Caloric restriction may leave its biggest mark in the cancer clinic. In March 2008, Longo surprised the medical community with a study showing that tumor-carrying mice forced to fast before chemotherapy showed fewer side effects and tolerated higher doses than normally fed mice. Longo theorized that short-term starvation drove healthy cells into a stress-resistance maintenance mode, but didn’t slow the activity of cancer cells. That would make all the difference in chemotherapy, which attacks the most rapidly dividing cells. In theory, Longo’s group had found a way to protect healthy cells during treatment. Because fasting can be dangerous, especially for weakened individuals, Longo urges cancer patients not to try it on their own. Clinical trials at USC Norris Cancer Hospital and at the Mayo Clinic in Rochester, Minn., are testing the safety of this approach in humans.
Valter Longo associate professor of gerontology
Longo recommends caloric restriction -- a euphemism for staying hungry. Since the 1930s, scientists have noticed that mice fed a lowcalorie diet lived longer than others fed a normal diet.
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U S C T R O J A N F A M I L Y M A G A Z I N E winter 2010
Elixir of Youth
There is an elixir of youth, and its name is youth. All substitutes have failed the test. It sounded too good to be true: You could enjoy red wine and longer life. Soon after its discovery in 2003, a grape ingredient called resveratrol made headlines in media from the British tabloids to The New York Times. In 2008, the group behind resveratrol, led by David Sinclair of Harvard Medical School, sold its small company to GlaxoSmithKline for $720 million – and no doubt celebrated with a fine glass of red. Resveratrol and related compounds still might prove their value in ongoing clinical trials against adult-onset diabetes, inflammation and cardiovascular disease. But as the journal Nature reported this year, scientists see technical flaws in the experiments that made resveratrol famous. Further, a Pfizer-funded study concluded that resveratrol and related compounds were dubious drug candidates due to their many potential side effects. As this feature went to press, two more studies came out. One, in the journal Cell, claimed that the gene allegedly activated by resveratrol – SIRT1 – slows Alzheimer’s symptoms in mice engineered to over-express the gene. A study in The Journal of Neuroscience, led by Valter Longo, found that while SIRT1 is important for learning and memory, over-expressing the gene does not improve cognition in mice. “This is a very controversial topic since [proteins in the SIRT1 family] have been shown to be both good and bad,” Longo notes. “In
our previous studies [in mice and mammalian cells], for example, we showed that it was the absence of SIRT1 that protected neurons.” At the very least, the conflicting results suggest that taking a walk around the block may do more good than driving to Walgreens for resveratrol pills. Widely prescribed for lowering cholesterol, statins also appear to reduce inflammation, which Finch and others have linked to aging and cell damage. “The great question,” says Finch, “is, ‘What can we learn from existing anti-inflammatory drugs and diet manipulations that influence the inflammatory process that are going to be applicable to maintaining human health?’ ” Statins may yet help scientists probe the connection between inflammation and aging. But whether statins themselves prolong life remains an open question. “Everybody thinks statins do good things, and so nobody wants to rock the boat,” Crimmins says. But when she and a group of geriatrics researchers from UCLA submitted an article to a leading journal showing that statins used in the treatment of cholesterol have no effect at all on survival in old people, the article was rejected. “Honestly, I was shocked,” she recalls. “The editors said, ‘We’re not interested in this paper because the use of statins is so ingrained in practice right now that it would upset things too much to say this kind of thing.’ “We don’t know what the statins are doing,” she adds. “But everybody thinks that statins in theory should be good for a lot of things, not just cholesterol; that they should lower your inflammatory burden; maybe they are good for your cognition.” If a food’s marketing literature, and maybe even the food itself, is “loaded with powerful antioxidants,” will it help you live longer? No one would love to say yes more than Kelvin Davies, a top authority on the damage caused by oxidative stress. Holder of the James E. Birren Chair in Gerontology with a joint appointment in molecular biology in USC College of Letters, Arts and Sciences, Davies coined the term “oxygen paradox” to describe the conundrum facing almost all life on earth. Animals need oxygen to breathe, but respiration produces free radicals – highly reactive and toxic oxygenated byproducts. Davies also discovered two “mechanics” in the cell that break
VA LT E R L O N G O H A S A N E S P R E S S O L U N C H AT E ATA L I A N C A F E I N G A R D E N A , C A L I F.
Interdisciplinary Gerontology