What exactly does senescence do to your cells as you age?
Senescent cells stop dividing, accumulate with age and cause damage throughout the body through a constant stream of inflammatory substances. They are both a protector (a brake on cancer) and a cause of damage, and that makes targeted intervention more complex than it appears.
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.
Claims are based on multiple review articles and mechanistic studies (PMID 30648461, 33328614, 36732079, 38654098, 33963378, 22773427, 37891477, 35216123). For the core of senescence (cell-division arrest, SASP, apoptosis resistance and accumulation) the evidence is strong and causally supported. For organ-specific effects (heart, bone, brain) the evidence is moderate and largely based on animal and association studies.
What are senescent cells and why are they bad for you?
Senescent cells are damaged cells that stop dividing but continue to live and chronically inflame their surroundings. They accumulate as you age and are strongly linked to age-related diseases, but because they also play a protective role, simply clearing them all away is not an option.
What do zombie cells do to your ageing?
Zombie cells accumulate as you age and accelerate ageing through inflammatory signals; how to tackle them is promising but still very much under investigation.
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.
Does clearing senescent cells with senolytics help against ageing?
Senolytics show impressive results in mouse studies, but in humans the evidence is too thin for use outside clinical trials. Self-medication with Dasatinib is inadvisable due to its side effects and cancer-biology risks.
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.