Reverse Aging News Spring 2015

Everolimus, Derivative of Rapamycin, Tested in Humans

Rapamycin is a drug that has been approved for use against certain kidney, lung, and breast cancers. It has also shown promise in extending life by retarding the start of diseases of aging like cardiovascular disease, cancer, and Alzheimer's disease. Rapamycin is produced by the soil bacterium Streptomyces hygroscopicus. It's name came from Rapa Nui, the indigenous name of Easter Island, where the compound was originally discovered in soil samples in the 1970s.

Swiss pharmaceutical colossus Novartis is starting to position a version of rapamycin as the first genuine anti-aging drug. “People have shown that rapamycin extends life span again and again and again,” said Matt Kaeberlein, PhD a University of Washington scientist whose work is focused on developing therapies for age-associated diseases by targeting the molecular mechanisms of aging.

So far, the drug has extended the life span of mice, not humans, but according to Kaeberlein “It appears to delay age-related decline in multiple different organ systems, which is something we would expect if we were fundamentally slowing the aging process....It's not just life span that is extended but many age related declines in function are also improved by Rapamycin so cardiac function is improved, cancer seems to be delayed, immune function at least to some extent is improved, cognitive function is improved. So it's not only that the mice are living longer, they are healthier longer into later age," Kaeberlein told Reuters.

Male mice on rapamycin lived 9 percent longer. Female mice averaged an additional 14 percent of life, the rough equivalent in humans of giving 60 year old women a drug that would keep them alive to 95th. Kaeberlein is now leading a rapamycin study on dogs. If it proves worthwhile it could lead to human testing. "This is a much more efficient approach to promoting health than waiting until people are sick with a disease and treating a disease at that point."

Rapamycin works at a basic level of cell biology. In the early 1990s, Sandoz scientists learned that rapamycin molecules inhibit a cellular pathway that regulates growth and metabolism. This pathway was named “target of rapamycin,” or TOR, and it's found in animals from yeast to humans. In mammals it's been dubbed mTOR. It can be likened to a circuit breaker. When mTOR is turned on cells grow and divide, when it's turned down the cells go into more of a conservation mode cleaning and recycling proteins using less energy. Scientists think that one reason why calorie restriction works in extending life is that it turns down activity in the mTOR pathway. Perhaps the biggest advocate of calorie restriction was Roy Walford, MD of UCLA who made his case for a nutrient dense low calorie diet in the anti-aging documentary "Reverse Aging Now." Rapamycin has the potential of creating the same effect. Humans evolved to survive between hunts. It turns out that the fallow period between plentiful food when the body is in stress resistant mode is good for anti-aging. Periodic fasts have a similar effect.

Rapamycin does suppress the immune system which is why it is used as a drug to aid patients with transplant rejection. Since immune systems are less effective in older people leading to an increased rate of infection, it could be the drug's weak spot. However this past December a new research study backed by Novartis conducted by Joan B. Mannick, Giuseppe Del Giudice et al. published in Science Translational Medicine had heartening news. According to the study, elderly human volunteers in Australia and New Zealand showed an immune response that improved by 20 percent when they took a derivative of rapamycin called everolimus to enhance the effectiveness of a flu vaccination. Since immune response declines with age, the fact that it was boosted indicates that the drug affected underlying molecular pathways at a deep level.

Rapamycin has been found to reduce age-related bone loss, reverse cardiac aging, reduce chronic inflammation and reverse Alzheimer's disease in mice. The new study was the first to examine rapamycin's effect on aging-related parameters in healthy older people. “It's a landmark study,” said Brian Kennedy, chief executive officer of the Buck Institute for Research on Aging in Novato, “It's the kind of study we need more of.”

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