Cellular senescence is a state in which cells stop dividing but do not die. First described by Leonard Hayflick and Paul Moorhead in 1961, when they observed that cultured human fibroblasts could divide only a finite number of times, senescence was long regarded as a simple curiosum of the tissue culture dish. Over the following decades, however, it became clear that senescent cells accumulate in tissues throughout the body as organisms age, and that they are not merely passive bystanders. They secrete a potent cocktail of inflammatory cytokines, growth factors, and matrix-remodeling enzymes known collectively as the senescence-associated secretory phenotype, or SASP, which can remodel tissue microenvironments, drive chronic inflammation, and disturb the function of neighboring healthy cells.

That inflammatory shadow is now implicated in an astonishing range of age-related conditions, from osteoarthritis and atherosclerosis to neurodegeneration and frailty. Animal studies have added weight to the argument: in mice, the genetic or pharmacological removal of senescent cells can delay tissue dysfunction and extend health span. A growing class of drugs, termed senolytics, selectively eliminates senescent cells, while senomorphics aim to suppress their harmful secretions without killing them. Early-phase clinical trials are underway in several disease areas, and the prospect of intervening directly in the biology of aging has moved from the fringe to the center of geroscience.

Yet as the Coimbra participants emphasized, the field’s momentum is not matched by clinical readiness. One of the most fundamental problems is definitional. Senescence is not a single entity. Cells can enter the state through telomere shortening, DNA damage, oncogene activation, mitochondrial dysfunction, or other stresses, and the resulting senescent cells differ profoundly depending on the trigger, the tissue of origin, and the duration of the state. Some senescent cells are transient and beneficial, orchestrating wound healing, embryonic development, and tissue repair, while others persist for months or years and become quietly destructive. The roadmap therefore calls for a functional classification of senescent states, a systematic taxonomy that would distinguish which senescent cells are doing harm, which are doing good, and in what contexts.

Without such a classification, the field risks repeating mistakes that have hampered other areas of medicine. The single most cited obstacle to clinical translation is the absence of standardized, clinically actionable biomarkers. Researchers currently identify senescent cells through combinations of markers, including the cell cycle inhibitor p16INK4a, lysosomal enzyme activity measured by senescence-associated beta-galactosidase, DNA damage foci, and SASP profiling. No single marker is both specific and sensitive, and protocols vary widely between laboratories, making it difficult to compare results across studies, to design clinical trials with reliable endpoints, or to know whether an intervention has actually changed the senescent cell burden in a patient’s tissues. The roadmap prioritizes the development of agreed-upon biomarker panels that can be measured reproducibly, ideally in accessible samples such as blood, and validated as predictors of clinical outcomes.

The vision that emerges from the SENESCENCE2030 network is one of precision senescence medicine, an approach modeled on the way oncology moved from blunt chemotherapy to molecularly targeted therapies matched to a tumor’s specific profile. In this vision, a clinician would one day characterize a patient’s senescent cell landscape, determining which senescent cell types are present, in which tissues, driving which pathologies, and select a senolytic or senomorphic intervention accordingly. Achieving this requires not only biomarkers but also a deeper understanding of senescent cell heterogeneity at the single-cell level, including the application of transcriptomic, epigenomic, and proteomic technologies to map senescent states in human tissues across the life course.

The roadmap is equally clear that scientific discovery alone will not be enough. Translational and regulatory frameworks must be strengthened if senotherapeutics are ever to reach the clinic. Because aging itself is not an approved indication for drug approval, clinical trials must target specific age-related diseases, which raises questions about trial design, patient stratification, and endpoints that reflect biological aging rather than a single symptom. Regulators will need validated surrogate markers to judge whether a senotherapeutic is working, and the field must agree on safety standards, particularly for senolytic drugs that remove cells which may still be performing useful functions in some tissues. The Coimbra consensus explicitly calls for dialogue between researchers, industry, and regulatory agencies to define these standards before large trials begin.

International collaboration emerges as the connective tissue holding the roadmap together. The SENESCENCE2030 network itself is a COST Action, CA23119, funded by the European Cooperation in Science and Technology, and it spans dozens of institutions across Europe, from Naples and Barcelona to Exeter, Graz, Groningen, and beyond, with participants contributing expertise ranging from cardiology and toxicology to oncology and tissue regeneration. The consensus document argues that the challenges ahead, including biomarker standardization, data sharing, trial harmonization, and training of a new generation of geroscientists, are too large for any single laboratory, company, or country. Shared biobanks, open datasets, and cross-border clinical networks are framed as prerequisites rather than aspirations. The meeting’s industry–academia workshop format was itself a deliberate exercise in bridging the gap between discovery science and product development, ensuring that company perspectives on scalability, manufacturing, and regulatory pathways informed the research agenda from the outset.

The stakes are considerable. Populations across the world are aging rapidly, and the burden of chronic age-related disease threatens health systems and economies alike. If senescence-targeting interventions can be made safe, targeted, and effective, they would represent a fundamentally new form of medicine, one that treats upstream biological drivers shared by many diseases rather than each condition in isolation. The authors of the roadmap, led by Marco Demaria of the European Research Institute for the Biology of Ageing in Groningen together with Aniello Cerrato and a broad consortium of co-authors, are candid that the field is at an inflection point. The biology is compelling and the first clinical experiments have begun, but without the shared definitions, validated markers, regulatory clarity, and coordinated networks the roadmap describes, senescence medicine risks stalling in a haze of irreproducible results and failed trials. What the Coimbra consensus offers is a collectively agreed plan, and a reminder that the transition from laboratory insight to patient benefit is a discipline in its own right, demanding as much rigor and cooperation as the discoveries that set it in motion.

Subject of Research: A consensus roadmap for translating cellular senescence research into precision senescence medicine

Article Title: A consensus roadmap from the SENESCENCE2030 network towards precision senescence medicine

Article References: Cerrato, A., Farsetti, A., Bordoni, L., Martins, R. R., Bengoetxea de Tena, I., Vrhovac Madunic, I., Mammadova, M., Raviola, S., Rima, M., Ozturk, M., Spinelli, R., Moisoi, N., Nicoli, F., Pangrazzi, L., Wouters, A., Albrakati, A., Abdellatif, M., Harries, L. W., Martini, G., … Demaria, M. (2026). A consensus roadmap from the SENESCENCE2030 network towards precision senescence medicine. Nature Aging. https://doi.org/10.1038/s43587-026-01222-y

Image Credits: AI Generated

DOI: 10.1038/s43587-026-01222-y

Keywords: cellular senescence, SENESCENCE2030, precision medicine, biomarkers, senolytics, aging, geroscience, Nature Aging, SASP, clinical translation, COST Action, senomorphic drugs