As we age, some of the cells in our body enter a state of senescence, in which they stop dividing but do not die. Those senescent cells can contribute to age-related disorders such as cancer, tissue degeneration, and inflammatory diseases.
In an advance that could lead to better ways to diagnose and treat those diseases, MIT researchers have developed a noninvasive way to detect biomarkers of senescence. Their method is based on Raman microscopy, which can reveal the biochemical composition of cells without harming them.
By combining Raman microscopy with gene expression data at single-cell resolution from the same cells, the researchers were able to identify unique “barcodes” that can be used to quickly identify senescent cells. This study was done in mouse cells, but the researchers are now working on adapting it for use with human tissue.
“You can imagine that one day we may develop an endoscope that can look inside your body and identify cellular senescence,” says Jeon Woong Kang, an MIT research scientist and one of the senior authors of the study.
The research is part of a National Institutes of Health initiative called the Cellular Senescence Network, which is pursuing a deeper understanding of senescence in hopes of developing therapies that could combat some of the tissue-damaging effects of senescent cells.
Peter So, director of the MIT Laser Biomedical Research Center (LBCR) and an MIT professor of biological engineering and mechanical engineering, and Jian Shu, an assistant professor at Massachusetts General Hospital (MGH) and Harvard Medical School, and an associate member of the Broad Institute and Ragon Institute, are also senior authors of the paper, which appears today in Nature Aging. Lead authors of the paper are Ke Zhang, an instructor at MGH and Harvard Medical School; Xingjian Chen, a postdoc at MGH and Harvard Medical School; Francesco Monticolo, a postdoc at MGH and Harvard Medical School; and Salvatore Sorrentino, a postdoc at MIT.
Characterizing senescence
Cell senescence is often triggered by DNA damage, which leads to an irreversible arrest of the cell cycle. These cells don’t die, but they undergo significant changes to their shape, metabolic processes, and gene expression profiles.
The immune system is responsible for clearing out these “zombie cells,” but as people age, this process becomes less efficient. When senescent cells accumulate, they may contribute to sagging skin, muscle weakness, and chronic conditions such as osteoarthritis and type 2 diabetes.
Cellular senescence also has beneficial effects, playing critical roles in embryonic development and tissue regeneration.
“Senescence is not just a pathological condition,” So says. “The idea behind the NIH Cellular Senescence Network is to take a very comprehensive approach to understand senescence and identify senescent cells, because it plays a role in so many normal physiological conditions and many pathological conditions.”
Scientists have already identified a few biomarkers for senescence, including two proteins called p16 and p21, which are involved in halting the cell cycle. However, those proteins can only be identified using a process that ends up destroying the cells.
The MIT team wanted to find a way to noninvasively identify senescent cells using Raman microscopy. Unlike RNA-sequencing, which consumes the cells as it analyzes them, Raman microscopy is a nondestructive technique that reveals the chemical composition of tissues or cells by shining near-infrared or visible light on them.
In the new study, the researchers used Raman microscopy in conjunction with spatial RNA sequencing — a technique that reveals where genes are active within a tissue — to identify new markers of senescence. By combining these two techniques, they were able to generate a much broader picture of the distinctive features of senescent cells, including gene expression levels, spatial location, and other biochemical information.