Inflammaging
Research topic(s)
One hallmark of biological aging is the increased occurrence of a chronic, sterile and low-grade inflammation, commonly known as inflammaging, which is involved in the development of age-associated diseases like dementia, osteoporosis or cancer. Our recent results show that inflammaging is associated with a shift in the biosynthesis of lipid mediators from specialized pro-resolving mediators (SPMs) towards pro-inflammatory prostaglandins and leukotrienes.
In this project we use metabololipidomic profiling to establish biomarkers for both healthy aging and inflammaging. We investigate the molecular and cellular mechanisms underlying inflammaging with focus on lipid mediators produced in innate immune cells, especially macrophages with distinct phenotypes. In this context we will elucidate the expression of lipoxygenases, cyclooxygenases and glutathione peroxidases and evaluate connected formation of various lipid mediators that regulate all stages of inflammation. In collaboration with other groups at the ZAJ, we also study immunomodulatory lipid mediators, cytokines, and chemokines released from tissue-resident macrophages in various body liquids and organs of several model organisms. Additionally, we aim to modulate the metabololipidome through the application of defined chemical tool compounds in order to identify strategies to intervene in the process of inflammaging.
Methods
- Human primary monocytes, macrophages and neutrophils.
- UPLC-MS-MS
- RP-HPLC
- Flow cytometry
- Immunofluorescence microscopy
- RT-PCR, Western blot
Selected Publications
Schädel P, Troisi F, Czapka A, Gebert N, Pace S, Ori A, Werz O. (2021) Aging drives organ-specific alterations of the inflammatory microenvironment guided by immunomodulatory mediators in mice.External link FASEB J, 35(5):e21558
Espada L, Dakhovnik A, Chaudhari P, Martirosyan A, Miek L, Poliezhaieva T, Schaub Y, Nair A, Döring N, Rahnis N, Werz O, Koeberle A, Kirkpatrick J, Ori A, Ermolaeva M. (2020) Loss of metabolic plasticity underlies metformin toxicity in aged Caenorhabditis elegansExternal link. Metab, 2, 1316-1331
Jordan PM, Gerstmeier J, Pace S, Bilancia R, Rao Z, Börner F, Miek L, Gutiérrez-Gutiérrez O, Arakandy V, Rossi A, Ialenti A, González-Estévez C, Löffler B, Tuchscherr L, Serhan CN, Werz O. (2020) Staphylococcus aureus-derived α-hemolysin evokes generation of specialized pro-resolving mediators promoting inflammation resolution.External link Cell Rep, 33: 108247.
Gilbert NC, Gerstmeier J, Schexnaydre EE, Börner F, Garscha U, Neau DB, Werz O*, Newcomer ME* (2020) Structural and mechanistic insights into 5-lipoxygenase inhibition by natural products.External link Chem Biol, 16: 783-790.
Werz O, Gerstmeier J, Libreros S, De la Rosa X, Werner M, Norris PC, Chiang N, Serhan CN (2018) Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity.External link Nat Commun, 9: 59.
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