What are "zombie cells" and how do you get rid of them?

Zombie cells, known in science as 'senescent cells', are body cells that at some point permanently stop dividing. This may sound harmless, but the cells do not disappear: they stay put and continuously secrete a cocktail of inflammatory substances, known as the SASP (Senescence-Associated Secretory Phenotype). These inflammatory substances damage surrounding healthy cells and have been linked to a range of age-related diseases. With age, zombie cells accumulate in increasing numbers across various tissues (PMID 24954210, 35974106, 30232451).

However, zombie cells are not always harmful. During normal embryonic development and in cases of acute tissue injury, they actually play a useful role: they alert the immune system and promote tissue renewal. The problem only arises when they accumulate and are not cleared away in time, as happens in chronic conditions. A concrete example: in diabetic foot ulcers, significantly higher levels of senescence markers were found in wound tissue, and in mouse models the accumulation of senescent cells noticeably slowed healing (PMID 39310100).

One of the reasons zombie cells accumulate as we age is that they cleverly evade the body's own clean-up system. Senescent skin cells produce a molecule called HLA-E, which blocks the immune system's 'killer cells' (NK cells and CD8+ T cells). This molecule effectively sends a false safety signal, preventing the zombie cell from being attacked and allowing it to persist (PMID 31160572). In the brain we see a similar problem: in mice with tau-related brain disease, senescent brain cells accumulated, leading to tau tangle formation and cognitive decline. Genetically removing those cells was able to prevent this. Whether this also applies to humans has not yet been proven (PMID 30232451).

To get rid of zombie cells, researchers around the world are investigating so-called senolytics: agents that selectively kill senescent cells without damaging healthy ones. The compound ABT263 (navitoclax) selectively killed senescent cells in mouse experiments and restored the function of blood and muscle stem cells. However, its safety and efficacy in humans have not yet been established (PMID 26657143). A specially designed peptide targeting the FOXO4-p53 survival mechanism of zombie cells forced those cells into self-destruction in aged mice and restored fitness and kidney function; again, this concerns animal research only (PMID 28340339).

A striking finding is that the existing diabetes medication canagliflozin (an SGLT2 inhibitor) reduced the number of senescent cells in fat tissue in mice and extended lifespan in mice with premature aging. The mechanism of action does not work through blood sugar reduction, but through activation of the body's own immune clean-up system. Again, these are animal data and translation to humans requires further research (PMID 38816549). Another positive sign is that researchers, using the SenMayo gene panel, have found measurable evidence in both mice and humans that pharmacological treatment with senolytics can actually reduce the number of senescent cells in bone and fat tissue. This provides a measurement tool for future clinical studies (PMID 35974106).

In short: the science surrounding zombie cells is promising and the causal role in aging is well supported. But virtually all promising therapies have so far only been tested in animal models. There is currently no proven safe method for humans to remove senescent cells. It is therefore too early to draw conclusions about the use of senolytics outside of clinical trials.