Experiencing the loss of close family members was associated with accelerated biological aging, even before midlife, according to a new study.
Nearly 40% of almost 4,000 study participants experienced such a loss by adulthood (aged 33-43). Those with two or more losses showed significantly older biological ages, as measured by multiple epigenetic clocks, compared to those without losses.
Losses in adulthood were more strongly associated with accelerated aging than those in childhood or adolescence. The study also found racial disparities in loss experiences: Black (56.67%), Hispanic (41.38%), and American Indian (56.08%) participants reported a higher proportion of losses compared to White participants (34.09%).
"Our findings suggest that accelerated biological aging may represent a key mechanism associating exposure to death of family members with later life risk of morbidity and mortality," noted study investigators
The research, published in JAMA Network Open, used data from the National Longitudinal Study of Adolescent to Adult Health to examine the relationship between familial loss and epigenetic markers of aging in a diverse sample of U.S. adults.
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. Investigators used a banked wave 5 blood sample for subsequent DNA methylation testing and epigenetic clock calculation from 2018 to 2024.
Data from 3,963 participants were analyzed, with a weighted mean age of 38.36 years at wave 5; 2,370 (50.3%) were male, 720 (15.97%) were Black, 400 (8.18%) were Hispanic, and 2,642 (72.53%) were White. Researchers collected information on losses of parents, siblings, partners/spouses, and children across 5 waves of the study from 1994 to 2018. DNA methylation data from blood samples at wave 5 was used to calculate four epigenetic clocks: Horvath, PhenoAge, GrimAge, and DunedinPACE.
Exposure variables included:
- Number of losses (0, 1, or ≥2)
- Parental loss at any time period
- Any loss in childhood/adolescence (<18 years) or adulthood (≥18 years)
- Parental loss in childhood/adolescence or adulthood
Models adjusted for age, race/ethnicity, parental education, sex, proportion of households in poverty, number of household members, caregiver smoking, and epigenetic assay batch.
Participants who experienced 2 or more losses showed significantly older biological ages for several epigenetic 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
Those with 1 loss also showed accelerated aging for GrimAge (β = 0.19; 95% CI, 0.09 to 0.29) and DunedinPACE (β = 0.17; 95% CI, 0.08 to 0.27).
Parental loss at any time period was associated with older biological ages:
- PhenoAge: β = 0.12; 95% CI, 0.02 to 0.21
- GrimAge: β = 0.21; 95% CI, 0.12 to 0.31
- DunedinPACE: β = 0.19; 95% CI, 0.11 to 0.28
Losses in adulthood showed stronger associations with biological aging compared to childhood/adolescent losses. For example, any loss in adulthood was associated with older GrimAge (β = 0.16; 95% CI, 0.07 to 0.26) and faster DunedinPACE (β = 0.15; 95% CI, 0.06 to 0.24), while childhood/adolescent losses showed no significant associations.
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).
While racial/ethnic minorities experienced a higher proportion of losses, interaction analyses found no statistically significant differences in the association between loss and biological aging across Black and White study participants.
Investigators had access to only one time point of epigenetic data, limiting the ability to assess changes in biological aging over time. Additionally, the sample sizes for some racial/ethnic groups were small, potentially limiting the power to detect interaction effects.
Conflict of interests can be found in the study.