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

Shota Nishitani,Akemi Tomoda,Hidehiko Okazawa,Daiki Hiraoka,Ryoko Kasaba,Koji Shimada,Takashi X Fujisawa

doi:10.3389/fgene.2022.803584

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.

Highlights

In non-human species, the established theory (LHT: Life History Theory) is that the greater the reproductive effort, the more finite energy is expended; females tradeoff life expectancy with reproductive effort (Hill and Kaplan, 1999)
We examined the association between reproductive effort, methylation age (mAge) acceleration measured using salivary DNA, and brain structures evaluated by voxel-based morphometry (VBM), in mothers
MAge acceleration calculated by the skin and blood clock was significantly negatively associated with parity status (β = −0.21, t = −2.21, P = 0.03), and number of deliveries (β = −0.28, t = −2.44, P = 0.02), while no associations were found with other parameters (Table 2 and Figure 1)

Summary

Introduction

In non-human species, the established theory (LHT: Life History Theory) is that the greater the reproductive effort, the more finite energy is expended; females tradeoff life expectancy with reproductive effort (Hill and Kaplan, 1999). Shadyab et al (2017) reported that the odds ratio (OR) of longevity in Caucasians was higher for mothers who gave birth more than once (two to four children; mean OR: 1.13) compared to that of those who gave birth once (OR: 0.91) or were nulliparous (OR: 1 as reference), even after adjusting for demographic characteristics, socioeconomic status, lifestyle behaviors, reproductive factors, and health-related factors (Shadyab et al, 2017) It was consistent with both the LHT and previous population demographics in most aspects, especially regarding having more children; the association between the number of deliveries and longevity was attenuated, and was certainly not higher in those with five or more children. While it may be true that having more than four children reduces life expectancy in women, the LHT may not be consistent with births of less than four children

Methods

Results

Conclusion