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. 2024 Jul 1;7(7):e2421869.
doi: 10.1001/jamanetworkopen.2024.21869.

Familial Loss of a Loved One and Biological Aging: NIMHD Social Epigenomics Program

Allison E Aiello  1   2 , Aura Ankita Mishra  3 , Chantel L Martin  4   5 , Brandt Levitt  4 , Lauren Gaydosh  6 , Daniel W Belsky  1   2 , Robert A Hummer  4   7 , Debra J Umberson  6 , Kathleen Mullan Harris  4   7
Affiliations

Familial Loss of a Loved One and Biological Aging: NIMHD Social Epigenomics Program

Allison E Aiello et al. JAMA Netw Open. .

Abstract

Importance: The link between familial loss of a loved one and long-term health decline is complex and not fully understood.

Objective: To test associations of losing a parent, sibling, child, or partner or spouse with accelerated biological aging.

Design, setting, and participants: Data from the National Longitudinal Study of Adolescent to Adult Health, a US population-based longitudinal cohort study, were analyzed. Participants were enrolled from 1994 to 1995 for wave 1, while in grades 7 to 12, and followed up through wave 5 in 2018. The study analyzed participant reports of loss collected at each wave from 1 to 5 over 24 years and used a banked wave 5 blood sample for subsequent DNA methylation testing and epigenetic clock calculation from 2018 to 2024. Data were analyzed from January 2022 to July 2024.

Exposure: Loss of biological parents or parental figures, partners or spouses, siblings, or children at waves 1 to 3 or during childhood, adolescence (aged <18 years), or adulthood at wave 4 to wave 5 (aged 18-43 years).

Main outcomes and measures: Biological aging assessed from blood DNA methylation using the Horvath, PhenoAge, GrimAge, and DunedinPACE epigenetic clocks at wave 5.

Results: Data from 3963 participants were analyzed, with a weighted mean (range) age of 38.36 (36.78-39.78) years at wave 5; 2370 (50.3%) were male, 720 (15.97%) were Black, 400 (8.18%) were Hispanic, and 2642 (72.53%) were White. Nearly 40% of participants experienced loss by wave 5 when they were aged 33 to 43 years, and participants who were Black (379 participants [56.67%]), Hispanic (152 participants [41.38%]), and American Indian (18 participants [56.08%]) experienced a greater proportion of losses compared with White participants (884 participants [34.09%]). Those who experienced 2 or more losses tended to have older biological ages for several of the clocks (PhenoAge β = 0.15; 95% CI, 0.02 to 0.28; GrimAge β = 0.27; 95% CI, 0.09 to 0.45; DunedinPACE β = 0.22; 95% CI, 0.10 to 0.34) compared with those with no losses. In contrast, there were no associations with 2 or more losses for the Horvath clock (β = -0.08; 95% CI, -0.23 to 0.06).

Conclusions and relevance: This study reveals associations between various measures of loss experienced from childhood to adulthood and biological aging in a diverse sample of the US population. These findings underscore the potentially enduring impact of loss on biological aging even before middle age and may contribute to understanding racial and ethnic disparities in health and mortality.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Aiello reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Martin reported receiving grants from National Institute of Minority Health and Health Disparities and the National Institute on Aging during the conduct of the study. Dr Belsky reported receiving personal fees from BellSant as consulting CSO and Scientific Advisory Board Chair and receiving consulting fees and personal fees from Hooke Clinic as member of the Scientific Advisory Board outside the submitted work; in addition, Dr Belsky had a patent for DunedinPACE with royalties paid from TruDiagnostic as inventor of DunedinPACE, a Duke University and University of Otago invention licensed to TruDiagnostic. Dr Harris reported receiving grants from the NIH during the conduct of the study. Dr Mishra reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the NIH (F32HD103400) and grants from the Eunice Kennedy Shriver NICHD of the NIH (P2CHD050924; Carolina Population Center) during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Weighted Means for Biological Aging Clocks (z Scored) by Number of Losses
Dots indicate means and bars indicate SEs. Values are weighted means.
Figure 2.
Figure 2.. Number of Losses and Biological Aging and Parental Loss at Any Time Period (Childhood/Adolescence to Adulthood) and Biological Aging
Clock values are z scored. Models adjusted for age, race and ethnicity, parental education, gender, proportion of households in poverty, number of household members, caregiver smoking, and epigenetic assay batch. See eTable 1 in Supplement 1 for full model specifications and estimates.
Figure 3.
Figure 3.. Any Loss in Either Childhood/Adolescence or in Adulthood and Biological Aging and Parental Loss in Either Childhood/Adolescence or in Adulthood and Biological Aging
Clock values are z scored. Models adjusted for age, race and ethnicity, parental education, gender, proportion of households in poverty, number of household members, caregiver smoking, and epigenetic assay batch. See eTable 1 in Supplement 1 for full model specifications and estimates.
See this image and copyright information in PMC

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