When asked, "How old are you?" Most people measure by how many birthdays they've had. But scientists have developed epigenetic clocks to measure how "old" your body really is. At the forefront of aging research, these clocks go beyond our calendar age to try and reveal our biological age—a true marker of how healthy we are.

However, scientists don't fully understand how they work. As a recent NYT article pointed out, it's a bit like having a sophisticated gadget without a manual. Our bodies' internal workings, especially our immune system, play a huge role, but the details remain unclear.

New research by Dartmouth Cancer Center scientists has taken the first step to change that. The team, led by Ze Zhang, Ph.D., Lucas Salas, MD, MPH, Ph.D., and Brock Christensen, Ph.D., is diving deep into the immune system to learn how different immune cells affect epigenetic clocks to make them more accurate and reliable.

In their study, "Deciphering the role of immune cell composition in epigenetic age acceleration: Insights from cell-type deconvolution applied to human blood epigenetic clocks," recently published in Aging Cell, the team determined how our body's biological age is related to our immune system.

Using novel tools they recently developed for immune profiling, they were able to more closely examine how immune cell profiles relate to biological age estimates from epigenetic clocks. In particular, the balance between naïve and memory immune cells seems to accelerate or slow down biological aging. Key innovations of the study include:

• Enabling the calculation of Intrinsic Epigenetic Age Acceleration (IEAA) with unprecedented immune cell granularity, allowing for a much more detailed understanding of the aging process at a cellular level.
• Offering a more direct comparison between immune cells and aging than the traditional Extrinsic Epigenetic Age Acceleration (EEAA) method, which only considers a limited range of immune cells.
• Adding a new layer of understanding to the biological interpretation of epigenetic clocks, by mapping out how various immune cell subsets contribute to epigenetic aging and providing insights that previous research has missed.

"Our findings open new doors to a much more detailed understanding of the relationships between the immune system and biological age at a cellular level, and the internal and external factors that influence how quickly we age," says Zhang.

The implications of these findings are far-reaching, offering new insights into the aging process and potential pathways for health interventions. Future studies will focus on incorporating groundbreaking findings that link immune cell composition to epigenetic aging into calculating biological age using epigenetic clocks—a significant shift in how we evaluate biological age that will ensure a more comprehensive and accurate assessment.

Upcoming research will delve directly into different immune cells' roles in various disease settings, particularly in different types of cancer. By unraveling the complex roles of immune cells influenced by epigenetic aging, the team's research could lead to more targeted and effective cancer treatments, a deeper understanding of how cancer develops, and new approaches for precision cancer prevention.

"This exciting trajectory can transform our understanding of disease and aging and open new possibilities in precision prevention, precision medicine, and targeted treatments," says Zhang. "With these steps, we move closer to a future where predicting and preventing diseases like cancer becomes more precise and effective, guided by the deepened knowledge of biological age and the immune system."