The cells that refuse to die: could scientists one day treat ageing?

By Siena McCaffrey

For decades, ageing has been understood as an inevitable consequence of time. Muscles weaken, tissues deteriorate, and cells simply cease to function as efficiently as they once did. Yet modern biology suggests growing old may be far more complex than simple ‘wear and tear’. Hidden deep within ageing tissues are so-called ‘zombie cells’, damaged cells that no longer divide normally but refuse to die.

Known scientifically as senescent cells, these dysfunctional cells form when DNA damage becomes too severe for a cell to continue dividing safely. Initially, this acts as a crucial protective mechanism, preventing unstable cells from proliferating and becoming cancerous. While senescent cells stop dividing, they do not disappear, instead they linger within tissues, releasing inflammatory chemicals that gradually damage surrounding cells. Rather than viewing ageing as a passive decline of the body simply “wearing out”, scientists increasingly believe the process is driven partly by the accumulation of these damaged cells. Senescent cells have already been linked to conditions ranging from arthritis to Alzheimer’s disease, reshaping how researchers understand growing old and raising a provocative possibility: that ageing itself may one day become medically treatable.

The question is no longer simply why humans grow old, but how much of the process science may eventually be able to change

Each day, cells within the human body are exposed to small amounts of stress and strain. Ultraviolet radiation, pollution, and even normal metabolic activity can gradually damage cellular DNA. Although cells possess sophisticated repair systems, these mechanisms are far from flawless, and over time, molecular errors begin to accumulate faster than they can be corrected. Human cells are not designed to divide indefinitely. In 1961, American anatomist Leonard Hayflick discovered that normal human cells can only replicate a limited number of times before permanently stopping, a phenomenon now known as the Hayflick limit. Part of the explanation lies in structures called telomeres, protective caps found at the ends of chromosomes which shorten slightly with each cell division. Eventually, these telomeres become too short for the cell to continue reproducing safely, and division ceases. 

Rather than allowing such cells to keep dividing uncontrollably, the body forces them to a suspended state known as senescence. In this state, cells remain alive but lose their ability to replicate. While this initially serves as an important defence against cancer, senescent cells gradually accumulate within tissues. Senescence is no quiet retreat, these cells continuously release inflammatory proteins and chemical signals into surrounding tissue, known as the senescence-associated secretory phenotype, or SASP. As this low-level inflammation persists, tissue repair becomes less efficient and nearby healthy cells may themselves be pushed towards senescence; a slow cascade of biological deterioration.

Researchers have linked this process to a range of age-related disease. In joints, senescent cells appear to contribute to the chronic inflammation characteristic of arthritis. Within blood vessels, they are thought to promote cardiovascular disease by impairing repair mechanisms. Some studies have even suggested that their accumulation in the brain may play a role in neurodegenerative conditions such as Alzheimer’s disease.

Some studies have even suggested that their accumulation in the brain may play a role in neurodegenerative conditions such as Alzheimer’s disease

This understanding of cellular senescence has prompted a growing and ambitious research effort. If senescent cells contribute to ageing, could targeting them allow scientists to treat aspects of the ageing process itself? In recent years, researchers have begun developing experimental drugs known as senolytics, designed specifically to target and eliminate senescent cells from the body. Preliminary studies in mice have produced promising results. In some experiments, eliminating senescent cells appeared to improve physical function, reduce inflammation, and extend aspects of healthy lifespan. Crucially, researchers are not chasing immortality. The focus has shifted instead towards extending “healthspan”, defined as the proportion of life spent in good health, free from chronic disease and disability.

Ageing may never be reversed entirely, but if its most damaging mechanisms can be slowed or interrupted, the experience of later life could be fundamentally altered. Whether senolytics will translate from mouse models to human medicine is still far from certain, and for now, immortality remains firmly within the realm of science fiction. Yet as scientists continue to uncover the biology of the cells that refuse to die, the question is no longer simply why humans grow old, but how much of the process science may eventually be able to change.

Image: Carcarrot via Wikimedia Commons