Zombie cells, stress, and the brain: The new science of growing old

‘Zombie cells’ and the energy paradox 

Senescent cells are cells that have permanently stopped dividing in response to damage or stress, yet remain alive. Scientists often refer to them as “zombie cells” because, although they no longer carry out their original functions, they release harmful substances that promote inflammation and accelerate the ageing of surrounding tissues.

A team led by psychobiologist Martin Picard at Columbia University found that these cells exhibit a metabolic rate twice as high as that of younger cells - a discovery that challenges the long-held view that ageing is solely associated with a general slowing of biological processes.

Picard proposed the 'brain–body energy-conservation model'. According to this hypothesis, the brain responds to the growing energy demands of ageing cells by reallocating the body’s resources. As a result, less energy is available for other processes such as muscle growth and hair pigmentation, which may explain the visible signs of ageing.

Scientists also believe the brain plays a central role in transmitting signals that trigger inflammation, the shortening of telomeres (protective caps at the ends of chromosomes), and cellular ageing. One molecule appears to be key in this mechanism: GDF15, which is released by cells under stress or damage. While many organs can produce GDF15, its receptors are found only in the brain, suggesting it may serve as a crucial messenger between body and brain.

Recent experiments have shown that GDF15 levels rise not only in response to physical stress, but psychological stress as well. This supports the idea that the brain plays a commanding role in ageing, responding to cellular stress signals by diverting the body’s energy, often at the cost of vital biological functions.

Stress at the molecular level

Scientists began exploring the connection between stress and ageing in the early 2000s. One of the first large-scale studies was led by Elissa Epel at the University of California, San Francisco. Her team found that women caring for children with chronic illnesses had significantly shorter telomeres compared to mothers of healthy children. Moreover, the length of the telomeres correlated directly with the duration of the caregiving stress.

Subsequent studies confirmed that other forms of chronic stress, including childhood trauma, workplace burnout, and low social status, can also leave a molecular imprint. These include telomere shortening and changes in the epigenome: chemical modifications to DNA that influence gene activity.

Social stress shortens lifespan in animals

Animal studies have provided further insight into how stress affects the body. A research team led by biologist Alessandro Bartolomucci at the University of Minnesota found that mice exposed to social stress, such as being attacked by dominant cage mates, accumulated molecular markers of cellular ageing more quickly, including increased levels of the protein called p16. Interestingly, mice subjected to physical restraint, such as confinement in narrow tubes, did not show the same biological signs of ageing.

Similar patterns were observed in rhesus macaques. Researchers at Arizona State University showed that monkeys with lower social status had increased activity of genes linked to inflammation. When the animals' social hierarchy was rearranged, those molecular markers shifted accordingly, indicating that some ageing-related processes may be reversible under changing social conditions.

Can ageing be slowed?

A growing body of evidence suggests that chronic stress affects nearly all key biological markers of ageing. Researchers believe that a deeper understanding of the brain’s role in these processes, particularly how it responds to stress, could reshape approaches to treating age-related diseases.

One promising direction involves the search for pharmaceutical and behavioral interventions. Physical activity, for instance, has been shown to slow telomere shortening in individuals under chronic stress. These findings are especially significant as scientists work to develop anti-ageing therapies. Experts caution that without accounting for stress as a variable, the effectiveness of such treatments cannot be fully assessed.

Earlier, Kazinform News Agency reported that the American scientist has made a significant breakthrough in understanding how axolotls - Mexican salamanders famous for their regenerative abilities - regrow limbs and organs.