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The epigenetic age and pregnancy.

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Jamila Nov 10, 2020
Does pregnancy change the mother's epigenetic age?

Whether pregnancy is beneficial or detrimental to the mother's health is an age-old dispute. There are two main theories concerning this: the regeneration theory and the disposable soma theory.

The regeneration theory suggests that pregnancy is beneficial to the mother because it may regenerate the mother's organs. Pregnancy is similar to heterochronic parabiosis, whereby beneficial factors from the young are transferred to the older person – these factors promote good health and longevity.

The disposable soma theory suggests that pregnancy is detrimental to the mother's health. This theory indicates that pregnancy has high costs, which compromise maternal longevity. Maternal resources are used to develop the child, which subsequently advances the maternal age.

Epigenetic alterations are a hallmark of ageing. That's why researchers developed epigenetic clocks based on epigenetic alterations. Researchers can determine an individual's epigenetic age by using these clocks; this can identify if an individual has accelerated ageing. The epigenetic clocks can be used to determine whether pregnancy accelerates ageing or not.

In one study, researchers found that the epigenetic age increased with young women's gravidity – It's also important to note that their telomere length had decreased with gravidity. In another study, researchers determined that each pregnancy accelerated the epigenetic age of young women. In the study, three epigenetic clocks were used (Hannum, Horvath, and Levine clocks).

So, it seems that having more children increased the women's epigenetic age, which would suggest that the pregnancies made them age. However, it might not be that simple. So, we need to find out whether the epigenetic age increases in various conditions. I have compiled some research ideas to use for future studies.

Research ideas
  • The studies above determine the epigenetic age of young women aged 20-22 years old with gravidity. The same research should be conducted but with more senior women to see if their epigenetic age also increases with gravidity.
  • Does the epigenetic age of women change throughout pregnancy, i.e. before, during, and after pregnancy?
  • Compare the epigenetic ages of women that have one birth to those that have multiple deliveries at the same time, i.e. twins, and triplets.
  • Find out whether mothers from three different age groups (18-25, 26-35, and 36-45) have similar epigenetic ages throughout their pregnancy (before, during, and after pregnancy)
Can you think of any more research ideas? Does pregnancy increase or decrease the mother's epigenetic age?

[1]Michaeli, Tal Falick, Yehudit Bergman, and Yuval Gielchinsky. "Rejuvenating effect of pregnancy on the mother." Fertility and Sterility 103.5 (2015): 1125-1128.

[2]Ziomkiewicz, Anna, et al. "Evidence for the cost of reproduction in humans: high lifetime reproductive effort is associated with greater oxidative stress in post-menopausal women." PloS one 11.1 (2016): e0145753.

[3]Armstrong, Nicola J., et al. "Aging, exceptional longevity and comparisons of the Hannum and Horvath epigenetic clocks." Epigenomics 9.5 (2017): 689-700.

[4]Ryan, Calen P., et al. "Reproduction predicts shorter telomeres and epigenetic age acceleration among young adult women." Scientific reports 8.1 (2018): 1-9.

[5]Kresovich, Jacob K., et al. "Reproduction, DNA methylation and biological age." Human Reproduction 34.10 (2019): 1965-1973

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General comments

Shubhankar Kulkarni
Shubhankar Kulkarni6 months ago
A recent study reported the changes observed in the epigenetic age between during pregnancy and 1 year postpartum. The average age of the 35 women included in the study was about 33 years. [1]

The results suggested that the epigenetic age decreased from mid-pregnancy to 1 year post-partum,
with respect to PEAA (Phenotypic Epigenetic Age Acceleration), GrimAge (a cumulative score of 12 epigenetic markers), DNAm PAI-1 (plasminogen activator inhibitor-1; a marker or cardiovascular disease), and immune cell population epigenetic age indices (EEAA - extrinsic epigenetic age acceleration, age-adjusted proportion of senescent CD8+ T cells and naïve CD8+ T cells). In non-pregnant adults, EEAA and the age-adjusted proportions of senescent CD8+ T cells increase over time, and the age-adjusted proportion of naïve CD8+ T cells decrease over time. [2, 3, 4] The current study reported that the opposite from pregnancy to the post-partum period. This suggested a regeneration of T cells from pregnancy to the post-partum period, potentially indicating a partial postpartum rejuvenation. Overall, pregnancy may slow some aspects of aging.

Limitations of the study:
1. Small sample size
2. Changes over the full length of the pregnancy (from before being pregnant) were not observed.
3. We do not know whether the women were previously pregnant or not.
4. The observed change in the epigenetic age between mid-pregnancy and 1 year post-partum could
be affected by a decrease in weight in the postpartum period.

1. Ross KM, Carroll J, Horvath S, Hobel CJ, Coussons-Read ME, Dunkel Schetter C. Immune epigenetic age in pregnancy and 1 year after birth: Associations with weight change. Am J Reprod Immunol. 2020 May;83(5):e13229. doi: 10.1111/aji.13229. Epub 2020 Mar 12. PMID: 32061136.
2. Kananen L, Marttila S, Nevalainen T, et al. The trajectory of the blood DNA methylome ageing rate is largely set before adulthood: evidence from two longitudinal studies. Age (Dordr). 2016;38(3):65.
3. Marttila S, Kananen L, Hayrynen S, et al. Ageing-associated changes in the human DNA methylome: genomic locations and effects on gene expression. BMC Genom. 2015;16:179.
4. Pawelec G, Larbi A, Derhovanessian E. Senescence of the human immune system. J Comp Pathol. 2010;142(Suppl 1):S39-S44.
Jamila 6 months ago
Shubhankar Kulkarni the study is very interesting. Thanks for bringing it to my attention. The study would have been even better if they had tested the epigenetic age prior to the pregnancy! Then we could've determined the epigenetic age throughout the different phases. It also would've helped to know more background information about the women like whether this was their first child or not.

Just a silly thought in my head, but what if pregnancy rejuvenates the female depending on their age. For example, in "older" females, the epigenetic age might decrease due to pregnancy, but in "younger" women, the epigenetic age increases/doesn't change as much due to pregnancy. So, the rejuvenating effect might only be seen in the "older" women. ☺️

Shubhankar Kulkarni
Shubhankar Kulkarni6 months ago
Jamila That can be true. There can be a J-shaped curve where the female's epigenetic age might decrease if she is pregnant in an age time window that is optimum for pregnancy. The epigenetic age of females pregnant before and after the time window might see an increase.
Shubhankar Kulkarni
Shubhankar Kulkarni6 months ago
Excellent idea! Epigenetic may help us solve the debate.
1. I would like to add another age group on the left-hand side of the spectrum since the reproductive age starts well before 18 years of age.
2. Different age groups are very much necessary for this research. The age group in which the increase in the epigenetic age with gravidity is the lowest can be, probably, considered as the best age to conceive, at least, biologically.
Jamila 6 months ago
Shubhankar Kulkarnigood idea. We would need to cover the spectrum of ages to get a better sense of how the age at the time of pregnancy impacts the ageing process.

That's also very true. The research has vast implications. Firstly, it would tell us whether the pregnancy is beneficial or detrimental for mothers. Secondly, if there is an age group that has no effect or a little increase in the epigenetic age, then this would be a good age to conceive, as you said.

However, there is also a possibility that certain age groups have a decreased epigenetic age because of pregnancy - this would be fascinating if it does happen.