What is the role of inflammation in cellular ageing?

Senescent cells stop dividing, but they do not go quietly. They secrete a cocktail of inflammatory substances, a property researchers call SASP. Those substances not only damage the immediate environment, but can also push neighbouring healthy cells into the same senescent state. In this way the process reinforces itself.

At the same time, that persistent, low-grade inflammation damages the immune system itself. Immune cells that become senescent lose their ability to clear away senescent cells. The result is a second vicious cycle: less clearance means greater accumulation of senescent cells, and with that even more inflammation. This pattern is also known as inflammaging, and has been consistently found across multiple studies.

The damage is not confined to one location. Chronically elevated inflammation in organs such as the liver, bone marrow and lungs is associated with age-related conditions including dementia, arthritis and type 2 diabetes. Whether inflammation is the instigator or rather a by-product differs by organ and has not yet been resolved in every case. In the brain it is reasonably well established that DNA damage and senescence in brain cells and immune cells contribute to neuroinflammation and memory decline.

Two protective mechanisms deserve attention. First: in people who live beyond 110 years of age, blood cells appear to have relatively high numbers of active ribosomes, the structures that make proteins. Laboratory experiments in which that activity was inhibited led to more inflammation, suggesting that a high protein-synthesis capacity keeps inflammation in check. Second, Nrf2, a protective switch in cells, plays a role. Nrf2 activity declines with age, causing oxidative damage and SASP-driven inflammation to increase. Activating Nrf2 could suppress inflammaging, although this is currently based on review studies and model research, not large clinical trials.

In the skin, this process is driven by harmful oxygen molecules released by UV damage or burns. Those molecules push connective-tissue cells in the skin into senescence, after which SASP substances damage other skin cells as well. In women there is also a local variant in the ovaries: ageing ovaries show more inflammation and accumulation of immune cells, along with more senescence in the cells that surround egg cells. Whether inflammation here is cause or consequence is not yet known.