Associate Professor, Erasmus University Medical Center
Hevolution/AFAR New Investigator Awards in Aging Biology and Geroscience Research - 2022
What inspired you to pursue aging research?
Funnily enough, most of my research is actually focused on early development and health, and the role epigenetic processes may play in this. The shift to aging research happened recently, when my research group performed a benchmark study characterizing how epigenetic patterns change across the first two decades of life. We were amazed to see that epigenetic markers that are strongly predictive of age (and aging) in adulthood, already show substantial differences between individuals in early life, raising the intriguing possibility that variability in these markers may already be shaped in part by factors that occur during development. This finding was the inspiration and starting point for the current project, which will seek to uncover the specific genetic and environmental factors that influence epigenetic markers of aging from prenatal life onward.
In your view, what does AFAR mean to the field, and what does it mean for you to receive an AFAR grant now?
AFAR has played, and continues to play, a critical role in the field, by stimulating and supporting cutting-edge biomedical research to advance our understanding and ability to promote of healthy aging across the lifespan—a major challenge of our times. Award of this AFAR Grant means a great deal to me, as it will enable me to pool the best resources, talented scientists, and protected time to develop my own ambitious, interdisciplinary research program and pursue what I believe to be one of the most exciting new areas in the field: how quality of aging and risk for diseases appearing in old age may already be shaped by factors that occur very early in life. I see this as a unique opportunity to bridge development and aging—two connected, fundamental processes at the core of our health and disease risk, which continue to be typically examined separately in research.
What is exciting about your research’s potential impact?
I believe that the idea of "winding back the clock" by probing the early origins of biological markers of unhealthy aging and risk for age-related diseases is really exciting. Our findings could contribute to a shift in the conceptualization of aging as a process that begins—and is influenced by factors that occur—early in life. This research could open up new opportunities for early risk detection as well as the identification of potentially modifiable factors that could be targeted to promote healthier aging already during development, before the onset of common age-related diseases.
How would you describe your research to a non-scientist?
DNA methylation (DNAm) is an epigenetic mechanism that regulates gene activity in response to both genetic and environmental influences. It is essential for healthy development and increasingly recognized as a key marker of how we age. Specifically, DNAm at specific locations can be used to estimate a person’s age—through so-called ‘epigenetic clocks’. Not only do the age estimates produced by epigenetic clocks relate highly to chronological age, but the difference between the epigenetic age and chronological age is a strong predictor of aging, with epigenetic age acceleration (epigenetic age>chronological age) predicting greater risk of age-related diseases and mortality, whereas epigenetic age deceleration (epigenetic age<chronological age) predicts longevity and lower disease risk. Research from my group has recently shown that DNA methylation sites that make up these clocks already show differences between individuals in early life. Intriguingly, we also find that these sites do not ‘behave’ in the same way across development (e.g. some differ between individuals already at birth while others begin to differ in childhood or adolescence; some change at a steady rate across development, while others differ in their rate of change). What drives these different patterns of change in early life is, however, largely unknown. In this project, we will examine which genetic and environmental factors shape epigenetic aging in early life, and how epigenetic aging in turn relates to health outcomes already during development. The results of this research may provide new clues as to what makes epigenetic clocks ‘tick’, and eventually, how we may slow them down to promote healthy aging.
