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. 2024 May 16;15(1):4140.
doi: 10.1038/s41467-024-48426-7.

Severe drought exposure in utero associates to children's epigenetic age acceleration in a global climate change hot spot

Xi Qiao #  1 , Bilinda Straight #  2 , Duy Ngo #  1 , Charles E Hilton  3 , Charles Owuor Olungah  4 , Amy Naugle  5 , Claudia Lalancette  6 , Belinda L Needham #  7
Affiliations

Severe drought exposure in utero associates to children's epigenetic age acceleration in a global climate change hot spot

Xi Qiao et al. Nat Commun. .

Abstract

The goal of this study is to examine the association between in utero drought exposure and epigenetic age acceleration (EAA) in a global climate change hot spot. Calculations of EAA in adults using DNA methylation have been found to accurately predict chronic disease and longevity. However, fewer studies have examined EAA in children, and drought exposure in utero has not been investigated. Additionally, studies of EAA in low-income countries with diverse populations are rare. We assess EAA using epigenetic clocks and two DNAm-based pace-of-aging measurements from whole saliva samples in 104 drought-exposed children and 109 same-sex sibling controls in northern Kenya. We find a positive association between in utero drought exposure and EAA in two epigenetic clocks (Hannum's and GrimAge) and a negative association in the DNAm based telomere length (DNAmTL) clock. The combined impact of drought's multiple deleterious stressors may reduce overall life expectancy through accelerated epigenetic aging.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Rainfall comparison by pregnancy.
Rainfall z-scores in comparison to 40-year mean for 3-month period leading to conception (indicative of pasture quality in first trimester) by pregnancy and mother’s reported residence, using CHIRPS rainfall data. Figure shows mean z-scores by pregnancy and location for drought-exposed and unexposed pregnancies in dry (blue columns) and wet (orange columns) seasons. Source data are provided as a Source Data file.
Fig. 2
Fig. 2. Conceptual model for study.
Drought exposure during pregnancy indicated (gold sun and red thermometer weather symbols and brown diagram of pregnant woman) hypothesized to predict child outcomes (brown infant diagram) through biological mechanisms of aging and phenotypic plasticity (blue DNA symbol), tested in this study with epigenetic age acceleration (blue forward arrows) using multiple epigenetic clocks, as labeled in Figure as follows: 1st generation clocks (blue clock) – Horvath, Hannum, SkinBlood, identified as lifespan predictors; 2nd generation clocks (green clock) – PhenoAge, GrimAge2, DNAmTL, identified as disease and mortality predictors; 3rd generation pace of aging predictors (yellow clock) – DunedinPACE, DunedinPoAm38; and pediatric clocks (orange clock) – PedBe and Wu, identified as child health and disease predictors.
Fig. 3
Fig. 3. Frequently reported pregnancy stressors by percentage reported.
Top stressors reported as experienced during drought pregnancy shown in comparison to reporting of those same stressors during drought-unexposed pregnancy (N reporting = 104 Drought-exposed, N reporting = 109 Drought-unexposed), based on percentage of women reporting the stressor by pregnancy. Stressors as indicated in figure columns are livestock deaths (blue), food insecurity (orange), feared husband (gray), hazardous livestock work (yellow), intimate partner violence (light blue), water insecurity (green), too weak to work (navy), forced to work too hard by husband during the pregnancy (brown), denied food by husband during pregnancy (husband refusing to provide food) (dark gray). Source data are provided as a Source Data file.
Fig. 4
Fig. 4. Correlation matrices of epigenetic clocks and epigenetic age accelerations (EAAs).
Figure 4a illustrates the correlation matrix for various epigenetic clocks, while Fig. 4b displays the matrix for correlations between epigenetic age acceleration (EAA) and aging pace metrics. The term “EAAPedBE” refers to the EAA estimated using the PedBE clock, a naming convention consistent across other EAA measurements presented. Positive correlations are denoted by red shades, whereas negative correlations are indicated in blue, with darker shades signifying stronger absolute correlation values. Source data are provided as a Source Data file.
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