In the past, senescent cells have been overlooked as an essential mechanism in the human body. More recently, studies have demonstrated that cellular senescence, a cell-cycle growth arrest state, contributes to the ongoing aging process. Research has shown deleterious repercussions on the body from the buildup of senescent cells with increasing age. Therefore, numerous studies have directed their efforts into targeting senescent cells as a means of combating aging and improving the quality of life.
Latest Research on senescent cells and aging
A study conducted by Kirkland et al. transplanted senescent cells onto mice, demonstrated an acceleration in aging-related processes compared to controls. Another study administered two types of drugs (dasatinib and a flavonoid) known to kill senescent cells in mice resulting in a better quality of life and lower mortality rates. The results of these studies, along with others, placed senescent cells at the forefront in the fight against aging. Currently, there has been an increase in investments by biopharma companies to identify drugs that can target senescent cells.
Cellular Senescence May Have Anti-Carcinogenic effects
Research by Serrano noted that cellular senescence is a tumor-suppressive state that prevents cells from becoming cancerous. The implication of this finding was pivotal in understanding the role of senescence as a mechanism to fight cancer. Other studies investigating the role of senescence revealed beneficial effects to the body. For instance, senescent cells can stimulate the healing of injuries via the release of certain hormones.
Furthermore, other studies have suggested that there is a profound impact of senescence in biological processes such as tissue differentiation and signaling. There continues to be a paramount of evidence suggesting the critical function of senescent cells in the body. For this reason, Dr. Campisi stated: “A major challenge she sees in developing senolytic drugs will be able to find compounds that kill groups of senescent cells that are harmful to their environment while sparing beneficial ones.”
Senolytics agents and aging
Researchers have encountered difficulties in targeting toxic senescent cells alone. A novel study was recently successful in identifying the correlation between levels of bcl2 and the ability of senescent human fibroblasts to evade death. Therefore, researchers decided to target anti-apoptotic pathways and later discovered two compounds (dasatinib and quercetin).
The efficacy of the drugs varied significantly depending on the involved pathways. Dasatinib showed damage to senescent fat cells, while quercetin showed damage to endothelial cells. Although each drug independently provided successful outcomes, a combined mixture of the two showed outstanding results. A study in mice with Alzheimer’s disease used combined drug therapy, which demonstrated reduced rates and severity of memory loss. However, researchers caution against overgeneralizing the results of their studies since these effects are not entirely attributed to targeting senescence cells.
Research efforts are still ongoing to identify better compounds that target specific pathways involved in aging. Three senolytic compounds were developed by Unity biotech with success in animal studies, one of which, UBX0101, destroyed senescent cells and stimulated cartilage development in mice with injured knees. However, it is essential to note that such compounds can also target non-senescent cells, which can interfere with other metabolic pathways.
Currently, several senolytic agents have been tested in mice. Advances in research have underlined genetically engineered T cells as a potential strategy to kill senescence cells. Given the success in mice, there is a steady move toward testing these agents in humans.
A phase I clinical trial in IPF patients is underway to examine the efficacy and safety of the combination therapy dasatinib/quercetin. Despite the early stages of the testing, researchers observed promising signs that the drug cocktail improved patients’ ability to perform daily tasks.
Another phase I clinical trial in patients with osteoarthritis revealed that after administration of UBX0101, patients’ joint function improved to a significant degree. These two main clinical trials are approved for phase II testing. Results from early clinical trials have shown senolytic agents as a promising mechanism in destroying senescence cells. However, scientists warn that more studies need to be conducted to keep an eye out for possible side effects that can occur due to the death of senescence cells.