Why acting your age is a thing of the past

  • Kendrick Brinson / Luceo for TIME

    Synchronized swimmers, all residents of the first Sun City community, prepare for a performance

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    As to growth-hormone supplementation, the jury is still out. A 1990 study of its effects on a group of men ages 61 and above, published in the New England Journal of Medicine , was broadly favorable. Subjects showed marked increases in lean body mass and no apparent side effects. But it was a small study, of short duration, as its author, Dr. Daniel Rudman, pointed out. His decorous note of scientific caution was destined to be ignored, and the study is now routinely cited in sales pitches for growth-hormone supplements.

    In 2003, the New England Journal of Medicine returned to the subject. This time, the conclusions weren't quite so encouraging. Growth hormone changes body composition but doesn't appear to improve function. And there are niggling concerns that growth hormone could accelerate the growth of cancer: a correlation between the development of prostate cancer and higher growth-hormone concentrations "does not demonstrate causality by growth hormone," the article noted, "but it does raise concern about giving older men growth hormone." The alternative? "Going to the gym is beneficial and certainly cheaper."

    Biology Is Destiny
    There is only one documented way to lengthen life — caloric restriction — and that hasn't been conclusively proven to work for humans, just for smaller organisms. No wonder there was so much excitement around a compound called resveratrol, which seems to mimic the effects of such a diet without the need for a punitive regimen. David Sinclair, an alumnus of MIT, now at Harvard University, spearheaded research on resveratrol, which is found in red grapes and activates sirtuins, enzymes involved in regulating metabolism. In 2008, Sinclair sold his company, Sirtris Pharmaceuticals, to GlaxoSmithKline for $720 million. But last year, a second-stage clinical trial of one Sirtris resveratrol drug was halted amid safety fears after causing kidney damage in cancer patients. Two other compounds remain in development.

    One problem with potential elixirs of youth is the danger that they may indeed stop aging — by killing the patient. Research into an enzyme called telomerase that appears to "immortalize" cells by lengthening the telomeres — the repetitive sequences of DNA at the end of each chromosome, which shorten when cells divide — has shown promising results. A study published in Nature last November indicated that mice with suppressed telomerase production aged swiftly but could be rejuvenated if the telomerase supply was restored. But high-strength compounds "are believed to be too toxic for human use. We need to do a lot of medicinal chemistry before we can get them to preclinical trials," e-mails Jon Cornell of Sierra Sciences, a Nevada-based biotech company focused on telomere research. In the meantime, both resveratrol and telomerase are available in weaker formulation as dietary supplements. TA-65, a nutraceutical that "can improve not only cell longevity but quality of life," according to its manufacturer's website, "does have a telomerase-activating effect," Cornell tells me. "But TA-65 is very weak compared to some of the other chemicals we've discussed." Why does Bill Andrews, Sierra Sciences' founder and an eminent geneticist and molecular biologist, endorse TA-65? "It's better than nothing," Cornell replies.

    As Young as They Feel
    A friend spots a bumper sticker on sale in Australia: I refuse to get old. Such slogans used to be ironic in intent. Amortals adopt them as mission statements, and the amortal form of positive thinking — refusing to contemplate age and death — can bring positive results, up to a point. "Strictly speaking, longevity is measured in numbers: it is the arithmetical accumulation of days, weeks, months and years that produces our chronological life," wrote the psychiatrist and gerontologist Robert Butler in his last book, The Longevity Prescription . "Yet aging — or, more accurately, its converse, staying young — is in no small measure a state of mind that defies measurement."

    That isn't a platitude, as Harvard psychology professor Ellen Langer set out to prove back in 1979. Her experiment, designed to see to what extent people think themselves younger or older, started with the retrofit of an isolated hotel in New England. The fixtures and fittings were exchanged for 1959 period equivalents; the refrigerator was stocked with foodstuffs available 20 years earlier. Then came the guests: men in their 70s and 80s, instructed not to view this as an exercise in nostalgia but to pretend they had traveled back two decades in time.

    This pretense proved decisive. A control group, taken from the same demographic, arrived to stay in the hotel after the first contingent had left. Their experience differed only in one key respect: they were allowed to acknowledge that this was an experiment and to reminisce about the world the retrofit evoked. In just a week, both groups chalked up physical and cognitive improvements. But the changes were much more pronounced among the time travelers.

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