Nutrient-sensing GHS-R in macrophage reprogramming and inflamm-aging

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Summary This administrative supplement is in regard to Dr. Yuxiang Sun grant R01AG064869-01, titled “Nutrient- sensing GHS-R in macrophage reprogramming and inflamm-aging” (7/1/2019- 4/30/2024). During the funding period of this award, Dr. Sun's team has been very productive; they publish 7-8 peer-reviewed papers each year. They are the first to report the novel function of nutrient-sensing ghrelin signaling in inflamm-aging and demonstrate that ghrelin receptor GHS-R is a major metabolic regulator and immune sensor in aging and age- associated diseases (Aging Cell 2011; Aging 2014, Aging 2016, Adv Exp Med Biol. 2018, J of Gerontol. 2020, Aging 2021). A new manuscript from her lab regarding the generation and metabolic/immune characterization of myeloid-specific GHS-R knockout mice has been submitted to JCI. The results in this manuscript reveal that GHS-R, via an insulin signaling cascade, metabolically reprograms macrophage polarization to promote meta- inflammation. In addition, they have also made critical contributions to a Nature 2022 paper, which uncovers a novel effect of ghrelin in monocyte-associated wound repair. The exciting discovery of ghrelin signaling in aging immunity adds a new dimension to ghrelin biology (previously primarily known for energy metabolism), and have profound impact on both ghrelin and aging fields. Immunometabolism is a newly emerged frontier of biological research, relevant to vast physiological/pathological conditions. Their continued investigation of macrophage GHS-R in inflamm-aging and age-associated diseases will help to advance the understanding of aging immunity and to identify novel immunotherapeutic strategy to improve lifespan and healthspan. Dr. Sun's work is largely focused on immune cells such as macrophages, a high capacity flow cytometer is essential for immune cell studies. Due to institutional consolidation, the flow cytometer core has been re-located to a different campus 15-20 min drive away. In addition, the core service fee has become unsustainable, they are billed $3000-$4000/month. She did not budget core service fee in her original module budget because it was free before the relocation. The flow cytometer issue has posed a major setback for her team, and significantly hindered their efficiency and productivity. For the successful completion of the NIA R01 grant, Dr. Sun's team urgently needs a flow cytometer. Dr. Sun has obtained a favorable quote for a 4 laser 48 channel flow cytometer Cytek Aurora for $295,001. She is recently awarded an $150,000 equipment grant from AgriLife Research at Texas A&M University that can be used toward the flow cytometer. However, she still needs additional $145,001 for the purchase. Dr. Sun has consulted my PO, Dr. Mulualem Tilahun. Here she is submitting this administrative supplement application to seek NIA's support of $145,001. This critically needed equipment will have paramount impacts on the success of this project and her collaborators/colleagues, as well as the education and career advancement of her trainees.