MIT Team Develops Noninvasive Method to Detect Senescent Cells

As people age, certain cells in the body enter a state called senescence, in which they stop dividing but remain alive. These cells can contribute to age-related conditions including cancer, tissue degeneration, and inflammatory diseases. MIT researchers have now developed a noninvasive way to detect biomarkers of senescence using Raman microscopy, a technique that reveals the biochemical composition of cells without damaging them, according to a study published in Nature Aging. The work, conducted in mouse cells so far, is part of a National Institutes of Health initiative called the Cellular Senescence Network.

Senescence is typically triggered by DNA damage that halts the cell cycle. While the immune system normally clears out these cells, that process weakens with age, allowing senescent cells to accumulate and contribute to sagging skin, muscle weakness, and conditions such as osteoarthritis and type 2 diabetes. Senescence also plays beneficial roles in embryonic development and tissue regeneration. "Senescence is not just a pathological condition," says senior author Peter So. Existing biomarkers, including the proteins p16 and p21, can only be identified through processes that destroy the cells.

To find a nondestructive alternative, the researchers paired Raman microscopy with spatial RNA sequencing, which shows where genes are active within tissue. Applying both methods to skin and lung tissue from 2-month-old and 26-month-old mice, they found that older cells in both tissues showed increased lipid synthesis and lipid accumulation, though the physiological effects of this remain unknown. Tissue-specific changes also emerged: senescent skin cells showed effects on pathways tied to muscle contraction and collagen remodeling, while aged lung tissue showed increased immune activation and inflammation-related gene activity.

Using this combined data, the team identified specific Raman peaks, linked to particular lipids, proteins, and other molecules, that correlate with senescence. "Combining the most important Raman features with the most important gene signatures, we were able to create a barcode that can help us to identify senescent cells in a more unbiased way," says Salvatore Sorrentino, one of the paper's lead authors. 

The researchers are now working to adapt the method for human tissue and to build a faster imaging system. Currently, analyzing a one-square-millimeter tissue sample takes about 30 hours; the team hopes to speed up detection of the Raman barcodes across larger samples.