Research team visualises ageing at the cellular level for the first time using an AI-based computer model.
With increasing age, the activity of our genes changes. Researchers have now developed an ‘Aging Clock’ to determine this process in immune cells. Copyright: Karin Kaiser/MHH/KI generiert
As we age, not only our bodies change, but also our immune systems. A recent study, led by the Centre for Individualised Infection Medicine (CiiM), a joint institution of the Hannover Medical School (MHH) and the Helmholtz Centre for Infection Research (HZI), shows how exactly immune cells age and the influence that infections and vaccinations can have on this process. A research team led by scientist Yang Li, MHH professor of bioinformatics, has developed a computer model that can be used to determine the ageing processes within individual immune cells. The researchers are making the innovative ‘ageing clock’ freely available for further scientific work. They hope that it will serve as a useful tool to better understand the ageing processes of the immune system, especially in the context of infectious and immune diseases. The study was published in the journal ‘Nature Aging’.
Marker genes for the ageing process
As we age, we become more susceptible to infections, vaccinations are no longer as effective and the risk of disorders such as autoimmune diseases increases. ‘To better understand how and where exactly the immune system changes with age, and which factors trigger or accelerate aging processes, we need to look at the players in our immune system – the immune cells,’ says Professor Li, Director of CiiM and Head of the Department “Bioinformatics for Individualised Medicine”. The researchers therefore investigated the question of how the aging process looks within different immune cell types. For their study, they used thousands of transcriptome data sets for five different immune cell types from freely accessible data and literature sources. The so-called transcriptome reflects the totality of all genes active in a cell at a given time. In total, the researchers had access to data from over two million immune cells taken from blood samples of around 1,000 healthy people aged between 18 and 97 years. Using machine learning, they created a computer model from this data. They call this model the ‘Single-Cell Immune Aging Clock’.
‘We were able to identify certain genes for each immune cell type that are involved in important immunological processes and whose activity changes during the ageing process. These genes act as marker genes for the respective immune cell type and serve as a reference in the later application of the model,’ explains Professor Yang Li. The identified genes play a crucial role in the development of inflammatory processes. The study also confirmed that ageing processes are particularly associated with inflammatory processes.
Comparing COVID-19 cases and tuberculosis vaccinees
The research team then used the aging clock to find out how a COVID-19 infection and a tuberculosis vaccination each affect the aging processes within the different immune cell types. In the data from the COVID-19 cases, aging processes were only observed in a single type of immune cell, the monocytes. However, in people with a mild case of the disease, the ageing was significantly less pronounced. Moreover, these changes appear to be reversible, because after about three weeks of recovery, the monocytes gradually returned to their original age profile. The research team also looked at the so-called CD8 T cells in a tuberculosis vaccination. Here, ageing was dependent on how many inflammatory processes were currently taking place in the body. At high levels of inflammation, the vaccination had a rejuvenating effect on the immune cells. Professor Li is convinced that the Ageing Clock will help us to better understand the effects of infections and vaccinations in the future and to develop new approaches for therapies and preventive measures that promote healthy ageing.
Text: Communication Team