Using the model organism Caenorhabditis elegans, researchers at the University of Cologne developed an ‘aging clock’ that reads the biological age of an organism directly from its gene expression, the transcriptome. The bioinformatics David Meyer and genetics professor dr. Björn Schumacher, director of the Institute for Genome Stability in Aging and Diseases at the CECAD Cluster of Excellence in Aging Research and the Center for Molecular Medicine Cologne (CMMC), describes their so-called BiT age (binarized) transcriptomic aging clock) in the article ‘BiT age: A transcriptome based aging clock near the theoretical limit of accuracy ‘in Aging cell.
We are all familiar with the chronological age – our age since birth. But biological age can sometimes be very different. Everyone ages differently. Scientists can use aging clocks to determine the biological age of an organism. Until now, aging clocks such as Horvath’s epigenetic clock have been based on the pattern of methylations, small chemical groups that attach to DNA and change with age. Using the transcriptome, the new clock takes into account the set of genes read from DNA (messenger RNA) to make proteins for the cell.
Until now, the transcriptome has been considered complex to indicate age. Sometimes genes transcribe a particularly large amount of mRNA, sometimes less. It has therefore not been possible so far to develop precise aging clocks based on no activity. Meyer and Schumacher’s new approach uses a mathematical trick to eliminate the differences in gene activity. The binary transcriptome aging clock divides genes into two groups – ‘on’ or ‘off’ – thus reducing the high variation. This makes the aging predictable from the transcriptome. ‘Surprisingly, this simple procedure allows a very accurate prediction of biological age, close to the theoretical limit of accuracy. The most important thing is that this aging clock also works at old ages, which was previously difficult to measure because the variation in gene activity is then particularly large, ‘Meyer said.
BiT age is based solely on approximately 1000 different transcripts of C. elegans, the lifespan of which is precisely known. Model organisms such as the nematode provide a controllable overview of the aging process, through which biomarkers can be discovered and the effects of external influences such as UV radiation or nutrition on longevity can be studied.
The new aging clock enables researchers to accurately predict the pro- and anti-aging effects of gene variants and various external factors in the nematode at a young age. The aging clock also showed that genes of the immune response as well as signal in neurons are important for the aging process. ‘BiT age can also be applied to predict human age quickly and with very high accuracy. The measurement of biological age is important to determine the influence of environment, diet or therapies on the aging process and the development of age-related diseases. This watch can therefore be widely applied in aging research. “Since BiT age is purely based on gene activity, it can be applied to basically any organism,” Schumacher explained.
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