Positive social factors may slow biological aging, but this has yet to be rigorously tested. This study investigated whether baseline levels or changes over time in social support and contact ...frequency prospectively predicted epigenetic age.
Health and Retirement Study participants (N = 1912, 46.3 % male, aged 42–87 at baseline) reported longitudinal social support and contact frequency data up to 3 times between 2006 and 2016 and provided blood in 2016. Baseline levels (intercepts) and changes over time (slopes) in social support from and contact frequency with spouses, children, friends, and other family were outputted from multilevel models and used to predict epigenetic age, estimated from Horvath, Hannum, GrimAge, PhenoAge, and Dunedin Pace of Aging.
In models adjusted for demographic and health characteristics, higher baseline levels of support from and contact frequency with friends were prospectively associated with a slower Pace of Aging (support: p = .002; contact: p = 0.009) and a lower GrimAge (contact: p = .001). In addition, higher contact frequency with children at baseline was prospectively associated with a lower GrimAge (p < .001), and higher contact frequency with family at baseline and an increase in family contact over time was associated with a lower Hannum age (baseline: p = .005; slope: p = .015).
Perceived support from and contact with close others, particularly friends, may have implications for healthy biological aging. Notably, the effect sizes for friends were comparable to the effect of body mass index on epigenetic age. Positive social factors were generally associated with second- and third-generation clocks, which may be more sensitive to psychosocial factors than first-generation clocks.
•It is unknown whether positive social factors predict slower biological aging.•We examined links between social support, contact frequency, and epigenetic age.•More social support from friends predicted younger epigenetic age.•More contact with children, friends, and family predicted younger epigenetic age.•Social factors were more consistently linked to GrimAge and Pace of Aging clocks.
Stress and immunological aging Reed, Rebecca G
Current opinion in behavioral sciences,
08/2019, Volume:
28
Journal Article
Peer reviewed
Open access
•Aging is accompanied by declines in immune function and increases in inflammation.•Stress in several domains is associated with immunological aging.•Biological pathways connecting stress and ...immunological aging are reviewed.•Protective factors include health behaviors, intra-personal and inter-personal resources.•Future work on stress resilience and healthy immune aging may extend healthspan.
Immunological aging, which encompasses age-associated declines in the immune system (immunosenescence) and increases in inflammation (inflammaging), is associated with morbidity and mortality. A growing body of research suggests stress is one factor that may accelerate immunological aging. This article provides a brief overview of immunological aging, describes key biological pathways acting at multiple lifespan stages linking stress and immunological aging, and reviews recent innovative work characterizing associations between stress in several domains and immunological aging, as well as potential protective and risk factors. Important directions for future research include careful characterizations of the complexities of stress and rigorous measurement of immunological aging processes. Advancing knowledge of stress resilience and healthy immune aging may ultimately slow disease onset and extend healthspan.
•Remote dried blood spot (DBS) self-collection in older adults is highly feasible.•Remote DBS yields high-quality spots, sufficient for assaying multiple biomarkers, with high participant ...adherence.•Inflammatory markers (CRP, IL-6, TNF-α) from self-collected DBS are reliable and valid.
Dried blood spots (DBS) provide a minimally invasive method to assess inflammatory markers and can be collected remotely at-home or in-person in the lab. However, there is a lack of methodological information comparing these different collection methods and in older adults. We investigated the feasibility (including adherence, yield, quality, and participant preferences) and measurement properties (reliability, validity) of remotely collected DBS inflammatory markers in older adults. Participants (N = 167, mean age = 72, range: 60–96 years) collected their own DBS (finger prick on filter paper) during three remote interviews over ∼ 6 months. Within 4–5 days on average of their last remote interview, a subset of 41 participants also attended an in-person lab visit that included a researcher-collected DBS sample, venous blood draw, and survey to assess participant preferences of DBS collection. DBS and venous blood were assayed for CRP, IL-6, and TNF-α. Adherence: 98% of expected DBS samples (493 out of 501) were completed and mailed back to the lab. Yield: 97% of DBS samples were sufficient for all assays. Quality: On average, 0.80 fewer optimal spots (60uL of blood that filled the entire circle) were obtained remotely vs. in-person (p = 0.013), but the number of useable or better spots (at least 30-40uL of blood) did not differ (p = 0.89). Preference: A slight majority of participants (54%) preferred in-person DBS collection. Reliability: DBS test–retest reliabilities were good: CRP (ICC = 0.74), IL-6 (ICC = 0.76), and TNF-α (ICC = 0.70). Validity: Inflammatory levels from DBS correlated strongly with levels from venous blood (r = 0.60-0.99) and correlated as expected with sociodemographic and physical health and function variables. Older adults can remotely collect their own DBS to acquire reliable and valid inflammatory data. Remote DBS collection is highly feasible and may allow for inflammatory markers to be assessed in larger, more representative samples than are possible with lab- or clinic-based research designs.
Objective: In a midlife sample of adults, the present study tested the extent to which changes in psychological stress relate to the progression of subclinical cardiovascular disease over multiple ...years and explored the potential moderating role of cardiometabolic risk. Method: Participants were screened to exclude those with clinical cardiovascular, respiratory, metabolic, and other chronic illnesses, as well as those taking psychotropic, cardiovascular, lipid, and glucose control medications. At baseline (N = 331) and then again at follow-up an average of 3 years later (N = 260), participants completed the 10-item Perceived Stress Scale, underwent assessments of their cardiometabolic risk, and underwent ultrasonography to measure carotid artery intima-media thickness (IMT), which is a surrogate indicator of subclinical atherosclerosis. Results: Regression models showed that the change in psychological stress from baseline to follow-up was positively associated with the corresponding change in IMT, with covariate control for age at baseline, sex at birth, and variability in length of follow-up across participants. Cardiometabolic risk factors did not statistically moderate this longitudinal association. In exploratory analyses, cardiometabolic risk factors also did not statistically mediate this association. Conclusion: These longitudinal findings suggest that increases in psychological stress in midlife relate to corresponding increases in subclinical atherosclerosis.
Objetivo: En una muestra de adultos de mediana edad, el estudio presente probó el grado en que los cambios en el estrés psicológico se relacionan con la progresión de la enfermedad cardiovascular subclínica durante varios años y exploró el posible papel moderador del riesgo cardiometabólico. Método: Los participantes fueron evaluados para excluir a aquellos con enfermedades clínicas cardiovasculares, respiratorias, metabólicas y otras enfermedades crónicas, así como a aquellos que tomaban medicamentos psicotrópicos, cardiovasculares, de lípidos y de control de glucosa. Al inicio (N = 331) y luego nuevamente en el seguimiento, un promedio de 3 años después (N = 262), los participantes completaron la Escala de Estrés Percibido de 10 ítems, se sometieron a evaluaciones de su riesgo cardiometabólico y a una ecografía para medir el grosor de íntima-media carotídeo (IMT por sus siglas en inglés), que es un indicador sustituto de la aterosclerosis subclínica. Resultados: Los modelos de regresión mostraron que el cambio en el estrés psicológico desde el inicio hasta el seguimiento se asoció positivamente con el cambio correspondiente en el IMT, con control de covariables para la edad al inicio, el sexo al nacer y la variabilidad en la duración del seguimiento entre los participantes. Los factores de riesgo cardiometabólico no moderaron estadísticamente esta asociación longitudinal. Conclusión: Estos hallazgos longitudinales sugieren que los aumentos en el estrés psicológico en la mediana edad se relacionan con los aumentos correspondientes en la aterosclerosis subclínica.
Public Significance StatementAmong midlife adults, increases in psychological stress were found to co-occur with increases in a marker of preclinical atherosclerosis in the carotid arteries over several years. These findings support future efforts to examine whether reducing psychological stress in midlife helps to protect against the progression of atherosclerosis and the later life risk of cardiovascular disease.
Between-partner physiological linkage can be in-phase (changes in unison), or anti-phase (changes in opposite directions). In the context of conversation we predicted that in-phase linkage would ...occur when partners exert strong influence on each other; anti-phase linkage would occur due to the behavioral coordination of turn taking. To test this, blood pressure, inter-beat interval, and skin conductance were recorded from 44 heterosexual couples while they discussed how they influence each other's health-related behaviors. Partner influence was assessed in two ways: 1) partners' global perceptions of how they try to influence each other's health; and 2) behavioral manifestations of influence, specifically demand–withdraw behavior. As predicted, both measures of partner influence moderated physiological linkage of blood pressure such that at low levels of influence linkage was “anti-phase” and at high levels linkage was “in-phase.” Several alternative hypotheses were ruled out; the effects were not due to relationship conflict, emotional experience, or simply the pattern of blood pressure over time. These results suggest that partner influence may be driving physiological linkage, which may be one avenue through which partners can affect each other's health.
► Negative partner influence moderated physiological linkage of blood pressure. ► At low levels of partner influence, linkage was anti-phase. ► At high levels of partner influence, linkage was in-phase or unsynchronized. ► Relationship conflict and emotional contagion did not moderate linkage. ► The pattern of blood pressure over time also did not moderate linkage.
Cytomegalovirus (CMV) and Toxoplasma gondii are organisms that may infect the brain and have cognitive and behavioral consequences. We hypothesized that these latent infections would be prospectively ...associated with poorer cognition and more problems in self-regulation among older adults.
Older adults (n = 138, mean age = 75.5 years, 59% women) had CMV and T. gondii serostatus tested, crystallized intelligence estimated (North American Adult Reading Test), and executive function (EF; e.g., Trail Making Test) and self-regulation (Behavior Regulation Inventory of Executive Function-Adult) assessed in visits occurring every 6 months (mean visits = 16).
CMV+ people (79%) had significantly poorer self-regulation versus CMV- people (21%; behavioral regulation: γ = 0.108, 95% confidence interval CI = 0.009-0.206; metacognition: γ = 0.117, 95% CI = 0.005-0.229), but not intelligence or EF. T. gondii+ people (24%) were not significantly different from T. gondii- people (76%) on any outcome. However, T. gondii+ men had better self-regulation versus T. gondii- men, and the opposite was true of women (behavioral regulation interaction: γ = 0.267, 95% CI = 0.093-0.441).
CMV latent infection was associated with more problems in self-regulation, and the magnitude of this difference was clinically significant. T. gondii latent infection was associated with more problems, but only for women. Latent infection might associate with self-regulation but not EF because of factors influencing self-regulation but not neuropsychological test performance, such as values and emotion. Efforts to link latent infection with EFs might, in the future, include the application of those functions to self-regulation in daily life.
Well-regulated emotions, both within people and between relationship partners, play a key role in facilitating health and well-being. The present study examined 39 heterosexual couples' joint weight ...status (both partners are healthy-weight, both overweight, 1 healthy-weight, and 1 overweight) as a predictor of 2 interpersonal emotional patterns during a discussion of their shared lifestyle choices. The first pattern, coregulation, is one in which partners' coupled emotions show a dampening pattern over time and ultimately return to homeostatic levels. The second, codysregulation, is one in which partners' coupled emotions are amplified away from homeostatic balance. We demonstrate how a coupled linear oscillator (CLO) model (Butner, Amazeen, & Mulvey, 2005) can be used to distinguish coregulation from codysregulation. As predicted, healthy-weight couples and mixed-weight couples in which the man was heavier than the woman displayed coregulation, but overweight couples and mixed-weight couples in which the woman was heavier showed codysregulation. These results suggest that heterosexual couples in which the woman is overweight may face formidable coregulatory challenges that could undermine both partners' well-being. The results also demonstrate the importance of distinguishing between various interpersonal emotional dynamics for understanding connections between interpersonal emotions and health.
The transcription factor BCL11A has recently been reported to be a driving force in triple-negative breast cancer (TNBC), contributing to the maintenance of a chemoresistant breast cancer stem cell ...(BCSC) population. Although BCL11A was shown to suppress γ-globin and p21 and to induce MDM2 expression in the hematopoietic system, its downstream targets in TNBC are still unclear. For its role in transcriptional repression, BCL11A was found to interact with several corepressor complexes; however, the mechanisms underlying these interactions remain unknown. Here, we reveal that BCL11A interacts with histone methyltransferase (PRC2) and histone deacetylase (NuRD and SIN3A) complexes through their common subunit, RBBP4/7. In fluorescence polarization assays, we show that BCL11A competes with histone H3 for binding to the negatively charged top face of RBBP4. To define that interaction, we solved the crystal structure of RBBP4 in complex with an N-terminal peptide of BCL11A (residues 2–16, BCL11A(2–16)). The crystal structure identifies novel interactions between BCL11A and the side of the β-propeller of RBBP4 that are not seen with histone H3. We next show that BCL11A(2–16) pulls down RBBP4, RBBP7, and other components of PRC2, NuRD, and SIN3A from the cell lysate of the TNBC cell line SUM149. Furthermore, we demonstrate the therapeutic potential of targeting the RBBP4–BCL11A binding by showing that a BCL11A peptide can decrease aldehyde dehydrogenase-positive BCSCs and mammosphere formation capacity in SUM149. Together, our findings have uncovered a previously unidentified mechanism that BCL11A may use to recruit epigenetic complexes to regulate transcription and promote tumorigenesis.
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. Cognitive Decliners (
= 24) were selected based on declines in a composite score derived from neuropsychological tests and matched with participants who did not show any decline, Maintainers (
= 24). Multilevel models with repeated DNAm measures within person tested the main effects of time, group, and group by time interactions. DNAm measures significantly increased over time generally consistent with elapsed time between study visits. There were also group differences: overall, Cognitive Decliners had an older PC-GrimAge and faster pace of aging (Dunedin PoAm, Dunedin PACE) than Cognitive Maintainers. There were no significant group by time interactions, suggesting accelerated epigenetic aging in Decliners remained constant over time. Older PC-GrimAge and faster pace of aging may be particularly sensitive to cognitive decline in midlife.
Objective: Women's financial resources were associated with more terminal maturity in natural killer lymphocytes, generally associated with loss of proliferative potential, during the "Great ...Recession". This preregistered analysis expanded on that finding in a longitudinal design including both genders and examining the role of cytomegalovirus (CMV) serostatus. Method: Older adults (N = 138, 57% women) were assessed longitudinally during 2012-2017; including self-reported psychological, social, financial, and status-skill resources, CMV antibody titers and serostatus, and assessment of T and natural killer lymphocyte terminal maturity (LTM). Results: Neither total nor financial resources were associated with LTM. Adjusting only for age, more psychological resources (e.g., meaning, hope, humor) were associated with lower T LTM (percent: γ = −1.11 −1.78, −.44; number: γ = −.99 −1.70, −.27). There were no significant interactions with age, gender, or CMV serostatus; however, additionally adjusting for serostatus reduced the effect of psychological resources (percent: γ = −.41 −93, .12; number: (γ = −.40 −.94, .13). Conclusions: Outside the context of the "Great Recession", psychological resources but not financial resources were associated with terminal maturity in T cells, a relationship related to CMV serostatus. Further studies in different and more diverse samples, and in different eras, are needed to understand what resources are most protective against immunological aging, when, and for whom.
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