Connecting research to society

Erik identified robust markers of human ageing

29 November 2013 Author: MolEpi - Molecular Epidemiology

The expression in blood of a novel gene network containing the ASF1A histon chaperone gene is a robust signature of human ageing. This observation was made by a collaboration of scientists from the Leiden University Medical Center (LUMC) and the Delft University of Technology (TU), The Netherlands. The ASF1A gene network, discovered in the joint analysis of four blood transcriptome studies and confirmed in an independent study, is indicative of chronological age and survival into old age. The findings were published online last week in the scientific journal “Aging Cell”.

Gene network containing ASF1A in blood is a novel potential biomarker for human ageing

The expression in blood of a novel gene network containing the ASF1A histon chaperone gene is a robust signature of human ageing. This observation was made by a collaboration of scientists from the Leiden University Medical Center (LUMC) and the Delft University of Technology (TU), The Netherlands. The ASF1A gene network, discovered in the joint analysis of four blood transcriptome studies and confirmed in an independent study, is indicative of chronological age and survival into old age. The findings were published online last week in the scientific journal “Aging Cell”.

Biomarker of healthy ageing

Despite our long life expectancy in the western world, chronological age is the major risk factor for mortality and virtually all common diseases. In the last decade the Molecular Epidemiology group at LUMC examined biological markers of healthy ageing and genetic markers of longevity in families surviving to exceptionally high ages (the Leiden Longevity Study). Although the expression of 10,000 genes in blood may be valuable for biomarker development, studies so far have been contradictory with respect to the signature of gene expression changes that mark the ageing process of individuals. We revisited multiple published data sets of gene expression profiles measured in human blood to get hold on the most robust ageing signatures.

Gene expression network in human blood

In total gene expression profiles in blood of four data sets consisting of 2,500 humans were jointly analysed. In collaboration between LUMC Molecular Epidemiology and the TU Delft Bioinformatics Lab, PhD student Erik van den Akker developed a novel algorithm designed to integrate co-expression of genes in the four datasets with knowledge on protein-protein interactions. Using this algorithm he identified four gene networks of which the expression in human blood associates with ageing in the four data sets and in an independent study of 3,500 participants of the Dutch Twin Registry at the Free University of Amsterdam (VU). Subsequent investigation of the novel ageing signatures in highly aged participants of the Leiden Longevity Study, revealed that the expression in blood of one of the networks significantly marks the survival probability during the ten years in which participants were studied. The biological function of this particular gene network needs to be elucidated. It contains the ASF1A gene, encoding a member of the family of histone chaperone proteins involved in assembly of chromosomes during DNA replication and repair. Remarkably, ASF1A has previously been implicated in healthy ageing of middle aged participants of the Leiden Longevity Study.

Perspective

The gene network will now be further investigated for its relation to age-related diseases. Clarification in the biological function of this ASF1A gene network may contribute to insight in the human ageing process and refinement of the network as a biomarker of ageing. The ageing signatures will be tested for their ability to classify elderly patients according to their disease risk and expected resilience to recover from medical treatment or surgery.

Publication

Van den Akker et al Aging Cell DOI: 10.1111/acel.12160

Poster prizes for Thies Gehrmann and Crystal Grant

28 June 2019 Author: MolEpi - Molecular Epidemiology

Public Lecture of Bas Heijmans at the University of the Netherlands

31 May 2019 Author: MolEpi - Molecular Epidemiology
more news