Senior author David Sinclair of the Harvard Medical School in Boston and colleagues at the National Institute on Aging, and the University of New South Wales in Sydney, said the essence of the finding is a series of molecular events that enable communication inside cells between the nucleus and mitochondria. Mitochondria are often referred to as the cell's "powerhouse," generating chemical energy to carry out essential biological functions.
As communication breaks down, aging accelerates. By administering a molecule naturally produced by the human body, the scientists restored the communication network in older mice. Subsequent tissue samples showed key biological hallmarks that were comparable to those of much younger animals.
"The aging process we discovered is like a married couple -- when they are young, they communicate well, but over time, living in close quarters for many years, communication breaks down," Sinclair said in a statement.
"And just like with a couple, restoring communication solved the problem."
Researchers have been skeptical of the idea that aging could be reversed, due mainly to the prevailing theory that age-related ills are the result of mutations in mitochondrial DNA -- and these mutations cannot be reversed.
Sinclair and his team studied the fundamental science of aging -- broadly defined as the gradual decline in function with time -- primarily focusing on a group of genes called sirtuins. Previous research showed one of these genes, SIRT1, was activated by the compound resveratrol found in grapes, red wine and certain nuts.
Ana Gomes, a postdoctoral scientist in the Sinclair lab, studied mice in which the SIRT1 gene was removed. The researchers accurately predicted when these mice would show signs of aging, including mitochondrial dysfunction, the researchers were surprised to find most mitochondrial proteins coming from the cell's nucleus were at normal levels -- only those encoded by the mitochondrial genome were reduced.
"This was at odds with what the literature suggested," Gomes said.
Gomes and colleagues discovered an intricate cascade of events that begins with the chemical NAD. Cells stay healthy as long as coordination between the genomes remains fluid. SIRT1's role is intermediary, akin to a security guard; it assures that a meddlesome molecule called HIF-1 does not interfere with communication, the researchers said.
Over time, the research team found, this loss of communication reduces the cell's ability to make energy, and signs of aging and disease become apparent.
The study, published in the journal Cell, found muscle from 2-year-old mice given the NAD-producing compound for one week, had tissue resembling that of 6-month-old mice. In human years, this would be like a 60-year-old converting to a 20-year-old in these specific areas, the researchers said.
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