When cells stop dividing, they do not necessarily disappear. Some remain in tissues, where they are known as senescent cells. Immune cells can remove them, but a study suggests why this task may become harder with age: the cells awaiting removal can weaken the cells meant to clear them away. Nature Aging (source, opens in new tab)Nature AgingDecline of chaperone-mediated autophagy in aging impairs macrophage clearance of senescent cellsOpen source (opens in new tab)
The researchers traced this problem to a process that breaks down selected proteins inside cells. Substances released by senescent cells disrupted that process in macrophages, immune cells that engulf other cells. As the macrophages became less effective, senescent cells were harder to remove—a cycle that could help explain why they accumulate.
A drug that activated the recycling process reduced the number of senescent cells in aged mice. It also reduced disease severity in mice with an experimental form of pulmonary fibrosis, which involves scarring of the lungs. These findings offer a direction for research, but do not establish a safe or effective treatment for people.
To examine the immune cells’ role, the researchers blocked this recycling process specifically in macrophages in mice. Senescent cells accumulated, and senescence took longer to resolve during wound healing. The result suggests that their persistence depends partly on the condition of the immune cells responsible for removing them.
The process, called chaperone-mediated autophagy, also affected the senescent cells themselves. Cells lacking it developed changes in their proteins, internal chemistry and the substances they released. These resembled changes seen in aged senescent cells, suggesting that declining recycling can alter how the cells behave as well as whether they are cleared away.
The human evidence is less conclusive. Observations in lung tissue linked the recycling process with ageing and idiopathic pulmonary fibrosis, a form of lung scarring with no known cause. They could not establish cause and effect, and still need validation. The question now is whether helping immune cells do their clearing work could produce benefits in people comparable to those observed in mice.
- Nature Aging · Peer-reviewed studyDecline of chaperone-mediated autophagy in aging impairs macrophage clearance of senescent cellslink.springer.com · opens in new tab
