BY NEIL EISBERG
An initiative to decode how ageing reshapes the human body has reached a major milestone.
The US National Institutes of Health (NIH) Cellular Senescence Network (SenNet) has published its first wave of discoveries, highlighted by a cover commentary in the journal Cell led by Rong Fan, Harold Hodgkinson professor of biomedical engineering at Yale School of Engineering and Applied Science and of pathology at Yale School of Medicine (YSM), US, alongside researchers from nine other institutions (Rong Fan et al, Cell, 2026, 189, (12), 3501).
The article establishes a scientific framework for dozens of interconnected studies that are now appearing in journals, including Nature Aging, Nature Genetics and Molecular Cell.
Together, they represent the first coordinated effort to map senescent cells – damaged or aged cells that stop dividing but refuse to die – at single-cell and spatial resolution.
When cellular senescence occurs, these so-called ‘zombie cells’ accumulate over time. They secrete harmful chemicals that trigger inflammation and damage surrounding tissue. This process drives ageing and fuels chronic diseases like arthritis, cancer and Alzheimer’s disease.
‘Cellular senescence is a fundamental hallmark of aging, yet we still know surprisingly little about where these cells reside in the human body and how they interact with their surrounding tissue environments,’ says Rong Fan, a member of the Yale Center for Research on Aging (Y-Age) and Yale Cancer Center. ‘SenNet is creating the first reference atlas of human senescence, providing a foundation for understanding senescence biology in ageing and developing future interventions.’
Yale has played a key role in the SenNet initiative through an interdisciplinary team of investigators, including Fan and YSM faculty members Stephanie Halene, Mina Xu and Yuval Kluger, in the Yale SenNet Human Tissue Mapping Center (TMC) and the murine TMC led by Deep Dixit, director of Y-Age.
One of the YSM-led SenNet studies in this interconnected collection, published in Cell Press Blue, offers a look at ‘immunosenescence’—the ageing of the immune system, and provides one of the first comprehensive maps of immune ageing in humans.
The researchers analysed human lymph nodes from donors of various ages, ranging from childhood to old age. They discovered that in older tissues there were localised groups of dysfunctional immune cells called B cells. This specific decay helps explain why our immune systems weaken as we get older, the researchers say.
The SenNet collection includes new cellular senescence atlases for the brain, liver and skin. It also introduces advanced artificial intelligence tools to classify different types of aged cells. Crucially, the data reveal that senescence is not a single state. Instead, it is a diverse spectrum of cellular profiles, called ‘senotypes’, that vary by tissue and disease.
As the project expands, scientists hope this open-source Human Senescence Atlas will accelerate precision therapies. The ultimate goal is not just to extend lifespan, but to improve human healthspan – the number of years lived disease-free.
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