October 17, 2022 -- University of California, San Francisco (UCSF) researchers have found some senescent cells help to heal damaged tissues, raising questions about the merits of killing them to address age-related diseases.
Senescence happens when cells stop multiplying but continue to live. The cells, which accumulate as people age, release chemicals that can trigger inflammation and have been implicated in the emergence of age-related conditions including Alzheimer's disease, arthritis, and cancer. In animals, the removal of senescent cells has reversed or reduced age-related diseases and extended lifespans.
The discoveries spurred more research into ways to remove senescent cells and thereby treat diseases of aging. Yet, researchers have also shown that the cells may signal immune cells to heal wounds and serve as a tumor suppressor, complicating the picture and suggesting the need for a targeted approach.
In a study published October 13 in the journal Science, researchers at UCSF set out their latest contribution to our understanding of the potentially positive effects of senescent cells. The team looked for cells that express the p16INK4a tumor suppressor, a biomarker of cellular senescence, by fusing the p16 gene with green fluorescent protein (GFP).
GFP served as a marker to reveal the location of the cells under ultraviolet light. Enhancing the quantity and stability of GFP in senescent cells uncovered populations in their natural habitats of living tissues, including a group of fibroblasts within the stem cell niche in the lungs of young mice.
The cells appeared next to epithelial stem cells in the lung shortly after birth. When the lung epithelial cells were injured by a toxic compound, the senescent cells appeared to sense the tissue inflammation and responded with increased secretion and stimulation of airway stem cells. The response promoted the regeneration of the epithelial cells.
Based on the results, the researchers concluded that p16INK4a-positive fibroblasts are "tissue-resident sentinels in the stem cell niche that monitor barrier integrity and rapidly respond to inflammation to promote tissue regeneration." Leanne Jones, PhD, director of the UCSF Bakar Aging Research Institute, discussed the implications of that finding for senolytics research in a statement.
"The studies suggest that senolytics research should focus on recognizing and precisely targeting harmful senescent cells, perhaps at the earliest signs of disease, while leaving helpful ones intact," Jones said. "These findings emphasize the need to develop better drugs and small molecules that will target specific subsets of senescent cells that are implicated in disease rather than in regeneration."