João Pedro de Magalhães on why we need to rethink aging and invest in fundamental research.
Dr João Pedro de Magalhães, a leading expert in biogerontology and comparative genomics, is at the forefront of research exploring the biological determinants of longevity and healthspan. His work has significantly contributed to distinguishing between the drivers and passengers of aging – an essential distinction for developing effective longevity interventions. As a speaker at this week’s Global Healthspan Summit (GHS2025), he joined a panel on comparative biology, a field that leverages insights from long-lived species to identify mechanisms that may be harnessed to extend healthy human lifespan.
The panel, Comparative Biology – What Can it Unlock?, explored how studying diverse species can reveal conserved aging mechanisms, challenge existing hypotheses derived from traditional model organisms and improve translational research. With an emphasis on identifying druggable targets and refining human-animal age equivalencies, the discussion underscored how cross-species analysis can inform therapeutic strategies. Dr de Magalhães emphasized the importance of the evolution of longevity and employing evolutionary genomics to try to understand why humans live as long as we do.
Longevity.Technology: The comparative biology panel at GHS2025 reflects a growing recognition that understanding healthspan requires a broader perspective than conventional model organisms allow. By studying species with exceptional lifespans – such as the bowhead whale or the naked mole rat – researchers can identify biological adaptations that contribute to longevity and resistance to age-related diseases. Dr de Magalhães highlighted the importance of distinguishing between causative and incidental aging factors, advocating for increased investment in fundamental aging research. Ahead of the panel, we caught up with him to get his take on epigenetic clocks, the potential of machine learning to identify lifespan-extending compounds and the drivers of human aging.
Dr de Magalhães told us he was looking forward to GHS2025, describing it as a “fascinating event with leading experts from all over the world.”
“It will be important for networking, establishing new collaborations and partnerships in both academia and industry,” he explained, adding that he thought it would be particularly valuable for developing new translational approaches that in the long-term help achieve real benefits to patients.
De Magalhães’ paper last year in Nature Genetics discussed distinguishing between driver and passenger mechanisms of aging. He explained that identifying the true drivers of human aging is a challenge we must tackle.
“The take home message is that we need to better understand what are the drivers of human aging,” he said. “We still don’t know why we age, what are the causal mechanisms of aging. I think that is a big limitation in the field, so we need to have greater focus and investment in increasing our fundamental understanding of the aging process.”
2024 was a productive year for de Magalhães as he also published (with David Gems and Roop Singh Virk) a paper on epigenetic clocks and programmatic aging. He told us that the major conclusion is that, at least to some degree, aging processes derive from programmatic mechanisms that start early in life.
“In a way this is a paradigm shift in that our prediction is that we age not because of inevitable and gradual accumulation of molecular damage but rather due to gene programs that run-on and become detrimental later in life,” de Magalhães explained. “This means that in order to delay age we need to change our biology, not just prevent some forms of molecular damage like oxidative damage.”
At the University of Birmingham, de Magalhães’ lab has been using machine learning to predict lifespan-extending compounds in mice. He told us that he and his team have identified several promising longevity compounds based on machine learning predictions, some of which they have validated experimentally and show that they extend lifespan in animal models.
“Significantly rilmenidine extends lifespan in worms and appears to mimic the benefits of caloric restriction,” he said. “Therefore, we are very interested in studying this compound in mammalian models, such as mice, and ideally perform a small clinical trial to assay its benefits. He added that given that rilmenidine is already used in the clinic to treat hypertension, his lab would like to do a small clinical trial to assay whether it will have broader health benefits in human beings beyond hypertension. “More recently we identified a further set of geroprotective compounds using human and mouse data, which we would love to test experimentally and are open to collaborations.”
Yesterday’s panel touched on the idea that the integration of computational biology and genomics is likely to accelerate discoveries in healthspan extension, and de Magalhães told us that research is already making use of these methods – and their importance and impact will continue to grow in the future.
“Given the complexity of human biology and of aging, and how much data we are generating in the life sciences, computational approaches and machine learning/AI play a crucial role in tackling this inherent complexity and allowing us to gain new insights as well predict the best targets and molecules for intervening in aging and preserving health.”
Catch up with footage from GHS2025 HERE.
