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An international collaboration led by a neurologist and experts in advanced genomics at Vanderbilt Health has coaxed one of the secrets of extreme longevity from a 194-year-old giant tortoise named Jonathan.

Jonathan's secret involves entropy, the tendency of biological systems to become disordered over time.

One of the hallmarks of aging is mitochondrial dysfunction. It results from increasing entropy, or disorder, in "promoters," the genetic on-and-off switches that regulate the efficiency of mitochondria, the energy-producing organelles in most animal cells. A reliable supply of cellular energy is essential for many biological processes.

Despite his many years, Jonathan somehow had avoided the toll of entropy. By painstakingly piecing together his genome, the researchers discovered that the promoters of genes involved in mitochondrial energy production retained a remarkably youthful "orderliness." In this respect, it was as if he had hardly aged at all.

These findings, published Oct. 7 in the journal Science Advances, suggest that it might be possible to protect mitochondria from the aging-related consequences of disordered gene expression, thereby extending a healthy human life span—the "healthspan," according to the paper's senior and corresponding author, Stephen (Wes) Clark, M.D., Ph.D., MSCI.

For decades, animal studies have hinted at the antiaging potential of certain generic drugs, such as rapamycin , which was developed in 1999 to prevent the rejection of transplanted organs, said Clark, president and chief scientist of the Kallel Foundation, a Nashville-based nonprofit organization focused on longevity research.

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