Cellular senescence

Cellular senescence is a state in which a damaged cell stops dividing but does not die, and instead keeps signalling to the tissue around it. It is one of the twelve hallmarks of aging set out by López-Otín and colleagues in 2023.

The state is useful before it is harmful. Halting division in a damaged cell is one of the body’s defences against cancer, and senescent cells also take part in wound healing and in the shaping of tissue during development. The problem is accumulation: these cells build up with age and are cleared less efficiently by an aging immune system.

What makes them interesting as a target is what they emit. Senescent cells secrete a mixture of inflammatory signals, growth factors and enzymes, and that secretion can push neighbouring cells towards the same state and drive chronic inflammation in the surrounding tissue. A small number of cells can therefore affect a much larger volume of tissue than they occupy.

This is the basis of senolytics, drugs intended to kill senescent cells selectively. The idea is unusually testable, and results in mice have been striking. Human trials so far are small and early, and the gap between the two is where most public writing on the subject quietly skips.