Cellular therapy targeting senescent cells may improve health in mice

A new cell therapy targeting senescent cells may improve metabolic and physical function in mice, according to an NIA-funded study. Senescent cells, which are cells that have stopped dividing but do not die off when they should, have been linked to many aspects of aging and disease. In the study, published in Nature Aging, senescent cells were safely and effectively removed from the tissues of mice, leading to better health.

Every day, damaged cells die and are replaced by new, healthy cells. As we age, the body may not remove damaged cells as efficiently as it used to, and although these cells stop dividing, they do not die. These damaged cells that linger - senescent cells - contribute to inflammation and age-related decline, such as metabolic dysfunction and decreased physical fitness. Drugs called senolytics eliminate senescent cells but require continuous treatment.

A new method of eliminating senescent cells involves modifying T cells, a type of immune cell, to express chimeric antigen receptors (CARs) on their surface. These CAR T cells are engineered to recognize and eliminate cells that express a specific protein found on many senescent cells. A team led by researchers from Cold Spring Harbor Laboratory, Memorial Sloan Kettering Cancer Center, and other institutions developed CAR T cells that recognize a protein found on many senescent cells.

The researchers tested the senolytic CAR T cell therapy in mice and found that it could eliminate senescent cells. The treatment improved metabolic function - for example, glucose tolerance - and exercise capacity in older mice. Next, they treated young mice given a high-fat diet to induce premature aging. These mice experienced similar improvements to their metabolic function. Additionally, the scientists gave young, healthy mice a single treatment of CAR T cells. The treatment prevented metabolic decline for more than a year; a substantial period, as their average lifespan is two years.

These findings suggest therapeutic potential for targeting senescent cells with CAR T cell therapy in humans. Future studies may explore the broader application of this targeted cellular therapy in addressing additional age-related diseases and potentially extending longevity, building on the outcomes observed in mouse studies.

This research was supported in part by NIA grants R01AG082800, R01AG065396, and U01AG077925.

Reference: Amor C, et al. Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction. Nature Aging. 2024;4(3):336-349. doi: 10.1038/s43587-023-00560-5.