New research suggests that youthful heart stem cells may be able to rejuvenate an aging heart and perhaps even reverse other signs of aging.
Researchers from the Cedars-Sinai Heart Institute in Los Angeles, CA, found that injecting aged rats with specialized stem cells taken from the hearts of newborns appeared to rejuvenate the older animals.
The treatment improved heart function, increased exercise capacity, and reversed several biomarkers of aging.
Over the past 100 years, there has been a remarkable improvement in human life expectancy worldwide. Soon, the world will have more older people than children.
Such a demographic transformation brings new challenges to medicine. Nowadays, even in poorer nations, most older people die from heart disease, diabetes, cancer, and other non-communicable illnesses as opposed to infectious and parasitic diseases.
In the United States, heart disease is the leading cause of death among men and women.
Another feature of an aging population is the increase in people with more than one health problem, for example diabetes and heart disease.
In their study report – which is published in the European Heart Journal – the researchers note that the incidence of cardiovascular disease “increases markedly” with age, and they discuss what happens in the aging heart.
For example, as the heart ages, it becomes stiffer and less able to relax, thereby increasing the risk of heart failure.
The authors also discuss what happens in heart cells as the heart ages. One of the features they mention is the progressive shortening, as cells divide, of telomeres, which are the “caps” that protect the ends of chromosomes.
The researchers explain that “critical shortening” of telomeres is associated with a number of heart problems that arise with age, such as heart dysfunction.
Certain “rejuvenating strategies” – including transfusing young blood and reprogramming cells – have shown promise in tackling some of these problems, note the authors, but none have yet “addressed age-related heart dysfunction.”
For their investigation, the researchers took cardiosphere-derived cells from newborn rats bred in the laboratory and injected them into the hearts of elderly rats aged around 22 months.
Cardiosphere-derived cells are immature cells that can mature into any of the three major types of heart cell: cardiomyocytes, endothelial cells, and smooth muscle cells.
The team also treated another group of rats of the same age, which acted as controls, with saline injections instead of cardiosphere-derived cells. They then compared both groups with young rats aged around 4 months.
Before treatment, at baseline, the rats underwent tests of heart function, exercise capacity, and various blood markers. The tests were then repeated a month after treatment.
Comparisons of the before and after tests showed evidence of improvement not only in the heart itself, but also in other markers.
For example, compared with the control rats treated with saline, the rats that received the youthful cardiosphere-derived cells showed improved diastolic function. Healthy diastolic function allows the heart to relax properly and fill with blood ready for pumping.
The older rats treated with the specialized stem cells also had longer telomeres in their heart cells, showing signs that their hearts had aged less rapidly than those of the control rats.
Finally, compared with the rats that did not receive the youthful cells, the treated rats also improved their exercise capacity by 20 percent and regrew hair faster.
On closer examination, the team discovered a possible explanation for the rejuvenating effect of the cardiosphere-derived cells.
“They secrete tiny vesicles that are chock-full of signaling molecules such as RNA and proteins,” explains senior author Eduardo Marbán, a professor of medicine and director of the Cedars-Sinai Heart Institute. “The vesicles from young cells appear to contain all the needed instructions to turn back the clock,” he adds.
The researchers point out that it will be up to future studies to find out whether or not treatment with the cardiosphere-derived cells increases lifespan.
They team suggests that future research must aim to find out whether the cells have to come from a young donor or not, as well as whether or not all the rejuvenating effects of the cells come just from the vesicles.
“Our previous lab studies and human clinical trials have shown promise in treating heart failure using cardiac stem cell infusions. Now we find that these specialized stem cells could turn out to reverse problems associated with aging of the heart.”
Prof. Eduardo Marbán