EAA and the Developmental Origins of Health and Disease
Development is a highly complex essential process (Fig. 1A ).
Factors such as environmental exposures may perturb DNAm during
development, and thereby lead to long-term changes that influence
susceptibility to disease. In early life, the majority of CpG sites
across the genome are hypomethylated, leaving them vulnerable to
aberrant methylation caused by environmental factors (Fig. 1A ).
Subsequent DNAm patterns may reflect exposures during these stages of
life and influence the epigenetic clock and EAA. Previous studies on
development have primarily focused on the pre-natal and early life
periods, but development also encompasses other life stages of rapid
change such as puberty and even menopause. Studies have shown that
exposures such as smoking in adolescence can alter DNAm during
adolescence89. Whether
this leads to impacts on epigenetic aging which continue in later life
remains under-explored.
It has been suggested that an individual’s EAA trajectory is established
in childhood and continues at the same rate throughout
adulthood90. However,
more work examining this question is needed. In addition, it is
necessary to study whether the rate of EAA is influenced by
environmental exposures during critical developmental periods such as
puberty, pregnancy, and menopause. Most current epigenetic clocks,
except the PedBE clock and gestational age clocks, were developed using
mainly adult samples. This means that CpG sites involved in early growth
and developmental processes may not be captured in these clocks.