What exactly does senescence do to your cells as you age?

Senescence is a state in which a cell permanently stops dividing. Once that happens, the cell can no longer multiply, even when growth signals arrive. On its own that sounds like a clever emergency-brake mechanism, and it is: damaged or rogue cells are stopped in their tracks before they can develop into cancer cells. During embryonic development and during tissue repair after an injury, senescent cells even play a useful, temporary role.

The problem starts when senescent cells accumulate. Instead of clearing themselves away through programmed cell death, they are remarkably resistant to doing exactly that. They remain present in your tissues and switch to a pattern of continuous secretion: dozens of signalling substances, growth factors and pro-inflammatory mediators are released into the surrounding environment. This phenomenon has been given the name 'SASP', which stands for the senescence-associated secretory phenotype. Through these substances, senescent cells also damage neighbouring cells that are still healthy.

As you grow older, those cells accumulate in more and more tissues simultaneously. The result is a smouldering, chronic inflammation that progressively undermines the ability of tissues to repair themselves. This has been linked to a range of age-related conditions. In the heart and blood vessels, senescence contributes to atherosclerosis and scarring. In bones and joints, the persistent local inflammation helps trigger bone breakdown and joint damage. In the brain, senescent cells have been found in Alzheimer's patients; in animal research, targeted removal of these cells improved brain pathology and memory, but how that works precisely in humans remains insufficiently understood.

A complicating factor is that senescent cells differ considerably from one another: what they look like and what they secrete depends on the cell type, the cause and the location in the body. This makes it difficult to measure senescence reliably in a living person, which in turn complicates the development of therapies.

The heart of the dilemma is this: senescence is both a protector and a cause of damage. Anyone who blindly tries to switch senescence off also removes a brake on cancer. That is precisely why future treatments must be aimed at selectively removing or dampening harmful, accumulated senescent cells, without affecting the beneficial varieties.