Impact of childhood maltreatment on aging: a comprehensive Mendelian randomization analysis of multiple age-related biomarkers

Aug 5, 2024Clinical epigenetics

How Childhood Maltreatment May Affect Aging Through Multiple Biological Markers

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Abstract

Childhood maltreatment is significantly associated with shorter and increased .

Shorter telomere length was observed in individuals with a history of childhood maltreatment.
Increased levels of HannumAge, GrimAge, and PhenoAge were found among those who experienced childhood maltreatment.
A significant association was noted between childhood maltreatment and higher frailty index scores.
No significant associations were found between childhood maltreatment and facial aging or cognitive performance.

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BACKGROUND: Childhood maltreatment () is linked to long-term adverse health outcomes, including accelerated biological aging and cognitive decline. This study investigates the relationship between CM and various aging biomarkers: , facial aging, intrinsic epigenetic age acceleration (IEAA), GrimAge, HannumAge, PhenoAge, frailty index, and cognitive performance.

METHODS: We conducted a Mendelian randomization (MR) study using published GWAS summary statistics. Aging biomarkers included telomere length (qPCR), facial aging (subjective evaluation), and epigenetic age markers (HannumAge, IEAA, GrimAge, PhenoAge). The frailty index was calculated from clinical assessments, and cognitive performance was evaluated with standardized tests. Analyses included Inverse-Variance Weighted (IVW), MR Egger, and Weighted Median (WM) methods, adjusted for multiple comparisons.

RESULTS: CM was significantly associated with shorter telomere length (IVW: β = - 0.1, 95% CI - 0.18 to - 0.02, pFDR = 0.032) and increased HannumAge (IVW: β = 1.33, 95% CI 0.36 to 2.3, pFDR = 0.028), GrimAge (IVW: β = 1.19, 95% CI 0.19 to 2.2, pFDR = 0.040), and PhenoAge (IVW: β = 1.4, 95% CI 0.12 to 2.68, pFDR = 0.053). A significant association was also found with the frailty index (IVW: β = 0.31, 95% CI 0.13 to 0.49, pFDR = 0.006). No significant associations were found with facial aging, IEAA, or cognitive performance.

CONCLUSIONS: CM is linked to accelerated biological aging, shown by shorter telomere length and increased . CM was also associated with increased frailty, highlighting the need for early interventions to mitigate long-term effects. Further research should explore mechanisms and prevention strategies.

Key numbers

-0.1

Decrease in

Measured using the IVW method with a 95% confidence interval.

1.33

Increase in HannumAge

Measured using the IVW method with a 95% confidence interval.

0.31

Increase in Frailty Index

Measured using the IVW method with a 95% confidence interval.

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Impact of childhood maltreatment on aging: a comprehensive Mendelian randomization analysis of multiple age-related biomarkers

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