Why do cells lose their ability to repair themselves over time?

Cells have multiple systems for repairing damage: they fix damaged DNA, produce new power plants (mitochondria) and clear out broken components. All of these processes slow down as you age, and that has tangible consequences. One example: with ageing, levels of NAD+, a substance cells need to drive DNA repair and energy production, decline. Without sufficient NAD+, the repair enzymes function less effectively, which contributes to muscle weakness, metabolic problems and cognitive decline.

At the same time, so-called 'senescent' cells accumulate in tissues. These are cells that have permanently stopped dividing after damage or stress. They do not clear themselves away, but they do continuously secrete inflammatory substances. Those substances damage the surrounding healthy cells and have been linked to conditions such as liver fibrosis, atherosclerosis, diabetes and osteoarthritis. In animal research, removing senescent cells was shown to reduce the symptoms of these diseases and to extend lifespan. Whether the same applies to humans is still being investigated.

Senescent cells are not always harmful, however. During wound healing and early development they play a temporarily useful role. The problem only arises when they accumulate permanently, as happens with ageing: at that point they actually inhibit repair and sustain a low-grade inflammation.

The cell's power plants, the mitochondria, also begin to function less well with ageing. The production of new mitochondria decreases, making the cell less resilient in the face of damage. In the skin there is an additional factor: the skin's support cells (fibroblasts) lose their biomechanical properties, and the skin's immune system weakens. This makes it harder to fight infections and close wounds, and increases the risk of chronic, non-healing wounds.

An interesting insight comes from research into naked mole rats, animals that live remarkably long lives. They possess a modified version of a DNA-surveillance protein that strengthens the repair process rather than slowing it down. Just a small adjustment to that protein was sufficient in cells to slow ageing. Whether something like this could ever be applied in humans remains speculative for the time being.