Mayo Clinic Study Links Biology of Aging and IPF, Opens New Paths for Possible Therapies

Mayo Clinic Study Links Biology of Aging and IPF, Opens New Paths for Possible Therapies

A new Mayo Clinic study has demonstrated new evidence of the link between the biology of aging and idiopathic pulmonary fibrosis (IPF).

The study, “Cellular senescence mediates fibrotic pulmonary disease,” appeared in this month’s issue of Nature Communications  and point towards new possible directions for therapies targeting IPF.

“Idiopathic pulmonary fibrosis is a poorly understood disease, and its effects are devastating,” Nathan LeBrasseur, PhD, the study’s senior author and director of Mayo’s Healthy Aging and Independent Living program said in a press release. “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.”

LeBrasseur and his team studied lung tissue samples from healthy people, as well as from people with mild, moderate and severe IPF, that had been obtained from the Lung Tissue Research Consortium of the National Heart, Lung and Blood Institute, a unit of the National Institutes of Health.

The markers of cellular senescence (cell aging) were found to be higher in IPF patients, suggesting a link between the biology of aging and increased disease burden. The researchers furthermore confirmed that the presence of senescent cells could indeed lead to inflammation and aberrant tissue remodeling, as well as fibrosis.

“We discovered that senescent cells, which accumulate in the idiopathic pulmonary fibrosis lung, are a viable source of multiple factors that drive fibrotic activation,” said Marissa Schafer, PhD, the study’s lead author and a postdoctoral fellow in LeBrasseur’s lab.

These findings represent a conceptual turn in how we think about IPF.

“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,” said LeBrasseur.

Researchers also replicated the process in mice and got similar results: mice with clinical features of IPF also showed increased counts of senescent cells. With the help of a genetic model, researchers were able to program senescent cells to self-destruct, as well as make a drug combination (dasatinib and quercetin) capable of eliminating senescent cells. Eliminating senescent cells in unhealthy mice was found to improve measures of lung function and physical health.

Senescent cells could therefore be considered a target for new therapies to help people with IPF.

“Previous work from the Center on Aging has shown in a number of models how senescent cells contribute to aging and aging-related conditions,” added LeBrasseur. “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.”

2 comments

Leave a Comment

Your email address will not be published. Required fields are marked *