Senolytic therapies are those that selectively destroy the senescent cells that accumulate in tissues with age. These cells secrete a potent mix of signals that produce chronic inflammation and degrade tissue function, particularly the ability of tissues to maintain and repair themselves. While many well known interventions that improve long-term health – exercise, calorie restriction, and so forth – are likely to modestly lower the burden of senescent cells over time, by increasing the pace of destruction or lowering the pace of creation, the senolytic label is reserved for therapies that can be applied to very quickly destroy a significant number of such cells. Animal studies suggest that removing as little as a third of the senescent cells in an old individual, via treatments such as the dasatinib and quercetin combination, is enough to produce quite profound reversal of pathology in numerous age-related diseases. A higher degree of clearance should be better.
Researchers are probing ways to activate the body’s regenerative potential to slow the clock on chronic conditions that set in as we age. “We’re quite interested in what it is it about aging that compromises the ability of our bodies to rejuvenate. We want to know what it is about the process of aging that leads to the molecular and cellular damage associated with different diseases and geriatric syndromes.”
Cell senescence, a state of growth arrest, plays a key role in aging. Damage to cells, and particularly their DNA, due to natural aging processes or environmental factors such as cigarette smoke, causes cells to become senescent. Senescent cells no longer divide and differentiate. They then lose their ability to repair tissue. Senescent cells secrete harmful proteins and chemicals, creating sort of a “toxic soil” locally, if not globally, that disrupts the function of stem cells. That can sap the body’s ability to heal from injury. Though senescent cells are relatively few, they accumulate with advancing age. Ultimately, they contribute to disease and failing health.
“What’s interesting about a senescent cell, is it is a robust secretory factory, if you will, pumping out cytokines, chemokines, and other factors into the local environment that creates all kinds of havoc. It compromises the health and function of neighboring cells and the surrounding tissue. In the field of aging, we often talk about inflammation as a primary cause of disease. Factors secreted by senescent cells clearly contribute to a state of chronic sterile inflammation, or a smoldering fire, which can burst into a conflagration and drive disease.”
“We’ve published one study that in at least the context of obesity, finds exercise can prevent senescent cell accumulation and, to some extent, clear senescent cells from the body. Exercise has profound effects on our cells and their capacity to repair different aspects of cell damage that are linked to aging and age-related diseases. For example, exercise improves the cells’ ability to repair DNA, manage oxidative stress, and turn on the garbage disposal and get rid of old damaged proteins.”