João started his journey from the Escola Superior de Biotecnologia in Porto, his hometown, where he graduated in Microbiology. He then was part of the UnIGENe research group at the Institute for Molecular and Cell Biology in Porto, and completed his doctorate at the University of Namur, Belgium, where he joined the Aging and Stress Group. He has worked with luminary and genomics pioneer George Church at Harvard Medical school, Boston, USA, where he did his postdoctoral studies. Today, he is a Reader (a title equivalent to Associate Professor) at the University of Liverpool, England, where he studies ageing 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.
João believes that gene sequencing of extraordinarily long-lived animals (such as the naked mole rat or the bowhead whale) as well as of human supercentenarians may provide important insights on the genes that control the aging process. This knowledge is potentially leading to drugs to mimic the effect of these genes in people to protect them from age-related diseases. To this end, he leads the research endeavours of the Integrative Genomics of Aging laboratory of the University of Liverpool.
Research papers by dr. de Magalhães have been published in several prestigious academic journals, such as Nature and Cell. Both he and his research have been featured in scientific outlets like Science and Scientific American, as well as on BBC, CNN, and the Washington Post to name just a few. He was also a speaker at TEDxGhent, and has been featured in the short video “What is Aging?” by PhD comics. As part of his efforts against ageing, dr. de Magalhães runs the website senescence.info, where he advocates for the defeat of aging, answers to common objections, and provides comprehensive information on the biology of ageing, genomics, and ways everyone can help to fight ageing, including advice on how to become a biogerontologist. One of João’s greatest projects is the Human Ageing Genomic Resources database, or HAGR, intended as a tool to help other researchers who study the genetics of human aging.
We had the opportunity to catch up with João amd ask him about his work.
What are you currently working on?
Although my work integrates different strategies, its focal point is developing and applying experimental and computational methods to help decipher the genome and how it regulates complex processes like ageing. In practice, that means developing and employing modern methods for genome sequencing and also bioinformatics to analyze large amounts of data, for example networks with hundreds of genes. We now know that aging and longevity, like many other biological processes, derive from many genes interacting with each other and with the environment. My lab (http://pcwww.liv.ac.uk/~aging/) develops methods to survey and analyze data from thousands of genes simultaneously to identify the most important ones. More specifically, we are now studying new genes associated with aging and longevity as well as new cancer and Alzheimer’s disease genes. If we can identify which are the key genes modulating aging or age-related diseases than this will open new opportunities for developing therapeutics. We are also studying new life extending compounds using animal models.
What do you think is the most important contribution you’ve made to the field?
I am probably best known for the online collection of databases I created, The Human Ageing Genomic Resources (HAGR). I designed HAGR to help researchers study the genetics of human ageing using modern approaches such as functional genomics, network analyses, systems biology and evolutionary analyses. They have been cited hundreds of times and are used widely by the biogerontology research community, facilitating a lot of studies. I am also known for the work I did on sequencing genomes of long-lived species, in particular the naked mole rat and bowhead whale. Lastly, my lab developed various computational approaches to analyze large amounts of data as well as predict new genes, processes and drugs associated with aging and longevity.
What is the approach to fighting ageing you find most promising, besides the one you’re pursuing?
There is certainly a lot of promise in stem cells and regenerative medicine. So I am optimistic that there will be new advances and therapies, although things normally take a long time in clinical translation.
What role do you think telomeres and telomerase therapy will play in a successful rejuvenation therapy platform?
I’m not sure they will play much of a role. I think telomerase may be used in regenerative medicine and to treat specific diseases, but it is unlikely to become a source of anti-ageing therapies because it also promotes tumorigenesis. Besides, mice have lots of telomerase and yet they age much faster than us.
It’s some years old but I wrote a review on this topic where I expressed my skepticism of telomerase as a therapy for aging.
You have done quite a lot of work with geroprotectors (substances that can potentially slow ageing) do you think taking supplements is a good longevity strategy?
I don’t think that question has a yes or no answer as it depends on the supplements and it also depends on the person. I am skeptic about the majority of supplements. While many compounds have been shown to extend lifespan in animal models, we don’t know whether they will be beneficial to people. There are fundamental limitations in the use of short-lived animal models to understand human aging, for example the fact that studies in animal models normally do not take into account individual differences (see here). In other words, laboratory studies are done in very well controlled conditions and in genetically homogeneous strains, but people are very different from each other both in terms of lifestyle and genetics. So what works for me may not work for you.
Besides, while there is this idea that it is possible to purify the components of healthy foods to avoid having to eat them, so far there is no evidence to suggest that most dietary supplements are an adequate replacement for a balanced diet. That said, if you do not have a very healthy diet then supplements may help balance that, so again it is a personal choice though determining exactly which supplements are necessary is not easy.
Do you expect to see the day ageing is finally defeated? What you will do after that?
I don’t think we will defeat aging within my lifetime. I mean, we can’t even defeat aging in simple animal models, or defeat a number of simpler human diseases (I have a nasty cold as I write this, like I have every year). So I don’t think we will cure aging in the foreseeable future.
Like many others in the life extension community, I think cryopreservation may be a plan B, even though it’s not a very attractive one (but it’s still better than dying!). That’s why in the past few years I have become more involved in cryobiology and cryonics. While I am not convinced that the current techniques used in cryonics allow preservation of the self, I think the field can progress rapidly to the point of us as developing reversible human cryopreservation well before aging is defeated.
If aging is defeated, I would then like to work on astrophysics and astrobiology. My long-term dream is to explore the stars.
What would be the major benefits of defeating ageing for our society?
Everyone wants to be healthy. If we defeat aging we will be eliminating the major cause of suffering and disease in the world, completely changing our society.
João embraces transhumanism as a philosophy, and firmly believes that technology and scientific progress may usher the human species into an age of peace and prosperity. As our advances will allow us to go beyond our current limits, he further argues, we might be able to discover the marvels that lie ahead in the universe. There is no doubt that João is doing more than his bit to help us reach that future, and we wish him to succeed.