Most of the therapeutic agents currently in development to combat ageing-related pathologies target senescent cells (senotherapy). A publication by Baker et al. in 2016 was an inspiring proof-of-principle of the anti-ageing effects of eliminating senescent cells, showing that, in mice, selective elimination of cells expressing the senescence marker p16INK4A (also known as CDKN2A) increased the healthspan of the mice.

In apparent contradiction to Baker et al., at 12 months, the mice submitted to continuous elimination of senescent cells were increasingly sick. The cells expressing the highest level of p16 at 12 months were liver sinusoidal endothelial cells (LSECs). Elimination of these senescent cells did not lead to the mobilization of neighbouring stem cells or progenitor cells to replace them, and instead resulted in fibrotic scars. Moreover, the authors provided evidence that the detrimental effect of the elimination of senescent LSECs was the decrease in the detoxification capacity of the liver. Finally, in mice, treatment with a combination of the senescent cell-eliminating drugs (senolytics) dasatinib and quercetin, which is beneficial in various pathological conditions, did not eliminate senescent LSECs, but senescent macrophages, which can indeed be detrimental to health.