SUN-091 Age-related Immunosenescence In Bgh Mice: Insights From The Spleen And Bone Marrow

Abstract Disclosure: B. Bashir: None. F. Benencia: None. S. Duran Ortiz: None. F. Brown: None. E.O. List: None. J.J. Kopchick: None. D.E. Berryman: None. Aging is an inevitable pathophysiological process that leads to progressive immune dysfunction known as immunosenescence. With the increasing size of the aging population, understanding immunosenescence is crucial, as it contributes to increased vulnerability to metabolic, infectious, and autoimmune conditions with age. Interestingly, growth hormone (GH) action has been shown to correlate with aging, e.g., excess GH shortens lifespan in bovine GH transgenic (bGH) mice, while no GH action due to disruption of the GH receptor gene (GHR-/- mice) results in the longest-lived laboratory mouse on record. Because GH receptors are highly expressed in immune cells (particularly B cells, macrophages, and T cells) and undergo age-related changes that impact immune function, we hypothesize that excess GH action positively correlates with immune aging and immunosenescence. This study aimed to characterize differences in B cell populations within lymphoid organs of young (3 months) and aged (12-13 months of age) bGH mice compared to wild-type controls. Single-cell suspensions were prepared from harvested spleens and bone marrow, followed by B cell staining with fluorophore-conjugated monoclonal antibodies and analysis by multicolor flow cytometry. bGH mice showed a significantly larger spleen as compared to age-matched WT controls for both ages and sexes, even when normalized to body weight. No significant differences in B cell populations were observed in the young cohort. However, aged bGH mice showed a decrease in anti-inflammatory follicular (FO) B cells and an increase in pro-inflammatory aging-associated B cells (ABCs) in both spleen and bone marrow compared to age-matched WT controls. In conclusion, bGH mice showed shifts in the lymphocyte population that are characteristic of premature aging, suggesting that excess GH action accelerates immunosenescence. These findings suggest the potential therapeutic use of the drug that decreases GH action, such as the GH antagonist, Pegvisomant (FDA-approved drug to treat acromegaly), to mitigate immune aging and improve various aspects of healthspan. Acknowledgments: This work is supported in part by the NIH grant AG059779, and the State of Ohio’s Eminent Scholar Program includes a gift from Milton and Lawrence Goll Presentation: Sunday, July 13, 2025