Comparative Fibroblast Physiology Identifies High-Altitude Specializations in Gelada

Mammals occupy diverse environments and face many physiological challenges, such as hypoxia. Several species, including certain human populations, have acclimated to high-altitude, chronically low-oxygen conditions. However, human high-altitude populations arose roughly 46,000 years ago, whereas other species, including primates like the gelada (Theropithecus gelada), have lived at elevations of 2,350-4,550m in the Ethiopian Highlands for at least 1 million years. Geladas exhibit a combination of morphological and physiological traits associated with altitude adaptation, including larger chest dimensions, reduced hemoglobin concentrations, and increased selection in hypoxia-related genes. To investigate the cellular mechanisms underlying hypoxia tolerance in geladas, we isolated dermal fibroblasts from ear biopsies collected from wild individuals (n = 25) in Ethiopia as part of the Simien Mountains Gelada Research Project. These cells were compared to dermal fibroblasts from sea-level humans (ATCC), and we also included fibroblasts from fat-tailed dwarf lemurs. Using an Amplex Red assay, we measured reactive oxygen species (ROS) production across species. Under baseline normoxic conditions (21% O 2 ), gelada fibroblasts generated 91% less ROS than human fibroblasts, suggesting a mechanism to limit hypoxia-induced cellular damage. Under hypoxic conditions (0.5% O 2 ), gelada fibroblasts produced 39% less ROS than humans (n=2) and 72% less than lemurs (n=1). We also assessed HIF1α accumulation by western blot following 6 hours of hypoxia (0.5% O 2 ) and found that gelada HIF1α accumulation was ~⅓ human levels, consistent with enhanced hypoxia tolerance. Future work will expand biological replication and incorporate additional comparison groups, including lowland baboons and high-altitude human populations. Funded by NSF 2022046 & NSF SBE-2010309. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.