Ageing laws for the human frontal cortex

Background: Lu et al. ( Gene regulation and DNA damage in the ageing human brain. Nature 429: 883 891, 2004) used post-mortem transcripts of the human frontal cortex to estimate age patterns of gene expression. However, post-mortem data are subject to duration censoring. Aim: This study aimed to provide a continuous-time view of ageing in the human brain at the genetic level and a differentiation of physiological functions with respect to age. Subjects and methods: Post-mortem transcripts of 30 individuals between the ages of 26 and 106 were used to estimate age-specific hazard rates for gene expression by taking into account duration information using multi-level survival data analysis. Results: Gene expression hazard rates were estimated, and combined longitudinally to produce a distribution of proportions of up- or down-regulated genes over age and function. Except for myelination/lipid metabolism, the stocks of up- regulated genes declined after 30 years of age. Conclusion: Combining data collected post-mortem with survival methods produces new estimates of the effects of age on gene expression.