Stress tests and biomarkers of resilience: Proceedings of the second state of resilience science conference.

The "Stress Tests and Biomarkers of Resilience" conference, hosted by the American Geriatrics Society and the National Institute on Aging, marks the second in a series aimed at advancing the field of resilience science. Held on March 4-5, 2024, in Bethesda, Maryland, this conference built upon the foundational work from the first conference, which focused on defining resilience across various domains-physical, cognitive, and psychosocial. This year's gathering centered around three factors: the biology that underlies resilient outcomes; the social, environmental, genetic, and psychosocial factors that impact that resilience biology; and the biomarker testing and imaging that predicts resilient outcomes for older adults.

Lifetime chronic stress exposures, stress hormones, and biological aging: Results from the Midlife in the United States (MIDUS) study.

Psychosocial stress and adversity have been linked to accelerated aging and increased risk for age-related diseases. Animal and in vitro studies have shown that exposure to stress hormones (catecholamines, glucocorticoids) can impact biological aging processes such as DNA damage and cellular senescence, suggesting they play a key role in links between stress and aging; however, these associations have not been well investigated in humans. We examined cross-sectional associations between chronic stress exposures, stress hormones, and biological aging markers in midlife adults and whether stress hormones mediated associations between stress and aging.

Transcriptomic markers of biological aging in breast cancer survivors: a longitudinal study.

Background: The purpose of this study was to examine the impact of breast cancer therapy on biological aging as measured by expression of genes for cellular senescence (p16INK4a, SenMayo), DNA damage response, and proinflammatory senescence-associated secretory phenotype.

Methods: This longitudinal, observational study evaluated women diagnosed with breast cancer (stage 0-III) prior to radiation therapy (RT) and/or chemotherapy (CT) and at repeated visits out to 2 years. Peripheral blood mononuclear cell gene expression was assessed using RNA sequencing on quality-verified RNA.

Pathways to maternal health inequities: Structural racism, sleep, and physiological stress.

Racial inequities in health are vast and well-documented, particularly regarding maternal and infant health. Sleep health, including but not limited to duration and quality, is central to overall health and well-being. However, research has not adequately addressed how racism embedded in structures and systems, in addition to individual experiences, may affect maternal health by impacting sleep.

Gerotherapeutics: Aging Mechanism-based Pharmaceutical and Behavioral Interventions to Reduce Cancer Racial and Ethnic Disparities.

The central premise of this article is that a portion of the established relationships between social determinants of health and racial/ethnic disparities in cancer morbidity and mortality are mediated through differences in rates of biological aging processes. We further posit that using knowledge about aging could enable discovery and testing of new mechanism-based pharmaceutical and behavioral interventions ("gerotherapeutics") to differentially improve the health of minoritized cancer survivors and reduce cancer disparities. These hypotheses are based on evidence that lifelong differences in adverse social determinants of health contribute to disparities in rates of biological aging ("social determinants of aging"), with minoritized groups having accelerated aging (ie, a steeper slope or trajectory of biological aging over time relative to chronological age) more often than non-minoritized groups.

Physical activity and cognition: longitudinal findings from the Thinking and Living with Cancer Study.

Background: Physical activity can improve cognition; however, little is known regarding the relationships between longitudinal objectively measured physical activity, cognition, and inflammation in older breast cancer survivors.

Methods: Older (aged 60 years and older) breast cancer survivors (n = 216) and frequency-matched noncancer control participants (n = 216) were assessed at baseline (presystemic therapy for survivors) and annually for up to 5 years. Assessments included hip-worn actigraphs worn for 7 days, neuropsychological tests, the Functional Assessment of Cancer Therapy-Cognitive Function perceived cognitive impairment subscale, and circulating levels of C-reactive protein and interleukin-6.

Alzheimer disease-related biomarkers and cancer-related cognitive decline: the Thinking and Living with Cancer study.

Purpose: We evaluated whether plasma Alzheimer disease (AD)-related biomarkers were associated with cancer-related cognitive decline among older breast cancer survivors.

Methods: We included survivors aged 60-90 years with primary stage 0-III breast cancers (n = 236) and frequency-matched noncancer control paricipant (n = 154) who passed a cognitive screen and had banked plasma specimens. Participants were assessed at baseline (presystemic therapy) and annually for up to 60 months.

Prediction of cognitive decline in older breast cancer survivors: the Thinking and Living with Cancer study.

Purpose: Cancer survivors commonly report cognitive declines after cancer therapy. Due to the complex etiology of cancer-related cognitive decline (CRCD), predicting who will be at risk of CRCD remains a clinical challenge. We developed a model to predict breast cancer survivors who would experience CRCD after systematic treatment.

Inequities in the Impacts of Hurricanes and Other Extreme Weather Events for Cancer Survivors.

In this minireview, we examine the impacts of hurricanes and other extreme weather events on cancer survivors, focusing on structural and social determinants of health. We briefly explore influences on biological, psychosocial, and behavioral outcomes and discuss risk and resilience factors in cancer survivorship during and after hurricanes. Our goal is to inform future directions for research that can identify areas in which we can most efficiently improve cancer outcomes and inform changes in health systems, clinical practice, and public health policies.

Evidence for the Association Between Adverse Childhood Family Environment, Child Abuse, and Caregiver Warmth and Cardiovascular Health Across the Lifespan: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Background: This study aimed to quantify the association between childhood family environment and longitudinal cardiovascular health (CVH) in adult CARDIA (Coronary Artery Risk Development in Young Adults) Study participants. We further investigated whether the association differs by adult income.

Methods: We applied the CVH framework from the American Heart Association including metrics for smoking, cholesterol, blood pressure, glucose, body mass index, physical activity, and diet.

Prenatal mood and anxiety disorders and associated cytokine changes.

Background: We examined whether women with prenatal mood and anxiety disorders would exhibit differential pro- and anti-inflammatory marker trajectories during the prenatal and postpartum periods compared to women without these disorders.

Methods: Approximately 179 pregnant women participated in a longitudinal study conducted in two urban areas. Blood samples for inflammatory markers were collected at six study visits.

Depressive symptom trajectories in older breast cancer survivors: the Thinking and Living with Cancer Study.

Purpose: To identify trajectories of depressive symptoms in older breast cancer survivors and demographic, psychosocial, physical health, and cancer-related predictors of these trajectories.

Methods: Recently diagnosed nonmetastatic breast cancer survivors (n = 272), ages 60-98 years, were evaluated for depressive symptoms (Center for Epidemiological Studies Depression Scale, CES-D; scores ≥16 suggestive of clinically significant depressive symptoms). CES-D scores were analyzed in growth-mixture models to determine depression trajectories from baseline (post-surgery, pre-systemic therapy) through 3-year annual follow-up.

Partner relationship quality and IL-6:IL-10 trajectories from pregnancy to a year after-birth.

Background: Inflammatory activity during pregnancy and the postpartum period shifts systematically due to pregnancy progression, delivery, and postpartum recovery. Factors that deregulate inflammatory activity increase the risk for adverse pregnancy outcomes and slower postpartum recovery. The IL-6:IL-10 or TNF-α:IL-10 ratio is potentially one way to capture peripheral inflammatory regulation; higher values indicate that anti-inflammatory IL-10 is less effective at regulating pro-inflammatory TNF-α or IL-6, skewing towards maladaptive pro-inflammatory profiles.

Social relationships and epigenetic aging in older adulthood: Results from the Health and Retirement Study.

Growing evidence suggests that social relationship quality can influence age-related health outcomes, although how the quality of one's relationships directly relates to the underlying aging process is less clear. We hypothesized that the absence of close relationships as well as lower support and higher strain within existing relationships would be associated with an accelerated epigenetic aging profile among older adults in the Health and Retirement Study. Adults (N = 3,647) aged 50-100 years completed ratings of support and strain in relationships with their spouse, children, other family members, and friends.

Short Sleep and Insomnia Are Associated With Accelerated Epigenetic Age.

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.

Parental Preconception Posttraumatic Stress Symptoms and Maternal Prenatal Inflammation Prospectively Predict Shorter Telomere Length in Children.

Objective: Parental trauma exposure and trauma-related distress can increase the risk of adverse health outcomes in offspring, but the pathways implicated in intergenerational transmission are not fully explicated. Accelerated biological aging may be one mechanism underlying less favorable health in trauma-exposed individuals and their offspring. This study examines the associations of preconception maternal and paternal posttraumatic stress disorder (PTSD) symptoms with child telomere length, and maternal prenatal C-reactive protein (CRP) as a biological mechanism.

Genetic Variants Associated with Longitudinal Cognitive Performance in Older Breast Cancer Patients and Controls.

There have been no published genome-wide studies of the genetics of cancer- and treatment-related cognitive decline (CRCD); the purpose of this study is to identify genetic variants associated with CRCD in older female breast cancer survivors. Analyses included white non-Hispanic women with non-metastatic breast cancer aged 60+ ( = 325) and age-, racial/ethnic group-, and education-matched controls ( = 340) with pre-systemic treatment and one-year follow-up cognitive assessment. CRCD was evaluated using longitudinal domain scores on cognitive tests of attention, processing speed, and executive function (APE), and learning and memory (LM).

Epigenetic aging in older breast cancer survivors and noncancer controls: preliminary findings from the Thinking and Living with Cancer Study.

Background: Cancer and its treatments may accelerate aging in survivors; however, research has not examined epigenetic markers of aging in longer term breast cancer survivors. This study examined whether older breast cancer survivors showed greater epigenetic aging than noncancer controls and whether epigenetic aging related to functional outcomes.

Methods: Nonmetastatic breast cancer survivors (n = 89) enrolled prior to systemic therapy and frequency-matched controls (n = 101) ages 62 to 84 years provided two blood samples to derive epigenetic aging measures (Horvath, Extrinsic Epigenetic Age [EEA], PhenoAge, GrimAge, Dunedin Pace of Aging) and completed cognitive (Functional Assessment of Cancer Therapy-Cognitive Function) and physical (Medical Outcomes Study Short Form-12) function assessments at approximately 24 to 36 and 60 months after enrollment.

Plasma levels of interleukin-6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study.

Background: Immune activation/inflammation markers (immune markers) were tested to explain differences in neurocognition among older breast cancer survivors versus noncancer controls.

Methods: Women >60 years old with primary breast cancer (stages 0-III) (n = 400) were assessed before systemic therapy with frequency-matched controls (n = 329) and followed annually to 60 months; blood was collected during annual assessments from 2016 to 2020. Neurocognition was measured by tests of attention, processing speed, and executive function (APE).

Remission of insomnia in older adults treated with cognitive behavioral therapy for insomnia (CBT-I) reduces p16 gene expression in peripheral blood: secondary outcome analysis from a randomized clinical trial.

Late life insomnia may increase risk for accelerated biological aging. Intervening to treat insomnia may provide protection from biological aging by reducing the prevalence of senescent cells in the immune system, as indicated by gene expression of a marker of cellular senescence, p16. In the present study, we determine whether treatment of insomnia in older adults with cognitive behavioral therapy for insomnia (CBT-I) would reduce p16 gene expression in peripheral blood mononuclear cells (PBMC), compared to a sleep education therapy (SET), an active comparator condition.

Childhood environment early life stress, caregiver warmth, and associations with the cortisol diurnal curve in adulthood: The coronary artery risk development in young adults (CARDIA) study.

Background: Early life stress (ELS) is associated with increased morbidity and mortality across the lifecourse. Studies observing a relationship between ELS and stress physiology (cortisol), may help explain the connection to poor health outcomes, but have been limited by cortisol measures used.

Purpose: We examined the association between ELS measured by a Risky Family (RF) environment questionnaire, and adult diurnal cortisol profile inclusive of multiple cortisol measures.

DNA methylation-based measures of biological aging and cognitive decline over 16-years: preliminary longitudinal findings in midlife.

DNA methylation-based (DNAm) measures of biological aging associate with increased risk of morbidity and mortality, but their links with cognitive decline are less established. This study examined changes over a 16-year interval in epigenetic clocks (the traditional and principal components [PC]-based Horvath, Hannum, PhenoAge, GrimAge) and pace of aging measures (Dunedin PoAm, Dunedin PACE) in 48 midlife adults enrolled in the longitudinal arm of the Adult Health and Behavior project (56% Female, baseline Age = 44.7 years), selected for discrepant cognitive trajectories.