Senolytics are a class of compounds being investigated for their potential to address aspects of aging. These molecules are designed to selectively target and clear specific cells from the body. Research is exploring how this process might influence health and disease.
The Role of Senescent Cells
As we age, our bodies accumulate senescent cells, which are often called “zombie cells.” These are cells that have stopped dividing due to damage or stress but resist the natural process of cell death. This state of irreversible cell cycle arrest is a protective mechanism that can prevent the proliferation of damaged or potentially cancerous cells. However, their persistence can become problematic over time.
The number of senescent cells increases in our tissues as we get older, in part because the immune system becomes less efficient at clearing them. These lingering cells are not merely inactive; they actively release a mixture of inflammatory proteins, known as the senescence-associated secretory phenotype (SASP). This cocktail of molecules can degrade surrounding tissue.
The chronic, low-grade inflammation caused by the SASP is a process sometimes called “inflammaging.” This inflammation can damage healthy cells, disrupt tissue function, and encourage nearby cells to become senescent. The accumulation of these cells and their secretions is linked to the development of various age-related conditions, including cardiovascular issues and neurodegenerative diseases.
How Senolytics Work
Senolytics function by selectively inducing apoptosis, or programmed cell death, in senescent cells. Senescent cells develop robust survival mechanisms to resist self-destruction. These are known as senescent cell anti-apoptotic pathways (SCAPs). These pathways are the primary targets for senolytic compounds.
Senolytics are designed to interfere with the particular survival proteins that senescent cells depend on, such as those in the B-cell lymphoma-2 (BCL-2) family of proteins. By disabling these defenses, senolytics effectively restore the cell’s ability to undergo apoptosis.
This targeted approach is designed to leave healthy, non-senescent cells unharmed. Because normal cells do not rely on these specific anti-apoptotic pathways to the same extent, they are less affected by the senolytic compounds. The result is the selective removal of the harmful senescent cells, reducing the inflammatory load on the tissue.
Types of Senolytic Compounds
Senolytic compounds can be broadly categorized into two main groups: naturally occurring substances and synthetic drugs developed in a lab. Research has identified several compounds in each category that demonstrate the ability to clear senescent cells.
Among the most studied natural senolytics are flavonoids, which are compounds found in many fruits and vegetables. Quercetin, for example, is present in onions, apples, and berries. Another well-researched natural flavonoid is fisetin, which is found in high concentrations in strawberries.
On the pharmaceutical side, researchers have repurposed existing drugs and developed new ones. Dasatinib, a drug initially approved for cancer treatment, was one of the first synthetic compounds identified as a senolytic. Another example is Navitoclax, also an anti-cancer drug, which targets the BCL-2 family of survival proteins. Often, these compounds are studied in combination, such as the widely researched pairing of Dasatinib and Quercetin (D+Q), to target a broader range of senescent cells.
Current Research and Human Applications
The majority of evidence for senolytics comes from preclinical animal studies. In mouse models, these compounds have been shown to delay, prevent, or alleviate a range of age-related conditions, including cardiovascular dysfunction, osteoporosis, and frailty. Research in aged mice has demonstrated that clearing senescent cells can improve physical function and extend healthspan, the period of life spent in good health.
Human research, while more preliminary, is growing. Small-scale clinical trials have begun to test the safety and efficacy of senolytics for specific diseases. The combination of Dasatinib and Quercetin has been studied in individuals with idiopathic pulmonary fibrosis (IPF). Results from an initial trial suggested improvements in physical function for these patients. Another trial involving individuals with diabetic kidney disease provided the first direct evidence that D+Q can reduce the number of senescent cells in human tissue.
Despite these promising early findings, senolytics are not yet approved by regulatory bodies like the U.S. Food and Drug Administration (FDA) for treating aging or age-related diseases. The long-term risks and potential side effects are not fully understood. Some natural senolytics like fisetin and quercetin are available as dietary supplements, but their effectiveness and safety for this purpose are still under active investigation in clinical trials. Researchers are focused on identifying who might benefit most from these therapies and the safest way to administer them.