Senescent Cells Implicated as a Cause of Idiopathic Pulmonary Fibrosis

The number of senescent cells in tissues grows with age, and these cells cause harm through forms of signaling that induce inflammation, destructively remodel the extracellular matrix, and alter the behavior of other cells for the worse. Now that clearance of senescent cells has been shown to robustly extend healthy life span in mice, there is a lot more interest in the research community in joining the dots between cellular senescence and specific age-related diseases. The past year has seen a range of publications that directly implicate senescent cells in various age-related diseases, or attempt to quantify exactly how much of the detrimental alterations in aged tissues are caused by these cells. In this particular case, researchers are looking at the lung condition known as idiopathic pulmonary fibrosis, and you might compare these results with another promising study of senescent cells in the lungs carried out last year. We can hope that the various companies developing clearance therapies will bring them to the clinic sooner rather than later.

A study has shown evidence linking the biology of aging with idiopathic pulmonary fibrosis, a disease that impairs lung function and causes shortness of breath, fatigue, declining quality of life, and, ultimately, death. Researchers believe that these findings are the next step toward a possible therapy for individuals suffering from idiopathic pulmonary fibrosis. "Idiopathic pulmonary fibrosis is a poorly understood disease, and its effects are devastating. Individuals with idiopathic pulmonary fibrosis express difficulty completing routine activities. There are currently no effective treatment options, and the disease leads to a dramatic decrease in health span and life span, with life expectancy after diagnosis between three to five years."

Researchers studied the lung tissue of healthy individuals and of persons with mild, moderate and severe idiopathic pulmonary fibrosis. Researchers found that the markers of cellular senescence, a process triggered by damage to cells and linked to aging, were higher in individuals with idiopathic pulmonary fibrosis, and senescent cell burden increased with the progression of the disease. Then, they demonstrated that factors secreted by senescent cells could drive inflammation and aberrant tissue remodeling and fibrosis, which are hallmarks of idiopathic pulmonary fibrosis. "Up to this point, research efforts have largely focused on understanding the unique elements that contribute to idiopathic pulmonary fibrosis. Here, we are considering whether the biology of aging is accelerated in this aggressive disease. What we've found is that senescent cells are prevalent, secreting toxic molecules that affect healthy cells in that environment and are essentially promoting tissue fibrosis."

Equipped with the findings from their studies of human lung tissue, researchers then replicated the process in mice. They found that, much like in humans, mice with clinical features of idiopathic pulmonary fibrosis also demonstrated increased amounts of senescent cells. Researchers used a genetic model programmed to make senescent cells self-destruct and a drug combination of dasatinib and quercetin which, in previous studies, was shown to eliminate senescent cells. Results showed that clearing senescent cells from unhealthy mice improved measures of lung function and physical health, such as exercise capacity on a treadmill. "We are exploring whether senolytic drugs, or drugs that can selectively kill senescent cells, can be used for the treatment of aging-associated conditions, including idiopathic pulmonary fibrosis. More research is needed to validate this, and our goal is to move quickly from discovery to translation to application, and, ultimately, meet the unmet needs of our patients."


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