A newly created mouse model has expanded the ability to study senescent cells, which are cells that in essence have stopped dividing but are still active and play an important role in aging. A team led by University of Connecticut researchers reported the new mouse model in Nature Aging. A review article accompanying the NIA-supported study emphasizes the importance of the new model to the aging biology research community. Other scientists can use the new animal model to advance research on senescent cells and test drug candidates.
Over time, senescent cells can build up in the body. The accumulation of senescent cells has been linked to many diseases of aging, such as diabetes, heart disease, and dementia.
Some senescent cells express large amounts of cell cycle proteins p16 and/or p21. Scientists rely on the measure of increased p16 or p21 in cells (among others) as an indicator of senescence. Current mouse models for research were designed using p16 to indicate the presence of senescent cells. However, not all senescent cells have high levels of p16. Because high levels of either p16 or p21 are indicative of senescent cells, the University of Connecticut team set out to create a new mouse model using p21 instead.
The team inserted genetic instructions that direct the mice to emit light in cells with p21, enabling these cells to be monitored in experiments. The higher the level of p21, the brighter the glow. The team tested and confirmed that the light-producing cells with increased p21 were senescent. In addition, the team also confirmed that stressful conditions, such as a high-fat diet, could cause cells to produce higher levels of p21 to collect in certain tissues in the mice. Further validation of the model was achieved by showing that selective clearance of p21 cells reversed age-related physical frailty in the mice.
With this new tool, scientists will be able to investigate how senescent cells that produce p21 contribute to aging. In addition to being able to explore the biology of senescent cells and their contribution to age-related health decline, scientists will also be able to test drug candidates that treat senescence.
This research was supported in part by NIA grants R37AG013925, P01AG062413, R33AG061456, R21AG063528, R01AG066679, R01AG068860, R01AG072301, and R03AG072374.
References:
- Gasek NS, et al. Strategies for targeting senescent cells in human disease. Nature Aging. 2021; 1(10), 870-879. doi: 10.1038/s43587-021-00121-8.
- Wang B, et al. An inducible p21-Cre mouse model to monitor and manipulate p21-highly-expressing senescent cells in vivo. Nature Aging. 2021; 1(10), 962-973. doi: 10.1038/s43587-021-00107-6.