A new aging clock that’s close to the theoretical limit of accuracy boasts unprecedented precision and offers new insights into how the aging process is influenced.
Two scientists at the CECAD Cluster of Excellence in Aging Research at Cologne University (pictured) have developed an aging clock method that can determine an organism’s biological age with unprecedented precision, meaning that new insights into how the environment, nutrition and therapies influence the aging process can be expected.
Longevity.Technology: Aging clocks can determine biological age, evaluate biomarkers and assess therapeutic, genetic, environmental or nutritional impacts on the aging process. Using clocks means researchers can investigate longevity drugs and therapies in shorter timescales, rather than waiting for trial participants to die in order to see if lifespan was affected. Not only does this speed-up therapy development, but use of clocks shines a light on the whole aging process and the numerous pathways involved, allowing us to understand it, unpick it and, ultimately, help us to undo aging altogether.
Using our old friend, the model organism C. 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 geneticist Professor Dr Björn Schumacher, director of the Institute for Genome Stability in Aging and Disease at the CECAD Cluster of Excellence in Aging Research and the Center for Molecular Medicine Cologne (CMMC), describe their clock as a binarised transcriptomic aging clock – or BiT age for short .
We are all familiar with chronological age – our age since birth – but biological age can differ from it, at times significantly. Everyone ages differently, and scientists can use aging clocks to determine an organism’s biological age. Previously, several 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 consideration 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, so 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 the differences in gene activity. The binarised transcriptome aging clock divides genes into two groups, either ‘on’ or ‘off’, which minimises high variation. This makes aging predictable from the transcriptome.
“Surprisingly, this simple procedure allows very accurate prediction of biological age, close to the theoretical limit of accuracy. Most 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,” said Meyer .
BiT age is based exclusively on approximately 1,000 different transcriptomes of C. elegans, for which the lifespan is precisely known. Model organisms such as the nematode provide a controllable view of the aging process, allowing biomarkers to be discovered and the effects of external influences such as UV radiation or nutrition on longevity to be studied.
“This clock could therefore find wide application in aging research … it can basically be applied to any organism …”
The new aging clock allows 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 signalling in neurons are significant for the aging process.
“BiT age can also be applied to predict human age quickly and with very high accuracy. Measuring 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 clock could therefore find wide application in aging research. Since BiT age is based purely on gene activity, it can basically be applied to any organism,” Schumacher explained .