Ageing laws for the human frontal cortex

Abstract

Background: Lu et al. (Gene regulation and DNA damage in the ageing human brain. Nature 429:883–891, ) 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.

• Ageing
• DNA
• survival data analysis
• interval censoring