“What a stupid question!”, you may be thinking…, “Of course, children age. Why would we bother with birthday parties if they didn’t?”. When measuring biological age, however, we are faced with a bit of a conundrum.
Most epigenetic clocks currently available on the market – epiAge included – are trained using a broad age cohort, from baby to centenarian. However, because preoccupations with ageing tends to increase along with chronological age, children, teens as well as (very) young adults are not the main target group of these clocks. This means that most B2C epigenetic age tests are slightly biased towards middle-age and above. So, results when testing a younger population may prove less reliable.
The challenges: how growing muddies the waters of ageing
But beyond this marketing cohort bias, the epigenetic testing of younger individuals comes with its own set of challenges. Indeed, development in children up to young adulthood does not evolve linearly. “In fits and starts” would be a better label to describe how this population grows. Even as a layperson minimally exposed to children and teenagers, it quickly becomes obvious that phases of immense development acceleration (think of e.g. the transition from baby to toddler or milestones such as puberty) alternate with stabilisation “plateaux” or much slower incremental growth.
What makes the endeavour even more complicated is that development is a very individual affair. Paediatric examination protocols focus on specific milestones that children should reach by a certain chronological age, but any seasoned practitioner will confirm that there are widespread variations not just in growth but also in the acquisition of e.g., motor or language skills. Some children may for instance require support with “potty-training” well into primary school age, while demonstrating exceptional language skills. By late adolescence or early adulthood, however, most individuals will have caught up with all the milestones – provided there are no underlying disorders or developmental challenges.
Beyond these two significant aspects is another, which is intimately related to the assessment of biological age. Genetic factors that provide the overall blueprint for the development of a child are of course an important influence. But just as significant – if not more so in childhood, are environmental factors as they translate into epigenetic modulation. Babies or young children who have been neglected, abused or exposed to stress and harmful substances (be it in utero or later), often display a significant and persistent (if hopefully temporary) developmental lag that can be reflected in biological age testing.
So, yes, children age, but as researchers Wang and Zhu (2021) put it: “DNAm [DNA methylation] age deviation in pediatrics […] may not entirely follow the same pattern presented in later life. Epigenetic age in the early 20 years enjoys a more dynamic paradigm.” This, in turn, explains why standard biological age clocks geared towards an adult population do not perform as well with younger individuals. New clocks for children and adolescents have been and are currently being developed and cross-sectional studies carried out. But owing to the novelty of the clocks, more cross-sectional and longitudinal studies are required.
Also, just as with adult-oriented clocks, the selection of appropriate CpGs (regions tested around the DNA), proves equally challenging with children since “measures of EAD [epigenetic age acceleration] are also appreciated by the fact that they are associated with a great number of developmental characteristics, including weight, body mass index (BMI), height, fat mass, bone density, subscapular skinfold, and upper-arm circumference.” (Wang & Zhu; 2021). Consequently, as already witnessed when testing the biological age of adults (Poganik & al.,2023), different clock designs will be more or less sensitive to various underlying conditions or influences.
Why determine children's biological age?
After this rapid exposé, a seminal question may remain: given all the challenges related to biological age determination in younger individuals, what do researchers hope to achieve with their endeavours? And is epigenetic age testing actually useful for this population group? The answer to the latter is a clear yes. The researchers developing the PAYA clock, for instance, had a very practical goal in mind when developing their model to determine the age of adolescents and young adults. They aimed to improve forensic age-assessment to determine the need for child protection in young people without birth date documentation (about ¼ of children globally), since current radiographic methods are very limited. To make the test as universally applicable as possible, these scientists are currently going to great pains to filter out as many environmental biases as possible (Aanes & al.; 2023).
In contrast, other researchers are precisely interested in the interplay between genetics and environment to explain, and hopefully remedy, abnormal developmental trajectories. In the words of Wang and Zhu (2021): “Since it is influenced by both genetic and environmental factors, DNAm [DNA methylation] has also emerged as a key mechanism of interest for understanding the gene-environmental interplay in normal development and related diseases. Thereby, the pediatric epigenetic clock is a thriving topic in unraveling the biological magic behind development and growth for youth.”
Sources
Wang J, Zhou WH. „Epigenetic clocks in the pediatric population: when and why they tick?“ Chinese Medical Journal (Engl). 2021 Sep 14;134(24):2901-2910. doi:10.1097/CM9.0000000000001723. Online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710336/
Aanes, H., Bleka, Ø., Dahlberg, P.S. et al. „A new blood based epigenetic age predictor for adolescents and young adults”. Scientific Reports 13, 2303(2023). https://doi.org/10.1038/s41598-023-29381-7. Online: https://www.nature.com/articles/s41598-023-29381-7
Jesse R. Poganik, Bohan Zhang, Gurpreet S. Baht, Alexander Tyshkovskiy, Amy Deik, Csaba Kerepesi, Sun Hee Yim, Ake T. Lu, Amin Haghani, Tong Gong, Anna M. Hedman, Ellika Andolf, Göran Pershagen, Catarina Almqvist, Clary B. Clish, Steve Horvath, James P. White, Vadim N. Gladyshev, “Biological age is increased by stress and restored upon recovery“, Cell Metabolism, Volume 35, Issue 5,2023, 807-820.e5, https://doi.org/10.1016/j.cmet.2023.03.015. Online: https://www.sciencedirect.com/science/article/abs/pii/S1550413123000931
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