Healthy brain activity relies on the presence of key astrocytic proteins: the excitatory amino acid transporters (EAAT1/2), inwardly rectifying K+ channel (Kir4.1), aquaporin-4 (AQP4) among others. In the aging cortex, we report a novel phenotype of individual, sparse, non-reactive astrocytes with unchanged morphology, but greatly reduced levels of EAATs, Kir4.1, AQP4, and other astrocytic proteins, while bordering cells retain robust immunolabeling. Astrocyte tiling remains intact leaving these domains without many essential astrocytic functions. Already documented in a concussive mouse model, atypical astrocytes (AtAs), are not yet reported in normal aging. Using WT mice (P3-P650), IHC analysis shows significant age and regional effects, with an earlier AtA onset in the retrosplenial (RSC) and prefrontal cortices compared to the hippocampal CA1 region. Additionally, the somatosensory cortex (SSC) was resistant to AtAs with no significant differences seen across age groups. Functional glutamate analysis ex-vivo (iGluSnFR imaging, glutamate uncaging) shows heterogenous glutamate transport within the RSC but uniform in the SSC, consistent with increased atypical astrocytic domains in the RSC. AtAs often occur near major blood vessels and have diminished endfeet proteins. Quantification of blood vessels in AtA domains reveals significantly diminished MFSD2A, an endothelial protein needed to maintain BBB integrity. Lastly, the cortex of human autopsy tissue (n=8, 2-86 years old) has presumptive AtAs with dramatically diminished EAAT2 levels and appear in a similar, age dependent manner to rodent AtA phonotype. Current studies aim to investigate the molecular underpinnings of AtA generation and their functional consequences to homeostasis.