It is common for physical function to decline with age, but researchers have had unclear understanding of how aging reshapes the body. A study out of Yale School of Medicine suggests progressive stiffening of the pulmonary artery as a primary source of age-related declines in lung and heart function. The paper, “Proximal Pulmonary Artery Stiffening as a Biomarker of Cardiopulmonary Aging,” was published in Aging Cell.
“When you’re caring for older people, about one out of every three patients over 65 will come in saying, ‘I’m short of breath.’ You can often do an extensive medical workup and still not find an explanation. Their heart, lungs and arteries seem relatively normal, yet their symptoms persist,” said Edward Manning, MD, PhD, in a university news release.
Dr. Manning, who is an assistant professor of medicine in Yale’s Pulmonary, Critical Care and Sleep Medicine (Yale-PCCSM), worked with colleagues and partnering institutions to explore if changes in pulmonary circulation contribute to chronic breathlessness. The team used preclinical models to examine structural, mechanical and molecular alterations that could act as biomarkers and possible therapeutic targets.
“We’ve learned that stiffening of the aorta is one of the strongest predictors of end-organ dysfunction — damage to vital organs such as the kidneys, brain and heart — throughout the body. But the lungs are supplied by the pulmonary artery, not the aorta, which raised a simple question: Does the pulmonary artery also stiffen with age, and could this impair lung function?” said Dr. Manning, who is also a physician at the West Haven VA Medical Center.
Research findings revealed age-related structural and mechanical changes in the proximal pulmonary artery, the portion nearest to the heart, including progressive stiffening and reduced capacity. Researchers associated these changes with measurable declines in lung function, right-heart performance and exercise capacity.
Shifts in gene expression and cell signaling within the pulmonary artery were also consistent with cellular aging and remodeling of the surrounding tissue. Further transcriptional analyses found a possible role for perivascular macrophages — immune cells along the outer wall of the pulmonary artery.
“These macrophages seem to help regulate communication among the cells that make up the arterial wall,” Dr. Manning said. “In older arteries, their signaling increases and they show signs of senescence, which suggests they could represent a therapeutic target to slow age-related changes in this tissue.”
Dr. Manning said the issue of which comes first — the chicken or the egg — still exists to explore.
“We’re still trying to understand the pathogenesis — whether the pulmonary artery stiffens, or whether damage in the smaller vessels and lung tissue leads to stiffening of the larger artery,” he said. “But our hypothesis is that once the large pulmonary artery becomes stiff, that change is closely linked to declining lung function.”
His hope with this research, Dr. Manning said, is to preserve pulmonary function and quality of life, not to merely prolong lifespan.
“Ultimately, the goal is simple. Breathe better, longer.”
