Core Viewpoint - The research identifies a new marker of aging related to impaired glucose metabolic reprogramming in red blood cells (RBCs) due to decreased BPGM enzyme activity, suggesting that inosine supplementation may improve RBC function and combat aging-related diseases [3][10]. Group 1: Aging and Health Implications - The rapid acceleration of population aging is placing immense pressure on global healthcare systems and creating economic burdens, with older adults being more susceptible to various diseases such as cardiovascular diseases, obesity, metabolic disorders, and neurodegenerative diseases [6]. - Aging-related diseases are often driven by tissue hypoxia, prompting extensive research into the cellular and molecular mechanisms of how tissues respond to hypoxia during aging [6][7]. Group 2: Mechanisms of Red Blood Cell Function - Mature RBCs, despite lacking a nucleus and complex organelles, can effectively promote oxygen release in both physiological and pathological low-oxygen environments due to strictly regulated metabolic reprogramming that does not rely on hypoxia-inducible factors (HIF) [7]. - The study reveals that the ability of RBCs to release oxygen declines with age, closely correlating with aging-related tissue dysfunction, and identifies a metabolic checkpoint involving reduced 2,3-BPG levels due to decreased BPGM activity [8][10]. Group 3: Inosine as a Potential Therapy - Inosine, transported by ENT1 in RBCs, serves as an important compensatory "fuel" during the aging process, particularly when glucose metabolism is impaired [8]. - Preclinical studies indicate that inosine supplementation successfully alleviates the decline in BPGM activity associated with aging, which leads to impaired glucose metabolism and reduced oxygen delivery [10][11].