New way to find “aged” cells marks fresh approach for research into ageing

Tokyo, Japan – Researchers from Tokyo Metropolitan University have created a new way of telling “aged” human cells apart from younger ones using electric fields. While key markers have been found for these “senescent” cells, current methods require biochemical “labels” which are difficult to apply and affect the cells themselves, making them difficult to study. The new method is label-free and less damaging. The team aims to diversify the method, extending it to other cell types.

Ageing starts at the cellular level. As we get older, aged or “senescent” cells accumulate in our body. Not only have these cells lost much of their original function, but they continue to emit compounds which trigger inflammation. There is a growing body of evidence for how they play a part in ageing-related conditions like arterial hardening, Alzheimer’s disease, and type 2 diabetes.

To understand and treat such ailments, scientists need to come to grips with how senescent cells affect our physiology. Naturally, this starts with identifying which of our cells are senescent, and which are not. Unfortunately, existing methods rely on selective “labeling,” e.g. the attachment of a fluorescent molecule to specific compounds known to be present in aged cells. Not only is this time-consuming and complex, but the process itself can change the properties of the very thing scientists want to study.

To get around this issue, a team led by Assistant Professor Ippei Yagi from Tokyo Metropolitan University has come up with an entirely different approach to identifying senescent cells. Instead of chemical labels, they put cells under an alternating electric field. This causes a slight rearrangement of charge, where one end of the cell is more positively charged than the other. When the electric field is not uniform over space, the cell migrates; in the case of an alternating field, the cell wanders backwards and forwards between the electrodes. As the frequency of the field is changed, the motion of the cell changes significantly at a value known as the cutoff frequency. The method, known as frequency-modulated dielectrophoresis (FM-DEP), aims to characterize cell type by measuring this value.

The team focused their efforts on human dermal fibroblasts, an important part of connective tissue in the skin. When they tested senescent cells against younger ones, they found that there was a marked difference in their cutoff frequencies. These changes come about from changes in the fatty (lipid) molecules which make up the membrane of the cells. Importantly, FM-DEP is rapid, easy to apply, and label-free.

The new method is not only a convenient tool for research into ageing, but may see application to regenerative medicine, and drug screening. The team hope to apply FM-DEP to other cell types as well, as a versatile new approach to cell identification.

This work was supported by JSPS KAKENHI Grant Numbers JP23K28453 and JP23KK0260.