Reciprocal phylogenetic conservation of molecular aging in mouse and human brain

Abstract

Studies of age-related molecular profiles have separately focused on the human and rodent brains, but the extent to which each organism predicts molecular events across species for the global signature of aging and for specific biological functions has only begun to be characterized. We previously showed that the molecular correlates of aging in the mouse cortex moderately, but significantly, predicted transcript changes in human frontal cortex. Using orthologous gene links between large-scale gene expression datasets, we now report a similar reciprocal human-to-mouse prediction of molecular aging in frontal cortex, but a limited and variable conservation of age-effects across a wide spectrum of biological functions. Thus, the moderate transcriptome correlations and partial functional concordance between late-life human and rodent cohorts (13-77 years in humans and 3-24 months in mice) suggest limitations of the mouse to model normal aging of the human brain cortex.