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.


OBJECTIVE
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.


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.


CONCLUSIONS
Combining data collected post-mortem with survival methods produces new estimates of the effects of age on gene expression.
Bonneuil
Noël
N
Institut National des Etudes Demographiques, Paris, France. bonneuil@ined.fr
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics*; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D011180:Postmortem Changes; D016016:Proportional Hazards Models; D016019:Survival Analysis; D015854:Up-Regulation / Q000235:genetics*