'Old' human blood cells transformed into 'young' brain cells

Researchers have turned an 80-year-old's blood precursor cells into neural stem cells, resetting the cells' 'biological age' in the process.

Researchers in Germany changed donated blood precursor cells directly into neural stem cells. They found that the cells' age – measured using an 'epigenetic clock' – slowly rewound, allowing them to track gradual changes in cellular dynamics. Conversely, when the blood cells were forced to differentiate through an intermediate pluripotent stem cell stage, their 'clocks' were reset much more quickly.

'We have directly converted red blood cell precursors into neural stem cells,' said Professor Oliver Brüstle, senior author of the paper published in Ageing Cell, and director of the Institute of Reconstructive Neurobiology at the University Hospital of Bonn. 'In our approach, rejuvenation occurred gradually and could be tracked for over 100 days.'

The team harvested blood cell precursors from both young and old donors. These cells were then reprogrammed using two different approaches: a one- or two-step method. In the two-step method, they first generated induced pluripotent stem cells (iPSCs) before further differentiation into neural stem cells (iPSC-NSCs). In the one-step approach, blood cells were directly reprogrammed into induced neural stem cells (iNSCs).

The 'biological age' of the cells was determined by assessing the degree of DNA methylation in the cells' genomes. DNA methylation can only act as a proxy for biological age, as it does not directly measure cellular function and can also vary between different tissues.

The researchers found that iPSC-NSCs had a rapid de-ageing to an embryonic equivalent age, whereas iNSCs took much longer to be 'rejuvenated'. iNSCs from donors aged 80-plus underwent significant de-ageing and eventually closely resembled the embryonic-like iPSC-NSCs.

The team also examined gene expression. While iNSCs rapidly acquired NSC morphology and marker expression, further transcriptomic changes in blood, nervous system, and cytoskeletal pathways also occurred gradually over a period of weeks. iNSCs derived from young and old donors initially differed in gene expression; however, they became progressively more similar over time.

The authors hope that the slow conversion in the one-step model could provide a window for understanding mechanisms underlying ageing.

'Since the epigenetic clocks are slowly reset over several weeks, we can use this model to investigate which factors and active substances accelerate or slow down the rejuvenation process,' said Professor Brüstle. 'After all, age is the most important risk factor for neurodegenerative diseases such as Alzheimer's.'