Senolytics

A fundamental aging mechanism that likely contributes to chronic diseases and age-related dysfunction is cellular senescence. Senescence is a fundamentally protective action, occurring when a cell receives a signal to stop replicating because it is too damaged to continue dividing. A cell might go senescent because it has developed a potentially cancerous mutation, because it has been irradiated, exposed to oxidative stress, or it has been injured in some way. In youth, senescent cells are cleared from the body almost as quickly as they arise. However, as we age, and due in part to age related changes in immune function, a reduced clearance of senescent cells occurs and there is an accumulation of senescent cells (sometimes called zombie cells).

There is good evidence that these senescent cells contribute to the process of functional loss we call Aging. For example- when senescent cells are transplanted into laboratory animals, their age-related loss of function is accelerated. When senolytics are also administered, this effect disappears. Furthermore, accumulations of senescent cells have been identified in increased numbers at various sites of tissue pathology.

Aging is the leading risk factor for the chronic diseases that account for the bulk of morbidity, mortality, and health costs in most people’s lives. Cellular senescence has been linked to immunologic, cardiovascular, neurologic, cognitive and muscular dysfunction as well as being linked to markers skin aging.

In laboratory mice, the removal of senescent cells with senolytic agents has been associated with the improvement of many of these functions and reduction in the markers we associate with normal aging. Recently, a 3-day course of senolytics, (Dasatinib and Quercetin-medications already approved by the FDA for other indications in humans)- has been demonstrated to decrease senescent cells in humans with drug-controlled diabetes mellitus and CKD (age range 55–79 years old) and to improve functional performance of the individuals treated.

There are currently no high-quality studies proving that senolytic therapy is effective in Humans. Studies in animals are promising, as are early results in people. There is a strong interest in pharmaceutical and biotech research to develop better molecules to clear senescent cells from the body. Senolytic therapy represents one strategy of addressing aging that is promising and for which imperfect but likely effective tools already exist.