| First Author | Flores RR | Year | 2017 |
| Journal | Aging Cell | Volume | 16 |
| Issue | 3 | Pages | 480-487 |
| PubMed ID | 28229533 | Mgi Jnum | J:241523 |
| Mgi Id | MGI:5902885 | Doi | 10.1111/acel.12571 |
| Citation | Flores RR, et al. (2017) Expansion of myeloid-derived suppressor cells with aging in the bone marrow of mice through a NF-kappaB-dependent mechanism. Aging Cell 16(3):480-487 |
| abstractText | With aging, there is progressive loss of tissue homeostasis and functional reserve, leading to an impaired response to stress and an increased risk of morbidity and mortality. A key mediator of the cellular response to damage and stress is the transcription factor NF-kappaB. We demonstrated previously that NF-kappaB transcriptional activity is upregulated in tissues from both natural aged mice and in a mouse model of a human progeroid syndrome caused by defective repair of DNA damage (ERCC1-deficient mice). We also demonstrated that genetic reduction in the level of the NF-kappaB subunit p65(RelA) in the Ercc1-/ progeroid mouse model of accelerated aging delayed the onset of age-related pathology including muscle wasting, osteoporosis, and intervertebral disk degeneration. Here, we report that the largest fraction of NF-kappaB -expressing cells in the bone marrow (BM) of aged (>2 year old) mice (C57BL/6-NF-kappaBEGFP reporter mice) are Gr-1+ CD11b+ myeloid-derived suppressor cells (MDSCs). There was a significant increase in the overall percentage of MDSC present in the BM of aged animals compared with young, a trend also observed in the spleen. However, the function of these cells appears not to be compromised in aged mice. A similar increase of MDSC was observed in BM of progeroid Ercc1-/ and BubR1H/H mice. The increase in MDSC in Ercc1-/ mice was abrogated by heterozygosity in the p65/RelA subunit of NF-kappaB. These results suggest that NF-kappaB activation with aging, at least in part, drives an increase in the percentage of MDSCs, a cell type able to suppress immune cell responses. |
