Targeted clearance of senescent cells slows ageing and restores organ function in multiple mouse models. However, human clinical evidence is absent, and clearing the wrong cell type can worsen damage, making a targeted approach essential.
Senescent cells, also known as 'zombie cells', are cells that have stopped dividing but do not die. They secrete a mix of pro-inflammatory substances known as the SASP, which damage surrounding tissues. In a healthy body they are useful: they assist with tissue repair and embryonic development, and are normally cleared by the immune system. But as we age this clearance process fails, causing them to accumulate and contribute to age-related conditions (PMID 24954210, 35974106).
Part of the explanation for why senescent cells accumulate is that they actively resist their own removal. In human skin tissue it has been shown that senescent cells place a molecular signal on their surface (the protein HLA-E) that instructs immune cells to 'do not attack'. Blocking this signal increased the immune response against these cells in laboratory experiments. Clinical applications of this do not yet exist (PMID 31160572).
In mouse studies, multiple ways of selectively clearing senescent cells, a process called 'senolysis', have been investigated. A specially designed peptide (FOXO4 peptide) restored physical fitness, coat density and kidney function in aged mice (PMID 28340339). The drug ABT263 cleared senescent stem cells from bone marrow and muscle tissue, leading to functional recovery in mice, but this drug also has side effects because it affects non-senescent cells such as platelets (PMID 26657143). In a mouse model of tau-related brain disease (comparable to processes seen in Alzheimer's), clearing senescent glial cells prevented the accumulation of tau proteins and cognitive decline (PMID 30232451).
The diabetes drug canagliflozin, a so-called SGLT2 inhibitor, also reduced the number of senescent cells in abdominal fat in obese mice and extended lifespan in mice with premature ageing. The effect did not appear to work through blood sugar reduction, but through stimulation of the body's own immune system. Notably, the study was partly funded by the drug's manufacturer. Whether this works in humans has not been demonstrated in the available sources (PMID 38816549).
An important caveat: not all senescent cells are equally harmful. In a mouse model of liver damage, clearing senescent macrophages reduced the damage, but clearing senescent vascular cells actually made the damage worse (PMID 39368477). Indiscriminately removing all senescent cells can therefore be counterproductive. A tool for accurately identifying senescent cells, the gene set SenMayo, has been validated in human tissue and may support future research and treatment, but it is not a standard clinical test (PMID 35974106).
In summary: the basic science is promising and there is strong evidence that senescent cells play a role in ageing and disease. However, almost all intervention data come from mouse studies. Human clinical data on the efficacy and safety of senolytics are absent from the available sources. The finding that clearing the wrong cell type can worsen damage underscores that this field requires caution and is still very much under development.
All claims are based on animal experimental research (mouse models) and in vitro/laboratory studies. Human clinical intervention data are not present in the provided sources. The SenMayo gene set has been validated in human tissue, but relates to diagnostics, not treatment. One study (canagliflozin) was funded by the drug's manufacturer.