Aging impairs mitochondrial metabolism and causes atrophy of human cortical astrocytes

Aging differently affects cellular components of the brain active milieu. Here, we analyzed astrocytes and neurons in the neocortical access tissue of younger (22 - 50 years) and older (51 - 72 years) human who underwent resection of glioma or other cancer metastases to the brain. Aging decreased the amount of reduced mitochondrial cytochromes in astrocytes but not neurons. The protein-to-lipid ratio was decreased in astrocytes and increased in neurons. Aged astrocytes showed morphological dystrophy quantified by the decreased length of branches, decreased volume fraction of leaflets, and shrinkage of the anatomical domain. Dystrophy correlated with the loss of gap junction coupling between astrocytes and increased input resistance. Aging was accompanied by the upregulation of glial fibrillary acidic protein and downregulation of membrane-cytoskeleton linker ezrin associated with leaflets. No significant changes in neuronal excitability or spontaneous inhibitory postsynaptic signaling were observed. Thus, brain aging is associated with the impaired morphological presence and mitochondrial malfunction of cortical astrocytes, but not neurons.