Cellular senescence plays a critical role in human health and well-being, like wound healing and embryonic development. But senescent cells—which have stopped dividing but haven’t yet died—can also hurt us if they accumulate in our tissues, causing inflammation and, in turn, some of the chronic conditions associated with aging. Scientists believe that clearing the buildup of harmful senescent cells could slow the progression of these diseases, and lengthen the human healthspan.
Two graduate students in Brown’s Center on the Biology of Aging, Jien Li PhD’30 and Anthony Agudelo PhD’28, are developing machine learning models to quickly and economically identify senescent cells. Support from the RoC Skincare Longevity Research Fund is enhancing their efforts. “We are given the ability to explore and think outside the box and try more interesting things,” Agudelo says. Li adds, “We feel encouraged, and as a direct result we can turn ideas into experiments much, much faster.”
Agudelo says that, just as people look different when we age, senescent cells look different as well. Using spatial omics data, he and his PhD adviser, Nicola Neretti ScM’99 PhD’01, identified patterns based on hundreds of biomarkers in human cells. “So I developed a machine learning model to see if we can identify senescent cells versus nonsenescent cells,” Agudelo says. Li and his adviser, John Sedivy, PhD, are building on that work. Focusing on “a multitude of different morphological features of a cell,” including the cytoskeleton, mitochondria, and nucleus, Li is building a model that analyzes cell structures for telltale signs of senescence. The aim of both projects is the same, Li says: “We’re trying to identify senescent cells, but using a much higher throughput, much more economical way to do it.”
Agudelo and Li say their research could enable the development of drugs that remove senescent cells. “If you can quickly identify which cells are senescent and which ones are not, or in between, you can very quickly tell if a drug is doing its thing,” Li says. “That can be helpful if you’re looking at hundreds or thousands of different drugs,” Agudelo adds. Both scientists point out that the ultimate goal of aging research is extending not just the lifespan, but the healthspan. “Clearing out senescence can mean pushing back the onset of a lot of these degenerative progressive diseases that happen over time, and people living happier, healthier lives,” Agudelo says.