The experiences we face early in life may leave lasting marks on our health, with effects that can echo across decades and throughout the body. A new study published in Science provides compelling molecular evidence that early life adversity can leave a lasting, system-wide signature on the epigenome. This biological layer helps regulate gene activity.
Led by researchers at Arizona State University and Vanderbilt University, along with collaborating institutions, the study examined 237 free-ranging rhesus macaques living on Cayo Santiago, a 38-acre island off Puerto Rico. The macaques have been followed throughout their lives, providing researchers with unusually detailed records of their experiences. The team paired these life histories with genomic data from 12 tissues collected in adulthood.
Researchers focused on DNA methylation, one of the most extensively studied epigenetic markers of ageing. Patterns of DNA methylation can be used to create “epigenetic clocks” that estimate both chronological age and biological age. The researchers developed highly precise tissue-specific clocks capable of predicting the macaques’ ages to within approximately one year.
The results revealed that ageing does not occur uniformly throughout the body. Age-related DNA methylation patterns differed substantially among tissues, with some, including the thymus and pituitary gland, showing particularly great and distinctive changes. Blood—the tissue most commonly examined in human studies—captured only part of this complex picture. Despite these differences, individuals who appeared biologically older in one tissue also tended to appear older in others, suggesting some coordination in ageing across the body.
The study’s most striking findings emerged when researchers examined early life adversity, including naturally occurring experiences such as maternal loss, low maternal social status and growing up in a crowded social group. Each type of adversity was associated with changes in particular regions of the genome. Once affected, however, those regions often showed similar changes across multiple tissues, revealing a coordinated molecular signature of early experiences throughout the body.
Researchers identified thousands of genomic regions where DNA methylation was associated with early life adversity. Many overlapped with regions affected by ageing, but the direction of these changes varied. In some cases, adversity-related patterns resembled accelerated ageing; in others, they moved in the opposite direction. The findings therefore challenge the idea that adversity causes the body to age faster.
Instead, early adversity appears to reshape the epigenome in more complex and tissue-specific ways, potentially altering the trajectory of molecular ageing rather than uniformly accelerating it. The findings also demonstrate why examining multiple tissues is important: relying primarily on blood samples may overlook significant biological effects occurring elsewhere in the body.
Because rhesus macaques share important biological and social characteristics with humans, the findings offer valuable insight into the developmental origins of health and disease. The study suggests that early life represents a critical period during which experiences can become biologically embedded, leaving molecular signatures that persist into adulthood. Understanding these signatures may ultimately help researchers explain how early experiences influence health trajectories across the lifespan.
More information: Baptiste Sadoughi et al, Age and early life adversity shape heterogeneity of the epigenome across tissues in macaques, Science. DOI: 10.1126/science.aea4922
Journal information: Science Provided by Arizona State University
