AI Tool Tracks Senescent Cells to Advance Research on Aging and Disease

A new study led by researchers at NYU Langone Health’s Department of Orthopedic Surgery has developed an AI-assisted technique to measure and track senescent cells, which are cells damaged by injury, aging, or disease and no longer grow or reproduce normally. These cells play a crucial role in wound repair and contribute to aging-related diseases such as cancer and heart disease. Understanding and monitoring their behavior could lead to better therapeutic strategies for reversing cellular damage and improving tissue regeneration. The technique combines high-resolution imaging and machine learning to analyze the morphological changes in the cell’s nucleus, which serves as its control center. Researchers trained a computer system to recognize several nuclear features indicative of senescence, including expansion, increased density of foci, and a more irregular shape. Additionally, the genetic material in the nucleus stained lighter with standard chemical dyes, further confirming senescence. The researchers created a Nuclear Morphometric Pipeline (NMP) that quantifies these changes into a single senescent score, ranging from -20 to +20, to describe the senescent state of a group of cells. They validated the NMP by testing it on healthy and diseased mouse cells of various ages, from 3 months to over 2 years. Older cell clusters had significantly lower NMP scores, indicating higher degrees of senescence. The NMP was also effective in tracking changes in different types of cells during muscle tissue repair in young, adult, and geriatric mice. It identified the presence and gradual decline of senescent muscle stem cells during the initial stages of repair, highlighting their role in wound healing. Furthermore, the NMP distinguished between healthy and senescent cartilage cells in geriatric mice with osteoarthritis, which are 10 times more prevalent in these older mice compared to younger, healthy ones. Michael Wosczyna, Ph.D., an assistant professor at the NYU Grossman School of Medicine and the senior investigator of the study, emphasized the broad applicability of the NMP for studying senescent cells across various ages, tissue types, and diseases. The team plans to extend their research to human tissues and combine the NMP with other biomarker tools to explore its potential in clinical settings. Wosczyna and his team aim to use the NMP to develop treatments that prevent or reverse the negative effects of senescence on human health. Sahil Mapkar, a doctoral candidate at the NYU Tandon School of Engineering and co-lead investigator, noted that existing methods to identify senescent cells are challenging and less reliable compared to the NMP, which uses a common nuclear stain. The researchers hope to make the NMP freely available to the scientific community, facilitating more robust and accessible studies of senescence. This breakthrough could have significant implications for the fields of regenerative medicine, aging research, and drug development. Industry experts have praised the study for its innovative approach and potential to advance the understanding and treatment of age-related conditions. NYU Langone Health is known for its cutting-edge research in orthopedic surgery and regenerative medicine, and this development underscores their commitment to advancing the frontiers of medical science. The team's next steps include further validation of the NMP in human tissues and exploring its integration with existing therapeutic approaches, particularly senolytics, which are drugs designed to target and eliminate senescent cells. If successful, this tool could revolutionize how researchers study and treat cellular senescence, potentially opening new avenues for extending healthy life spans and improving the quality of life for older individuals.