Early life adversity, pubertal timing, and epigenetic age acceleration in adulthood

Abstract

Background: Given associations linking early life adversity, pubertal timing, and biological aging, we examined the direct and indirect effects of early life trauma on adult biological aging (via age of menarche).Methods: Participants were premenopausal women (N = 183). Path models evaluated whether early life trauma predicted early pubertal timing and thereby, adult epigenetic age acceleration (indexed via four epigenetic clocks: Horvath DNAm Age, Hannum DNAm Age, DNAm PhenoAge, and DNAm GrimAge). Secondary analyses explored the effects of type of trauma (abuse and neglect) and adult chronic stress status (caregiver of child with autism and non-caregiver).Results: Early life trauma and earlier age at menarche independently predicted accelerated aging based on one of the four epigenetic clocks, DNAm GrimAge, though early life trauma was not associated with age of menarche. Childhood abuse, but not neglect, predicted faster epigenetic aging; results did not differ by chronic stress status. Conclusions:Early trauma and early menarche appear to exert independent effects on DNAm GrimAge, which has been shown to be the strongest epigenetic predictor of mortality risk. This study identifies a potential correlate or determinant of accelerated epigenetic aging-menarcheal age. Future research should address the limitations of this study by using racially diverse samples.

The pediatric buccal epigenetic clock identifies significant ageing acceleration in children with internalizing disorder and maltreatment exposure

“…This apparent moderation supports a subtype of internalizing disorder that manifests in relation to stress and has distinct biological features and pathophysiological pathways ( Heim et al, 2004 ; Teicher and Samson, 2013 ). Using the more accurate and developmentally-sensitive methodology of the PedBE clock, our results provide validation for previous studies results that reported accelerated epigenetic ageing in children with affective disorders or maltreatment exposure based on adult epigenetic clocks ( Austin et al, 2018 ; Hamlat et al, 2021 ; Han et al, 2018 ; Jovanovic et al, 2017 ; Marini et al, 2020 ; Sumner et al, 2019 ; Shenk et al, 2021 ). We extend these findings by providing the stratified moderation analysis identifying a subtype of internalizing disorder and maltreatment exposure that demonstrates accelerated epigenetic ageing.…”

“…Interestingly, elevated levels of inflammation in pre-pubertal children have been reported to affect the onset of menarche ( Michels et al, 2020 ). Early menarche onset has been shown to associate with accelerated epigenetic ageing based on DNA methylation in the GrimAge epigenetic clock ( Lu et al, 2019 ) that has validity for adults and predicts mortality risk ( Hamlat et al, 2021 ), in line with the above theoretical considerations of a trade-off between rapid maturation and increased morbidity or mortality. Future studies should scrutinize the role of sex differences in accelerated epigenetic ageing and pubertal pacing in response to stress.…”

“…Several studies provide evidence for increased telomere shortening in adults exposed to ELS ( Kananen et al, 2010 ; O’Donovan et al, 2011 ; Rentscher et al, 2020 ; Surtees et al, 2011 ; Tyrka et al, 2010 ) as well as children with ELS ( Drury et al, 2012 ; Mitchell et al, 2014 ; Shalev et al, 2013 ). Furthermore, epigenetic ageing indicators provide evidence for accelerated ageing in adults and children exposed to poverty, trauma, abuse, threat, and neighborhood violence early in life ( Austin et al, 2018 ; Hamlat et al, 2021 ; Jovanovic et al, 2017 ; Marini et al, 2020 ; Sumner et al, 2019 ; Wolf et al, 2018 ). One study in adults reported that epigenetic ageing acceleration within a group of depressed individuals was accentuated by the severity of ELS ( Han et al, 2018 ).…”

Effects of Early Life Stress on the Developing Basolateral Amygdala-Prefrontal Cortex Circuit: The Emerging Role of Local Inhibition and Perineuronal Nets

“…Structural and functional modifications would be geared toward ensuring increased survival and faster reaching of reproductive capabilities ( Colich et al, 2020 ) in unfavorable conditions. This might come to the expense of accelerated aging since a recent report demonstrated that early life trauma predicted accelerated aging based on epigenetic clocks even though the trauma was not associated with age of menarche in this particular study ( Hamlat et al, 2021 ). Childhood abuse, but not neglect, predicted faster epigenetic aging, emphasizing differences between the type of early adversity encountered.…”

Development of DNA methylation-based epigenetic age predictors in loblolly pine (Pinus taeda)

“…Accelerated epigenetic aging is associated with age related losses in organismal function and in humans, and predicts risk for age-associated disease and mortality (Levine et al, 2018;Perna et al, 2016;Zheng et al, 2016). In addition, epigenetic-to-chronological age discordance mirrors variation in life history traits (Anderson et al, 2021;Hamlat, Prather, Horvath, Belsky, & Epel, 2021). For example, birth weight, age and size at maturity, as well as the timing of reproductive senescence are all correlated to epigenetic age in humans, demonstrating intriguing links between aging processes and life history variation (Binder et al, 2018;Ryan et al, 2018;Simpkin et al, 2015).…”