How does the new barcode work?

Existing markers for senescence, especially two proteins called p16 and p21, require staining or sequencing methods that kill the cell. Raman microscopy is gentler: it shines near-infrared or visible light on a sample and reads back the chemical vibrations of lipids, proteins, and other molecules inside.

The MIT group paired Raman microscopy with spatial RNA sequencing, a technique that maps which genes are active and where, on skin and lung tissue from 2-month-old and 26-month-old mice. They then compressed both readouts from the same cells into a barcode — a small set of Raman peaks whose intensity tracks with senescence.

Lead author Salvatore Sorrentino, an MIT postdoc, summed up the goal: "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."

Senior author Shu added that the two methods capture "complementary views" of the same cells. Because the barcode leans on just a handful of Raman bands, a future imager could read the signature in seconds rather than days.

What did the mouse study show?

Lipid synthesis jumped in senescent cells from both skin and lung tissue, alongside visible lipid buildups. The team does not yet know how that fat surge alters cell physiology, but they flagged it as one of the most consistent aging signals they found.

Tissue-specific effects also emerged. Aged skin cells showed changes in pathways tied to muscle contraction and to remodeling of collagen, the structural fiber that keeps skin firm. Aged lung tissue lit up with genes linked to immune activation and inflammation.

Both findings fit the broader picture that senescent cells do not behave the same way everywhere in the body, which is part of why a single biomarker like p21 has not translated into a routine clinical test.

What's next?

The researchers are racing to speed up imaging. Thirty hours per square millimeter is far too slow for routine biopsies, so the group is building a faster Raman scanner aimed at clinical samples.

"You can imagine that one day we may develop an endoscope that can look inside your body and identify cellular senescence," Kang said.

The team is also adapting the workflow from mouse to human tissue, a step the paper acknowledges is still ahead. For now, the barcode lives only in mouse cells, and the researchers caution that mouse and human senescence can differ. The NIH and Massachusetts General Hospital funded the work.