Journal Article Annotations
2024, 3rd Quarter

Aging

Annotations by Zachary Harvanek, MD, PhD
October, 2024

Short Sleep and Insomnia Are Associated With Accelerated Epigenetic Age.
Intervening After Trauma: Child-Parent Psychotherapy Treatment Is Associated With Lower Pediatric Epigenetic Age Acceleration.

Of interest:

- Trauma, adversity, and biological aging: behavioral mechanisms relevant to treatment and theory.

PUBLICATION #1 — Aging

Short Sleep and Insomnia Are Associated With Accelerated Epigenetic Age.

Cynthia D J Kusters, Eric T Klopack, Eileen M Crimmins, Teresa E Seeman, Steve Cole, Judith E Carroll.

Abstract: Psychosom Med. 2024 Jun 1;86(5):453-462. doi: 10.1097/PSY.0000000000001243. Epub 2023 Aug 21.

Objective:
Short sleep and insomnia are each associated with a greater risk of age-related disease, which suggests that insufficient sleep may accelerate biological aging. We examine whether short sleep and insomnia alone or together relates to epigenetic age among older adults.

Methods:
A total of 3795 men (46.3%) and women aged 56 to 100 years from the Health and Retirement Study were included. Insomnia was defined as reporting at least one insomnia symptom (difficulty falling asleep, waking up at night, or waking up too early in the morning) and feeling unrested when waking up most of the time. Those reporting <6 hours of bedtime were categorized as short sleepers. Three second- or third-generation epigenetic age acceleration clocks were derived from the 2016 Health and Retirement Study Venous Blood Study. The linear regression analysis was adjusted for age, sex, race/ethnicity, education, and obesity status.

Results:
Insomnia and short sleep were associated with acceleration of GrimAge of 0.49 (95% confidence interval [CI] = 0.03-0.94 years; p = .04) and 1.29 (95% CI = 0.52-2.07 years; p = .002) years, respectively, as well as a faster pace of aging (DunedinPACE; 0.018 [95% CI = 0.004-0.033; p = .02] and 0.022 [95% CI = -0.004 to 0.048; p = .11]). Compared with healthy sleepers, individuals with the combination of short sleep and insomnia had an accelerated GrimAge (0.97 years; 95% CI = 0.07-1.87 years, p = .04) and a greater DunedinPACE (0.032; 95% CI = 0.003-0.060, p = .04).

Conclusions:
Our findings indicate that short sleep, insomnia, and the combination of the two are linked to epigenetic age acceleration, suggesting that these individuals have an older biological age that may contribute to risk of comorbidity and mortality.

Annotation

The finding:
In the Health & Retirement Study, the authors found that both insomnia and shorter sleep duration were associated with faster aging in both the GrimAge and DunedinPACE epigenetic clocks, though not in the PhenoAge clock. Furthermore, they identified connections between insomnia and specific components of the GrimAge clock related to inflammatory pathways, including PAI-1, GDF15, B2M, and Cystatin-C. Notably, these results were more pronounced in Black and Hispanic individuals, as well as in men.

Strength and weaknesses:
Strengths of this study include the large sample size of the Health & Retirement Study as well as its broad recruitment pool, as well as the use of models accounting for obesity, which is associated with both sleep and epigenetic aging. Limitations include the primarily white, older population and the use of self-report to measure insomnia and sleep duration.

Relevance:
These findings suggest a connection between insomnia and biological aging. These might suggest that treatment of insomnia could be beneficial in protecting against accelerated aging, though further, intervention-focused studies are needed.

PUBLICATION #2 — Aging

Intervening After Trauma: Child-Parent Psychotherapy Treatment Is Associated With Lower Pediatric Epigenetic Age Acceleration.

Alexandra D W Sullivan, Sarah M Merrill, Chaini Konwar, Michael Coccia, Luisa Rivera, Julia L MacIsaac, Alicia F Lieberman, Michael S Kobor, Nicole R Bush.

Abstract: Psychol Sci. 2024 Sep;35(9):1062-1073. doi: 10.1177/09567976241260247. Epub 2024 Aug 14.

Early-life adversity increases the risk of health problems. Interventions supporting protective and responsive caregiving offer a promising approach to attenuating adversity-induced changes in stress-sensitive biomarkers. This study tested whether participation in an evidence-based dyadic psychosocial intervention, child-parent psychotherapy (CPP), was related to lower epigenetic age acceleration, a trauma-sensitive biomarker of accelerated biological aging that is associated with later health impairment, in a sample of children with trauma histories. Within this quasi-experimental, repeated-measures study, we examined epigenetic age acceleration at baseline and postintervention in a low-income sample of children receiving CPP treatment (n = 45; age range = 2-6 years; 76% Latino) compared with a weighted, propensity-matched community-comparison sample (n = 110; age range = 3-6 years; 40% Latino). Baseline epigenetic age acceleration was equivalent across groups. However, posttreatment, epigenetic age acceleration in the treatment group was lower than in the matched community sample. Findings highlight the potential for a dyadic psychosocial intervention to ameliorate accelerated biological aging in trauma-exposed children.

Annotation

The finding:
In this study, the authors found that child-parent psychotherapy in children that had been exposed to interpersonal trauma reduced epigenetic age acceleration compared to a historical control. They utilized a pediatric-specific epigenetic clock (PedBE clock) demonstrated to be effective using buccal swabs, as well as the broadly-used Horvath clock.

Strength and weaknesses:
Strengths of this study include pre- and post-intervention epigenetic measures in dyads undergoing structured psychotherapy treatment. Their conclusions are supported by the replication of findings across the PedBE and Horvath clocks. Weaknesses include the use of a non-randomized control group and a modest sample size.

Relevance:
These results suggest that psychotherapy for trauma in young children may protect against the biological and epigenetic sequalae of trauma on aging.

PUBLICATION #3 — Aging

Trauma, adversity, and biological aging: behavioral mechanisms relevant to treatment and theory.

Kyle J Bourassa, David A Sbarra.

Abstract: Transl Psychiatry. 2024 Jul 12;14(1):285. doi: 10.1038/s41398-024-03004-9.

Although stress and adversity are largely universal experiences, people exposed to greater hardship are at increased risk for negative health consequences. Recent studies identify accelerated biological aging as a mechanism that could explain how trauma and adversity gives rise to poor health, and advances in this area of study coincide with technological innovations in the measurement of biological aging, particularly epigenetic profiles consistent with accelerated aging derived from DNA methylation. In this review, we provide an overview of the current literature examining how adversity might accelerate biological aging, with a specific focus on social and health behaviors. The most extensive evidence in this area suggests that health-compromising behaviors, particularly smoking, may partially explain the association between adversity and accelerated aging. Although there is relatively less published support for the role of social behaviors, emerging evidence points to the importance of social connection as a mechanism for future study. Our review highlights the need to determine the extent to which the associations from adversity to accelerated aging are consistent with causal processes. As we consider these questions, the review emphasizes methodological approaches from the causal inference literature that can help deepen our understanding of how stress and trauma might result in poor health. The use of these methodologies will help provide evidence as to which behavioral interventions might slow aging and improve health, particularly among populations that more often experience adversity and trauma.

Annotation (unstructured)

This review provides an overview of the literature of the potential relationships between trauma, adversity, and biological aging, including metrics used for measuring aging, specific components of trauma and adversity that are associated with accelerated aging, and behavioral mechanisms that may be connecting adversity and aging. The review concludes by discussing methodologies that help with drawing causal inference, including randomized controlled trials and longitudinal studies.

Overall, the first part of the review provides an accessible overview of how stress and adversity may be related to biological aging that would be broadly of interest to the academy. The second half of the article provides a detail-oriented dive into specific methodologies that will be of interest primarily to clinical researchers interested in incorporating aging metrics into their studies.