TY  - JOUR
A1  - Valbuena Perez, Jenny Vanessa
A1  - Linnenberger, Rebecca
A1  - Dembek, Anna
A1  - Bruscoli, Stefano
A1  - Riccardi, Carlo
A1  - Schulz, Marcel Holger
A1  - Meyer, Markus Robert
A1  - Kiemer, Alexandra Kathrin
A1  - Hoppstädter, Jessica
T1  - Altered glucocorticoid metabolism represents a feature of macroph-aging
T2  - Aging cell
N2  - The aging process is characterized by a chronic, low‐grade inflammatory state, termed “inflammaging.” It has been suggested that macrophage activation plays a key role in the induction and maintenance of this state. In the present study, we aimed to elucidate the mechanisms responsible for aging‐associated changes in the myeloid compartment of mice. The aging phenotype, characterized by elevated cytokine production, was associated with a dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis and diminished serum corticosteroid levels. In particular, the concentration of corticosterone, the major active glucocorticoid in rodents, was decreased. This could be explained by an impaired expression and activity of 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1), an enzyme that determines the extent of cellular glucocorticoid responses by reducing the corticosteroids cortisone/11‐dehydrocorticosterone to their active forms cortisol/corticosterone, in aged macrophages and peripheral leukocytes. These changes were accompanied by a downregulation of the glucocorticoid receptor target gene glucocorticoid‐induced leucine zipper (GILZ) in vitro and in vivo. Since GILZ plays a central role in macrophage activation, we hypothesized that the loss of GILZ contributed to the process of macroph‐aging. The phenotype of macrophages from aged mice was indeed mimicked in young GILZ knockout mice. In summary, the current study provides insight into the role of glucocorticoid metabolism and GILZ regulation during aging.
KW  - cellular immunology
KW  - cytokines
KW  - inflammation
KW  - mononuclear cell
KW  - mouse models
KW  - reactive oxygen species
KW  - steroid control of aging
KW  - TSC22D3
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/56228
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-562287
SN  - 1474-9726
VL  - 19
IS  - 6, Art. e13156
PB  - Wiley-Blackwell
CY  - Oxford [u.a.]
ER  -