Contents lists available at ScienceDirect Psychoneuroendocrinology journal homepage: www.elsevier.com/locate/psyneuen Psychological well-being and gene expression in Korean adults: The role of age Sung-Ha Lee a, *, Incheol Choi a,b, *, Eunsoo Choi c , Minha Lee b , Yuri Kwon b , Bumjo Oh d , Steven W. Cole e a Center for Happiness Studies, Seoul National University, Seoul, South Korea b Department of Psychology, Seoul National University, Seoul, South Korea c Department of Psychology, Korea University, Seoul, South Korea d Department of Family Medicine, SMG- SNU Boramae Medical Center, South Korea e Department of Psychiatry and Biobehavioral Sciences, Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, United States ARTICLE INFO Keywords: Social genomics CTRA Psychological well-being Subjective well-being Ageing effect Autonomy ABSTRACT Background: Happiness has traditionally been thought to comprise two parts - pleasure (hedonia) and meaning (eudaimonia). Even though the two types of happiness are correlated, genomics studies have found distinct transcriptional correlates of hedonia and eudaimonia, particularly in the Conserved Transcriptional Response to Adversity (CTRA) marked by up-regulation of proinflammatory genes and down-regulation of interferon-related genes. Eudaimonia has been associated with reduced CTRA gene expression in several studies, whereas hedonia shows no consistent association with the CTRA. However, most of these social genomics studies have been conducted in Western cultures with Caucasian samples, so it is unclear if these findings extended to non-Western cultures with other ethnic groups. Moreover, it is unknown whether age might modify the association between CTRA gene expression and eudaimonia. To this end, we examined in a sample of Koreans the relationship between CTRA profiles and measures of hedonia and eudaimonia, as well as the role of age in modulating the strength of those relationships. Methods: Blood samples were collected from 152 healthy Korean adults (mean age = 44.64; 50 % female). Well- being was measured using the Mental Health Continuum short form (MHC-SF), Ryff Scales of Psychological Well- being (PWB), and subjective well-being (SWB) scales. RNA transcriptome profiles were obtained by RNA se- quencing. Mixed effect linear model analyses examined the association between CTRA gene expression and measures of MHC-SF, SWB, PWB (total scores and six subscales) and additional analyses examined a possible moderating role of age. Results: CTRA gene expression was significantly downregulated in association with the MHC-SF eudaimonic scores as well as the PWB total scores. Among the six domains of PWB, autonomy showed the strongest inverse correlation with CTRA profiles. Moreover, the inverse association between CTRA and PWB was stronger for older participants. Conclusion: Eudaimonia is associated with reduced CTRA gene expression in a Korean population, with parti- cularly marked relationships for autonomy. Findings also suggest that aging with meaning may bring biological advantage in later life. 1. Introduction Adverse environmental circumstances can trigger biological re- sponses throughout the body, including changes in gene expression. One example of this is a gene regulatory response that occurs in white blood cells (leukocytes), known as the Conserved Transcriptional Response to Adversity (CTRA) (Cole, 2019). The CTRA is characterized by increased expression of genes involved in inflammation and de- creased expression of genes involved in Type I interferon-mediated antiviral responses (Cole, 2013, 2014, 2018; Slavich and Cole, 2013). This pattern has been observed across different adverse social condi- tions such as loneliness, chronic stress, and post-traumatic stress dis- order (Cole, 2010; Kohrt et al., 2016). The CTRA response results in part from a signaling pathway where the sympathetic nervous system https://doi.org/10.1016/j.psyneuen.2020.104785 Received 30 November 2019; Received in revised form 17 June 2020; Accepted 22 June 2020 ⁎ Corresponding authors at: Center for Happiness Studies, Seoul National University, Bldg. 220, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea. E-mail addresses: lsh80@snu.ac.kr (S.-H. Lee), ichoi@snu.ac.kr (I. Choi). Psychoneuroendocrinology 120 (2020) 104785 0306-4530/ © 2020 Elsevier Ltd. All rights reserved. T