The development of senolytic therapies, capable of selectively destroying senescent cells in old tissues, is a very promising area of medicine. When present even in comparatively small numbers, senescent cells actively maintain a disrupted, inflammatory state of tissues via their secretions. A dozen or more biotech companies are working senolytic therapies of various types. If anything, however, far too little work is taking place on the assessment of first generation senolytic drugs in humans, given that these treatments have produced impressive degrees of rapid rejuvenation in aged mice in many different studies. Those drugs are readily available at low cost, and can in principle be prescribed off-label by physicians.
Accumulation of senescent cells can occur due to diminished clearance ability of the immune system or persistent exposure to senescence-inducing stimuli that produce more cells than can be cleared in time. Such accumulation can lead to a chronic inflammatory state in the surrounding tissue microenvironment, also referred to as inflammaging, that further promotes senescence in neighboring healthy cells.
Due to the deleterious effects of cellular senescence, the senescent cell has been the target of active research to tackle age-related pathologies either through the approach of seno-rejuvenation or senolytics. In a pioneering study done in 2011, researchers showed that by removing p16Ink4a-positive senescent cells, there was observable delayed tissue dysfunction and extended healthspan in a progeroid mouse model.
Senolytics refers to a class of pharmacological agents that eliminate senescent cells by inducing apoptosis. Compared to their healthy counterparts, senescent cells are highly resistant to apoptosis even in the presence of cellular stresses due to activation of pro-survival and anti-apoptotic pathways. One of the most common senolytics approaches is to inhibit pro-survival pathways such as those regulated by the BCL-2 protein family and PI3K/AKT pathway. Beyond the use of senolytic drugs, there is also increasing interest in the use of engineered immune cells for senolytics purposes, stemming from the observation on the role of immune system to clear senescent cells. In a recent study, developed chimeric antigen receptor (CAR) T cells as senolytic agents to target cells expressing urokinase-type plasminogen activator receptor (uPAR).