João Pedro de Magalhães is one of a number of people from the small online transhumanist community of twenty years past who went on to focus on aging research. The present all too short human life span is the most pressing and harmful of limits upon the human condition, and the more people who seek to do something about that, the better. Like many of the more established researchers in the field, de Magalhães has come to think that radical life extension of decades or more in our lifetimes is unlikely, however. To my eyes that is only true if the SENS approach based on repair of root cause molecular damage fails to gather significantly greater support over the next two decades. There is a lot of room yet to achieve great things, especially now that the first SENS approaches are close to the clinic, such as senescent cell clearance.
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 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. I’m not sure that telomeres and telomerase 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.
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.