Evidence for reduced neurogenesis in the aging human hippocampus despite stable stem cell markers

Reduced neurogenesis in the aging mammalian hippocampus has been linked to cognitive deficits and increased risk of dementia. We utilized postmortem human hippocampal tissue from 26 subjects aged 18-88 years to investigate changes in expression of six genes representing different stages of neurogenesis across the healthy adult lifespan. Progressive and significant decreases in mRNA levels of the proliferation marker Ki67 (MKI67) and the immature neuronal marker doublecortin (DCX) were found in the healthy human hippocampus over the lifespan. In contrast, expression of genes for the stem cell marker glial fibrillary acidic protein delta and the neuronal progenitor marker eomesodermin was unchanged with age. These data are consistent with a persistence of the hippocampal stem cell population with age. Age-associated expression of the proliferation and immature neuron markers MKI67 and DCX, respectively, was unrelated, suggesting that neurogenesis-associated processes are independently altered at these points in the development from stem cell to neuron. These data are the first to demonstrate normal age-related decreases at specific stages of adult human hippocampal neurogenesis.