species, for example in this very recent study. We also have some results coming out soon on the interactions between aging and cancer using multi-omics (see here for a quick preview). We also recently got funding to develop a new project that I’m very excited about: we aim to apply machine learning to discovery and predict drug combinations that retard aging.
Lastly, in addition to my university lab, I am also now CSO of Centaura, an ambitious Swiss-based company. We are developing new gene and cell therapies with multiple applications, including in aging.
Thanks so much for taking the time for this interview! Finally, where can our readers follow you if they want to learn more and stay up to date on your work?
We would like to thank Dr. Magalhães for taking the time to speak to us about the field and about his work with longevity pharmacology.