A drug that has been shown to extend the life span of mice also improves the health of the rodent's heart - and holds promise of similar benefits in people, according to a new study by researchers at the Buck Institute for Research on Aging.
The study, which appears online in the journal Aging Cell, reports that rapamycin, an immunosuppressant drug approved for use by the U.S. Food and Drug Administration to help prevent organ rejection after transplants, improves the cardiac function of mice. It has previously been demonstrated that the drug can extend the life span of mice by as much as 14 percent.
"These findings are significant because we have no interest in simply extending life span without an accompanying improvement in the health and quality of life," said Buck Institute CEO Brian Kennedy, a co-author of the paper.
Buck Institute faculty Simon Melov, the senior author of the study, said, "We don't want to extend decrepitude. We don't want to extend longevity without improving organ and tissue function."
In the study, researchers assessed the effects of adding rapamycin to the diets of 18 mice over a three-month period. The mice were 24 months old, the human equivalent of 70 to 75 years of age. Similar to humans, the aged mice exhibited enlarged hearts, a general thickening of the heart wall and a reduced efficiency in the heart's ability to pump blood.
These mice and an equal number of 24-month-old mice which
were not fed rapamycin were examined with ultrasound echocardiography before and after the three-month treatment period - using metrics closely paralleling those used in humans.
Melov said age-related cardiac dysfunction was either slowed or reversed in the treated mice. The treated mice saw a reduction in heart size and a reduction in inflammation.
"When we measured the efficiency of how the heart pumps blood, the treated mice showed a remarkable improvement from where they started. In contrast, the untreated mice saw a general decline in pumping efficiency at the end of the same three-month period," Melov said. "This study provides the first evidence that age-related heart dysfunction can be improved even in late life via appropriate drug treatment."
The study showed that rapamycin treatment also resulted in beneficial behavioral, skeletal and motor changes.
Melov said, "We also carried out behavioral assessments which showed the treated mice spent more time on running wheels than the mice who aged without intervention."
The Buck researchers utilized genome analysis tools to identify sets of genes that rapamycin modulates in the heart.
Melov said, "Rapamycin affected the expression of genes involved in calcium regulation, mitochondrial metabolism, hypertrophy and inflammation."
Future studies will focus on better understanding the molecular targets that drive age-related heart dysfunction, and why rapamycin treatment is so beneficial to the aging hearts. This knowledge might allow scientists to eventually develop a drug even more effective than rapamycin.
But Melov said researchers at other institutions are already investigating rapamycin's potential role in slowing the onset of age-related disease in humans.
"There are several clinical trials underway that are looking specifically at this, particularly with a view for cardiac rehabilitation in the elderly," Melov said. Heart disease is the leading cause of death in the United States, claiming nearly 600,000 lives per year, according to the federal Centers for Disease Control and Prevention.
"It's a pretty interesting time," he said, "because we're really starting to see a movement from just doing these type of studies in model systems to actually carrying out clinical trials in human beings."
Contact Richard Halstead via e-mail at firstname.lastname@example.org
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