Cortical O2 supply and metabolism are suppressed in the aged mice

• 成果类型: Article
• 署名作者: Kang, Hongyi; Zhou, Sitong; Giannetto, Michael; Mcconnell, Evan D.; Kang, Ning; Sun, Qian; Zhao, Hetince; Wei, Helen S.; Kramer, Kevin; Guo, Yaojun; Costa, Juliana S.; Villeda, Saul A.; Nedergaard, Maiken; Wan, Jiandi
• 署名单位: University of Rochester; University of California System; University of California Davis; State University of New York (SUNY) System; Stony Brook University; Stony Brook University Hospital; University of Kentucky; University of California System; University of California Davis; University of California System; University of California San Francisco; University of California System; University of California San Francisco
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2522765123
• 发表日期: 2026-01-27
• 页码: e2522765123
• 关键词: cerebral blood; neurovascular coupling; capillary; microfluidic; neurodegeneration; cerebral-blood-flow; TRANSIT-TIME HETEROGENEITY; oxygen-consumption; VASCULAR CONTRIBUTIONS; MEMBRANE TRANSPORTERS; cognitive impairment; alzheimers-disease; BRAIN OXYGENATION; neuronal-activity; neural activity

摘要

Current evidence suggests that the rejuvenating effects of parabiosis on brain function arise from the exchange of blood factors that enhance synaptic plasticity, promote neurogenesis, and reduce neuroinflammation in aged animals. However, aging is also associated with diminished tissue oxygenation. Here, we report that erythrocytes (red blood cells, RBCs) from aged mice exhibit reduced responsiveness to low oxygen tension (PO2) and release O2 slower than those from young mice. In vivo, sensory stimulation evoked a smaller and delayed capillary RBC flow in aged mice. Although activity-evoked PO2 dips were diminished in aged mice; experimentally reducing PO2 to comparable levels did not restore capillary flow in aged mice, consistent with diminished RBC O2 responsiveness observed ex vivo. Notably, RBCs from aged mice in heterochronic parabiosis pairs (young-aged) displayed faster responses to low PO2 compared to those from aged mice in isochronic pairs (aged-aged). Together, these findings across multiple levels of analysis demonstrate that aging impairs RBC responsiveness to O2 and suggest that improved RBC-mediated O2 delivery contributes to the rejuvenating effects of parabiosis.