Most cells have a finite healthy life-span. While they have access to a wide range of repair mechanisms, molecular damage builds up over time, steadily undermining cellular function. In some cases dysfunctional cells can be replaced by activity of resident stem cells, but eventually this leads to decline of organismal function, commonly known as aging. Remarkably, some organisms appear to escape this fate. By studying the biology underlying this phenomenon, we can uncover the regulatory mechanisms that govern cellular resilience and discover how to protect tissues from the effects of time.

The free-living planarian Schmidtea mediterranea is an outstanding model for this type of research. Schmidtea has many different cell types types, remarkably similar to our own, but possesses the extraordinary ability to recover from any injury and regenerate complex structures, including its brain. This capacity is driven by the neoblasts: a population of adult pluripotent stem cells that never lose their vigor or their ability to divide. In fact, some planarian strains rely on asexual reproduction based on regeneration, and their neoblasts thus have successfully powered countless generations of new clones for millions of years.

Using (single-cell) RNA profiling, proteomics, and computational modeling, we analyze the gene expression signatures that distinguish long-lived neoblasts from their short-lived progeny. By identifying the pathways overrepresented in these immortal cells, we combine molecular, cell biological, genetic, proteomic, and computational methods to decode the regulation of pluripotency and the secrets of long-term cellular health.