Senescent Cells Consume their Neighbors

The accumulation of lingering senescent cells is an important contributing cause of degenerative aging. In this intriguing report, researchers note that senescent cells resulting from chemotherapy treatment can consume neighboring cells in order to prolong their survival. This is most likely the case for senescent cells in general, whatever their origin. This cellular cannibalism is probably detrimental to tissue function to some small degree, but, since senescent cells are always a tiny minority of all cells, even in old tissues, it is nowhere near as detrimental as the inflammatory signaling profile that accompanies cellular senescence. Unless this consumption of nearby cells is absolutely vital to the survival of a large fraction of long-lived senescent cells, the mechanisms involved are unlikely to present a useful point of intervention.

Multicellular life requires individual cells to cooperate in a way that benefits the organism. Cells that are uncooperative because they are damaged or dysfunctional, and that pose a threat, are either eliminated by cell death or undergo a usually irreversible growth arrest called senescence. Senescent cells typically never divide (although there are some rare examples of cells exiting senescence and resuming division), but they can persist in tissues and contribute to ageing and cancer progression.

Senescent cells are metabolically active6, and this is characterized by their secretion of proinflammatory molecules as part of a phenomenon termed the senescence-associated secretory phenotype (SASP) response. Senescent cells can promote cancer progression and resistance to anticancer therapy in some contexts, as a result of the secretion, through SASP, of growth factors and immune-signalling molecules called cytokines.

Chemotherapy that damages the DNA of cancer cells can result in their death or their entry into senescence. Researchers investigated the effects of chemotherapy-driven senescence in breast cancer cells in mice. Under the microscope, they saw senescent cells eating and digesting entire neighbouring cells. This striking observation was made in breast tumours formed of mixtures of transplanted cancer cells, which were engineered to express red or green fluorescent proteins. It can be difficult to observe a cell being internalized by another cell in cancer tissues. By growing tumours with mixtures of fluorescently labelled cells, the authors could clearly identify red- or green-labelled cells being taken up into neighbouring cells labelled by the other colour.

Ingested cells are broken down in a digestive organelle called the lysosome. Crucially, senescent cells that ate their neighbours survived longer in vitro than those that did not. This finding suggests that metabolic building blocks retrieved from the lysosomal digestion of neighbouring cells were being used by senescent cells to promote their survival. The authors tested chemotherapy-induced senescent cells of other types of cancer, including lung cancer and a bone cancer called osteosarcoma, and found that these cells also cannibalize neighbouring cells. Together, these findings suggest that cell cannibalism might be an activity that is broadly associated with the induction of senescence, rather than being linked to particular types of cancer or to the status of proteins such as p53.

Link: https://doi.org/10.1038/d41586-019-03271-3

Comments

While not a direct therapeutic target this behavior shows how much we don't know about the cells. Cold this or similar mechanisms be used to deliver updated mitochondria? Is this an atavistic behaviour from when we were single celled species? Are senecent and cancer cells more prone to this behavior. What about neurons do they eat each other too?

Posted by: Cuberat at October 31st, 2019 5:35 AM

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