What is the role of inflammation in cellular ageing?
Inflammation and cellular senescence reinforce each other in two vicious cycles, leading to tissue damage and age-related diseases. Both protecting your cells against oxidative damage (think sun protection and lifestyle) and future targeted therapies aim to break this cycle.
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.
The claims are based on multiple published studies with varying levels of evidence: the SASP-inflammaging link is strongly supported; the connection to organ damage and disease is associative; findings on ribosomes and Nrf2 are preliminary (model studies and reviews). Total number of participants is unknown and was not reported in the abstract data.
Does chronic inflammation accelerate the ageing of your cells?
Chronic inflammation demonstrably accelerates cellular ageing through a negative spiral that is difficult to break. The best evidence-based approach to tackling that spiral is through lifestyle factors that dampen low-grade inflammation, such as sufficient exercise and a diet low in ultra-processed products.
Why do some cells stop dividing as you age?
Cells stop dividing as a protection against damage and cancer, but the accumulation of such stopped cells contributes over the years to inflammation and age-related diseases. Drugs that target this are promising in animal research, but are not yet ready for use outside clinical studies.
Why do damaged proteins accumulate in your cells as you age?
As you age, several systems that clear away damaged proteins weaken simultaneously and amplify each other's failure. This is one of the central mechanisms behind age-related diseases, but how to stop it in a targeted way is still actively being researched.
Do my stem cells run out as I get older?
Your stem cells do indeed decline with age: they repair tissue less effectively and become partly exhausted. Regular exercise, good sleep and not overeating are the best-supported ways to slow this process.
Does quercetin work against ageing and inflammation?
Quercetin shows promising signals in the laboratory and in animals, but in humans there is not yet solid evidence. Taking supplements on the basis of this early-stage research gets too far ahead of the science.
What is the role of chronic inflammation in the development of cancer?
Chronic inflammation is a proven driver of cancer: it promotes every step of tumour formation and makes tumours more resistant to treatment. Controlling persistent inflammation, for example through weight management or treatment of chronic infections, is therefore a relevant strategy for lowering your cancer risk.