As our cells age, their metabolism changes, they accumulate DNA damage, and they become more prone to damaging inflammation. Finding ways to slow or even reverse these changes may help people live longer and healthier lives. Dr. Vadim Gladyshev received an NIH Director’s Pioneer Award and an NIH Director’s Transformative Research Award to investigate mechanisms that control aging and study possible methods to extend our lifespan.  

Dr. Gladyshev’s team tested whether specific mixtures of molecular compounds could ‘reset’ mouse cells to reverse effects of aging. To make this determination, they looked for any changes in the cells’ genetics, metabolism, or protein makeup. The research team found that treatment with the mixtures reversed cellular changes associated with aging, including reducing damage to a molecule called RNA and lowering the levels of aging-related products of the metabolism. The treatments also restored cellular DNA to a biologically younger state by lowering the amount of modifications to DNA that had accumulated with age. The researchers linked many of these effects to specific metabolic changes that occurred after treatments with the compound mixtures.  

The compounds used in the treatments are potentially easier to tailor to specific cell types at controlled doses compared to other factors that have been tested for anti-aging effects in cells before. This suggests the exciting possibility of using this method as a cellular rejuvenation treatment that could restore cells to a biologically younger state and slow or even reverse aging to extend our lifespan. These initial experiments were performed in mouse cells; more research is needed to determine what effects occur if this treatment is given to whole animals or to human cells, and to understand what off-target, unintended consequences may occur.  

Reference: Mitchell W, Goeminne LJE, Tyshkovskiy A, Zhang S, Chen JY, Paulo JA, Pierce KA, Choy AH, Clish CB, Gygi SP, Gladyshev VN. Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation. Elife. 2024 Mar 22;12:RP90579. doi: 10.7554/eLife.90579.