%0 Journal Article %1 Ashour_2023 %A Ashour, DiyaaElDin %A Rebs, Sabine %A Arampatzi, Panagiota %A Saliba, Antoine-Emmanuel %A Dudek, Jan %A Schulz, Richard %A Hofmann, Ulrich %A Frantz, Stefan %A Cochain, Clément %A Streckfuß-Bömeke, Katrin %A Ramos, Gustavo Campos %D 2023 %I Oxford University Press (OUP) %J Cardiovascular Research %K myown %R 10.1093/cvr/cvad068 %T An interferon gamma response signature links myocardial aging and immunosenescence %U https://doi.org/10.1093%2Fcvr%2Fcvad068 %X Aims: Aging entails profound immunological transformations that can impact myocardial homeostasis and predispose to heart failure. However, preclinical research in the immune-cardiology field is mostly conducted in young healthy animals, which potentially weakens its translational relevance. Herein, we sought to investigate how the aging T-cell compartment associates with changes in myocardial cell biology in aged mice. Methods and results: We phenotyped the antigen-experienced effector/memory T cells purified from heart-draining lymph nodes of 2-, 6-, 12-, and 18-month-old C57BL/6J mice using single-cell RNA/T cell receptor (TCR) sequencing (sc-seq). Simultaneously, we profiled all non-cardiomyocyte cell subsets purified from 2- and 18-month-old hearts and integrated our data with publicly available cardiomyocyte sc-seq datasets. Some of these findings were confirmed at the protein level by flow cytometry. With aging, the heart-draining lymph node and myocardial T cells underwent clonal expansion and exhibited an up-regulated pro-inflammatory transcription signature, marked by an increased interferon-γ (IFN-γ) production. In parallel, all major myocardial cell populations showed increased IFN-γ responsive signature with aging. In the aged cardiomyocytes, a stronger IFN-γ response signature was paralleled by the dampening of expression levels of transcripts related to most metabolic pathways, especially oxidative phosphorylation. Likewise, induced pluripotent stem cells-derived cardiomyocytes (iPSC-CM) exposed to chronic, low grade IFN-γ treatment showed a similar inhibition of metabolic activity. Conclusions: By investigating the paired age-related alterations in the T cells found in the heart and its draining lymph nodes, we provide evidence for increased myocardial IFN-γ signaling with age, which is associated with inflammatory and metabolic shifts typically seen in heart failure.

@article{Ashour_2023, abstract = {Aims: Aging entails profound immunological transformations that can impact myocardial homeostasis and predispose to heart failure. However, preclinical research in the immune-cardiology field is mostly conducted in young healthy animals, which potentially weakens its translational relevance. Herein, we sought to investigate how the aging T-cell compartment associates with changes in myocardial cell biology in aged mice. Methods and results: We phenotyped the antigen-experienced effector/memory T cells purified from heart-draining lymph nodes of 2-, 6-, 12-, and 18-month-old C57BL/6J mice using single-cell RNA/T cell receptor (TCR) sequencing (sc-seq). Simultaneously, we profiled all non-cardiomyocyte cell subsets purified from 2- and 18-month-old hearts and integrated our data with publicly available cardiomyocyte sc-seq datasets. Some of these findings were confirmed at the protein level by flow cytometry. With aging, the heart-draining lymph node and myocardial T cells underwent clonal expansion and exhibited an up-regulated pro-inflammatory transcription signature, marked by an increased interferon-γ (IFN-γ) production. In parallel, all major myocardial cell populations showed increased IFN-γ responsive signature with aging. In the aged cardiomyocytes, a stronger IFN-γ response signature was paralleled by the dampening of expression levels of transcripts related to most metabolic pathways, especially oxidative phosphorylation. Likewise, induced pluripotent stem cells-derived cardiomyocytes (iPSC-CM) exposed to chronic, low grade IFN-γ treatment showed a similar inhibition of metabolic activity. Conclusions: By investigating the paired age-related alterations in the T cells found in the heart and its draining lymph nodes, we provide evidence for increased myocardial IFN-γ signaling with age, which is associated with inflammatory and metabolic shifts typically seen in heart failure.}, added-at = {2023-06-09T14:03:20.000+0200}, author = {Ashour, DiyaaElDin and Rebs, Sabine and Arampatzi, Panagiota and Saliba, Antoine-Emmanuel and Dudek, Jan and Schulz, Richard and Hofmann, Ulrich and Frantz, Stefan and Cochain, Clément and Streckfuß-Bömeke, Katrin and Ramos, Gustavo Campos}, biburl = {https://www.bibsonomy.org/bibtex/2aa9f7d96eb8a48cb0f2799f339a5993c/cusysmed}, day = 4, doi = {10.1093/cvr/cvad068}, interhash = {a5db425cb78e3cbb9598955bcb85f61d}, intrahash = {aa9f7d96eb8a48cb0f2799f339a5993c}, journal = {Cardiovascular Research}, keywords = {myown}, month = may, publisher = {Oxford University Press (OUP)}, timestamp = {2024-04-16T15:58:52.000+0200}, title = {An interferon gamma response signature links myocardial aging and immunosenescence}, url = {https://doi.org/10.1093%2Fcvr%2Fcvad068}, year = 2023 }