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Alterations of oxygen metabolism with aging, especially decreased levels of O\n                    <jats:sub>2<\/jats:sub>\n                    with age resulting from endocrine and cardiovascular dysfunction as well as desensitization of cellular response to hypoxia, may exacerbate inflammaging, which in turn creates further oxygen metabolic dysfunction. During aging, decline in levels of erythrocyte 2,3-bisphosphoglycerate (2,3-BPG), BPG mutase, and adenosine A2B receptor, a key adenosine signaling receptor that can augment 2,3-BPG expression, may fail to protect sensitive brain tissue from subtly reduced O\n                    <jats:sub>2<\/jats:sub>\n                    levels, in turn resulting in increased numbers of activated microglia and secretion of proinflammatory cytokines, ultimately promoting inflammaging and senescence of endothelial cells. Interventions to restore O\n                    <jats:sub>2<\/jats:sub>\n                    levels directly or via increasing 2,3-BPG may help promote cognitive health in old age, but significant work to quantify the degree of reduced O\n                    <jats:sub>2<\/jats:sub>\n                    during aging in mammals, and especially humans, needs to be pursued.\n                  <\/jats:p>","DOI":"10.1089\/rej.2021.0051","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T13:04:18Z","timestamp":1627391058000},"page":"319-324","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Response to Hypoxia in Cognitive Decline"],"prefix":"10.1177","volume":"24","author":[{"given":"James W.","family":"Larrick","sequence":"first","affiliation":[{"name":"Panorama Research Institute and Regenerative Sciences Institute, Sunnyvale, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmine W.","family":"Larrick","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Immunology, University of California, San Francisco, San Francisco, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew R.","family":"Mendelsohn","sequence":"additional","affiliation":[{"name":"Panorama Research Institute and Regenerative Sciences Institute, Sunnyvale, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"e_1_3_3_2_2","volume-title":"Biochemistry, Hemoglobin Synthesis","author":"Farid Y","unstructured":"Farid Y, , Bowman NS, , Lecat P. 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