Epigenetic Change with Age in Mice is Not Linear
Epigenetic marks such as DNA methylation control expression of genes and cell behavior. They change with age, a reflection of the processes of damage and dysfunction that occur with age. Researchers here focus on DNA methylation in one organ in mice to demonstrate that age-related changes are not linear over time. The individual goes through stages and phase transitions from one state of cellular behavior to another. This is worth considering when thinking about how epigenetic clocks that measure biological age might work in practice, especially when used as a way to evaluate the efficacy of potential rejuvenation therapies.
Analyzing the data of aging mouse colon tissues, we have identified multiple sets of CpG sites exhibiting sudden methylation changes at two different time points. One group of sets undergoes a rapid methylation change during the early-to-midlife transition, while another group exhibits accelerated methylation changes during the mid-to-late-life transition. Interestingly, DNA methylation switches at similar time points were observed in rat peripheral blood DNA. Notably, the division of the lifespan into three stages is already supported by the raw methylation data.
Our data goes in line with a digital aging hypothesis which views aging as a process consisting of discrete steps resulting from mechanisms showing variation in rate during lifespan. The existence of transitions between discrete stages reveals the more controlled, or even programmed, nature of epigenetic aging and opens questions about the regulation and consequences of these abrupt changes. It also indicates that essential insights into the nature of aging may be missed when comparing only two ages.