Epigenetic Clock Deceleration and Maternal Reproductive Efforts: Associations With Increasing Gray Matter Volume of the Precuneus

Abstract

Reproductive efforts, such as pregnancy, delivery, and interaction with children, make maternal brains optimized for child-rearing. However, extensive studies in non-human species revealed a tradeoff between reproductive effort and life expectancy. In humans, large demographic studies have shown that this is the case for the most part; however, molecular marker studies regarding aging remain controversial. There are no studies simultaneously evaluating the relationship between reproductive effort, aging, and brain structures. We therefore examined the associations between reproductive efforts (parity status, number of deliveries, motherhood period, and cumulative motherhood period), DNA methylation age (mAge) acceleration (based on Horvath’s multi-tissue clock and the skin & blood clock), and the regional gray matter volumes (obtained through brain magnetic resonance imaging (MRI) using voxel-based morphometry) in 51 mothers aged 27–46 years of children in early childhood. We found that increasing reproductive efforts were significantly associated with decelerated aging in mothers with one to four children, even after adjusting for the confounding effects in the multiple linear regression models. We also found that the left precuneus gray matter volume was larger as deceleration of aging occurred; increasing left precuneus gray matter volume, on the other hand, mediates the relationship between parity status and mAge deceleration. Our findings suggest that mothers of children in early childhood, who have had less than four children, may benefit from deceleration of aging mediated via structural changes in the precuneus.

Epigenetic clocks and female fertility timeline: A new approach to an old issue?

“…However, they failed to detect an increase of DNAmAge in case of low socio-economic status, a robust “stressor”, even if they justified it as a plausible effect of young age compensation. The narrow age range chosen could indeed introduce some biases ( Ryan et al, 2018 ) that may explain at least in part the difference with previous works ( Nishitani et al, 2022 ).…”

“…It is not hard to believe a possible trade-off between reproductive effort and life expectancy ( Bolund et al, 2016 ). Reproductive effort could change brain structures involved in the sociability required for parenting, likely influencing both mAge acceleration and lifespan ( Nishitani et al, 2022 ). Based on a cohort of n = 51 mothers aged 27–46 years, Nishitani et al explored the relation between epigenetic age and the regional gray matter volumes measured by magnetic resonance imaging (MRI).…”

“…However, their findings should be considered in the context of some limitations. Saliva samples did not let the adoption of second-generation epigenetic clock, and nulliparous women should be included in future studies to confirm their results ( Nishitani et al, 2022 ). On the other hand, this study opens new fascinating scenarios.…”

Correlates of estimated lifetime cruciate ligament survival inform potential rupture risk reduction strategies: findings from the Exceptional Aging in Rottweilers Study

“…It is plausible that biological mechanisms underlying the observed association may be related to epigenetic changes in gene expression. Parity has been associated with a deceleration of human aging 69 , and it has been proposed that chromatin modification (epigenetic memory) may enhance cardiovascular adaptation, resulting in improved reproductive outcomes after first pregnancy 70 . Future studies should attempt to replicate the association between the production of offspring and CCL rupture risk reduction.…”

Evaluation of the pooled sample method in Infinium MethylationEPIC BeadChip array by comparison with individual samples

“…Research on epigenomes and their interaction with genetics that reflect the “nurture and environment” aspect has shifted focus from solely studying genetic sequences in various fields [ 1 ]. Epigenomic research, initially dominated by cancer research [ 2 ], has recently expanded to include studies on the relationship between various phenotypes, such as aging [ 3 – 7 ], nutrition and diet [ 8 ], environmental pollutants [ 9 , 10 ], immunity [ 11 , 12 ], neurological disorders [ 13 ], psychiatric disorders [ 14 – 17 ], and psychological traits [ 18 , 19 ], and is expected to increase further [ 20 ].…”