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  • Haapanen, M. J.; Perälä, M. M.; Salonen, M. K.; Kajantie, E.; Simonen, M.; Pohjolainen, P.; Pesonen, A. K.; Räikkönen, K.; Eriksson, J. G.; von Bonsdorff, M. B. (2018)
    Background: Evidence suggests that early life stress (ELS) may extend its effect into adulthood and predispose an individual to adverse health outcomes. We investigated whether wartime parental separation, an indicator of severe ELS, would be associated with frailty in old age. Methods: Of the 972 participants belonging to the present sub-study of the Helsinki Birth Cohort Study, 117 (12. 0%) had been evacuated abroad unaccompanied by their parents in childhood during World War II. Frailty was assessed at a mean age of 71 years according to Fried's criteria. Results: Thirteen frail men (4 separated and 9 non-separated) and 20 frail women (2 separated and 18 non-separated) were identified. Compared to the non-separated men, men who had been separated had an increased relative risk ratio (RRR) of frailty (age-adjusted RRR 3.93, 95% CI 1.02, 15.11) that persisted after adjusting for several confounders. No associations were observed among women (RRR 0.62; 95% CI 0.13, 2.94). Conclusions: These preliminary results suggest that ELS might extend its effects not just into adulthood but also into old age, and secondly, that men may be more vulnerable to the long-term effects of ELS.
  • Alastalo, Hanna; von Bonsdorff, Mikaela B.; Räikkönen, Katri; Pesonen, Anu-Katriina; Osmond, Clive; Barker, David J. P.; Heinonen, Kati; Kajantie, Eero; Eriksson, Johan G. (2013)
  • Zannas, Anthony S.; Jia, Meiwen; Hafner, Kathrin; Baumert, Jens; Wiechmann, Tobias; Pape, Julius C.; Arloth, Janine; Ködel, Maik; Martinelli, Silvia; Roitman, Maria; Roeh, Simone; Haehle, Andreas; Emeny, Rebecca T.; Iurato, Stella; Carrillo-Roa, Tania; Lahti, Jari; Räikkönen, Katri; Eriksson, Johan G.; Drake, Amanda J.; Waldenberger, Melanie; Wahl, Simone; Kunze, Sonja; Lucae, Susanne; Bradley, Bekh; Gieger, Christian; Hausch, Felix; Smith, Alicia K.; Ressler, Kerry J.; Mueller-Myhsok, Bertram; Ladwig, Karl-Heinz; Rein, Theo; Gassen, Nils C.; Binder, Elisabeth B. (2019)
    Aging and psychosocial stress are associated with increased inflammation and disease risk, but the underlying molecular mechanisms are unclear. Because both aging and stress are also associated with lasting epigenetic changes, a plausible hypothesis is that stress along the lifespan could confer disease risk through epigenetic effects on molecules involved in inflammatory processes. Here, by combining large-scale analyses in human cohorts with experiments in cells, we report that FKBP5, a protein implicated in stress physiology, contributes to these relations. Across independent human cohorts (total n > 3,000), aging synergized with stress-related phenotypes, measured with childhood trauma and major depression questionnaires, to epigenetically up-regulate FKBP5 expression. These age/stress-related epigenetic effects were recapitulated in a cellular model of replicative senescence, whereby we exposed replicating human fibroblasts to stress (glucocorticoid) hormones. Unbiased genome-wide analyses in human blood linked higher FKBP5 mRNA with a proinflammatory profile and altered NF-kappa B-related gene networks. Accordingly, experiments in immune cells showed that higher FKBP5 promotes inflammation by strengthening the interactions of NF-kappa B regulatory kinases, whereas opposing FKBP5 either by genetic deletion (CRISPR/Cas9-mediated) or selective pharmacological inhibition prevented the effects on NF-kappa B. Further, the age/stress-related epigenetic signature enhanced FKBP5 response to NF-kappa B through a positive feedback loop and was present in individuals with a history of acute myocardial infarction, a disease state linked to peripheral inflammation. These findings suggest that aging/stress-driven FKBP5-NF-kappa B signaling mediates inflammation, potentially contributing to cardiovascular risk, and may thus point to novel biomarker and treatment possibilities.
  • Khulan, B.; Manning, J. R.; Dunbar, D. R.; Seckl, J. R.; Raikkonen, K.; Eriksson, J. G.; Drake, A. J. (2014)
  • Berger, Eloise; Castagne, Raphaele; Chadeau-Hyam, Marc; Bochud, Murielle; D'Errico, Angelo; Gandini, Martina; Karimi, Maryam; Kivimäki, Mika; Krogh, Vittorio; Marmot, Michael; Panico, Salvatore; Preisig, Martin; Ricceri, Fulvio; Sacerdote, Carlotta; Steptoe, Andrew; Stringhini, Silvia; Tumincy, Rosario; Vineis, Paolo; Delpierrel, Cyrille; Kelly-Irving, Michelle (2019)
    Chronic inflammation has been proposed as having a prominent role in the construction of social inequalities in health. Disentangling the effects of early life and adulthood social disadvantage on inflammation is key in elucidating biological mechanisms underlying socioeconomic disparities. Here we explore the relationship between socioeconomic position (SEP) across the life course and inflammation (as measured by CRP levels) in up to 23,008 participants from six European cohort studies from three countries conducted between 1958 and 2013. We find a consistent inverse association between SEP and CRP across cohorts, where participants with a less advantaged SEP have higher levels of inflammation. Educational attainment is most strongly related to inflammation, after adjusting for health behaviours, body mass index and later-in-life SEP. These findings suggest socioeconomic disadvantage in young adulthood is independently associated with later life inflammation calling for further studies of the pathways operating through educational processes.
  • Lähdepuro, Anna; Savolainen, Katri; Lahti-Pulkkinen, Marius; Eriksson, Johan G.; Lahti, Jari; Tuovinen, Soile; Kajantie, Eero; Pesonen, Anu-Katriina; Heinonen, Kati; Räikkönen, Katri (2019)
    Early life stress (ELS) may increase the risk of anxiety throughout the life course. Whether this effect extends to late adulthood is poorly known. In our study comprising 1872 participants from the Helsinki Birth Cohort Study born in 1934-1944, we investigated the association of various forms of ELS and their accumulation with self-reported anxiety symptoms at the age of 65-77 years. Data on childhood socioeconomic status and separation from parents were based on national registers for all participants. Information on self-reported emotional and physical trauma, parental divorce, and death of a family member in childhood was obtained from 1277 participants. We found that experiencing emotional trauma, physical trauma, and low socioeconomic status in childhood were associated with increased anxiety symptoms in late adulthood [B = 0.44 (95% CI = 0.31-0.58); B = 0.33 (95%CI = 0.20-0.46); B = 0.10 (95%CI = 0.01-0.19), respectively]. These associations remained significant even after controlling for other forms of ELS. Accumulation of early life stress also increased the levels of late-adulthood anxiety symptoms and the risk of anxiety regarded as clinically significant. Screening for potentially stressful childhood experiences in elderly populations may help identifying individuals with increased anxiety symptoms and planning preventive and therapeutic interventions for those exposed to ELS.