In a recent study published in the journal Nature Human Behavior, researchers evaluated the causal effects of mental well-being on genetically independent aging phenotype (aging GIP).
Human life expectancy has increased over time; however, the aging population presents challenges to individuals and society. Mental well-being correlates with lifestyle behaviors and morbidity. Studies have linked mental well-being with physical health and increased survival. Besides, socioeconomic status (SES) is interlinked with aging and mental well-being. However, a causal relationship between healthy aging and mental well-being has yet to be established.
Study: Mendelian randomization evidence for the causal effect of mental well-being on healthy aging. Image Credit: Darren Baker / Shutterstock
About the study
In the present study, researchers assessed the effects of mental well-being on aging phenotypes. This Mendelian randomization (MR) study evaluated the causal associations between aging phenotypes and mental well-being traits and screened candidate mediators in the relationship between aging GIP and the well-being spectrum. Besides, the team also explored whether the causal effects were SES-independent.
Summary-level genome-wide association study (GWAS) data were derived from people of European descent. Exposures included the well-being spectrum, life satisfaction, neuroticism, depressive symptoms, and positive affect. The covariates were three SES indicators – education, occupation, and income. Overall, 106 candidate mediators were identified for screening; mediators included 23 lifestyle factors, 20 physical function traits, 53 diseases, and 10 behaviors and performances.
Mediators were selected based on a set of criteria: the mediator should have a causal association with aging GIP and direct causal effect independent of the well-being spectrum; the well-being spectrum should have a causal association with the mediator (and not vice versa); the association of the mediator with aging GIP and that of well-being spectrum with mediator should be in the same direction.
Outcomes included the aging GIP and its components (self-rated health, resilience, longevity, healthspan, and parent lifespan). Linkage disequilibrium score regression was performed to examine genetic correlations between mental well-being traits, aging phenotypes, and SES indicators. Univariable MR (UVMR) analysis assessed the causal effect of mediators and mental well-being traits on aging phenotypes.
UVMR and multivariable MR (MVMR) analyses were performed to investigate the causal effects of SES indicators on mental well-being traits. MVMR analysis, adjusted for SES indicators, examined the direct impact of the well-being spectrum on aging phenotypes. A two-step MR analysis tested the mediating effect(s) between the well-being spectrum and aging GIP.
Findings
Genetic correlations were observed between all mental well-being traits and the aging GIP and its components, except for longevity. The well-being spectrum was associated with an increased aging GIP. Consistently, the well-being spectrum showed positive causal associations with resilience, healthspan, parental lifespan, and self-rated health.
Positive affect and life satisfaction were positively associated with these aging phenotypes, while depressive symptoms and neuroticism were inversely associated. SES indicators and well-being traits were also correlated. Higher-income, education, and occupation were causally associated with improved mental well-being. The well-being spectrum was independently associated with higher aging GIP, adjusted for SES indicators.
Of the 106 candidate mediators, 33 met the screening criteria and were included. Unhealthier lifestyle factors, physical functions, and behaviors, and performances were associated with lower aging GIP. Later smoking initiation age and higher cheese consumption, appendicular lean mass (ALM), cognitive performance, high-density lipoprotein cholesterol (HDL-C), and fresh fruit intake were associated with higher aging GIP.
Heart failure, hypertension, stroke, and coronary heart disease had the highest effect sizes on the aging GIP. Antihypertensive medication, smoking initiation age, and television watching time individually mediated at least 7% of the effect of the well-being spectrum on the aging GIP. Non-steroidal anti-inflammatory drugs, waist-to-hip ratio, fresh fruit intake, ALM, HDL-C, triglycerides, and age at menarche individually mediated up to 4.81% of the total effect.
Conclusions
In sum, the study illustrated the causal effects of mental well-being on aging phenotypes independent of SES. Better mental well-being was associated with improved aging GIP. The causal effect was partly explained by 33 mediators, including lifestyles, physical functions, diseases, and behaviors and performances. Overall, the results highlight the need to prioritize mental well-being for healthy aging.
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