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Using the model organism Caenorhabditis elegans, researchers at the University of Cologne have developed an “aging clock” that reads the biological age of an organism directly from its gene expression, the transcriptome. Bioinformatician David Meyer and Professor of Genetics Dr Björn Schumacher, Director of the Institute for Genome Stability in Aging and Disease at CECAD’s Cluster of Excellence in Aging Research and the Center for Molecular Medicine Cologne (CMMC), describe their so-called BiT (binarized transcriptomic aging clock) age in the article “ BiT age: a transcriptome-based aging clock close to the theoretical limit of accuracy ” in Aging cell.
We all know the chronological age – our age from birth. But biological age can differ, sometimes significantly. 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 model 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 that are read from DNA (messenger RNA) to make proteins for the cell.
Until now, the transcriptome was considered too complex to indicate age. Sometimes genes transcribe a particularly large amount of mRNA, sometimes less. Therefore, until now, it has not been possible to develop precise aging clocks based on gene activity. Meyer and Schumacher’s new approach uses a mathematical trick to eliminate differences in gene activity. The transcriptome’s binarized aging clock divides genes into two groups – “on” or “off” – thus minimizing high variations. This makes aging predictable from the transcriptome. “Surprisingly, this simple procedure allows a very precise prediction of biological age, close to the theoretical limit of precision. More importantly, this aging clock also works at high ages, which were previously difficult to measure because the variation in gene activity is particularly high then, ”Meyer said.
The BiT age is based exclusively on approximately 1000 different C. elegans transcriptomes, the lifespan of which is precisely known. Model organisms such as the nematode provide a controllable view of the aging process, allowing the discovery of biomarkers and the study of the effects of external influences such as UV radiation or nutrition on longevity.
The new aging clock allows researchers to accurately predict the pro and antiaging effects of genetic variants and various external factors in the nematode at a young age. The aging clock has also shown that genes for the immune response as well as signaling 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 in determining the influence of the environment, diet or therapies on the aging process and the development of age-related diseases. This clock could therefore find wide application in research on aging. Since BiT age is based solely on gene activity, it can be applied to any organism, ”Schumacher explained.
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