A research consortium funded by the National Institutes of Health (NIH)has established a new framework to identify and catalog senescent cells - cells that stop dividing but remain active in the body. Because senescent cells accumulate with age and are thought to contribute to many age-related conditions, researchers are working to better understand the roles they play in health and disease. In a compendium of papers published in the June 11 issue of Cell, the consortium presents the first comprehensive atlas of senescent cells across the human body, a foundational step toward developing new therapies for age-related diseases.
In healthy tissues, senescent cells support wound healing and serve as a defense mechanism by preventing the growth of tumors. They are normally cleared by the immune system, but as immune function declines with age, senescent cells accumulate in the body instead of being eliminated. Over time, these cells then release harmful signals that contribute to chronic disease and other age-related conditions. While removing these cells has been shown to diminish the impact of aging, their rarity and diversity have made them difficult to study.
To address this challenge, the NIH Common Fund launched the Cellular Senescence Network (SenNet) program in 2021 to identify and characterize senescent cells across the human body.
Through the new papers, researchers in the consortium are introducing the concept of "senotypes," a new classification system that groups senescent cells based on where they are found in the body and the conditions surrounding them.
"By mapping where different senotypes are found and what makes them unique, we aim to build a more complete picture of senescent cells across the body," said Nicole Kleinstreuer, Ph.D., NIH Deputy Director for Program Coordination, Planning, and Strategic Initiatives (DPCPSI), who leads the NIH Common Fund. "This knowledge could help researchers move toward more targeted therapies that focus on harmful cells while preserving beneficial ones."
Through the concept of senotypes, SenNet researchers are recognizing that cells can differ widely depending on tissue type, health status, and environment. This framework is essential for building a large-scale atlas of cellular senescence across the lifespan.
In their latest work, SenNet researchers share significant progress toward advancing cellular senescence research and building a comprehensive atlas across human tissues. Highlights from the new research include:
Mapping senescence across the body: The SenNet atlas charts senescent cells in tissues from areas of the body such as the brain prefrontal cortex, lungs, and lymph nodes.
Discovering new biomarkers: The consortium developed new computational tools to identify unique biological features of senescent cells. Using these tools, researchers identified markers in blood that can predict kidney disease, frailty, and the future risk of diabetes in human aging studies.
Innovating new technologies: The research showcases novel single-cell, spatial omics, and AI-based methods designed to overcome the challenge of identifying and analyzing rare senescent cells within complex human tissues.
The research also points to potential future applications in disease research and therapeutic development, including identification and early testing of "senolytics," a class of experimental drugs designed to selectively eliminate senescent cells.
Since its launch in 2021, SenNet has grown into a large, collaborative research effort supported by multiple NIH Institutes and Centers and led by the National Institute on Aging (NIA) and the National Cancer Institute (NCI). By combining expertise across institutions and disciplines, SenNet is building comprehensive, publicly accessible atlases that describe where senescent cells are found, how they differ, and how they influence human health.
