Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-κB–driven inflammation and cardiovascular risk, 2019, Zannas et al.

Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-κB–driven inflammation and cardiovascular risk

Anthony S. Zannas,a,b,c,d,1 Meiwen Jia,a Kathrin Hafner,a Jens Baumert,e Tobias Wiechmann,a Julius C. Pape,a Janine Arloth,a,f Maik Ködel,a Silvia Martinelli,a Maria Roitman,a Simone Röh,a Andreas Haehle,g Rebecca T. Emeny,h Stella Iurato,a Tania Carrillo-Roa,a Jari Lahti,i,j Katri Räikkönen,i Johan G. Eriksson,k,l Amanda J. Drake,m Melanie Waldenberger,e Simone Wahl,e Sonja Kunze,e Susanne Lucae,a Bekh Bradley,n,o Christian Gieger,e Felix Hausch,g Alicia K. Smith,o,p Kerry J. Ressler,o,q,r Bertram Müller-Myhsok,a,s,t Karl-Heinz Ladwig,e,u Theo Rein,a Nils C. Gassen,a,v and Elisabeth B. Bindera,o,1

Significance

Diseases of the aging are the leading cause of morbidity and mortality. Elucidating the molecular mechanisms through which modifiable factors, such as psychosocial stress, confer risk for aging-related disease can have profound implications. By combining studies in humans with experiments in cells, we show that aging and stress synergize to epigenetically upregulate FKBP5, a protein implicated in stress physiology. Higher FKBP5 promotes inflammation by activating the master immune regulator NF-κB, whereas opposing FKBP5, either genetically or pharmacologically, prevents the effects on NF-κB. Further, the aging/stress-related epigenetic signature of FKBP5 is associated with history of myocardial infarction, a disease linked to inflammation. These findings provide molecular insights into stress-related disease, pointing to biomarker and treatment possibilities.

Keywords: aging, epigenetics, FKBP5, inflammation, psychosocial stress

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561294/